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Monoamine oxidase inhibitors in Amazonian hallucinogenic plants : ethnobotanical, phytochemical, and… McKenna, Dennis Jon 1984

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MONOAMINE OXIDASE INHIBITORS IN AMAZONIAN HALLUCINOGENIC PLANTS: ETHNOBOTANICAL, PHYTOCHEMICAL, AND PHARMACOLOGICAL INVESTIGATIONS By DENNIS JON MCKENNA B. A . , U n i v e r s i t y of C o l o r a d o , 1973 M . S c , U n i v e r s i t y of H a w a i i , 1979 A THESIS SUBMITTED  IN  PARTIAL  FULFILLMENT  THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF  PHILOSOPHY in  THE FACULTY OF GRADUATE STUDIES (Department  We a c c e p t  this  t o the  of  Botany)  thesis  required  as c o n f o r m i n g standard  THE UNIVERSITY OF BRITISH COLUMBIA February © D e n n i s Jon  1984  McKenna,  1984  OF  In  presenting this  requirements of  British  it  freely  in partial  f u l f i l m e n t of  f o r an a d v a n c e d d e g r e e a t  Columbia, available  agree t h a t for  thesis I  agree that  for reference  the  University  the L i b r a r y  s h a l l make  and s t u d y .  I  permission for extensive  copying of  understood that financial  copying or p u b l i c a t i o n of  Department o f  Botany  The U n i v e r s i t y o f B r i t i s h 1956 Main Mall V a n c o u v e r , Canada V6T 1Y3  )E-6  (3/81)  this It  this  g a i n s h a l l n o t be a l l o w e d w i t h o u t  permission.  Date  further thesis  s c h o l a r l y p u r p o s e s may be g r a n t e d by t h e h e a d o f my  d e p a r t m e n t o r by h i s o r h e r r e p r e s e n t a t i v e s . for  the  26 A p r i l , 1984  Columbia  is thesis my  written  i i  ABSTRACT Ethnobotanical, investigations  of  The e x t a n t  phytochemical,  two Amazonian h a l l u c i n o g e n s a r e  literature  e t h n o p h a r m a c o l o g y of hallucinogens is  is  modify  the  s o u r c e of  reviewed.  resin  of  other  certain  woody  Virola  while  resin.  different  botanical  owe t h e i r  hallucinogenic  sources,  are  investigated;  d e a m i n a t i o n by v i s c e r a l  both ayahuasca  activity  to  although having  are  potent  reversible  the  tryptamines  T h i s mechanism may u n d e r l y  potent  the  of  economic c l a s s e s utilization  mestizo folk living  of V i r o l a  in  spp.  the  oral  orally-  from  entirely  and t h e V i r o l a  found  and/or  (MAO). as  MAO; t h u s  activity  in  5-methoxy-  oxidative The  they  /3-carboline  may  protect  them o r a l l y of  ayahuasca  d r u g s . Ayahuasca  s o u r c e of  are  hallucinogens,  m e d i c i n e among t h e  the  drugs  viz.,  is  lower  active. and  an socio-  s e m i - u r b a n Amazonian c e n t e r s , as  snuffs  h a l l u c i n o g e n s but  MAO and r e n d e r  orally-ingested Myristicaceous of  an  or  cambial  tryptamines  limited activity  from v i s c e r a l  the  p r e s u m a b l y due t o  inhibitors  is  indole a l k a l o i d s ,  monoamine o x i d a s e  alkaloids,  part  prepare  Although derived  when i n g e s t e d o r a l l y ,  strengthen  made i n t o h a l l u c i n o g e n i c others  both are  ayahuasca  caapi  which  N,N-dimethyltryptamine  N,N-dimethyltryptamine;  integral  beverage  (Myristicaceae)  and / 3 - c a r b o l i n e s . The major  these p r e p a r a t i o n s  the  is  and  Myristicaceous  admixture plants  spp.  presented.  chemistry,  Banisteriopsis  hallucinogens  i n g e s t e d d r u g from t h e  inactive  liana  The genus V i r o l a  by some Amazonian t r i b e s ,  tryptamines  botany,  The h a l l u c i n o g e n i c  and v a r i o u s  effect. the  on t h e  t h e M a l p i g h i a c e o u s and  p r e p a r e d from the  (Malpighiaceae)  and p h a r m a c o l o g i c a l  but  hallucinogenic  the  preparations  is  c o n f i n e d t o a few  and even among some of  these  i n d i g e n o u s Amazonian  groups i s  a rapidly  tribes,  disappearing  practice. The p h a r m a c o l o g y and b i o c h e m i s t r y carboline  derivatives  biosynthesis, interactions degradative and o t h e r  distribution,  the  of  ethnographic  are  presented  of  analysis  presented,  are  (Chapter  and t h e  Pucallpa,  by B o r a  Peru,  and W i t o t o  Myristicaceous restricted raised  to  that  are  their  the  Bora  the  ayahuasca  is  drugs,  the  remained  pastes  are  are ayahuasquero  preparation  of  use of  use of  of  the  Observations in  ayahuasca  the  oral  ethnologically The p o s s i b i l i t y  is  pharmacological a c t i v i t y  a reflection  may have c o n t r i b u t e d  on  and t h e V i r o l a p a s t e s  compared t o  unreliable  for  procedures  also described.  and W i t o t o t r i b e s .  somewhat  the M y r i s t i c a c e o u s variability,  of  are  in  by an  the  used  observations  preparation  d e s c r i b e d . The  d r u g s , w h i c h has the  materials  ayahuasca  in  voucher  and t h e methods  i n c l u d e d . The c o n t e m p o r a r y  medicine  fieldwork  Herbarium  II),  informants  pastes  biological activity  self-experiments  is  and  properties,  orally-ingested Vi rola  and t h e methods u s e d i n  in mestizo folk  III).  described. Ethnographic  orally-ingested Virola on t h e  relationships,  reviewed.  d r u g s a m p l e s and p l a n t  are  ayahuasca  near  followed  Their  and e t h n o b o t a n i c a l  documented.. The f o l k - m e d i c a l use of living  II).  and 0 -  endogenous s y n t h e s i s  documented ( A p p e n d i x  collection  use of  (Chapter  structure/activity  biological activities  collections  chemical  tryptamine  m e t a b o l i s m i n mammals, h a l l u c i n o g e n i c  Amazon B a s i n a r e  the  reviewed  w i t h MAO i n h i b i t o r s ,  Results  in  is  of  their  to a d e c l i n e  of  chemical in  the  use of  the  pastes. The a l k a l o i d s B.  caapi,  of  a number of  and a d m i x t u r e p l a n t s  ayahuasca  were q u a l i t a t i v e l y  qualitatively  analyzed using thin-layer  high-pressure  l i q u i d chromatography  chromatography/mass spectrometroy contained their  hallucinogenic  however the  insufficient  b l o c k a d e of similar  visceral  alkaloid  alkaloids  varied  of  properties  (HPLC)  the  different batches  assuming t h a t  proportions  of  concentration  in  alkaloid  constituents. in  several  genetic found  differences.  in a l l  Psychotria  carthagenensis.  Several  for  but  alkaloids,  only  were  only  of  Different  and i n  factors  of  in  B.  of  the alkaloid  caapi  rather  were  than  DMT were and i n  one  but DMT was not d e t e c t e d the  single  traces  of  major other  uncommon a d m i x t u r e p l a n t s one, Abuta g r a n d i f o l i a ,  gave an u n a m b i g u o u s l y p o s i t i v e  had  remarkably  concentrations  DMT was  admixtures;  were d e t e c t e d .  Peru.  concentration  Diplopterys cabrerana  these  of  reaction.  the  constituents  v i r i d i s samples a n a l y z e d ,  of  in  ayahuasca  by  p r e p a r e d by  recognized c u l t i v a r s  collection  detected  of  above  activated  Considerable variation  Substantial  Psychotr ia  orally  individual  parts  f o u n d but may be due t o e n v i r o n m e n t a l  used;  the c o n c e n t r a t i o n s  same p r a c t i t i o n e r  total  for  of DMT was w e l l  ayahuasca  in various  p r e p a r e d by t h e both  of  is  samples  to account  doses t y p i c a l l y  batches  and t h e p r o p o r t i o n s of  ayahuasqueros  consistent  it  MAO. D i f f e r e n t  in batches  (TLC),  and gas  0-carbolines at  of  and  (GC/MS) The a y a h u a s c a  c o m p o s i t i o n s , however  considerably  cultivars  chromatography  i n most s a m p l e s t h e c o n c e n t r a t i o n  threshold l e v e l ,  total  levels  brews,  in  base alkaloids  were  screened  (Menispermaceae)  V  Alkaloids  in twenty-eight  s a m p l e s were q u a l i t a t i v e l y TLC,  GC, p r e c i p i t a t i o n  eight  tests,  bases,  also present  carbolines  were n o t  the  Iryanthera  indolic was  base,  the  identified  substantial  proportions snuff  varied  amounts of  greatly  including various  contained  tryptamines.  concentrations and l e a f  between  of  alkaloids  0-carbolines,  contained  for  using  1  activity  was  greater  than  DMT was  t h e most a c t i v e MAOI of  one  to  bark  0.25  detectable  as MTH/3C and  assay  * - C - s e r o t o n i n as various  several  of  rat-liver  substrate.  tryptamine  orders  of  tryptamines  and  0-  activity  magnitude  measured w i t h t r y p t a m i n e the  but  the  as MAOI were d e t e r m i n e d . The MAOI  /3-carboline d e r i v a t i v e s  and  constituents.  i_n v i t r o  of  one  of V i r o l a  f r o m 0.04  samples c o n t a i n e d  the  relationships  derivatives  the  paste  were t r a c e  M e t h o d s were d e v i s e d  carboline  types  15-20 mg/g d wt;  ranging  but  highest  w h i c h were i d e n t i f i e d  DMTH/3C. The 0 - c a r b o l i n e s  Structure/activity  Samples  Drug s a m p l e s w i t h t h e  (MAO)  orally-  were a n a l y z e d . A l l  samples.  the  ester,  a d m i x t u r e s were a n a l y z e d and a l l  O n l y two V i r o l a  monoamine o x i d a s e  Fourteen  Seven s a m p l e s of  the  0-  An  methyl  but  of  none of  alkaloids.  tryptamines,  s a m p l e s had c o n c e n t r a t i o n s  mg/g d wt. levels  of  levels  samples.  as N-methyl-tryptophan  spp.  twenty-  DMT and 5-MeO-DMT  bark and l e a f  found in Osteophloem platyspermum.  contained  the  using  amounts of NMT a n d / o r  contained detectable  i n g e s t e d d r u g s made from V i r o l a  of  alkaloids.  of  samples c o n t a i n e d a l k a l o i d s ;  species  leaf  determined  i n most s a m p l e s . D e t e c t a b l e  found i n  eighteen Vi rola  b a r k and  and GC/MS. S i x t e e n  w i t h much s m a l l e r  tryptamine  six  and q u a n t i t a t i v e l y  samples c o n t a i n e d d e t e c t a b l e  were t h e major  of  Myristicaceous  derivatives.  tested  while  vi  h a r m i n e was t h e most a c t i v e o f m i x t u r e s of than  the  rather  0-carbolines  were not  0-carbolines. significantly  s i n g l e most a c t i v e c o m p o n e n t ,  than a s y n e r g i s t i c  ayahuasca several  the  were h i g h l y  orders  m i x t u r e s of  elicited  a c t i v e a s MAOI even when d i l u t e d  by  of  action.  The a c t i v i t y  having  similar  was c o m p a r a b l e  concentrations  orally-ingested Virola as MAOI.  The i n h i b i t i o n  matched by m i x t u r e s  of  paste  elicited highest  sample and a c r u d e  only  a slight  concentrations.  l i m i t e d MAOI a c t i v i t y tryptamines; inhibitors the  degree  total  the  of  of  which  of  or  indicate  suggest  MAO by 0 - c a r b o l i n e s may e x p l a i n  of  ayahuasca,  but  for  the  oral  activity  unlikely  of  that  mechanism must  therefore  alternative  is  spp.  constituents  that Vi rola  which are  active  as  reviewed  hepatic  which  indicates  MAO, may a c t u a l l y  that  be more  m e t a b o l i s m and i n a c t i v a t i o n  of  the  the  to  the  the  the  oral  pastes.  to  inhibition activity  mechanism can  account  Some  be c o n s i d e r e d . One p o s s i b l e  may c o n t a i n inhibitors  microsomal mixed-function oxidases is  this  the M y r i s t i c a c e o u s  alternative  that  significantly  that  peripheral  is  at  non-nitrogenous  of  it  elongata  inhibition  contribute  These r e s u l t s  they  An a l k a l o i d -  due p r i m a r i l y  0-carbolines  p r o b a b l y do not  inhibition.  is  less  standards  from V .  non-specific  the p a s t e s  were  tryptamine  fraction  These o b s e r v a t i o n s  traces  present  lignan  to  and  pastes  h a v i n g c o m p a r a b l e p r o p o r t i o n s and c o n c e n t r a t i o n s . free  additive of  than ayahuasca was c l o s e l y  effective  i n d i c a t i n g an  mechanism of  magnitude.  Samples  more  Samples  p'-carbol i n e s  proportions. effective  of  Multi-component  (MFOs).  these  non-alkaloid of  Experimental  enzymes,  important  hepatic  rather  i n the  evidence than  peripheral  o r a l l y - a d m i n i s t e r e d DMT and  related  compounds.  viii  TABLE OF CONTENTS Abstract T a b l e of  ii Contents  viii  List  of  Tables  xiv  List  of  Figures  xvi  Acknowledgements Abbreviations  xviii  Used  in Text  xxiii  Dedication Part  I:  Chapter  xxv  Introduction I:  South America  I.  Introduction Botany  1  Botany  Hallucinogens 2 .....2  and C h e m i s t r y  Myristicaceous A.  Review  The M a l p i g h i a c e o u s and M y r i s t i c a c e o u s  of  II.  and L i t e r a t u r e  of  the M a l p i g h i a c e o u s  and  Hallucinogens and C h e m i s t r y  5 of  Malpighiaceous Hallucinogens B.  Botany  and C h e m i s t r y  Myristicaceous III.  5  of  Hallucinogens  Ethnopharmacology  7  of M a l p i g h i a c e o u s and  Myristicaceous  Hallucinogens  IV.  A.  Source  B.  Postulated  C.  Admixture P l a n t s  Plants  Ethnographic  Myristicaceous V.  8 and Methods of  Mechanism of  Preparation  Action  11 14  A s p e c t s of  Malpighiaceous  and  Hallucinogens  Scope and O b j e c t i v e s A.  Fieldwork  B.  Laboratory  9  of  the  16 Present  Investigation  20 21  Investigations  22  ix VI.  Literature  Chapter  II:  Cited  25  Chemistry  and P h a r m a c o l o g y  of  Tryptamines  and | 3 - c a r b o l i n e s I.  Occurrence,  29  Distribution,  and B i o s y n t h e s i s  of  Tryptamines  and / 3 - c a r b o l i n e s II.  Pharmacology  III. of  29 of  A.  Structure/Activity  B.  M e t a b o l i s m of  C.  Hallucinogenic  Biochemistry /3-carboline A.  B.  II:  Hallucinogenic Tryptamines  33  Tryptamines  and MAO I n h i b i t i o n  43 of  /3-carboline  derivatives  2.  /3-carbol i n e s as H a l l u c i n o g e n s  46  3.  Endogenous s y n t h e s i s  47  Other  Neurological of  and  of  /3-carbol i n e s  48  Cited  51  Investigations  of M a l p i g h i a c e o u s  Hallucinogens  Ethnobotanical  for  and 58  C o l l e c t i o n s and  Ethnographic 59  Collections  C o l l e c t i o n and I d e n t i f i c a t i o n  59 of  Herbarium Voucher  Specimens B.  .44  Biological  /?-carbol i n e s  Ethnobiological  III:  as Monoamine O x i d a s e I n h i b i t o r s  44  /3-carbolines  Ethnobotanical A.  39  Pharmacology  Observations I.  36  1.  Myristicaceous Chapter  33  Relationships  Psychopharmacology  Literature  Part  and  Tryptamines  derivatives  Activities IV.  Hallucinogenic  C o l l e c t i o n of Phytochemical  59 Plant Material Analysis  and Drug  Samples 60  II. E t h n o g r a p h i c  Observations  A.  Ethnographic  Aspects  of  B.  Ethnographic  Aspects  of  Orally-active III.  Literature  Part  III:  Chapter  Pastes  69 83  and  Pharmacological  •  84  Alkaloid Constituents  Source-plants,  II.  61  Cited  Phytochemical  IV:  Ayahuasca  Myristicaceous  Investigations  I.  60  of  Ayahuasca  Brews,  and A d m i x t u r e P l a n t s  85  Introduction Materials A.  85  and Methods  Field  Collections  87 of  Drug Samples  and  Plant Materials B.  Two-dimensional  C.  High Pressure  Thin-layer  Chromatography  L i q u i d Chromatography  1.  Analytical  2.  Quantitative  3.  Sample  GC/MS A n a l y s e s  E.  A l k a l o i d Tests  88 94  Conditions  94  Methods  96  Preparation  D.  Admixture III.  87  97 99  and TLC of  Uncommon  Plants  100  R e s u l t s and D i s c u s s i o n  101  A.  Ayahuasca  101  B.  A l k a l o i d Content  Brews of  Banisteriopsis  caapi  Cultivars C.  A l k a l o i d Content  107 of  Ayahuasca  Admixture P l a n t s  ....110  1.  DMT-containing Admixtures  110  2.  Uncommon A d m i x t u r e P l a n t s  113  xi IV.  Summary  V.  Literature  Chapter V:  116 Cited  Alkaloid Constituents  Myristicaceous I. II.  Materials  121 121  and Methods  Detection  of  B.  Quantitative  C.  Preparation  Analysis  in M y r i s t i c a c e o u s of  Tryptamine  Myristicaceous  Samples  ..122  Standards  125  Samples  GC Q u a n t i t a t i o n  Results  B.  122  Alkaloids  of  128  and D i s c u s s i o n  Detection  130  and I d e n t i f i c a t i o n  Myristicaceous  V.  Orally-active  Hallucinogens  A.  A.  IV.  of  118  Introduction  for III.  .*  of  Alkaloids  in  Samples  1.  Bark and l e a f  2.  Snuff  130 samples  and p a s t e  Quantitative  Analyses  130  samples  140  of M y r i s t i c a c e o u s  Samples  ...148  Summary  153  Literature  Chapter VI:  Cited  155  Orally-active  Malpighiaceous  and  Myristicaceous  H a l l u c i n o g e n s as Monoamine O x i d a s e I n h i b i t o r s  158  I.  158  II.  Introduction Materials  and Methods  A.  Preparation  of  Rat-liver  B.  Preparation  of  Reaction  of  Labelled  Substrate  161 Cytosol Mixture  161 and A d d i t i o n 162  xii C.  Assays Using Tryptamine  and  /3-carboline Standards D. for E.  Preparation  Preparation  Results A.  and Q u a n t i t a t i o n  Ayahuasca  and Q u a n t i t a t i o n P a s t e Samples  of  f o r MAO A s s a y  166  and D i s c u s s i o n  168  / 3 - c a r b o l i n e s and T r y p t a m i n e s as MAOI : Relationships  168  1.  /3-carbolines  168  2.  Tryptamines  173  Activity  of  A y a h u a s c a and A y a h u a s c a  Analogs  a s MAOI C.  Samples 165  Structure/Activity  B.  of  MAO A s s a y  Myristicaceous III.  163  177  Activity  of  Myristicaceous  Pastes  and  P a s t e A n a l o g s as MAOI IV.  Summary  V.  Literature  Chapter VII:  184 190  Cited  192  The C o m p a r a t i v e  Ethnopharmacology  M a l p i g h i a c e o u s and M y r i s t i c a c e o u s  of  Hallucinogens:  Summary and C o n c l u s i o n s  195  I.  Introduction  195  II.  Ayahuasca  196  III. IV. V.  Myristicaceous Conclusion Literature  Hallucinogens  198 205  Cited  207  xi i i Appendix  I:  Biodynamic  Constituents  in  Ayahuasca  Admixture P l a n t s Literature  Appendix  II:  208 Cited  List  of  •.  Herbarium Voucher  Collections  214  223  xiv L I S T OF TABLES Table  I  - Orally  and P a r e n t e r a l l y  Active  Psychotropic  Tryptamine D e r i v a t i v e s Table  II in  Table  - hRf V a l u e s Solvent  III  34  o f T r y p t a m i n e and / 3 - c a r b o l i n e  System  I  Standards  & II  89  - HPLC Q u a n t i t a t i o n  of U n d i l u t e d Ayahuasca  Samples Table  104  IV - HPLC Q u a n t i t a t i o n  of L y o p h i l i z e d Ayahuasca  Samples  105  T a b l e V - HPLC Q u a n t i t a t i o n o f Banisteriopsis  caapi  Cultivars  109  T a b l e VI - DMT C o n t a i n i n g A d m i x t u r e P l a n t s HPLC,  - Analysis  by T L C ,  and GC/MS  111  Table VII - D e t e c t i o n of A l k a l o i d s i n Uncommon A d m i x t u r e P l a n t s Table VIII Table  .114  - Tryptamine Standards  - GC A n a l y t i c a l  Data  ....126  IX - D e t e c t i o n o f A l k a l o i d s i n M y r i s t i c a c e o u s B a r k and L e a f  Samples  132  T a b l e X - D e t e c t i o n of A l k a l o i d s i n Myristicaceous  P a s t e and S n u f f  T a b l e XI - Q u a n t i t a t i v e in M y r i s t i c a c e o u s T a b l e XII  Analysis  Samples  of Tryptamines  Samples  149  - Alkaloid Concentration in Myristicaceous  Samples A s a y e d f o r MAOI A c t i v i t y Table XIII of  135  - Structure/Activity  167  Relationships  0 - c a r b o l i n e s a s MAO I n h i b i t o r s  T a b l e X I V - MAOI A c t i v i t y  Paste  170  o f A y a h u a s c a Samples a n d  M i x t u r e s of /3-carbolines  171  X V  T a b l e XV - MAOI A c t i v i t y Myristicaceous T a b l e XVI  of  Tryptamine D e r i v a t i v e s  Pastes  - Biologically  Active  174 Constituents  of  Ayahuasca  Admixture P l a n t s T a b l e XVII  - List  and  of H e r b a r i u m V o u c h e r C o l l e c t i o n s  209 225  xvi L I S T OF FIGURES Figure  1 - Some N a t u r a l l y - O c c u r r i n g  Tryptamine D e r i v a t i v e s Figure  30  2 - Some N a t u r a l l y - O c c u r r i n g  /3-carboline D e r i v a t i v e s Figure  3 - Positions  31  of T r y p t a m i n e and / 3 - c a r b o l i n e  in Two-dimensional T h i n - l a y e r Figure  Chromatography  4 - O n e - d i m e n s i o n a l TLC of T r y p t a m i n e  in Solvents  I  Standards 91  Standards  and II  92  Figure  5 - HPLC E l u t i o n  Profile  of A y a h u a s c a Sample  Figure  6 - TLC A n a l y s i s  of P e r u v i a n  Figure  7 - GC Q u a n t i t a t i o n  Figure  8 - UV S p e c t r u m of N - m e t h y l - t r y p t o p h a n  95  A y a h u a s c a Samples  102  of T r y p t a m i n e S t a n d a r d s Methyl  127 Ester  from L e a v e s of O s t e o p h l o e m p l a t y s p e r m u m Figure  139  9 - Mass S p e c t r u m of N - m e t h y l - t r y p t o p h a n  Methyl  from L e a v e s of O s t e o p h l o e m p l a t y s p e r m u m Figure  139  10 - Mass S p e c t r u m of MTH/3C from  La C h o r r e r a Q o ' - k o e y Figure  Ester  1 1  142  - Mass S p e c t r u m of DMTH/3C f r o m  La C h o r r e r a Qo' -koey  ...142  Figure  12 - MAOI A c t i v i t y  of A y a h u a s c a  179  Figure  13 - MAOI A c t i v i t y  of / 3 - c a r b o l i n e M i x t u r e s  181  Figure  14 - MAOI A c t i v i t y  of  182  Figure  15 - MAO I n h i b i t i o n  - La C h o r r e r a Q o ' - k o e y  /3-carboline/DMT M i x t u r e s  by M y r i s t i c a c e o u s  Pastes 185  xv i i Figure  16 - MAO I n h i b i t i o n  A l f r e d o Moreno Sample Figure  17 - MAO I n h i b i t i o n  Marcos F l o r e s Figure  18  - MAOI  Constituents  by M y r i s t i c a c e o u s  Pastes  -  #1  187  by M y r i s t i c a c e o u s  Sample  #1  Activity  of  Pastes  188  Non-alkaloid  of M y r i s t i c a c e o u s  Pastes  189  xvi i i ACKNOWLEDGEMENTS An i n t e r d i s c i p l i n a r y here  owes i t s  successful  encouragement, fieldwork  formed an it  was c a r r i e d and but  have been c o m p l e t e d a t accomplished goodwill the  is  that  scientific  one of  to  in  for  work  t o make t h i s  m e n t i o n e d by name but In  facilities  of  collection  permits  formerly  of  the  bureaucracy,  Maxwell  research  I  States,  of am  thanks.  Use  of  help  Director  the  in  Srs.  very  herbarium  obtaining  Elias  helpful  Mucha,  in  guiding  In  Pucallpa  i n numerous ways by  We were  good w i n e ,  and good s t o r i e s  on  c o m p a n i o n , and an e x c e l l e n t  La B r i s a  informant, friend;  the  particularly  and Wes T h e i s o n .  of  of  Peruvian  patience.  owners  of  and J o s e P u r i s a c a  de V e r a n o ,  became a v a l u e d  Peru,  be  Rutter,  Nixon,  been  and  some can  t h e maze of  and h e l p e d  has  Accordingly,  UBC,  their  not  characteristics  Only  were a l s o  them f o r  could  the  international  appreciated. at  The  laboratory  Ramon F e r r e y r a ,  Instituto Linguistico Dick  of  Ferreyra's  through  hospitably  family,  this  Prado".  Forestry  by Conner and Mary  Nicole  traveling  of  reported  p e r m i s s i o n of  my d e e p e s t  by D r .  greatly  gringos  w i t h good f o o d ,  occasions Cocha.  are  and we thank  the  Long and h i s  give  "Javier  de A g r i c u l t u r a  we were r e c e i v e d members o f  Natural  Faculty  inexperienced  filled  I  t h e Museo and D r .  the M i n i s t e r i o two  to a l l  the  the U n i t e d  possible.  Lima we were a s s i s t e d  t h e Museo H i s t o r i a  that  societies.  in Canada,  helping  to  co-operation  spirit  i n d e b t e d t o many p e o p l e ,  sort  individuals.  most e x e m p l a r y free  the  co-operation,  with the  their  that  of  the  prelude  The f a c t  the  endeavor  to  numerous  out  for  all.  testament  is  of  indispensable  government  project  completion  and a s s i s t a n c e  investigations; Peruvian  research  she  an  several at  Yarina  enjoyable  was  Ted  xix instrumental no t h a n k s  i n h e l p i n g us t o a c c o m p l i s h many of  can p o s s i b l y  in P u c a l l p a ,  I  Shuna and h i s  repay  enjoyed brother  the  her  adequately.  hospitality  Pablo  of  Shuna and I  our  goals,  On my s e c o n d  Sr.  thank  Francisco  and  stay  Montes  them f o r  their  kindness. In  I q u i t o s we were g r e a t l y  Flores,  Dean of  Amazonense, Ayala's  Universidad  extensive  possible Ayala's at  to  successfully  R u i z and S r . efforts.  the  she was  instrumental  for  export  Iquitos  of  collections  safely  these  fieldwork  use of field  the  airlifted  introduction i n f o r m a n t s at  office  of  the  g a r d e n of  Dr.  Sr.  Puco U r q u i l l o .  Adriana's  collecting their to  Loyaza,  they  and e f f o r t  I q u i t o s who h e l p e d out  assistant  curator  of  Davis,  the Harvard  in  the M i s s o u r i Botanical  s u c c e s s f u l c o m p l e t i o n of  our  permits  c o u l d be  our  valuable  many f a v o r s ,  she put  time  quiet  and we a r e  very  i n on our b e h a l f .  some way  Botanical  are Dr.  Al  Other  Gentry,  G a r d e n s ; M r . Wade  Museum, who was fieldwork  this  us t o h o l d o u r  our most  for  Juan  Drug Company;  to Canada. A d r i a n a a l s o p r o v i d e d one of  it  facilities  Adriana  t h e ANDC u n t i l  grateful  the  thanks;  s p e c i m e n s , and a l l o w e d  invaluable  of  of  t h e Amazon N a t u r a l  and good humor were a l l  in  At  significantly  support,  people  there.  t o our  Dr.  made  herbarium  was made by S r a .  to A l f r e d o Moreno,  the  (UNAP).  i n h e l p i n g us o b t a i n p h y t o s a n i t a r y  live in  men a s i n c e r e  Ayala  Herbario  assistance  has c o n t r i b u t e d  a contribution  head of  live  of  the  Rio Ampiyacu area  p u r s u e our  taxonomic  and e x p e r t i s e  No l e s s  the  the  Jose Torres c o n t r i b u t e d g r e a t l y  We owe a l l  generosity  of  of  Franklin  Amazonia P e r u a n a  we made f r e e  The e x c e l l e n t  by D r .  and d i r e c t o r  Nacional  knowledge  invitation,  UNAP.  work.  Qualificacion  assisted  in  instrumental  the Rio  to  Ampiyacu  XX  area;  and t h e crew  logistical  support  contribution great  or  of  small,  the M i n i s t e r i o the  export  Ing. are  of  Carlos  all  of  is  very  RV H e r a c l i t u s ,  that  p o r t i o n of  these  live  Many p e o p l e  the  in  Among them a r e  assisted, Dr.  has D r .  supported every  this  project,  its  of  collections,  task  beyond t h e  His  is  efforts  far  in  this  acknowledgement. c o n t r i b u t e d to Matakaitis, University Rodrigues  respect  Other  the  R.  the  determinations. Prof.  R.  E.  Dr.  Schultes of  and e v e r y the  for  taking  T i m o t h y Plowman  of  the  Rivier  support  and encouragement  the U n i v e r s i t e  correspondence,  useful  sincerely  them f o r  of  Harvard  for  initial  of  this  the  researcher.  deserve  the  F i e l d Museum and  Missouri,  of  warmest  elsewhere Penny the  and D r .  W.  do Amazonense(INPA) t i m e away to  in  these  the K a r o l i n s k a Botanical  de L a u s a n n e ,  the p r o j e c t  A.  from more  Institute,  Museum, and D r . all  provided  through  s u g g e s t i o n s , and sage a d v i c e ; their  the  e n c o u r a g e d and  i d e n t i f i e d most of  other  to devote  Bo H o l m s t e d t of  at  Pesquisas  matters  Laurent  thank  or  A n d e r s o n and Bronwen G a t e s  them a l l  p r e s s i n g and i m p o r t a n t  C a s t r o . We  determinations,.including  Instituto  M a n a u s . We thank  with  among them  from i t s  capabilities  of M i c h i g a n , A l G e n t r y of  of  a t i m e - c o n s u m i n g and monumental  people at  voucher  D r s . W.  us  advised,  Plowman  c o m p l e t i o n , he has a l s o  herbarium voucher which  employees  co-operation.  only  to  however  Emilio V i l l a r  C h i c a g o F i e l d Museum; not  conception  Several  and h e r b a r i u m v o u c h e r s ;  in North America a l s o  aspect  groups,  the  Iquitos also assisted  M a r c h a n d , and I n g .  some way.  partial  expedition;  or  much a p p r e c i a t e d .  plants  their  who p r o v i d e d  individuals  de A g r i c u l t u r a  for  in  the  for  Salazar  grateful  h e l p e d us  of  informed i n s i g h t s  we  and f o r  the  xxi example  they  set  for  C o m p l e t i o n of d e p e n d e d on t h e among them D r . excellent samples;  various  C.-K.  G.  Wat  Bellward,  laboratory  methods u s e d  in  advice  preparation. are  I  Their  work-up of  like  to  thank  support,  or  financial.  other  of  the  was a s t e a d f a s t  traveling  "we"  he u n d e r t a k e s  and w e l l .  Other  and i n t a n g i b l e  like  Studies  at  her  of  of  the  who  the  Luna,  colleague in  UBC f o r  people  s u c c e s s of  gave  work  list  the  people  I  and I  a r o u n d . He i s w i s h him l u c k  thank  for  and Joe  McKenna;  support  and t o t h e D e p a r t m e n t  of  all  Botany  f o r m of for  a  it  fine  it  many  are  worth  to the F a c u l t y i n the  when  their  T e r e n c e McKenna,  it  his  handle  project  t o make  He  in  to t h i s  financial  kept  were many t i m e s  contributions  given  the  the  knowing he w i l l to  project  acknowlegements.  P e r u and a l w a y s  that  wish  this  i s Don MacRae,  these  there  future,  or  emotional,  humor engaged whatever  t o e x p r e s s my a p p r e c i a t i o n  Fellowships;  various  enzyme  aspects  moral,  used in  someone l i k e  you knows how much you have would  of  development  other  the  companion in  s e n s e of  t o have  to  H i g h on t h i s  pronoun  f r i e n d and an e x c e l l e n t  Luis  people;  provided  use of  rat-liver  either  p s y c h o l o g i c a l weather;  Humphrey,  the  several  prevailing  tangible  several  who  the  to these  and h i s  easily  for  the  head l e v e l  whatever  work  and M a l c o l m F i n l a y s o n ,  who have c o n t r i b u t e d  reassuring  this  t h e GC/MS a n a l y s e s  facilities  spiritual,  was  of  Balza,  who p e r m i t t e d  contributions  t h r o u g h some form of  half  p h a s e s of  everywhere.  acknowledged.  would a l s o  institutions  in  t h e MAO a s s a y s ;  on t h e  gratefully  and F e l i p e  assistance  radioisotope  useful  technical  c o - o p e r a t i o n and g o o d w i l l  technical Dr.  a s p i r i n g ethnopharmacologists  Sheila  e a c h of it.  I  of  Graduate  UBC  Graduate  support  in  the  xxi i form of  a Teaching A s s i s t a n c e s h i p .  t h e members of  my g r a d u a t e  contributed considerable thesis.  Finally,  my f r i e n d , Towers. the  too).  enthusiasm  variety  warmest  of  inadvertently  and s i n c e r e s t  committee  this  not  least  project  he has  these  like  who  to  the  of  all,  be my s u p e r v i s o r ,  s u p p o r t has gone  (although  To e a c h and a l l  overlooked  for  would a l s o  and e f f o r t  but c e r t a i n l y  e n d ; and h i s  financial  time  who a l s o happens t o  His  very  research  I  review I  of  wish  Dr.  this  to  thank  Neil  has been u n s t i n t i n g far  beyond the  and a l s o  of  to  mundane that,  t o anyone  who d e s e r v e d t o be m e n t i o n e d ,  thanks.  thank  have  furnished plenty  people,  to  I  I  have  g i v e my  ABBREVIATIONS USED IN TLC - t h i n - l a y e r  TEXT  chromatography  GC - gas c h r o m a t o g r a p h y GC/MS - gas c h r o m a t o g r a p h y / m a s s s p e c t r o m e t r y UV -  ultra-violet  HPLC - h i g h p r e s s u r e  l i q u i d chromatography  SAR - s t r u c t u r e / a c t i v i t y  relationships  MAO - monoamine o x i d a s e MAOI - monoamine o x i d a s e MFO - mixed f u n c t i o n CNS - c e n t r a l MTHF SAM -  oxidase  nervous  system  5-methyltetrahydrofolate S-adenosyl-methionine  INMT - i n d o l e - N - m e t h y l TA -  inhibitor  transferase  tryptamine  NMT -  N-methyltryptamine  DMT -  N,N-dimethyltryptamine  DMT-NO - N , N - d i m e t h y l t r y p t a m i n e - N - o x i d e 5-MeO-TA -  5-methoxy-tryptamine  5-MeO-DMT - 5 - m e t h o x y - N , N - d i m e t h y l t r y p t a m i n e 5HT - 5 - h y d r o x y - t r y p t a m i n e  (serotonin)  5HO-DMT - 5 - h y d r o x y - N , N - d i m e t h y l t r y p t a m i n e IAA  - indole acetic  acid  DET -  N,N-diethyltryptamine  DPT -  N,N-dipropyltryptamine  DIPT - N , N - d i i s o p r o p y l t r y p t a m i n e DAT -  N,N-diallyltryptamine  DBT -  N,N-dibutyltryptamine  THH -  tetrahydroharmine  (bufotenine)  xx i v 6-MeO-THH -  6~MeO-tetrahydroharman  6-MeO-MTH/3C - 6 - m e t h o x y - 2 - m e t h y l - t e t r a h y d r o - p - c a r b o l i n e ,  6-MeO-DMTH|3C - 6-methoxy- 1 , 2 - d i m e t h y l - t e t r a h y d r o - / 3 - c a r b o l i n e TH/JC -  tetrahydro-/3-c'arboline  MTH/3C - 2 - m e t h y l - t e t r a h y d r o - / ? - c a r b o l  ine  DMTH/3C - 1 , 2 - d i m e t h y l - t e t r a h y d r o - 0 - c a r b o l i n e THH3C /3CC -  tetrahydroharman-3-carboxylate  /3-carboline-3-carboxylate  /3CEE - / 3 - c a r b o l i n e - 3 - c a r b o x y l a t e  ethyl  ester  This the whose  thesis  is  indigenous knowledge  a legacy  of  respectfully folk  of  healers  botanical  value  for  dedicated of  the  medicine  all  of  to  Amazon, constitutes  humanity.  1  PART I:  INTRODUCTION AND LITERATURE  REVIEW  2  CHAPTER  I.  I:  THE MALPIGHIACEOUS AND MYRISTICACEOUS*  Introduction D u r i n g the  the  botany  last  three  and c h e m i s t r y  enormously. efforts  of  collect  the  succeeded  source-plants  than  species  these,  100—are  the w o r l d ,  plant  h a l l u c i n o g e n s has  working  in  only  and l e s s  the  laboratory,  for  these  field  the  is  e s t i m a t e d at  an  insignificant  than [2].  twenty  of  expanded  identify  peoples, i n many  [1,2].  species  higher  contain  that  plants  cases  4 0 0 , 0 0 0 and fewer  throughout  s p e c i e s may be plants  and s i n c e  alkaloids,  many more h a l l u c i n o g e n i c  and  The number  number—somewhat  Most h a l l u c i n o g e n i c constituents,  and  biodynamic  between  these  of  co-operative  to  who have  properties  to a l k a l o i d a l  undiscovered  the  u t i l i z e d by a b o r i g i n a l  properties  likelihood  knowledge  known t o ' be e x p l o i t e d as h a l l u c i n o g e n s  d e s c r i b e d as major  of  scientific  and c h a r a c t e r i z i n g  responsible  plant of  in  isolating  constituents  800,000;  of  ethnobotanists,  in  higher  d e c a d e s our  T h i s has been a c c o m p l i s h e d t h r o u g h t h e  phytochemists working  of  HALLUCINOGENS  OF SOUTH AMERICA  there  species  owe  at is  their  least a  5000  strong  remain  [2].  Scientific  interest  in  the  botanical  and c h e m i c a l  sources  * N o t e : Usage of t h e t e r m s ' M a l p i g h i a c e o u s ' and ' M y r i s t i c a c e o u s ' i n t h i s t h e s i s f o l l o w s t h a t e s t a b l i s h e d by S c h u l t e s [ 7 , 8 ] ; u s e d i n r e f e r e n c e t o p l a n t s p e c i m e n s or p l a n t m a t e r i a l t h e y r e f e r t o members of t h e M a l p i g h i a c e a e and M y r i s t i c a c e a e , respectively; used i n r e f e r e n c e to drug samples or h a l l u c i n o g e n s , they r e f e r t o d r u g s d e r i v e d p r i m a r i l y from s o u r c e - p l a n t s i n t h e M a l p i g h i a c e a e or M y r i s t i c a c e a e .  3  of  h a l l u c i n o g e n s has p a r t l y  from,  the  increased  own s o c i e t y . as  they  today  are  as  was t e n  valued  to  new.  In  likewise  food,  magical,  Perhaps  nowhere  fact,  or  in  the  world,  fully  significant  in  the  that  of  in  the  ten  ethnobotanical geographic Northwest  in  or  ecological  medicinal,  itself  This  something  of  or  all  plants  extent  S o u t h A m e r i c a . Of  literature  so New W o r l d  of  [4,5].  fully centers  two-thirds of  hundred  this  have  the  fact  is  major  their  distribution  e x c e p t i o n s b e i n g the  in  the  peyote and  cactus  the  asymmetrical  h a l l u c i n o g e n s may be p a r t l y to e t h n o l o g i c a l  it  r e m a r k e d upon  have  Oaxaca, Mexico. T h i s oddly  and p a r t l y  that  throughout  that  t h e A m e r i c a n Southwest  t h e New W o r l d  of  Even more c u r i o u s  hallucinogens  have  purposes.  the  t h e New W o r l d ;  on  for  knowledge and use  to  rely  sorts,  recreational  developed to the of  Paleolithic,  forced to  and has been r e p e a t e d l y  significance,  factors  the  native  Amazon—the n o t a b l e  of  the  and p a l l i a t i v e s  them a r e  mushrooms of  are  employed as h a l l u c i n o g e n s  and e t h n o l o g i c a l  distribution  since  Aboriginal peoples,  plants  (Lophophora w i 1 1 i a m s i i ) Psilocybe  they  society.  late  least  w o r l d has  plants  ethnobotanical the  hallucinogens  s o u g h t and u s e d p s y c h o a c t i v e  60% of  is  [3],  practice  at  religious,  of  not a s w i d e s p r e a d a ago  our  "psychedelics,"  been known and  upper Amazon B a s i n  so s p e c i e s  or  h a l l u c i n o g e n s have  medicines,  endemic h a l l u c i n o g e n i c has  hallucinogens, is  resulted  s u c h compounds i n  t o be u s e d i n c o n t e m p o r a r y  earlier.  actively  various  use of  twelve years  i n human c u l t u r e s  for  u p o n , , and p a r t l y  the m i s c o n c e p t i o n t h a t  and p r o b a b l y even nature  or  continue  rise  relatively  use of  sometimes c a l l e d ,  it  given  "recreational"  W h i l e the  nevertheless has  followed  ones.  due  Ecological  to  4  factors boast  of  Basin, of  may c o n t r i b u t e the  hence  in  sheer  species  it  not  is  representative  a role  d e p e n d as  tribes.  no o t h e r  on t h e  abundance,  this  we would e x p e c t  to  psychoactive  Largely  within the  the  the  region  Rio  O r i n o c o , on t h e  the  east  by t h e the  of' t h e  the  of  to  exploit  environment,  the  the  and  plant  kingdom  locally  carried  out  s o u r c e s and most  hallucinogenic  plants  identified  [6],  upper Amazon B a s i n p r o p e r ,  i.e.,  s o u t h by t h e  c o n j u n c t i o n of  Rio U c a y a l i  the  in  hallucinogenic  on t h e  while c e r t a i n  in  Vi rola  spp.  are  Within within the  and on  plants  is  the  The f o r m e r  known v a r i o u s l y  used  Colombia,  hallucinogenic  the M y r i s t i c a c e a e . brew  Peru,  Banisteriopsis  of  n o r t h by  drainage,  b o r d e r s of  i n d i g e n o u s complex of  basis  or y a g e ,  group  ethnobotanical,  botanical  have now been  and V i r o l a  the  world  those  vegetal  knowledge  t h e major  Malpighiaceae  caapi,  the  investigations  d o m i n a t e d by two g e n e r a :  for  the  diversity  bounded on t h e West by t h e A n d e s ,  and B r a z i l , totally  of  Amazon t r i b e s  lowland areas  of  interdisciplinary  two d e c a d e s ,  the  in  may  plants.  constituents  by N o r t h w e s t  species  especially)  and p h y t o c h e m i c a l  last  active  this  not  b e c a u s e of  ethnological,  of  exploitation  (if  factors  as do  other  plants  t h o r o u g h l y a s do t h e Amazonian  f i n d that  w o u l d e x t e n d as w e l l  cross-section  Ethnologic  n o r does any  can  i n t h e Amazon  p r o p o r t i o n of  environment  juxtaposition  and i n t e n s e  on e a r t h  a typical  indigenous peoples  vegetal  as  places  w h i c h abounds  constituents.  environment  Given  available  diversity  t h e Amazon B a s i n ,  vegetal  other  s p e c i e s has a g r e a t e r  that  totally  inhabiting the  in  few  s u r p r i s i n g that  containing psychoactive play  that  as  is  the  ayahuasca,  most w e l l  known  5  as  the  s o u r c e of  utilization r e g i o n of of  potently  extends  the  the O r i n o c o headwaters since  constituents  of  been  identified,  however;  a careful  problems,  pharmacologist, Some of the  study  the  point  of  v i e w of  interesting  investigations  little  t h a t many of  of  reported  and C h e m i s t r y  in  Rio  to  Apaporis  I n d i a n groups-  [7],  One might  interest  have  the  unwarranted,  pertaining  to  these  interesting  biochemist,  have been a l l  but  problems, are  this  of  chemical  t h e most  the  these  the  Amazon h a l l u c i n o g e n s  literature  and t o x i c o l o g i s t ,  t h e more  Botany  very  and  T h i s assumption i s of  reveals  from t h e  Northwest  whose c e n t e r  t h e Waika  southern Venezuela  remains  phytochemist.  indigenous drugs  n o r t h to  t h e main s o u r c e p l a n t s  there  or  snuffs  P u i n a v e I n d i a n s of  in  the p r i m a r y  botanist  11.  from t h e  Colombian Vaupes,  suppose t h a t  of  hallucinogenic  ignored. the  subject  thesis.  o f M a l p i g h i a c e o u s and Myr i s t i c a c e o u s  H a l l u c inogens  A.  Botany  and C h e m i s t r y of  The woody  liana  Banisteriopsis  Griseb.)Morton  (Malpighiaceae)  hallucinogenic  beverage  "vine  of  it  known by o t h e r  is  natema, used,  B.  the  souls")  and p i n d e inebrians  Tetrapterys s o u r c e s of  (Spruce basis  in d i f f e r e n t names,  A l t h o u g h B.  Morton,  drink  forms t h e  vernacular  [8].  caapi  of  Hallucinogens ex the  commonly known as a y a h u a s c a  although  methystica the  the M a l p i g h i a c e o u s  B.  [8].  of  caapi  have a l l  is  usually  (Ndz.)  the  Morton,  been r e p o r t e d  On o c c a s i o n a y a h u a s c a  is  for  t h e Amazon  i n c l u d i n g yage,  quitensis  Schultes  regions  (Quechua  caapi, species and as  prepared  from  6  the  b o i l e d bark  a d d i t i o n of however,  any  the  added i n t o  or  stems of  other  leaves  the  The l e a v e s  [10]  as an a d m i x t u r e ,  to  Diplopterys  I,  also  Comm., are  or m o d i f y  species  the  name of  taxonomic  the admixtures and P s y c h o t r i a Jacq.  are  (Nicotiana  spp.),  Brugmansia  s p p . , and B r u n f e l s i a  constituents  harmine,  harmaline,  dimethyltryptamine are  constituents  a constituent [15] et  chemical  of  harmic  [18,19] amide,  from the  study  that  of  Rivier  are  Fig  1 & 2,  of  B.  caapi  [16]  D.  cabrerana  the  B.  the  of  spp. ayahuasca  and L i n d g r e n  0-carboline  the  and [15].  major  alkaloids  and N,NII).  and P. of  tobacco  The  /3-carbolines isolated  been  as  reported  viridis.  6 /3-carboline  Hashimoto bases,  ketotetrahydronorharmine,  a c i d methyl  caapi  including  and has a l s o  isolation  (cf.  viridis  w h i l e DMT has been  carthagenensis  from  u s e d most  found t h a t  Chapter  [17]  norharmine,  harmic of  to date  investigators  (cf.  acetyl  leaves  common,  and t e t r a h y d r o h a r m i n e ,  reported  harmine N-oxide,  also  ayahuasca  in both P s y c h o t r i a  al.  is  these  of  [11,  (Rubiaceae).  Solanaceae  active  this  to ayahuasca  the  U s i n g GC/MS a n a l y s i s ,  Gates.  1 9 8 0 ] . A l t h o u g h sun.dry s p e c i e s  cabrerana  ingredients  effect reported  revision  in  botanical  the  have been  Admixtures  its  are  (Cuatrecasas)  rusbyana,  carthaqenehsis  The most d e t a i l e d  the  more commonly,  u t i l i z e d as a d m i x t u r e s  Diplopterys  without  admixture p l a n t s  cabrerana  [9,12,13,14,15]),  and P s y c h o t r i a  species  strengthen  one M a l p i g h i a c e o u s  T. , pers.  commonly a r e R.&P.  various  been c h a n g e d i n a r e c e n t  numerous f a m i l i e s Appendix  of  these  ingredients;  known as B a n i s t e r i o p s i s  s p e c i e s has Plowman,  bark  in order  [9].  Formerly  of  botanical  or  brew  one of  ester,  in a d d i t i o n  to  and h a r m a l i n i c the  three  main  acid)  7  constituents. pyrrolidine leaves the  of  (0.007  bases  B.  plant,  These workers  B.  shihunine  caapi.  however,  - 0.0001 %)  significantly  to  Botany  of  and t h e i r  low  the  the V.  Amazonian  pharmacological  (Myristicaceae)  trees,  flora.  At  present  in  the  the  preparation  genus a r e  poorly  confusion For  [21]  to  the  about  Virola  instance,  the  most  elongata, Thus,  and r o o t s  of  is  well  substantial  that  basis  as the  established, Virola  amounts  as N , N - d i m e t h y l t r y p t a m i n e ,  of  Central  spp.  has  of  viz.,  be  concepts led  to  phytochemical revision  cuspidata is  species or  ,  known t o  and V .  six  and  cuspidata,  Species  and  60  component  calophylloidea  as many as  for  of  systematic  theiodora  implicated  a number of  are  d e p e n d i n g on w h i c h  one may say have been  recent  while V.  Hallucinogens  V.  and t h i s  ethnobotanical  The p h y t o c h e m i c a l hallucinogens  elucidated,  the  calophylla.  spp.  elongata,  hallucinogens.  that V i r o l a  ayahuasca.  abundant  six  in  some 45 t o  forests  in  states  to V.  of  of  includes  peruviana,  accepted,  contain  native  from  contribute  Myristicaceous  and p o s s i b l y V .  genus  Vi rola  the  the  concentrations  activity  theiodora,  equivalent  are  of  [20]  of  constituents  they  V.  literature.  w i t h V.  that  calophylloidea,  considerable  the  unlikely  V.  utilized within  extremely  and f o r m i n g an e s p e c i a l l y  calophylla,  Vi rola  it  isolation  and d i h y d r o s h i h u h i n e  and C h e m i s t r y  South A m e r i c a ,  the  trace  make  tropical  reported  T h e s e compounds a r e  The genus V i r o l a species  also  as  of are  equated concepts  few as  three  hallucinogens! use of  since  species  Vi rola  spp.  bark,  sap,  the  have been  hallucinogenic  shown  as leaves, to  tryptamines  such  5-methoxy-N,N-dimethyltryptamine,  and  8  other  tryptamine  derivatives,  methoxy-N-methyltryptamine, (cf.  Fig.  isolated  1).  f r o m some V i r o l a of  theiodora  and V .  rufula,  was  (Leguminoseae)  Brazil  2)  A g u r e l l et  while a s i m i l a r  isolated  which a l s o  s o u r c e of [2].  spp.  (Fig.  and  al.  [22]  In  contains  a hallucinogenic  a later  publication  [23]  workers  species;  compound 2-methyl-TH/3C was d e t e c t e d  V.  calophylla,  instances  the  V.  elongata,  V.  investigated  in which  of  this  cuspidata  and c o - w o r k e r s  harmalan,  and V i r o l a  is  the  t h e major [24]  only  species,  isolated  but no t r y p t a m i n e s  biochemical character  probably d i s t i n c t  from V .  species  alkaloids  and 6 - M e O - t e t r a h y d r o h a r m a n  distinctive  theiodora.  III.  Virola  In  are  in  all  far  6-MeO-  l e a v e s and  were d e t e c t e d .  and t h e  the  /3-carbol i n e s .  from t h e  indicates  elongata  so  6-MeO-harman,  w h i c h have been c l a i m e d t o be e q u i v a l e n t Rodrigues  and  | 3 - c a r b o l i n e s were t r a c e components compared t o  tryptamines;  Cassady  indeterminate  and  detected  peruviana  related  L.  Caribbean  b o t h compounds i n V . the  and an  these  6-MeO-l,2-  derivatives  i n the  the  from V i r o l a  peregrina  tryptamine  snuff  been  reported  compound,  from A n a d e n a n t h e r a  5-  tryptamine  have a l s o  6-MeO-2-methyl-tetrahydro-/3-carboline  dimethyl-TH/3C,  the  5-methoxy-tryptamine,  /3-carboline a l k a l o i d s  isolation  is  i n c l u d i n g N-methyltryptamine,  that other  to V.  This  V.  stems rather  cuspidata  Vi rola  elongata  is  spp. by  [21].  Ethnopharmacoloqy  of M a l p i g h i a c e o u s and  Myristicaceous  H a l l u c inogens A l t h o u g h t h e most psychoactive  important  constituents  of  s o u r c e - p l a n t s and t h e  the M a l p i g h i a c e o u s  and  presumed  9  Myristicaceous  h a l l u c i n o g e n s have been  e t h n o p h a r m a c o l o g y of incompletely  A.  b o t h g r o u p s of  P l a n t s and Methods of  The h a l l u c i n o g e n a y a h u a s c a or c r u s h e d stems of  mode of  some a r e a s and t h e its  the  brew  still  the  caapi  time  (1-2  cases,  concentration, present  harmine,  in the m i x t u r e .  the  harmaline,  of  fire the  d u r i n g the In  any  the  even  region;  is  is  of  boiled for  a  while  affect  k i n d s of c a n be  condensation  active  readily  followed  by  and t h u s m i g h t  prolonged b o i l i n g  well  and  the p r e p a r a t i o n  a relatively  in  prepared.  the  [25],  I.  as  h i g h p r o p o r t i o n of and p o s s i b l y  other  0-  DMT, d e p e n d i n g on  added.  Myristicaceous  tree,  to  to a f r a c t i o n  0-carbolines  and t e t r a h y d r o h a r m i n e ,  i n g e s t i o n of  in Appendix  would be e x p e c t e d t o  case  the  not c o n c e n t r a t e d ,  infusion  reaction)  bark  f o r many h o u r s ,  brew  and a low t o m o d e r a t e amount of  The use of  (sap)  boiled  and i s  by a l d e h y d e  brew.  how much a d m i x t u r e was  around the  from r e g i o n  a low  preparation  i n g e s t e d would c o n t a i n  carbolines,  listed  p r o p o r t i o n s , and p e r h a p s  be formed as a r t i f a c t s  finally  w i t h one o r more of  regions,  hours)  (Pictet-Spengler  of  over  a cold-water  formed from t r y p t a m i n e s  concentration  varies  in other  t h e method of  cyclization  still  p r e p a r e d by b o i l i n g t h e  together  preparation  volume;  other  alkaloids  is  m e n t i o n e d above or  concentrated  short  Obviously  is  Preparation  stems and a d m i x t u r e s a r e  is  original  relatively in  B.  admixture plants  The e x a c t  hallucinogens  the  understood.  Source  sundry  identified,  species  preparations though the  for  hallucinogens  derived  leaves,  from t h e  bark,  or  centers  "resin"  roots  of  the  10  t r e e may a l s o c o n t a i n i n g e s t i o n of  the  ethnologically  the a c t i v e  resin  into  appears  two major  alkaloids.  t o be d i v i d e d g e o g r a p h i c a l l y categories.  In  around the  R i o O r i n o c o - R i o Vaupes d r a i n g a g e  Venezuela,  and B r a z i l ,  from t h e d r i e d , tribes  include  linguistic tribe.  powdered the  more o f t e n  is  [26,  directly ashes  practice  of  attention  of  of  the  carried  village  El  "kind"  derived out  of  Bora,  out  Encanto  by S c h u l t e s ,  identity  on t h e R i o  A m p i y a c u near  the  sources  i n d i c a t e d by t h e  resin  the  resin  and  for  rolled  is  be  use  inhabiting Putamayo.  [7,27,28] indicated  i n the  of  found  Colombian  near that  the the  in Witoto)  Bora  was  was  carried  and W i t o t o  and Puco U r q u i l l o  settlement the  the  the  field-work  Nuevo,  Virola  has come t o  from the  but  other  of of  called  Subsequent  Brillo  of  The  and Swain  [29]  alone  and seems t o  Caraparana  Peruvian Bora  of  These  (Yanomamo)  either  use of V i r o l a  and Plowman  Firma,  the R i o  resin  the drug i s  theiodora.  of T i e r r a  species.  may v a r y .  separated  locality  snuff  utilization  from t h e  recently  by S c h u l t e s  Swain,  a  Muinane and W i t o t o t r i b e s  o o - k o o ' - n a (as  from V i r o l a  settlements  only  The o r a l  Caraparana-Igaraparana  of  whose  centered  various  ingestion,  prepared  and e t h n o l o g i c a l l y  among t h e  Vi r o l a  from t h e V i r o l a  by o r a l  and  Colombia,  a s h e s or powdered l e a v e s  plants,  as a s n u f f .  region  d i s p e r s e d Waika  i n g e s t i o n of V i r o l a  Field-work  best  is  ethnobotanists  resin  primarily  widely  pellets  other  oral  geographically Vi rola  or of  various  The s e c o n d mode of  resin  of  K u b e o , T u k a n o , and  mixed w i t h t h e  a s an h a l l u c i n o g e n  the  of  may be p r e p a r e d  resin  in  resin  the  see b e l o w ] .  the  indigenous people prepare  Puinave,  s u b g r o u p s of  The s n u f f  plants  the  The mode of  of  preparation  Pebas. of  the  The  on best  oral  11  drug V.  (known i n Bora loretensis,  Witoto V.  informants  I_.  at  had not  for  Puco U r q u i l l o  and s p e c i e s  been  the  the  of  well  other  ulei  present  the  in  formation alkaloid  constituents [30]  has not  B.  A l t h o u g h the preparation  different  but  of  of  alkaloids  present  in  ( . 0 0 0 1 3 mg/g) s n u f f s and  DMT a n d / o r  they  are  the  to  5-MeO-DMT, of  as  /3-carbolines  originally  cooking process. s n u f f s have the  of  of  The  been  orally-ingested  investigated.  Action  source-plants  and a d m i x t u r e p l a n t s  the M a l p i g h i a c e o u s h a l l u c i n o g e n s  The a y a h u a s c a  Iryanthera  would be e x p e c t e d  c o m p o s i t i o n of  of  all  s p e c i e s , ' or as a r e s u l t  d u r i n g the  the M y r i s t i c a c e o u s  active alkaloids  are  b o t h of  responsible  concentrations;  utilized are  snuffs for  and  the  t h e s e Amazonian  brews c o n t a i n  w i t h DMT d e r i v e d  lesser  The genus  concentrations  because  Mechanism of  pharmacological a c t i v i t y hallucinogens.  of  some V i r o l a  the  Iryanthera,  as an h a l l u c i n o g e n ;  some V i r o l a  from t h o s e u s e d f o r  similar  genus  The  elongata,  t e s s m a n n i i , were  drug.  pastes  been p r e v i o u s l y  Postulated  pastes,  of  from t r y p t a m i n e s  characterized pastes  resin  either  pavon i s,  that V.  detected a trace  lesser  V.  indicated.  Both the M y r i s t i c a c e o u s  tryptamines;  be p r e s e n t ,  related  the  concentrations  might a l s o  major  of  ingested Myristicaceous  as  the  u l e i , and I.  I_.  bark.  substantial  elongata;  indicated  implicated previously  contain  the  I.  in  preparation  subsequent a n a l y s i s 5-MeO-DMT i n  was V .  s u r i n a m e n s i s were a l s o  macrophylla,  suitable  orally  ku'-ru-k_u)  and V .  surinamensis,  viz.,  as  from t h e  / 3 - c a r b o l i n e s as admixture  the M y r i s t i c a c e o u s  the  plants drugs,  on  in  12  the  other  hand, c o n t a i n  the  primary  active  hallucinogenic  constituents,  but  tryptamine  derivatives  0-carbolines  may be  as m i n o r c o m p o n e n t s . A l t h o u g h DMT and 5-MeO-DMT a r e potent-psychotomimetics, peculiarity  of  active  apparently  [31]  their  monoamine o x i d a s e that  is  Therefore  parenterally  On t h e  other  activity  these  hand,  concentrations significance thus  cf. of  on t h e  of  this  that are  oxidative  tryptamines  taken  Vi rola  tryptamines  order the  of  10"  6  -  10~  8  limited  active  in  the  the M y r i s t i c a c e o u s orally-ingested  the  form of  are  not  orally  a snuff active,  sidesteps  of  the  snuffs  diverse hallucinogenic  used n o r t h  tryptamines  for  of  that  of  is  the  is'the native  ingestion  the  parenteral  inactivation  it  these  the  now c l e a r ;  so t h i s  their  The  d r u g s may  in each c a s e ,  properties  is  these  at  Myristicaceous  psychotomimetic  in  short-  M [32,33,34].  s p e c i e s and  preparation  hallucinogenic  neatly  are  e t h n o p h a r m a c o l o g y of  i n the  be  w i t h a MAO i n h i b i t o r .  The p h a r m a c o l o g i c a l r a t i o n a l e  administration  can  _in. v i t r o  of m e t h y l a t e d ,  resin  they  effective  h a l l u c i n o g e n s u s e d i n P e r u and C o l o m b i a ,  preparations.  or  monoamine o x i d a s e ,  brews,  the  administered  potent  Banisteriopsis  qua non f o r  must be  extremely  involved  sine  peripheral  biogenic  although having  be u n d e r s t o o d : a l t h o u g h d i f f e r e n t  presence  orally  are  to  R i o N e g r o and t h e  not  a  l o c a l i z e d enzyme  activity,  together  II),  are  d e a m i n a t i o n of  (some d e r i v a t i v e s  Chapter  extremely  d e a m i n a t e d by  their  present  100 mg r a n g e ,  they  either  0-carbolines,  admixtures are  the  the  as h a l l u c i n o g e n s  inhibitors  is  5 to  the m i t o c h o n d r i a l l y  if  the  the  they  to manifest  active  500-1000 mg r a n g e ; acting  because  for  in order  rendered o r a l l y  in  pharmacology  (MAO),  responsible  amines.  active  as  by  of  active route  of  peripheral  13  MAO. for  Presumably the  the  activity  of  tryptamines  alone  the  In  snuffs.  M a l p i g h i a c e o u s ayahuasca Myristicaceous other  pastes,  mechanism)  tryptamines. carbolines  is  brews  before  active  of  these  (cf.  II  and  Chapter  established. orally  in order  this  this  of  has not  been  1.)  2.)  active  by MAOIs,  enough d a t a  that  this  is  tryptamines  Chapter  II  Hallucinogenic  n a t i v e drug p r e p a r a t i o n s  that  the  i n g e s t i o n of  exceed the  known t h r e s h o l d d o s e f o r  DMT i s  active  the  tryptamine  then at  60-75 mg would have t o be i n g e s t e d hallucinogenic inhibition,  effects,  in  least  for  smaller  since  m e t a b o l i s m under  these  well rendered tryptamines but  /3-carbolines  tryptamines  are  sufficient dose  would  15 mg and  if  preferably  the drug to m a n i f e s t  d o s e s of  a greater  years  compounds, e . g . ,  Under c o n d i t i o n s of  substantially  hallucinogenic degradative  effects.  for  an a v e r a g e these  recent  by some MAOIs,  (cf.  3.)  in  /3-carbolines;  demonstrated  not  human  c a n be  been s p e c i f i c a l l y  concentrations  the  fairly  has not  these  by t h e /3-  in q u e s t i o n are  this  in  the  experimentally  on t h e  point  specifically  [35]).  some  investigated  The t r y p t a m i n e s  The m e t h y l a t e d  and  as  d r u g s has been a c c u m u l a t e d  [31])  (or  activate  tryptamines  have been shown t o be p o t e n t i a t e d j_n v i v o  present  ingested  to o r a l l y  the  account  p o s t u l a t e d mechanism can be a c c e p t e d .  by t h e m s e l v e s ;  pharmacology  to  the  orally  S e v e r a l q u e s t i o n s need t o be  must be shown t h a t :  orally  of  has been p r o p o s e d [ 9 , 1 0 , 1 3 , 2 7 , 2 8 , 2 9 ]  experimentally It  case  and t h e  activation  u n d e r l y i n g mechanism, but confirmed.  the  sufficient  the M A O - i n h i b i t i n g /3-carbolines  required  The o r a l  are  its  p e r i p h e r a l MAO DMT may  elicit  proportion could  conditions.  4.)  escape  /3-carbolines,  1 4  or  some o t h e r  preparation  type  in  MAO and t h u s  sufficient  orally  investigations objectives  C.  of MAOI,  of  of  some of  of  investigation  determinants  of  case  plants  are  the  there  it  is  the  a virtual  used,  which  of  an a r e a  well  the  ayahuasca  addition  of  the  any  almost  of  drug  is  of  potential  are  d e s e r v i n g of  at  this  further  and  included  admixtures ritual,  a d m i x t u r e s have  chemically  s p e c i e s which  or  the  not  been contain  The  pharmacological  a complete mystery,  research  e t h n o p h a r m a c o l o g i s t s and p h y t o c h e m i s t s .  which  characterized;  medical value.  time,  in  b e i n g made and consumed  a d m i x t u r e s may make t o is,  the  admixture  some a d m i x t u r e s has  they  in  tryptamine-  always  ayahuasca  of  the  admixtures,  botanical  the  as  On o c c a s i o n  utilization  Besides  deserves  plants  employed. P a r t i c u l a r l y  much l e s s  identity  biodynamic c o n s t i t u e n t s  activity  these  and i n many c a s e s  that  admixture  p h a r m a c o p o e i a of  the  identified,  botanical  of  d e p e n d i n g on t h e m a g i c a l ,  been b o t a n i c a l l y  contribution  primary  thesis.  h i g h d e g r e e of  Many of  established,  q u e s t i o n s were among t h e  influence  seems t h a t  purposes for  the  Experimental  pharmacological a c t i v i t y .  [9,10,13,14,15].  however  inhibit  h a l l u c i n o g e n s which  sophistication.  occasionally  medical  tryptamines.  native  c o n t a i n i n g admixtures which are ayahuasca,  to e f f e c t i v e l y  these  reached a rather  pharmacological  native  this  admixtures are  ayahuasca has  the  d e s c r i b e d in  is  their  customarily, of  the  these  d r u g s may be p r e p a r e d w i t h o u t but  in  Plants  Another aspect further  present  concentration  potentiate  t h e work  Admixture  are  The  by phytochemical  and  1 5  information  that  is  available  on a p p r o x i m a t e l y  70 of  the  species  known t o be u s e d as a d m i x t u r e s has been summarized i n A p p e n d i x I.  The a d m i x t u r e p l a n t s Myristicaceous of  attention  pastes  in  the  admixtures  often  Elizabetha  princeps  Justicia  often  Justicia snuff G.  T.,  Jacq.  pectoralis  whether  known as  this  var.  snuffs,  comm.,  ex Bentham)  var.  by  plant  There are that  itself. contains  is  use of a d m i x t u r e s  orally-ingested Myristicaceous [27,28,29] rolled  is  that  in the  leachings species.  of  Schultes  salt  Gustavia  are  certain  and Swain  "salt".  [28]  Among t h e  Eschweilera  subinacum M a r t .  also  E.  this  that  [36,  snuff  is  is  on t h i s  has been  bark  leaves  of  the  Prance, prepared  is  not  species. of  the  noted resin  being  various process  plants  source  Kunth  the  (Lecythidaceae)  (Lecythidaceae),  and s e v e r a l  Dammer. S i n c e o n l y  palm  are  the  have d e s c r i b e d t h e u s e d as  of  psychoactive  of V i r o l a salts  are  leaves  "make  a snuff  the  or  and  pr i n c e p s  reports  plants,  Martius  (Sterculiaceae)  i n c l u d i n g Geonoma j u r u a n a  of  added t o  the p e l l e t s  itayensis  p o e p p i g i a n a Berg ex.  are  (Leguminosae)  the manufacture  pastes  a s h e s made from t h e  preparing this the  of  snuff  t h e powdered  available  in  ocassionally  "salts"  two  Leonard  bark  are  deal  The  biodynamic c o n s t i t u e n t s  no p h y t o c h e m i c a l d a t a  The o n l y  Hooker  occasionally Whether  the  a great  of V i r o l a  and f r e q u e n t l y  [26]. 1983]  received  stenophylla  stenophylla  of  literature.  preparation  A s h e s made from t h e  better."  pers.  from J . or  the  the  (Shomb.  pectoralis  smell  and s n u f f s have n o t  used i n  [26].  added t o  the p r e p a r a t i o n  ethnopharmacological  pectoralis  (Acanthaceae)  used i n  of of  and  Theobroma  species  the ashes  of  these  16  plants very  are  used in the  unlikely  these  that  admixtures.  overlooked make the  in  free  of  alkaloids.  (Moraceae) widely  base  are  be a d d e d t o ashes  literature,  form.  to  general  the  which  that  and t h u s  added t o  are  the  ashes the  are  coca  in order  t o make  pastes  and may a c t u a l l y  it  alkaloids  Cecropia  the  oral  which  their  is  Virola ashes  must  The a d d i t i o n  may be an e x t e n s i o n  influence  uptake  spp.  that  strong.  from  to  a b s o r p t i o n and  of  is  been  added  active  c o c a powder  use  it  derived  seems t o have  convert  the  pellets  c o n s i d e r e d common knowledge  the M y r i s t i c a c e o u s rule,  constituents  same g r o u p s t h a t  is  Virola  T h i s may f a c i l i t a t e  similarly  It  is  the  A s h e s made from l e a v e s  u s e d by the  preparations.  biodynamic  alkaline  to the the  any  of  One p o s s i b i l i t y ,  the  mixture  preparation  of  of  this'  biological  activity.  IV.  Ethnographic  Aspects  of M a l p i g h i a c e o u s  and  Myristicaceous  Hallucinogens The  f o c u s of  botanical,  chemical,  Malpighiaceous understanding cultural unlike large  most  of  other  degree  the  of  prevailing  plant  their  in  in  use.  turn,  hallucinogens;  of  agents, of  the  partially  and n e u r o p h y s i o l o g i c a l cultural  aspects  The e f f e c t s  expectations nature  this  d r u g s must a l s o  pharmacological  and t h e  will,  psychological  reported  and p h a r m a c o l o g i c a l  these  by the  expectations,  research  and M y r i s t i c a c e o u s  context  experience,  the  the  user.  of  on  the  however,  a  full  the  hallucinogens, influenced  to a  These  individual's  drug  be d e t e r m i n e d variables,  myths and b e l i e f s  is  the  consider  of are  thesis  by  and p a r t i a l l y  s u r r o u n d i n g the  drug  by  17  in q u e s t i o n .  This  "traditional" most use  place  hallucinogen setting  of  a  specific  instance,  boundaries  lies  for  between  somewhere  are  and a l l  available  to  the  that  In  traditional  traditional and body a r e are  those  mental  that  health.  hallucinogens, body,  illness  shaman.  manipulation  of  In  are  shaman or  the  causes,  to  from t h e  sense trends  Thus i t which  is  the  (real  or  dimensions,  s h o u l d occupy  traditional  healer's  or  are  not  priest, by  doctor,  of  methods  "holistic"  therapies are  methods p r a c t i c e d  surprising  recognition  that  b o t h the  magical  such a prominent  or  by  that  therapies and  mind and  the  degree  supernatural  position  in  the  mind  plant  t o and a c e r t a i n  armamentarium.  clearly  physical,  improving both p h y s i c a l  imagined)  the  healer  at  access  for  cultures  and t h e most e f f e c t i v e  affect  usually  to  unit  profoundly  and  i n modern m e d i c i n e  therapeutic  not  affording  of  by the  B o t h p r o c e e d from the  directed  is  or a c o m b i n a t i o n  treatment  this  set  and  traditional  may be p r e c i p i t a t e d  recent  integrated  as w e l l as  the  and m e d i c i n e  the W e s t e r n c o n c e p t s  amenable  healer. an  of  magic,  illness,  that  the  divination,  spirit-world.  supernatural  different  drug--for  in  used,  of  chosen  an  w h i c h have c h a r a c t e r i z e d not  the  religion,  and p s y c h o t h e r a p i s t ;  these,  carefully  of  between  or  Use  cause  function  psychological,  context.  are  and c e r e m o n y ,  consuming the  in  our own c u l t u r e ,  hallucinogens  ritual is  as w e l l as  shaman or m e d i c i n e man, and t h e r e  to d i s c o v e r  the  Unlike  i n which  drug experience  w i t h the  delineated;  cultures.  s u r r o u n d e d by  purpose  communicate  o u r own c u l t u r e  a magico-religious  by t h e  or  in  societies in  is  the  manipulated  true  non-Western  traditional takes  is  the  of  1.8  It  is  not w i t h i n  the  voluminous ethnographic to  the  use of  references  plant  [37,38]  Reichel-Dolmatoff account  of  the  snuffs  Tukano I n d i a n s , Virola  snuff  provide [39]  Myristicaceous  pastes  r e c o r d e d by S c h u l t e s observations  t h e methods of  ayahuasca Chapter  and t h e  accessible  industrial the  encountered pastes of  to  chiefly  populations  many of  to  review  literature  p o s i t i o n of in  the  healing;  overview  this  subject.  and  detailed  of  [27]  preparation,  the  equally  present  in Chapter  orally  use of  nothing  fragmentary  and the  the  has d e s c r i b e d t h e  religious  beyond t h e  and  and c o s m o l o g y of  Yanomamo. V i r t u a l l y or  orally  known of ingested  information  Both  observations  and s u b j e c t i v e  ingested pastes  of  fragmentary  Other  use,  the  use  is  investigation.  III.  related  traditional  ayahuasca  religion  the  are  also  are related  effects to  of  be f o u n d  in  III.  Ethnographic  pastes  a general  made d u r i n g t h e  d i s c u s s e d more f u l l y to  in  w h i l e Chagnon [40]  magical,  thesis  has p r o v i d e d a f a s c i n a t i n g  among t h e  the m e d i c a l ,  this  and a n t h r o p o l o g i c a l  hallucinogens  central  Myristicaceous  scope of  are  the  aspects  of  the  outside  observer  because ayahuasca  use of than  is  outskirts  and t r a d e c e n t e r s  s u c h as  in not  the  and l i n g u i s t i c  ethnographic  a factor  in  the m e s t i z o p o p u l a t i o n  the in  settlements  speak a d i a l e c t i c a l  necessarily  as  the  first  of  Myristicaceous  large  barriers  study  of of  the  riverine  which  Hence  are  Myristicaceous  ayahuasca.  u r b a n or  form of  language).  more  I q u i t o s and P u c a l l p a .  study  these  the  are  u s e d among u r b a n m e s t i z o  r e s i d i n g on t h e  cultural  ayahuasca  Most  members  semi-urban  Spanish  Face-to-face  (though  not  interviews  can  19  thus  be c o n d u c t e d w i t h i n f o r m a n t s ,  fruitful  p r o c e d u r e than  speaking  interpreter.  investigator this  also  is  facilitates  Contemporary appears urban  often  use of  s e a r c h of  employment  gathering ethnographic  in  culture.  Over  of the  and b e l i e f  these  years  this  society  elements  its  This  mestizo  migrant  diverse  societies  tribal  origins,  class. the  in which  reside  a living  is  the  the Amazon i s  only  is  ethnomedicine place  often  in t h e i r derived  is  the  own  at  extends own  from  larger s y s t e m of  incorporates  the  same p e r i o d of  urban c e n t e r s  it  laborers  lore  in  missionaries).  same  T h i s p r o c e s s of  it  cases  with  though i t  Hence m e s t i z o f o l k - m e d i c i n e as  m e d i c i n e b a s e d on t h e  centers  syncretically  valued  f o l k ' m e d i c i n e have d i s i n t e g r a t e d  of  large  similar  d i f f u s e d through the  tradition,  the m e s t i z o s o c i a l  tribal  contact  drug-plant  a m a l g a m a t i o n has o c c u r r e d o v e r the  and  The many  these  and become m e l d e d i n t o a c o h e r e n t  medicine.  of  p e o p l e of  (usually  due t o p r i o r  mestizo  to  systems  and  populations  traditions.  petroleum,  the m e d i c i n a l p l a n t s  traditional  outside  and have b r o u g h t w i t h them t h e i r  s o u r c e s has g r a d u a l l y  unique  tribal  lumber,  diverse  of  i n Amazonian m e s t i z o  diverse  the  b a c k g r o u n d of  t o a knowledge  the  information.  b a c k g r o u n d s have m i g r a t e d t o  fused with C h r i s t i a n i t y The c u l t u r a l  a more  f o u n d among m e s t i z o s who use a y a h u a s c a  industries,  traditions  generally  toward  have become m e l t i n g p o t s ;  cultural  resource-based  is  conducted through a Spanish-  A more open a t t i t u d e  ayahuasca  different  tribal  interviews  t o be an amalgam of  settlements  and t h i s  time  cultural  time  that  antecedents  most  of  and/or d i s a p p e a r e d .  practiced  today  s y s t e m of  in  the  traditional  of many c u l t u r e s ;  where s u c h knowledge has  i n many  been  20  preserved.  Hence  it  is  f o l k - m e d i c i n e and the  important, plants  that  even  urgent,  form i t s  basis  investigators  with s c i e n t i f i c  backgrounds in  pharmacology,  phytochemistry,  and b o t a n y  still  The a y a h u a s c a  exists.  provide  an e x a m p l e .  admixtures  Some of  to ayahuasca  potentially  medically  useful  have so f a r  The i n s i s t e n c e ,  nearly  teaches  properties  of  conjunction hand.  mestizo  insights  aspects of  may be seen of  the  of  the  from t h e  chemistry,  this  use of  problems.  were t o  ayahuasca  and e t h n o b o t a n i c a l  pharmacology  of  botany,  for  about  some of  in  field  specific  in of  contemporary  and  several  ethnography remain  research described these  investigations of  in  unresolved  a p p r o a c h was a d o p t e d ,  used i n  the  them  hallucinogens  the  the M a l p i g h i a c e o u s and  rationale  that  Investigation  investigations  h a l l u c i n o g e n s and t h e p l a n t s scientific  of  known.  [14,38,41,42,43].  pharmacology,  investigate  combined w i t h l a b o r a t o r y  not  preceding d i s c u s s i o n that  An i n t e r d i s c i p l i n a r y  ethnographic  is  be d i s m i s s e d out  Present  u n d e r s t o o d . The o b j e c t i v e s  thesis  how many o t h e r s may  use them by t a k i n g  t h e M a l p i g h i a c e o u s and M y r i s t i c a c e o u s  poorly  and  one l e a r n s  cannot  I  be u s e d as  investigation  m e d i c i n e may be f o u n d i n  V . Scope and O b j e c t i v e s It  the  in Appendix  biodynamic  that  [14],  into  opportunity  among a y a h u a s q u e r o s ,  i.e.,  and how t o  medicine,  known t o  constituents;  universal  with ayahuasca  folk  highly  mestizo  be s t u d i e d by  while the  listed  species  escaped  medicine,  plants  Further  the  contain  have v a l u e t h a t  ayahuasca  admixtures  that  in.which were  the c h e m i s t r y  and  Myristicaceous  their  aspects  manufacture. of  the  The  investigation  21  is  given  the  in  the a p p r o p r i a t e  research  are  A.  Work  Field  enumerated  T h i s had s e v e r a l  1.  chapters;  over-all  objectives  of  below.  complementary  C o l l e c t i o n of  the  objectives:  ethnobotanical  and  ethnographic  the  source-plants  informat i o n . This in  included information  the manufacture  methods of  of  ingestion,  the d r u g s ,  o c c a s i o n s when t h e y  context  of  information  2.  use.  on t h e i r  preparations  folk  which  plants  and d r u g  were made a n d , when p o s s i b l e , their  preparation  were a l s o  samples  phytochemical a n a l y s i s .  even t h o u g h t h e y or  were not  informants.  Any o t h e r  t o have m e d i c i n a l they  cultural the p l a n t s  were not c o n s t i t u e n t s  of  source p l a n t s collected.  As many c o l l e c t i o n s  and  Plant  of  u s e d t o make d r u g  any a d m i x t u r e p l a n t s  Special  indicated  w h i c h were i n d i c a t e d  applications  drug  s p e c i e s a s p o s s i b l e were made,  necesarily  plants  and  s p e c i m e n s and  i n d i c a t e d as b e i n g so u s a b l e .  were made t o c o l l e c t  used,  collected.  the  i n c l u d e d both herbarium voucher  M a l p i g h i a c e o u s and M y r i s t i c a c e o u s  the  samples.  collections  preparations  drugs are  of M a l p i g h i a c e o u s and M y r i s t i c a c e o u s  admixtures used in  for  the  names of  taxonomy was a l s o  used  preparation,  c o n s u m e d , and t h e  Native vernacular  C o l l e c t i o n of  Collections  are  to  t h e methods of  the p u r p o s e s f o r  and t h e  their  related  were a l s o c o l l e c t e d hallucinogenic  efforts  by  by  informants  even  though  preparations.  22  3.  A s s e s s m e n t of  the  biological activity  a c t i v e M a l p i g h i a c e o u s and  of  orally-  Myristicaceous  hallucinogens. Although there of  action  of  the  Malpighiaceous reports  of  existent. active  considerable  their  effects  Thus i t  is  observer  in  the  the  field-work  preparations  are,  particularly  important  Myristicaceous psychological  in  fact,  pastes, effects  in  these  substantiating not  system s u r r o u n d i n g these of  observers  assumed t h a t  who i s  was  the case their  have not  are  evidence  determine  effective. of  the  literature, r a r e or  drugs are  immersed i n  to  mechanism  and  non-  orally-  is  required  the  cultural  d r u g s . Thus one of  orally  since  the  ethnobotanical  on o u t s i d e  only  as h a l l u c i n o g e n s ;  objectives  d i s c u s s i o n of  orally-ingested Myristicaceous  hallucinogens  f r o m an o u t s i d e belief  is  the  whether This  these  was  orally-ingested  physiological  previously  and  been e x p e r i e n c e d by a  non-Indian.  B.  Laboratory  Investigations  T h e s e were d e s i g n e d t o complement t h e and t o  resolve  several  field  q u e s t i o n s w h i c h c o u l d be  investigations approached  experimentally:  1. Q u a n t i t a t i v e  investigations  constituents  t h e M a l p i g h i a c e o u s and  of  of  the  active Myristicaceous  hallucinogens. Although previous active constituents  of  investigators these  have d e t e r m i n e d t h a t  drugs are  in a l l  likelyhood  the  23  psychotomimetic on t h e  levels  sparse. in a  It  tryptamines  of  is  alkaloids  not  "typical"  known,  dose of  and / 3 - c a r b o l i n e s , q u a n t i t a t i v e in  for  these  instance,  ayahuasca  t h r e s h o l d dose r e q u i r e d to e l i c i t Similarly, ayahuasca  although and t h e  rendered o r a l l y has not  it  quantitative relative  orally  active  or V i r o l a the  relatively  t h e amount of DMT  snuff  exceeds  psychotomimetic  the  effects.  t h e DMT i n  ingested Myristicaceous  /3-carbolines are  to e f f e c t i v e l y  inhibit  present  MAO.  pastes  is  tryptamines  the p l a n t  sufficient  the  kinds  and / 3 - c a r b o l i n e s  and  in  the  drug  of  the  drug  samples.  C o m p a r i s o n of  preparations  in  it  Therefore  methods were d e v i s e d t o d e t e r m i n e  s a m p l e s and i n  is  by the M A O - i n h i b i t i n g / 3 - c a r b o l i n e s ,  p r o p o r t i o n s of  2.  whether  has been p r o p o s e d t h a t  been shown t h a t  concentrations  preparations  data  the  alkaloid  with the a l k a l o i d  constituents constituents  of  the  source-plants. Quantitative to determine  and q u a l i t a t i v e  t o what e x t e n t  samples d i f f e r e d  from t h a t  plants  screened  were a l s o  quantitatively  3.  drugs  tryptamines  of for  is  the  c o m p o s i t i o n of  source-plants.  alkaloids  in  and i n  order  the  drug  Admixture  some  cases  analyzed.  the e f f e c t  alkaloid constituents  The mechanism of these  the a l k a l o i d  I n v e s t i g a t i o n of  their  methods were a p p l i e d  that  action  the  of  drug samples  on MAO in  postulated  for  the  /3-carbolines p r o t e c t  f r o m d e a m i n a t i o n by p e r i p h e r a l  the  and  vitro. oral  activity  psychoactive  monoamine o x i d a s e ,  of  24  thus p e r m i t t i n g this  their  uptake  mechanism had not  into  the  been e x p e r i m e n t a l l y  T h e r e f o r e methods were d e v e l o p e d f o r various  drug p r e p a r a t i o n s  MAO i n h i b i t o r s .  and t h e i r  The MAOI a c t i v i t y  carboline  derivatives  establish  structure/activity  compounds  in c o n c e n t r a t i o n s  drug p r e p a r a t i o n s whether  standards  preparations partly  approximating those  perfect  the  unacceptable necessary  to  of  I_n  techniques.  time  of  synthetic the  determine  of  synthetic crude  activity  drug was  vivo  the drug  preparations  p l a n n e d but were not  l e n g t h of  and 0-  in combination.  whether.the  constituents.  as  to  found in  o b s e r v e d w i t h the  t h e MAOI o c t i v i t y  u s i n g a n i m a l s were o r i g i n a l l y due t o t h e  in order  synergistically  to determine  due t o n o n - a l k a l o i d a l of  Mixtures  of  activity  tryptamine  i n an e f f o r t  o b s e r v e d w i t h the m i x t u r e s  in order  investigations  synthetic  correlations.  was compared w i t h t h a t  activity  c o n s t i t u e n t s ' for  of  were a l s o a s s a y e d  reasonable,  demonstrated.  a s s e s s i n g the  was a l s o a s s e s s e d  t h e compounds might a c t  The MAOI a c t i v i t y  CNS. A l t h o u g h  required  carried  out  to develop  and  25  VI.  Literature  Cited  1.  S c h u l t e s , R. E. (1970) The B o t a n i c a l and C h e m i c a l D i s t r i b u t i o n of H a l l u c i n o g e n s . A n n u a l Review of P h y s i o l o g y 21:571-98  2.  S c h u l t e s , R. E. & A . Hofmann (1980) The Botany and C h e m i s t r y of H a l l u c i n o g e n s . 2nd E d i t i o n • C h a r l e s C . Thomas, P u b l i s h e r s , S p r i n g f i e l d , 111.  3.  G r i n s p o o n , L. & L. B. Reconsidered. Basic  4.  S c h u l t e s , R. Narcotics.  E. (1963) The B o t a n i c a l S o u r c e s of The P s y c h e d e l i c Review 1:145-66  5.  Schultes,  E.  6.  E f r o n , D. H . , B. H o l m s t e d t , & N. S. K l i n e ( e d s . ) (1967) E t h n o p h a r m a c o l o g i c S e a r c h f o r P s y c h o a c t i v e D r u g s . U. S. P u b l i c H e a l t h S e r v i c e P u b l i c a t i o n # 1645  7.  R.  8.  S c h u l t e s , R. E. (1957) The I d e n t i t y of t h e M a i i p i g h i a c e o u s N a r c o t i c s of S o u t h A m e r i c a . H a r v a r d B o t a n i c a l Museum L e a f l e t s 18:1-56  9.  P i n k l e y , H. V . (1969) P l a n t A d m i x t u r e s t o A y a h u a s c a , the S o u t h A m e r i c a n H a l l u c i n o g e n i c D r i n k . L l o y d i a 32:305-14  R.  Hallucinogenic  (1970)  Plant  B a k a l a r . (1979) P s y c h e d e l i c B o o k s , I n c . New Y o r k .  The New W o r l d I n d i a n s and  Plants.  Morris  Drugs  the  New W o r l d  Their  Arboretum B u l l e t in  21:3-14  E. S c h u l t e s (1979) E v o l u t i o n of t h e I d e n t i f i c a t i o n of M y r i s t i c a c e o u s H a l l u c i n o g e n s of S o u t h A m e r i c a . J o u r n a l E t h n o p h a r m a c o l o q y 1:211-239 1979  the of  10.  Der M a r d e r o s i a n , A . H . , H. V . P i n k l e y , & M. F. D o b b i n s IV. (1968) N a t i v e Use and O c c u r r e n c e of N,N-dimethyltryptamine i n t h e L e a v e s of B a n i s t e r i o p s i s r u s b y a n a . A m e r i c a n J o u r n a l of Pharmacy 140:137-147  11.  G a t e s , B. (1979) (Malpighiaceae)  New Names i n B a n i s t e r i o p s i s and D i p l o p t e r y s of t h e Guayana H i g h l a n d . B r i t t o n i a 3 1 : 1 0 8 - 9  26  12.  S c h u l t e s , R. E . , (1979) New D a t a on the M a l p i g h i a c e o u s N a r c o t i c s of S o u t h A m e r i c a . H a r v a r d B o t a n i c a l Museum L e a f l e t s 23:137-47  13.  S c h u l t e s , R. E. (1972) E t h n o t o x i c o l o g i c a l S i g n i f i c a n c e A d d i t i v e s t o New W o r l d H a l l u c i n o g e n s . P l a n t S c i e n c e B u l l e t i n 18: 34-41  14.  L u n a , L. E. (1983) The C o n c e p t of P l a n t s as T e a c h e r s Among F o u r M e s t i z o Shamans of I q u i t o s , N o r t h e a s t P e r u . Paper p r e s e n t e d a t the Symposium on Shamanism, X l t h I n t e r n a t i o n a l C o n g r e s s of A n t h r o p o l o g i c a l and E t h n o l o g i c a l S c i e n c e s , Phase 2. V a n c o u v e r , B. C , A u g u s t 20-23 1983.  15.  R i v i e r , L. & J . L i n d g r e n (1972) A y a h u a s c a , t h e American H a l l u c i n o g e n i c D r i n k : E t h n o b o t a n i c a l Investigations. Economic B o t a n y 2 9 : 1 0 1 - 1 2 9  16.  D e u l o f e u , V . (1967) C h e m i c a l Compounds I s o l a t e d from B a n i s t e r i o p s i s and R e l a t e d S p e c i e s , p p . 393-402 i n D. E f r o n , B. H o l m s t e d t , & N. S. K l i n e ( e d s . ) Ethnopharmacoloqic Search f o r P s y c h o a c t i v e D r u g s . U. P u b l i c H e a l t h S e r v i c e P u b l i c a t i o n .#1645  17.  of  South and C h e m i c a l  H. S.  A g u r e l l , S . , B. H o l m s t e d t , & J . E. L i n d g r e n (1968) A l k a l o i d Content of B a n i s t e r i o p s i s r u s b y a n a . A m e r i c a n J o u r n a l of Pharmacy 140:148-151  18. H a s h i m o t o , Y. & K. K a w a n i s h i (1975) New O r g a n i c Amazonian B a n i s t e r i o p s i s c a a p i . P h y t o c h e m i s t r y  B a s e s from 1 4:1633-35  19.  H a s h i m o t o , Y. & K. K a w a n i s h i (1976) New A l k a l o i d s B a n i s t e r i o p s i s c a a p i . P h y t o c h e m i s t r y 15:1559-60  from  20.  K a w a n i s h i , Y . , Y. Dihydroshihunine Natural Products  21.  W. A . R o d r i g u e s . (1980) R e v i s a o T a x o n o m i c a d a s E s p e c i e s de V i r o l a A u b l e t ( M y r i s t i c a c e a e ) do B r a s i l . A c t a A m a z o n i c a 1:1-123  22.  A g u r e l l , S . , B. H o l m s t e d t , J . E. L i n d g r e n , & R. E. Schultes. (1968) I d e n t i f i c a t i o n of Two New / J - c a r b o l i n e A l k a l o i d s i n South American H a l l u c i n o g e n i c P l a n t s . Biochemical P h a r m a c o l o g y 17:2487-88  Uhara & Y. H a s h i m o t o (1982) S h i h u n i n e from B a n i s t e r i o p s i s c a a p i . J o u r n a l of 45:637-8  and  27  23.  B. H o l m s t e d t , J . E. L i n d g r e n , T . Plowman, L. R i v i e r , R. E. S c h u l t e s & 0 . T o v a r . (1980) I n d o l e A l k a l o i d s i n Amazonian M y r i s t i c a c e a e : F i e l d and L a b o r a t o r y R e s e a r c h . H a r v a r d B o t a n i c a l Museum L e a f l e t s 2 8 : 2 1 5 - 2 3 4  24.  J.  25.  A l l e n , J . R. F . , & B. H o l m s t e d t (1980) The S i m p l e 0c a r b o l i n e A l k a l o i d s . P h y t o c h e m i s t r y 19:1573-1582  26.  S c h u l t e s , R. E. & B. H o l m s t e d t (1968) The V e g e t a l I n g r e d i e n t s of t h e M y r i s t i c a c e o u s S n u f f s of t h e N o r t h w e s t Amazon. Rhodora 7 0 : 1 1 3 - 1 6 0  27.  Schultes,  28.  S c h u l t e s , R. E. & T . Swain (1976) an O r a l H a l l u c i n o g e n . J o u r n a l of 324  29.  S c h u l t e s , R. E . , T . S w a i n , & T . Plowman (1977) V i r o l a O r a l H a l l u c i n o g e n Among t h e B o r a s of P e r u . H a r v a r d B o t a n i c a l Museum L e a f l e t s 25:259-272  30.  A g u r e l l , S . , B. H o l m s t e d t , & J . E. L i n d g r e n (1969) A l k a l o i d s i n C e r t a i n S p e c i e s of V i r o l a and O t h e r S o u t h A m e r i c a n P l a n t s of E t h n o p h a r m a c o l o g i c I n t e r e s t . A c t a Chemica S c a n d i n a v i c a 23:903-916  31.  S h u l g i n , A . T . (1976) M a x w e l l Gordon ( e d . ) Academic Press  32.  U d e n f r i e n d , S . , B. W i t k o p , B. G . R e d f i e l d , & H. W e i s s b a c h (1958) S t u d i e s w i t h R e v e r s i b l e I n h i b i t o r s of Monoamine O x i d a s e : H a r m a l i n e and R e l a t e d Compounds. B i o c h e m i c a l P h a r m a c o l o g y 1:160-165  33.  M c l s a a c , W. M. & V . E s t e v e z (1966) Structure-action R e l a t i o n s h i p s of / 3 - c a r b o l i n e s as Mono-amine O x i d a s e I n h i b i t o r s . B i o c h e m i c a l Pharmacology 26:1625-27  M. C a s s a d y , G. E. B l a i r , R. F. R a f f a u f & V . E. T y l e r . (1971) The I s o l a t i o n of 6-methoxyharmalan and 6methoxyharman from V i r o l a c u s p i d a t a . L l o y d i a 34:161-162  R.  E.  Hallucinogen.  (1969)  Harvard  Virola  as an  Botanical  Orally-administered  Museum L e a f l e t s  22:229-40  F u r t h e r N o t e s on V i r o l a as P s y c h e d e l i c Drugs 8 : 3 1 7 -  as  Psychotomimetic Agents. c h . 4 in Psychopharmacological Agents V o l .  an  IV.  28  34.  B u c k h o l t z , N. S. & W. 0 . Boggan (1977) Monoamine O x i d a s e I n h i b i t i o n i n B r a i n and L i v e r P r o d u c e d by 0 - c a r b o l i n e s : Structure-activity R e l a t i o n s h i p s and S u b s t r a t e Specificity. B i o c h e m i c a l Pharmacology 26:1991-96  35.  S q u i r e s , R. F. Pharmacology. Snyder ( e d s . ) Plenum P r e s s ,  36.  C h a g n o n , N . , P. L e Q u e s n e , & J . M. Cook (1971) Yanomamo H a l l u c i n o g e n s : A n t h r o p o l o g i c a l , B o t a n i c a l , and C h e m i c a l F i n d i n g s . C u r r e n t A n t h r o p o l o g y 12:72-74  37.  H a r n e r , M. ( e d . ) (1973) H a l l u c i n o g e n s and Shamanism. U n i v e r s i t y P r e s s , London.  38.  F u r s t , P. Chandler  39.  Reichel-Dol-matof f, S t u d y of N a r c o t i c Temple U n i v e r s i t y  40.  C h a g n o n , N. (1968) Yanomamo: The F i e r c e R i n e h a r t , and W i n s t o n , New Y o r k .  41.  De R i o s , Healing  42.  De R i o s ,  T. (ed.) (1976) H a l l u c i n o g e n s and S h a r p , San F r a n c i s c o .  M. D o b k i n in  the  Oxford  and C u l t u r e .  G . (1975) The Shaman and t h e J a g u a r : A D r u g s Among t h e I n d i a n s of C o l o m b i a . Press, Philadelphia.  (1972)  Peruvian  M. D o b k i n  Internat ional 43.  (1978) Monoamine O x i d a s e I n h i b i t o r s : A n i m a l i n L. L. I v e r s o n , S. D. I v e r s o n , & S. H. Handbook of P s y c h o p h a r m a c o l o g y V o l . 14. New Y o r k .  (1971)  Journal  of  Visionary Amazon.  Vine:  Chandler,  Ayahuasca: Soc i a l  People•  Holt,  Psychedelic San  Francisco.  The H e a l i n g  Psychiatry  Vine.  17:256-69  De R i o s , M. D o b k i n (1970) B a n i s t e r i o p s i s i n W i t c h c r a f t H e a l i n g i n I q u i t o s , P e r u . Economic B o t a n y 2 4 : 2 9 6 - 3 0 0  and  29  CHAPTER 1 1 : CHEMISTRY AND PHARMACOLOGY OF TRYPTAMINES AND 0-CARBOLINES I.  Occurrence,  Distribution,  and B i o s y n t h e s i s  of  Tryptamines  and  fl-carbolines The s i m p l e d e r i v a t i v e s 1 & 2)  are  plant,  animal,  of  among the most w i d e l y and f u n g a l  simple d e r i v a t i v e s  of  tryptamine  new s p e c i e s a r e  e.g.,  [3])  stands 1980,  and u n d o u b t e d l y  in  need of  64 s i m p l e  higher  plant  identified.  revision.  families  C o m p a r i s o n of instances,  also  contain  structurally  s u r p r i s i n g since  tryptophan moieties  and/or  [4,5]  Smith  of  the  the  or v i a  of  related  fungi  /3-carbolines are  in  (cf., [1]  of  [2]  in  had been in  [1]  and  [2]  observation  biosynthesized  tryptamine [6].  shows  derivatives  this  condensation with  derivatives  nature,  list  tryptamine  3 , 4-dihydro-/3-carbol ines  tryptamine  the  publication  cited  of  in  Agaricales  presented  /3-carbolines;  N-acetylation  in the .  d i s t r i b u t e d among 25  containing  via  and t h e  t i m e of  species  plants  tryptamine  c y c l o d e h y d r a t ion to biosynthesis  tabulation  (Fig.  1977, some 19  identified  b e i n g added t o  and 3 s p e c i e s  i n many  not  At  As of  families  /3-carboline d e r i v a t i v e s  that  is  the  [1,2].  had been  plant  continually  and 0 - c a r b o l i n e  distributed alkaloids  kingdoms  d i s t r i b u t e d among 26 h i g h e r [1];  tryptamine  from  1 or  2 carbon  followed  by  The  has been r e v i e w e d  by  [7], Both tryptamine  d e t e c t e d as Bufotenine  derivatives  and / 3 - c a r b o l i n e s have  endogenous m e t a b o l i t e s and v a r i o u s  related  constituents  of  genera H y l a ,  Leptodactylus,  i n mammals,  been  i n c l u d i n g man.  5-hydroxy-indolethylamines  f r o g and t o a d venoms Rana,  [8],  b e i n g common i n  and B u f o .  A wider  are the  s p e c t r u m of  Figure  Name of Compound  Abbreviation  tryptophan 5-hydroxytryptophan tryptamine TA 5-hydroxytryptamine 5HT N-methy1 tryptamine NMT 5-methoxytryptamine 5-MeO-T 6-methoxytryptamine 6-MeO-T 5-methoxy-N-methy1 tryptamine 5-MeO-NMT 5-methoxy-N-acety1 tryptamine (melatonin) N.N-dlmethyl tryptamine DMT 5-hydroxy-N,N-dimethyltryptamine 5H0-DMT (bufotenine) 5-methoxy-N,N-d1methyltryptamine 5MeO-DMT 4-hydroxy-N,N-dimethyltryptamine 4H0-DMT (psilocln) 4-phosphoryl-N.N-dlmethyl tryptamine (psilocybin) 4-phosphoryl-N-methy 1 tryptamine (baeocystIne) 4-phosphoryltryptamine (norbaeocys 11ne) N-methyl-tryptophanmethyl e s t e r ( a b r l n e methyl e s t e r ) N.N-dlmethyltryptophan * c f . Table  R  1 - Some N a t u r a l l y - O c c u r r i n g Tryptamine D e r i v a t i v e s *  Substitution i  Pattern:  R>  R,  Ra  R>  Rt  H  H  COOH  H  H  H  H H  H H  COOH H  H H  OH H  H H  H  H  H  H  OH  H  H  CH,  H  H  H  H  H  H  H  H  OCH,  H  H  H  H  H  H  OCH,  H  CH,  H  H  OCH,  H  H  0=CCHJ  H  H  OCH,  H  CHi  CH,  H  H  H  H  CH,  CH,  H  H  OH  H  CHi  CH,  H  H  OCH,  H  CHi  CH,  H  OH  H  H  CHi  CH,  H  OPO,H  H  H  H  CH,  H  0PO,H  H  H  H  H  . H  OPO,H  H  H  H  CH,  COOCH,  H  H  H  CH,  CH,  COOH  H  H  H  1 f o r s t r u c t u r e s of some p s y c h o a c t i v e s y n t h e t i c tryptamine d e r i v a t i v e s .  Figure 2 - Some N a t u r a l l y - O c c u r r i n g 0 - c a r b o l i n e D e r i v a t i v e s  Additional  Trivial  Name  norharman norharma1 an tetrahydronorharman harman harma1 an tetrahydroharman harmine harma1ine tetrahydroharmine harmic amide a c e t y l norharmine harmine N-oxide ketotetrahydronorharm i ne harmic a c i d methyl e s t e r harma1inic acid harmol harmalol 6-methoxy-harman 6-methoxy-harma1 an 6-methoxy-tetrahydroharman 6-methoxy-2-methy1-tetrahydro0-carbol1ne 6-methoxy-1,2-dlmethyl-tetrahydro 0-carboline 2-methyl-tetrahydro0-carboline 1,2-dimethy 1 - t e t r a h y d r o 0-carboline 0-carboline-3carboxylate 0-carboline-3-carboxy1 ate ethyl ester tetrahydroharman-3carboxylate brevicoline  Substitutents  Ring Type  R=  & Their L o c a t i o n  A B  H H  -  -  -  -  C A  --  --  B  H CH, CH,  -  -  C  CH,  A  -  B  CH, CH,  c -0CH, c -0CH,  -  C  CH,  A A A  CONH. C=OCH, CH,  c c c c  -  C  =0  c -OCH,  -  A B A B A B  C00CH,  c -OCH, c -OCH. c -OH c -OH  -  CH,  c. -OCHi C i -OCH,  C  CH,  CI  C  H  N, - C H , ,  C.-0CH,  6-MeO-MTHjC  c  CH,  Ni  -CH,,  Ct-OCH,  6-Me0-DMTHflC  c  H  Ni -CH,  MTHflC  c  CH,  Ni -CH,  DMTHjC  A  H  c , -COOH  flCC  A  H  c , -C00CH,  0CCEE  C  CH,  A  COOH CH, CH, CH,  CH,  -0CH, -0CH, -0CH, -0CH,. Ni-->0  c i—  -  -  -OCH,  c , -COOH  Abbreviat ion  ~  u>  32  bufotenine derivatives bufoviridine,  the  is  closely  derivatives, and  [9]),  and i t s  related  to  bufotenine  Bufo  species  ester,  is  rather  50-160 mg/g of  heart,  and a l s o  in r a b b i t  and baboon b r a i n s , [10].  The _i_n v i v o  been d e m o n s t r a t e d s t a t e of  blood,  as w e l l as f o r m a t i o n of in  rabbit  i n human and r a t  interesting cytotoxicity carboline detected  of  light  of  aromatic  derivatives  the  this  of  have been fluid,  liver,  tissues  in  rat  brain  pig,  species  protein  [12]  1981  has have  III.A,  aromatic  /3-carboline which  is  d i s c o v e r e d photo[13].  ethanol  recent  has  The  section  fully  An a r o m a t i c  /3-carbolines  [10].  derivatives  (cf.  and the  recently  [11,14] provide comprehensive  guinea  i n mammals as of  tissues  [11].  following  the  and  these  Endogenous /3-  and t e t r a h y d r o i s o q u i n o l i n e s  i n human u r i n e  is  characterized  steer,  Endogenous / 3 - c a r b o l i n e  from a g i n g human l e n s  in  [8];  tryptamines  Both t e t r a h y d r o - / 3 ~ c a r b o l i n e s  isolated  rather  DMT from l a b e l l e d p r e c u r s o r s  also  been  the  synthesis  l u n g and i n  have been d e t e c t e d  i n man.  the  in other  [10].  derivatives  below,  tryptamine.  t o a d , mouse,  been summarized i n  below).  (see  a hallucinogenic  knowledge of DMT b i o s y n t h e s i s  been d e t e c t e d  skin  cerebrospinal  lung,  Although  tryptamine  5-MeO-DMT a t  which c a t a l y z e  brain,  bufothionine.  than a h a l l u c i n o g e n  i n c l u d i n g DMT, 5-MeO-DMT, and b u f o t e n i n e i n human l u n g ,  including  not h a l l u c i n o g e n i c  known t o c o n t a i n  transferases  genus,  bufotenine,  contains of  last  hallucinogenic  itself  Bufo a l v a r i u s  of  sulfate  the  staggering concentration  Methyl  ester  a c t i n g as a p r e s s o r  The s k i n of  only  found in the  sulfate  dehydrobufotenine, it  is  loading.  reviews.  have  been  References  has  33  11.  Pharmacology  A.  of  Hallucinogenic  Structure/Activity  Most c l i n i c a l hallucinogenic  methylated  Relationships  and p h a r m a c o l o g i c a l  tryptamines  metabolism and/or  the  tryptamine  derivatives  the  investigation  is  hallucinogenic  activity  Investigations  of  animal test the  a paucity  of  available sites  scientific  structural  tryptamine  for  this  information  or  homologs of  however. is  in  the  two  are  DMT i n w h i c h  (DET),  (DIPT),  N,N-dibutyltryptamine  (DBT).  i n man e x c e p t orally  has  the  of adequate  much of  a step  the  the  The  currently  important  indole (cf.  ring, Table  determinants  the I).  side-chain The N - a l k y l  substituents  include  these  for  are  N,N(DPT),  homologs  DMT i t s e l f ,  N,N-  (DAT),  and  are  N,N-dibutyltryptamine,  a c t i v e except  of  substitution  N,N-diallyltryptamine of  in  summarized t h e  are  moieties  for  on  humans.  represents  reviews.  that  All  on  as  discrimination  N,N-dipropyltryptamine  diisopropyltryptamine  apparently  [15]  the N,N-dimethyl  r e p l a c e d w i t h more a l i p h a t i c  psychoactive  recent  side-chain nitrogen  diethyltryptamine  in  no  the drug  such  from " u n d e r g r o u n d " s o u r c e s  [16,17]  nucleus  activity  that  As a r e s u l t ,  derived  Shulgin  tryptamine  hallucinogenic  influences  derivatives  purpose;  of  literature  fact  information  on t h e  carbons,  are  of  of  c o m p l i c a t e d by t h e  direction,  vitro  states  relationships  dubious c r e d i b i l i t y .  of  in p a t h o l o g i c a l  d e v e l o p e d by A p p e l and c o - w o r k e r s  available  _i_n  structure/activity  model.exists  right  with  p o s s i b l e endogenous s y n t h e s i s  There  h a l l u c i n o g e n s are  studies  have f o c u s e d on t h e i r  schizophrenia. systematic  Tryptamines  and  which  all is  Table I - O r a l l y and P a r e n t e r a l l y A c t i v e Psychotropic Tryptamine D e r i v a t i v e s *  Name of Compound  R,  Ri  tryptamine H H DMT CH, CH, DET CH, CH, DPT n-prop n-prop OAT C,H» CH, DIPT i-prop 1-prop 5Me0-DIPT i-prop i-prop 5MeO-DMT CH, CH, psilocin CH, CH, CZ-74 CiH% C H» serotonin H H bufotenine CH, CH, H H IT-290 4-hydroxy-a-methy1 tryptamine H H MP-809 H H 5-f1uoro-a-methy1 tryptam i ne H H 5-methoxy-a-methy 1 tryptamlne H H 4-hydroxy-d i i sopropy1 tryptamine 1 -prop 1-prop 4-hydroxyN-1sopropyl,N-methy1 tryptamine i-prop CH, N-t-butyl-. tryptamine H t-butyl 3 - [ 2 - ( 2 , 5 - d i m e t h y l p y r r o l y l ) e t h y l ]indole ( sIde-cha1n=1-ethyl(2,5-dimethylIpyrrole)  S u b s t i t u t i o n Pattern R, R«  R.  Dosage (mg)  Route: Oral/Parenteral  H H H H H H H H H H H H CH,  H H H H H H H H OH OH H H H  H H H H H H OCH, OCH i H H OH OH H  100t 60 60 60 60 30 12 6 12* 15* 100* 16b 30  par/ora1? par par/ora1 par/ora1 par/ora1 ora 1 ora 1 par ora 1 ora 1 ora 1 par oral  CH, CH,  OH H  H CH,  20# 606  ora 1 ora 1  CH,  H  F  25*  ora 1  CH,  H  OCH,  3  ora 1  H  OH  H  12*  ora 1  H  OH  H  6*  ora 1  H  H  H  ?*  ora 1  H  H  H  ?  ?  * Data compiled from [9,16,17.18]. t Autonomic symptoms; l i t t l e c e n t r a l a c t i v i t y . * The phosphate e s t e r s a r e p s i l o c y b i n and CEY-19. r e s p e c t i v e l y ; both a r e stoichiometr1ca11y e q u i v a l e n t to the 4-hydroxy isomers. * C a r d i o v a s c u l a r and autonomic symptoms; l i t t l e c e n t r a l a c t i v i t y , b A p r e s s o r amine rather than a h a l l u c i n o g e n i n man. ^ An a n t i d e p r e s s a n t rather than a h a l l u c i n o g e n In man. * Based on anonymous r e p o r t s i n the lay press. No c l i n i c a l s t u d i e s have been  published.  35  orally  inactive  Presumably  the  in doses exceeding oral  inactivity  by monoamine o x i d a s e derivatives  having  a c t i v e due t o  (cf.  the N , N - d i a l k y l  substitution  N-alkyl  hindrance  derivatives  e n h a n c e d by h y d r o x y l  of  = 4-hydroxy-DMT).  oral  of  the  anionic  psilocin  formation  of  is  at  the  and  is  on t h e  I).  deamination  those are  orally of  all  4-position; parent  an i n t r a m o l e c u l a r  it  ionic  this  compound,  The mechanism u n d e r l y i n g but  of  considerably  indole  unelucidated,  r i n g h y d r o x y l and t h e  its  enzyme. P o t e n c y  activity  DMT ( p s i l o c i n  due t o  due t o  m e n t i o n e d above  oral  Table  substituents the  substitution  also confers  activity  DMT i s  d i s c u s s i o n below)  bulkier  steric  of  1000 mg ( c f .  the  probably  is  bond between  charged side-chain  nitrogen;  the  this  c o n f i g u r a t i o n c o u l d form a " p s e u d o " C r i n g and t h u s p r o t e c t side-chain isomer  of  and a c t s severe  from d e a m i n a t i o n psilocin,  primarily  bufotenine, on the  cardiovascular  lachrymation, Apparently  anionic  is  inactive  peripheral  stimulation,  5-hydroxyl  the  uptake  of  methyl  analogue  of  the  autonomic  salivation, but  zwitterionic  the  central  (5-MeO-DMT)  as an h a l l u c i n o g e n  i n man but  is  DMT,  is  but  milligram basis  (cf.  closely  structurally  related  Table  an o r d e r I).  of  systems,  causing  hypertension, effects  permit  the with  system.  The  parenterally active.  [17].  the  interferes  is  orally  p s y c h o l o g i c a l and s o m a t i c  approximately  hallucinogen  bond and  nervous  bufotenine  not  5-hydroxyl  no c e n t r a l  of  similar  as an  oxygen s u b s t i t u e n t  compound i n t o  exhibits  the  s u b s t i t u t i o n d o e s not  intramolecular  character the  Interestingly  and h y p e r v e n t i l a t i o n ,  the  f o r m a t i o n of  [93.  the  the  5-MeO-DMT  symptoms i n man as  m a g n i t u d e more p o t e n t  CNS  5-0-  active  B o t h 5-MeO-DMT and b u f o t e n i n e to  the  neurotransmitter  on a are  36  serotonin. are  The N , N - d i i s o p r o p y l  both o r a l l y  known of  the  analogues  a c t i v e as h a l l u c i n o g e n s  hallucinogenic  activity  the  mono-tert-butyl  derivative  is  be o r a l l y  In alkyl  to  indole  substituents,  substitution  site  substitution  of  on t h e  of  these  hindrance  of  on t h e  B.  affecting  [9,17].  enzymatic  a-ca'rbon  hallucinogenic confers  of  The mechanism of is  undoubtedly  deamination  has been r e c e n t l y  of  the  underground  represents activity.  which c a t a l y z e  the  fluid  and N - m e t h y l t r y p t a m i n e  indole-N-methyltransferases specificity  but  in  activity to  in  the  steric  a-substituent.  a-  shown t o a c t is  as  available  Tryptamines m e t a b o l i s m of  synthesis  DMT i n mammals  O-methyl  of DMT, 5-MeO-DMT, and  i n human l u n g ,  there  the  is  brain,  blood,  5-hydroxytryptamine,  i d e n t i f i e d as  in d i f f e r e n t  INMTs have been c h a r a c t e r i z e d  oral  have been  1 2 0 ] . Tryptamine, have been  Methyl  and 5-MeO-a-  I n d o l e N- and  have been c h a r a c t e r i z e d  and c e r e b r o s p i n a l  third  N,N-dialkyltryptamines.  and d e g r a d a t i v e [10].  a  N-  psychotomimetic  No i n f o r m a t i o n  Hallucinogenic  reviewed  and a l i p h a t i c  related  by t h e  MAO [ 1 9 ] .  a-substituted  M e t a b o l i s m of  substrate  oral  and a - e t h y l t r y p t a m i n e  The s y n t h e t i c  in  substituents  chain  a-carbon  inhibitors  transferases  ring  side  analogues  activity  bufotenine  in  compounds a - m e t h y l t r y p t a m i n e  methyltryptamine competitive  the  the  methyltryptamine case  active  [17].  addition  activity  is  N-monosubstituted,  tryptamines;  1iterature  Little  the  or N - c y c l o a l k y l to  i n man [ 1 8 ] .  of  N-dealkyl,  "reputed"  of DMT and 5-MeO-DMT  substrates  considerable  for  variation  o r g a n i s m s and t i s s u e s . Australian  grass  Two  Phalaris  37  tuberosa  w h i c h have  different  (tryptamine)  and t h e  are  in  required  Presence proven  of  but  different (SAM)  the  secondary  would e x p l a i n  functions  of  as  (MTHF) have  the  the  of  de-methyl activity  via  [22].  [22]  have  formation  6 x 1 0~  metabolite. from r a t s  IAA 8  SAM, a r e  in t h i s  in  been  and i s  Incubation  NO f o r m a t i o n , was  of  potent  methionine  synthesis  acid of  2-  tryptamine, formation  inhibitors  brain  in  the  by B a r k e r ,  DMT has a l s o in  probably  methyl indole  B o t h DMT and SAH,  involved  reviewed  whole  was t h e  pretreated  in  [10],  et  been  of  the  regulation al.  major 2 x IO'  of  metabolite 5  M,  recently study  using  6 x 10"  8  when DMT was  DMT-NO was  IAA  the  iproniazid  f o r m a t i o n by 8 3 % ; however  i n h i b i t e d by 9 0 % , and no MTH/3C was  as  incubated  major  M DMT i n homogenates  w i t h t h e MAO i n h i b i t o r  of  [10].  A quantitative  homogenates  the  INMT  f o u n d I AA, NMT, MTH/JC, and DMT-N-ox i d e  M, but a t  inhibition  been  transmethylation  the  reaction.  reviewed  rat  both  [21].  affinities  of HCHO from t h e  mechanisms  m e t a b o l i s m of  DMT [22]  metabolites.  of  Possible  DMT m e t a b o l i s m i n  the  amine  S-adenosyl  w i t h NMT and  a Pictet-Spengler  INMT a c t i v i t y  deuterated  in  that  i n mammals has not  The t e t r a h y d r o - / 3 - c a r b o l i n e  derivative  investigated  at  tertiary  amine  (MTH/3C) and t e t r a h y d r o - / 3 - c a r b o l i n e  i_n v i t r o  enzymatic  Degradative  of  indicating  substrate  donors  primary  f o l l o w e d by n o n - e n z y m a t i c c o n d e n s a t i o n w i t h t h e  substrates  the  [22].  the  the  b o t h SAM and 5 - m e t h y l t e t r a h y d r o f o l i c  incubated  respectively  donors  INMT  been f o u n d t o p a r t i c i p a t e  when  occurs via  the  same s p e c i e s .  methyl-tetrahydro-0-carboline (TH0C)  of  for  (NMT),  varying  the methyl  however,  amine  biosynthesis  two or more t y p e s  tissues  reaction;  affinities  obtained resulted  NMT and DMTformed.  38  B a s e d on t h e s e  observations,  the  authors  h i g h p r o p o r t i o n of  IAA  resulting  oxidative- deamination  poor of  from t h e  substrate  NMT i s  probably arose  f o r MAO [ 2 3 , 2 4 ] ;  some 9 t i m e s  faster  the  tryptamine the  a n d / o r NMT w i t h t h e  interesting  ions)  of  which  that  rat  liver  addition  tryptamine, that  pathway  DMT [ 2 5 ] .  6-hydroxylation peripheral  tissues,  Other  minor of  the  it  (psilocin)  deamination  might  apparently have  of  the  of  degradation  fate  of  1  have made of  for  of  of  in  the  to  pretreated  be an  rise  with  d o e s not  in  important  have  in  to metabolic  shown t h a t ,  DMT m e t a b o l i s m  These  the  the  in  the  DMT m e t a b o l i s m  giving  studies  this  of  tertiary  results  occur  in  studies  while  in brain  indicate  s i d e - c h a i n may be a  " C - p s i l o c i n in  metabolites,  than  [22].  f o c u s e d on t h e m e t a b o l i s m of  [26,27].  route  urinary  faster  intermediate  cyclization  from a o i m a l s  characteristic  a  (carbinolamines,iminium  studies  compound. rat  u n c h a n g e d p s i l o c i n and 4 - h y d r o x y - I A A total  [22]  rearrangement  More r e c e n t  is  trace  C-hydroxylation  NMT, and DMT-NO,  investigators  hydroxy-DMT oxidative  Earlier  6-hydroxylation  is  as  a  oxidation  6-hydroxy-DMT and 6-hydroxy-DMT-NO  speculation for  al.  can u n d e r g o i n t r a m o l e c u l a r  detected  to  et  direct  microsomes o b t a i n e d  iproniazid  detected  intermediates  tetrahydro-/3-carbolines.  r a t e of  HCHO formed as an  amine N - o x i d e  identical  NMT. DMT i t s e l f  nonenzymatic condensation  DMT. B a r k e r  observation  a m i n e s and t e r t i a r y formation  of  of  that  metabolite  t h a n DMT and 280 t i m e s  may be formed from t h e  N-demethylation  speculated  as a s e c o n d a r y  relative  DMT-NO. The t e t r a h y d r o - 0 - c a r b o l i n e s metabolites  [22]  [26]  remainder  that  relatively  A metabolic  indicated  accounted  for  4-  that  only  being present  study  40% of as  39  extremely  hydrophilic  identified  psilocybin  p s i l o c y b i n was  alkaline  blue-colored product  the  in  kidney  which  they the  blue product but  of  these  metabolic  and r e l a t e d  tryptamines  oxidative  deamination  by MAO i s  of  the major,  pathway  the  o - q u i n o n e of  was u n a f f e c t e d  be o x i d i z e d t o  not  in  the  colored  the  [28].  of DMT,  recognition  necessarily  for  KCN.  including  investigations  lies  available  by  the  only,  degradative  that or  metabolism  t h e s e compounds.  C. H a l l u c i n o g e n i c The a c t i v i t y inhibitors carbolines,  of  a series  activity  Tryptamines  investigated extensive  tryptamines out. of  harmaline.  derivatives  [23,24,29].  studies  of  substituted  w h i c h had  The a c t i v i t y  of  1.5%  of  structure/activity  [29]  examined  have the  and / 3 - c a r b o l i n e s on  5HT u p t a k e .  a n a l o g was  t h e /3-  t o MAOI a c t i v i t y  tryptamines of  as MAO  Unlike  the  L e s s i n and c o - w o r k e r s  t h e most p o t e n t  dimethyltryptamine  Inhibition  with respect  as MAOI and i n h i b i t o r s  tryptamines  and MAO  some t r y p t a m i n e  however,  been c a r r i e d  SAR of  of  has been  relationships not  by  mammalian c y t o c h r o m e o x i d a s e  psilocin,  even  found  m e t a b o l i z e d to a  hydroxy-indoles  products  of  the  c o u l d be i n h i b i t e d by  were shown t o  The s i g n i f i c a n c e  rapidly  s p e c u l a t e d was  p s i l o c i n and o t h e r  the p r e s e n c e  studied  h o m o g e n a t e s . They  then  s e r o t o n i n and b u f o t e n i n e in  [27]  positively  dephosphorylated to p s i l o c i n  of MAO i n h i b i t o r s ,  Subsequently,  and Weber  p s i l o c i n was  The f o r m a t i o n of  presence  rat  readily  phosphatase;  psilocin.  w h i c h c o u l d not be  as g l u c u r o n i d e s . H o r i t a  i n c u b a t i o n of that  metabolites,  Among t h e  6-MeO-a,a-  the  inhibitory  N,N-dimethyltryptamine,  potency  of  2-methyl-DMT  40  and 5-benzyloxy-DMT as MAOI investigated  [23]  concentrations. than  the  other  at  In  substrate, as  all  while  al.  substituted  lowest  dimethyltryptamines MAOI a c t i v i t y  of  are  of  of MAO-A ( c f .  a-methyltryptamines, as  activity  observed  of  postulate Chapter  a series  than  bromogramine w h i c h gave concentration  5-  The o r d e r  of  and  substrate.  derivatives  tested  was DMT>5were  of  tryptamine  investigated, potentiation  t h e MAOI  the  i n h i b i t i o n at  behavioural  derivatives  not been  except  72% of  for  5-  the  the  of  Patients  receiving  the  "strangeness".  been  oral  of  DMT i n human  treatment  DMT a t  a  with  reduced  e x p e r i e n c e d none of  of  symptoms of  has  derivatives  The e f f e c t  and 3 d a y s a f t e r  or d i s t u r b a n c e s  typify  the  parenterally-active  i p r o n i a z i d treatment  hallucinations  a feeling  q u e s t i o n of  investigated.  i p r o n i a z i d [30].  and p h a r m a c o l o g i c a l  by MAO i n h i b i t o r s  specific  was a s s e s s e d b e f o r e  p e r c e p t i o n which only  of  of DMT and o t h e r  dose f o l l o w i n g visual  comparable  a l t h o u g h the  has a p p a r e n t l y volunteers  gramine d e r i v a t i v e s  of DMT.  The p o t e n t i a t i o n effects  the  VI). of  1  more p o t e n t  as  tryptamine  methyl-DMT>5 MeO-DMT>5-hydroxyl-DMT. The DMT d e r i v a t i v e s generally  also  with tyramine  w i t h the  t h e MAOI a c t i v i t y  tryptamine  was  found with  consistent  inhibitor  more  DMT as MAOI was  inhibition  was  using tryptamine  the  was  substrate  inhibition  activity  investigated  gramines,  greatest  intermediate  These r e s u l t s  [24]  and  The a c t i v i t y  DMT may be a s p e c i f i c  Ho e t  guinea p i g l i v e r  DMT had s i g n i f i c a n t l y  substrate;  the  the  inhibitor  cases  substrate,  substrate.  that  various  derivatives.  i n f l u e n c e d by t h e w i t h 5HT as  in  t i m e and the d r u g ;  Patients  the  space they  receiving  reported  a dose  41  equivalent  to that  response.  The f i r s t  psychosis,  but  were p r e s e n t , eyes c l o s e d ; feeling  of  the  less but  the  or  less  colorful,  the  the  of  s t u d i e d the  pupillary  reduced e f f e c t s  pressure  of  dilatation,  iproniazid,  but  t h e MAOI  more t h a n d o s e of  treatment.  iproniazid.  DMT i n  but n o t  the in  of  DMT.  that  exacerbated  a  the  Moore and c o - w o r k e r s  i n body  and  temperature,  and EEG  in  rabbits.  effects  altered  [32]  of DMT on  elevated  rectal  blood  by p r e - t r e a t m e n t  investigated  the  on DMT h a l f - l i f e  increased h a l f - l i f e  with a  The a u t h o r s  speculated  that  of  in in  p r o l o n g e d DMT  treatment  with  effect  rat both  half-life larger  a b s e n c e of MAOI p r o l o n g e d t h e h a l f - l i f e  liver.  to  prior  acid butanolamide,  Tranylcypromine  Interestingly,  authors  This  observation  i p r o n i a z i d and t r a n y l c y p r o m i n e  after  the  i n d u c e d by DMT. A r t e r i a l  Wang-Lu and Domino [33]  reacted  due t o MAO i n h i b i t i o n ,  b l o c k e d the  and b r a i n and f o u n d a g r e a t l y  tissues  trials  i p r o n i a z i d p r o l o n g e d the  and m y d r i a s i s  persistent  often  chlopromazine,  blood pressure or  by a  the  may have been due  brain  greatly  and EEG were not m a r k e d l y  iproniazid.  brain  the  of DMT [ 3 1 ] .  Chlorpromazine attentuated  liver  in  on DMT-induced c h a n g e s  temperatures  manifested with  on t h e s e  s u p p o r t e d by t h e  effects  parameters  hallucinations  patients  1-methyl-d-lysergic  effects  methiothepin  these  Based  two-phase  u s u a l DMT  and  and o n l y  to which the  serotonin antagonist,  psychotomimetic  the  5HT b l o c k i n g e f f e c t s  was a l s o  administration  to  s e c o n d phase was c h a r a c t e r i z e d  5HT c o n c e n t r a t i o n  observation  i p r o n i a z i d had a  similar  indifferently.  thus m i t i g a t i n g  powerful  was  to  pronounced; i l l u s i o n s  speculated that higher  prior  stage  "strangeness"  negatively, [30]  given  this  in  may be  42  due t o  the  clearance other  fact  that  from b r a i n  is  enzymes c a p a b l e  inhibited. presence  Half-life  is  mainly  of  a weak MAOI and t h a t  d e p e n d e n t on MAO. L i v e r  m e t a b o l i z i n g DMT even  in b r a i n  of MAOI i n d i c a t i n g  t h e m e t a b o l i s m of [34]  DMT i t s e l f  and l i v e r  that  similar  effects  w i t h SKF-525A,  found that  i p r o n i a z i d p r o l o n g e d the  liver  significantly  with respect  variety  of  hepatic  behavioural plasma primary also  indicated  parent  further  involved  in  that  central  compounds a r e available influences  [25].  the  than  inactive  literature  indicates  effects  prolong  increased  effects  not  been  have  especially  relationships  remarkable  that  of  of  tryptamine  probable metabolic  tryptamines,  derivatives  interconversion  and / 3 - c a r b o l i n e s  compounds i n  the  [22,57],  [16].  important  of  and wide  the or the It  due t o  the  detected  in  related  Although  the  significant effects  of  DMT w i t h /3-  T h i s apparent close  oversight  structural  and 0 - c a r b o l i n e s of DMT, the  a  MAO i s  DMT and  MAOI do have  investigated.  of  DMT i_n v i v o .  of DMT a r e  interactions  i n view of  mice  of DMT  tissue  6-hydroxy-metabolite  that  in  brain,  inhibitor  on b o t h t h e m e t a b o l i s m and b e h a v i o u r a l  carbolines  of  an  evidence  as h a l l u c i n o g e n s  specific  classes  in  6-hydroxy-derivatives  the  the  the  DMT i n  in plasma,  t h e m e t a b o l i s m of  DMT, a p p a r e n t l y  is  SKF-525A,  providing  the  and c h l o r p r o m a z i n e and  DMT l e v e l s  result  in  Shah and Hedden  behavioural  of DMT or  compound r a t h e r  some s t u d i e s  elevated  have  enzymes p a r t i c i p a t e  m i c r o s o m a l e n z y m e s , d i d not  thus  enzyme  iproniazid,  to c o n t r o l s .  effects  levels,  similar  and m e t a b o l i s m of  pretreated  may  t h o u g h MAO i s  DMT f o l l o w i n g MAO i n h i b i t i o n .  studied behavioural  and a l s o  was  its  [1,2],  other  involvement  neuro-regulatory  of  both  functions  43  s u c h as MAO a c t i v i t y probable role mechanism of the  of  closely  oral  activity  strongly related,  III.  of  Vi rola  not  only  yet  pastes  i n mammalian  (cf.  tryptamines  little  species  from Peganum h a r m a l a  by J .  isolation  Fritsche  spite  of  [35].  long h i s t o r y ,  and p h a r m a c o l o g y of understood. 'related  g-carboline  Derivatives  monoamine o x i d a s e in  /3-carbolines.  [36],  by G o e b e l of  in  there  of  1927, and t h e i r  1959 t h a t  section  /3-carbolines;  same  elucidation  of  in  remain  [37]  total  and  inhibitors  and w i l l  In  poorly  harmaline  aspects  both  biochemistry  of  focuses p r i m a r i l y other  of  1930 [ 3 5 ] .  the  reversible  isolation  1847, f o l l o w e d a.  has been a r e s u r g e n c e  p h a r m a c o l o g y have been d i s c u s s e d i n here.  the  from the  derivatives in  since in  harmine  competitive  The p r e s e n t  psychopharmacology  mentioned  science  many a s p e c t s  /3-carboline  are  are  also  The s t r u c t u r e  S i n c e the d i s c o v e r y  derivatives  available  and / 3 - c a r b o l i n e s  was p u b l i s h e d by S p a t h and L e d e r e r their  The  of  compounds was a c c o m p l i s h e d by Manske synthesis  but  I).  and  systems.  have been known t o  by t h e  the  their  /3-carbolines  later  in  known a b o u t  and P h a r m a c o l o g y  few y e a r s  the  is  Biochemistry  harmaline  combinations  Chapter  structurally  very  and  the h a l l u c i n o g e n s ayahuasca  suggests that  pharmacologically, interactions  [11,14,29]  tryptamine//3-carboline  orally-ingested  evidence  of  and amine u p t a k e  of  interest on  their  only  of  be  the  44  A.  Psychopharmacology  1.  /3-carbolines  The a c t i v i t y reversible  of  [38],  inhibitors  al.  c o m p a r i s o n of the  use of  investigations  [36].  of  these  animals  [42,43,44,45]  of MAO e x i s t ;  sensitive  studies  these  harmaline  (and p r e s u m a b l y o t h e r  inhibitor  of MAO-A. Some SAR s t u d i e s  5HT,  [39,40,41]  of MAO-A w h i l e  b o t h MAO A and B [ 4 6 ] ;  metabolized mainly different studies  is  not  as  in  the  parameters.  Mclsaac  I  [42]  of  50  specificities,  [38],  have u s e d [41].  /3-phenylethylamine  values  [46].  and o t h e r  and E s t e v e z  [38]  a  that  selective  others  In  is  are  used  tryptamine,  are  a  specific  substrates  probably  view o f  used i n  have  5HT i s  and t y r a m i n e  there  and have  demonstrated is  are •  / 3 - c a r b o l i n e MAOI  substrate  and enzyme s p e c i e s  at  designated  MAO i n h i b i t o r s ,  others  tryptamine  that  forms of MAO,  as s u b s t r a t e  s u r p r i s i n g that  differences  s o u r c e of MAO,  Other  /3-carbolines)  by MAO-B in v i v o  substrates  it  Fuller  and s t i l l  and / 3 - p h e n y l e t h y l a m i n e  substrate of  properties.  Direct  c o m p l i c a t e d by  as t h e  substrate  kinetic  tryptamine  & Estevez  [40,41],  are  substrates.  to v a r i o u s  have u s e d t y r a m i n e  by M c l s a a c  & Boggan  different  activity  structure/  have p r o v i d e d e v i d e n c e  MAO-A and MAO-B, have d i f f e r e n t differentially  competitive  d e m o n s t r a t e d by  and t i s s u e s  different  Inhibitors  as  Subsequently,  and B u c k h o l t z  use of  two s p e c i e s  first  were i n v e s t i g a t e d  results  different  and a l s o by t h e  least  [39],  the  Derivatives  as Monoamine O x i d a s e  of MAO was  relationships  Ho et  /3-carboline  j3-carboline d e r i v a t i v e s  U d e n f r i e n d and c o - w o r k e r s activity  of  the  different  considerable  structure/activity  using tyramine  as  substrate  45  found t h a t while  fully  with other between  studies.  Little  with those  were more p o t e n t methyl  it  for  of  than  substitution  increased  as  [38]  $-carbolines  substrate  than with t r y p t a m i n e  substituents  resulted  that  gave  N  2  results  as  2  Methyl,  and N  decrease  of  the  or c a r b o x y l  substitution  essentially  substitution  of  activity  of  the  enhanced the  the  derivatives.  studied tetrahydro-/3-carbolines found t h a t  they  (N )  tetrahydro-/3-carbolines  aromatic  See  were more p o t e n t  9  MAO but  w i t h 5HT as Chapter out  in  the  inhibitors  less  nucleus of  C,  active  than  substitution N  2  _  of  acetyl  Methyl  only  enhanced  slightly  and Boggan  in  of  carboxyl  significantly  i n mouse b r a i n  for  the  influence  although  Buckholtz  IV  substitution  times  but  between  /3-carboline  a b o l i s h e d the a c t i v i t y . nitrogen  general  derivatives.  or N - p r o p y l  reduce a c t i v i t y ,  indolic  Boggan  in potency  in a c t i v i t y ,  Ethyl  in  liver  s t u d i e d the 9  and  but  derivatives;  values  50  substrate.  [39]  ethyl,  unsubstituted derivatives. significantly  for  various I  found  /3-carbolines  with a study c a r r i e d  on C , , N ,  in progressive  d i d not  was  agrees  7-methoxy-/3-carbolines  s u b s t i t u t e d compounds b e i n g some e i g h t e e n the  that  results  differences  lower  as MAOI  dihydro-  Buckholtz  reported  noted for  Ho and c o - w o r k e r s  on MAOI a c t i v i t y .  activity.  MAO. O t h e r  most  various  in potency  unsubstituted  except  Generally  work.  a result  C, decreased a c t i v i t y  brain  present  activity;  6-methoxy- or u n s u b s t i t u t e d  at  these  or  substrate  and b r a i n MAO were a l s o  a c o m p a r i s o n of  least  difference  reduced the  using tryptamine  were most a c t i v e  in potency,  7- m e t h o x y l a t e d ,  substitution  agreement  had t h e  were i n t e r m e d i a t e  6- or  hydroxyl  liver  (3-carbolines  tetrahydro-(3-carbolines  derivatives  [41]  aromatic  [40]  and l i v e r brain  than  and in  46  liver.  6-MeO-TH/3C was w i t h o u t  had a b o u t  the  2.  same a c t i v i t y  of  that  is  [47]  and N a r a n j o  hallucinogenic  known a b o u t  conducted Naranjo  in  [48]  seem c l e a r , carbolines several  over  of  however,  is  their  activity  5HT and e p i n e p h r i n e therefore,  that  responsible  for  the  many of  the  results  from a s i n g l e  at  the  hallucinogenic  than  the  [cf.  40,41].  activities  It  of  e x c e s s of  one g r a m , but  observed threshold  d o s e s between  comparable e f f e c t s harmaline apparently  at  was o r a l l y less  a c t i v e at however  Naranjo 4 mg/kg; the  tetrahydroharmine=100  mg h a r m a l i n e  Naranjo  that  [50]  a n a l o g of comparable effects".  reported  harmaline, levels  of  gave  inhibitors  the  of  mechanism  some / 3 - c a r b o l i n e s . at  doses  [49]  in  reported  observed that  tetrahydroharmine  resulted  t h e a n a l o g of  to  unlikely,  [48]  6-MeO-harmalan,  are  hallucinogenic  was  300 mg from a s i n g l e  the  gave  harmine,  trail.  6-substituted  activity  6-MeO-tetrahydroharmine  6-MeO-harman,  of /3-  which  inactive  equation  threshold oral  What does  action  200-250 mg. S l o t k i n  50 mg i . v .  active,  orally  by  doses r e q u i r e d  is  action  the  been  reported  c a n be i n v o k e d as  hallucinogenic  and  of  have  t h r e s h o l d dosage l e v e l s  h a r m i n e was  i.v.  Pennes  human t r i a l .  reported that  at  but  activity  human s t u d i e s  [47]  effects  of  as MAOI o r as c o m p e t i t i v e  uptake  these  studies  /3-carboline d e r i v a t i v e s  that  only manifests  liver  hallucinogenic  No s y s t e m a t i c  25 y e a r s ;  were o b t a i n e d  the  from t h e  o r d e r s of m a g n i t u d e g r e a t e r  manifest  Hoch  [48].  activity  in  Hallucinogens  / 3 - c a r b o l i n e s stems p r i m a r i l y  Hoch  activity  i n b r a i n as TH/3C.  /3-carbolines as  The l i t t l e  inhibitory  has  at  1.5  mg/kg;  "milder apparently  47  not  been  investigated.  3.  Endogenous S y n t h e s i s  The h y p o t h e s i s might  play  mental  a role  in  i n the  d i s o r d e r s has  researchers idea  ever  1952 [ 5 1 ] .  indicating  that  under c e r t a i n  of  etiology  fallen  The  Mclsaac  [53]  evidence  has  20]  pretreated  favor  factor  demonstrated that  conditions  first  i n mammalian was t h e  adrenoglomerulotropin, TH/3C. T h i s  initial  in mental  first  Mclsaac's site for  of  original  and a l s o  a pineal  under  birds  [5'6],  in a v a r i e t y  of  the  evidence  tissues  been u n e q u i v o c a l l y  is  in  rats The  and M c l s a a c  identical  that  to  1-methyl-6-MeO  c o u l d not  the  pineal  [55].  gland  is  be Although a  likely  f o r m a t i o n has been c o n f i r m e d  that  [54]  hormone,  /3-carbolines are  now o v e r w h e l m i n g .  identified  mild  (Antabuse).  t h e c l a i m was withdrawn  endogenous / 3 - c a r b o l i n e  Subsequently  ir\ v i v o  identification  hypothesis  suggest  cyclodehydration  illness.  and a c e t a l d e h y d e  w h i c h was  c o n f i r m e d and e v e n t u a l l y  to  1-methyl-6-MeO-TH/3C c o u l d be  i_n v i t r o  tentative  systems  (5-methoxy-N-acetyltryptamine),  i p r o n i a z i d and d i s u l f i r a m  isolated  even  obtained  h y p o t h e s i s a p p e a r e d t o be c o n f i r m e d when F a r r e l c l a i m e d t o have  p r o p o s e d the  not been r e s o l v e d ,  has been  [52]  other  among  formed from t h e  hormone m e l a t o n i n  with  of  h a l l u c i n o g e n s can a r i s e  c o n d i t i o n s . Mclsaac  hallucinogens  s c h i z o p h r e n i a or  still  [cf.  formed from 6-MeO-tryptamine physiological  of  i n and out  issue  c o u l d be an e t i o l o g i c a l  i n Mammals  endogenously synthesized  an endogenous / 3 - c a r b o l i n e ,  the p i n e a l  /3-carbolines  s i n c e Osmund and S m y t h i e s  though u n e q u i v o c a l  that  that  of  only  synthesized  / 3 - c a r b o l i n e s have  i n human p l a s m a and p l a t e l e t s ,  and  48  in  the  rat  gland. are  whole  Most  of  the  6-methoxy-,  carbolines, been  that  6-hydroxy-,  the in  or  fully  aromatic  arcuate  of  nucleus  acid  of  Recent  products  of  etiology  and harman were i d e n t i f i e d Presumably  condensation  of  these  alcoholism  amines  are  s u c h as  primary  references  for  comprehensive  B.  has shown  are  with  5-methylhas c e n t e r e d  [59,60],  i n human u r i n e  the  mammalian  has been  amine/aldehyde  with acetaldehyde,  biochemistry,  harman  indolamines  interest  constituents  biogenic  [11,14]  characterized  on  the  endogenous / 3 - c a r b o l i n e s , and o t h e r  [61],  It  from  adrenal  tetrahydro-/3-  derivative  non-enzymatically (MTHF).  and  endogenous / 3 - c a r b o l i n e s  tetrahydroisoquinolines, the  nucleus,  [11].  c o n d e n s a t i o n of  released  involvement  in  arcuate  unsubstituted  some i n s t a n c e s  tetrahydrofolic possible  the  rat  f o r m e d as a r e s u l t formaldehyde  forebrain,  endogenous / 3 - c a r b o l i n e s so f a r  however  found in  [57,58]  brain,  pharmacology,  after  2-methyl-TH/3C ethanol  formed v i a serotonin  metabolite  of  recent  and p a t h o l o g y  of  condensation  loading  the or  dopamine  ethanol.  See  r e v i e w s of  the  endogenous  alkaloids.  Other  Neurological  and B i o l o g i c a l  Activities  of /3-  carbolines  /3-carbolines e x h i b i t and b i o l o g i c a l It  is  not  activities  w i t h i n the  them i n d e t a i l ; completeness.  they  a wide s p e c t r u m of in a d d i t i o n  s c o p e of are  this  to  The a p p r o p r i a t e  those  review  mentioned here references  neurophysiological discussed  to d i s c u s s each  for  the  sake  above. of  of  s h o u l d be c o n s u l t e d  for  49  further  i n f o r m a t i o n . A number of  inhibit  the  uptake  epinephrine carboline  into  of  5HT, d o p a m i n e ,  synaptosomal  derivatives  human e r y t h r o c y t e s ,  are  rat  has a l s o  carboxylate have been the  ethyl  suspensions  brain, of  implicated  (BCCE)  [62,63]  benzodiazepine (Valium)  a comprehensive  derivatives water flow  exert  [37],  transport across  any e f f e c t  in  t h e membrane  nor-epinephrine  harmaline  effects,  cardiovascular  mechanisms,  effects  anti-trypanosomal mutagenic been n o t e d the  effects,  in  (rabbits)  found t h a t  activity  or co-mutagenic [67]  interaction  and  effect  of  [cf.  on Na and  hydrosmotic  harmaline  mechanism of  to  elicit  and/or  action.  tremorogenic  influence  some a n i m a l s  homeothermic  (rats,  mice)  against of  activities  systems.  For  exhibited  other  instance  Hopp  significant  Trypanosoma l e w i s i . certain  than  The  /3-carbolines  has  and t h e mechanism r e s p o n s i b l e may be r e l a t e d of  and  [37],  harmine  effect  for  related  with vasopressin  and a l s o  a l s o have b i o l o g i c a l  [66]  derivatives  been p r o p o s e d  compounds have  on n e u r o p h y s i o l o g i c a l  and c o - w o r k e r s  [37,64].  by some /3-  stimulating  Failure  pretreated  and r e l a t e d  in others  0-carbolines their  toad s k i n ,  causing hypothermia  hyperthermia  have a l s o  suggested a c o m p e t i t i v e  Harmine,  axon  in  a l t h o u g h o t h e r compounds,  Harmaline  [64,65],  in preparations  O t h e r /3-  /3-carboline  "vasopressin"-like  isolated  and  as p o s s i b l e e n d o g e n o u s l i g a n d s receptors,  to  /3-carboline-3-  and o t h e r  review].  a potent  shown  of membrane A T P a s e s  b i o g e n i c amines  i n c l u d i n g p u r i n e s and k y n u r a m i n e s , 63 f o r  [ 37,40],  and s q u i d r e t i n a l  been r e p o r t e d  ester  nor-epinephrine,  inhibitors  I n t e r f e r e n c e with synthesis carbolines  / 3 - c a r b o l i n e s have been  /3-carbolines w i t h n u c l e i c  acids  [ 68,69].  to More  50  recently,  the  photogenotoxic described  ultra-violet-mediated activity  [13,70],  of  photocytotoxic  and  some 0 - c a r b o l i n e d e r i v a t i v e s  has  been  51  IV.  Literature  Cited  1.  Smith, T. Plants.  A . (1977) T r y p t a m i n e and R e l a t e d P h y t o c h e m i s t r y 16:171-75  Compounds i n  2.  A l l e n , J . R. Alkaloids.  3.  S k a l t s o u n i s , A . L . , F. T i l l e q u i n , & M. K o c h . (1983) Plantes de N o u v e l l e - C a l e d o n i e L X X X I I I . A l c a l o i d e s d e s T i g e s F e u i l l e e s de M e l i c o p e l e p t o c o c c a . J o u r n a l of N a t u r a l Products 46:732-35  F . , & B. H o l m s t e d t (1980) The S i m p l e P h y t o c h e m i s t r y 1 9 : 1 5 7 3 - 1 5 8 2 . 1980  0-carboline  .4. O ' D o n o v a n , D . G . , & M. F. K e n n e a l l y (1967) The B i o s y n t h e s i s of E l e a g n i n e . J o u r n a l of t h e C h e m i c a l S o c i e t y S e c t . C : 1 1 0 9 - 1 0 5.  O ' D o n o v a n , D. G . (1976) P r o c e e d i n g s of Academy S e c t i o n B. 7 6 : 1 8 7  6.  S l a t o r , M . , & I. J . M c F a r l a n e . (1968) The B i o s y n t h e s i s and M e t a b o l i s m of Harman i n P a s s i f l o r a e d u l i s . P h y t o c h e m i s t r y 7:605-11  7.  S m i t h , T . A . (1977) R e c e n t A d v a n c e s i n t h e B i o c h e m i s t r y of P l a n t A m i n e s . C h a p t e r 2 i n P r o g r e s s i n P h y t o c h e m i s t r y V . 4. L. R e i n h o l d , J . B. H a r b o u r n e , and T . Swain ( e d s . ) . A c a d e m i c Press.  8.  D a l y & B. W i t k o p . (1971) C h e m i s t r y and P h a r m a c o l o g y of F r o g Venoms. C h a p t e r 39 i n Venomous A n i m a l s and T h e i r Venoms V . II, W. B i i c h e r l & E. E. E. B u c k l e y ( e d s . ) . A c a d e m i c P r e s s  9.  K a n t o r , R. E . , S. D. D u d l e t t e s , & A . T . S h u l g i n . (1980) 5Methoxy-a-Methyl-tryptamine ( a , 0 - d i m e t h y l s e r o t o n i n ) , a H a l l u c i n o g e n i c Homolog of S e r o t o n i n . B i o l o g i c a l P s y c h i a t r y 15:349-52  10.  the  Royal  Irish  B a r k e r , S. A . , J . A . M o n t i , & S. T . C h r i s t i a n . (1981) d i m e t h y l t r y p t a m i n e : An Endogenous H a l l u c i n o g e n . I n t e r n a t i o n a l Review of N e u r o b i o l o g y 2 2 : 8 3 - 1 1 0  11. M e l c h i o r , C , and M. A . C o l l i n s . (1982) The Route and S i g n i f i c a n c e of Endogenous S y n t h e s i s of A l k a l o i d s i n Mammals. CRC C r i t i c a l Reviews i n T o x i c o l o g y 9:313-356  N,N-  52  12.  D i l l o n , J . , A . S p e c t o r , & K. N a k a n i s h i . (1976) I d e n t i f i c a t i o n of / 3 - c a r b o l i n e s I s o l a t e d from F l u o r e s c e n t Human L e n s P r o t e i n s . N a t u r e 2 5 9 : 4 2 2 - 3  13. McKenna, D. & G. H. N. C y t o t o x i c A c t i v i t y of 2 0 : 1001-1004  T o w e r s . (1981) U l t r a - v i o l e t Mediated /3-carboline A l k a l o i d s . Phytochemi s t r y  14.  B l o o m , F . , J . B a r c h a s , M. S a n d l e r , & E. U s d i n ( e d s . ) (1982) g - c a r b o l i n e s and T e t r a h y d r o i s o q u i n o l i n e s . p r o c e e d i n g s of a symposium h e l d at t h e S a l k I n s t i t u t e , La J o l l a , C a , D e c . 12-13, 1981. A l a n R. L i s s , p u b l i s h e r , New Y o r k  15.  A p p e l , J . B. F. J . W h i t e , & A . M. H o l o h e a n (1982) A n a l y z i n g M e c h a n i s m ( s ) of H a l l u c i n o g e n i c Drug A c t i o n w i t h Drug D i s c r i m i n a t i o n P r o c e d u r e s . N e u r o s c i e n c e and B i o b e h a v i o u r a l R e v i e w s 6:529-36  16.  S h u l g i n , A . T . (1976) M a x w e l l Gordon ( e d . ) Academic P r e s s  17.  S h u l g i n , A . T . (1982) C h e m i s t r y of P s y c h o t o m i m e t i c s . C h a p t e r 1 i n F. H o f f m e i s t e r & G . S t i l l e ( e d s . ) Handbook of E x p e r i m e n t a l P h a r m a c o l o g y V o l . 55 P t . I l l : Psychotropic Agents Pt. I l l : A l c o h o l & Psychotomimetics, Psychotropic Ef f e c t s of C e n t r a l - A c t i n g D r u g s . S p r i n g e r - V e r l a g  18.  S h u l g i n , A . T . & M. F. C a r t e r (1980) N,Nd i i s o p r o p y l t r y p t a m i n e (DIPT) and 5-Methoxy-N,Nd i i s o p r o p y l t r y p t a m i n e (5-MeO-DIPT). Two O r a l l y A c t i v e T r y p t a m i n e A n a l o g s w i t h CNS A c t i v i t y . C o m m u n i c a t i o n s i n Psychopharmacology 4:363-69  19.  G r e i g , M. K., R. A . W a l k , & A . J . G i b b o n (1959) The E f f e c t of T h r e e T r y p t a m i n e D e r i v a t i v e s on S e r o t o n i n M e t a b o l i s m i_n v i t r o and i n v i v o . B r i t i s h J o u r n a l of P h a r m a c o l o g y 127:110-  20.  R o s e n g a r t e n , H. & A . J . F r i e d h o f f (1976) A Review of R e c e n t S t u d i e s of t h e B i o s y n t h e s i s and E x c r e t i o n of H a l l u c i n o g e n s Formed by M e t h y l a t i o n of N e u r o t r a n s m i t t e r s or R e l a t e d Substances. Schizophrenia B u l l e t i n 2:90-105  21.  Mack, J . P. G . , & M. S l a y t o r (1979) I n d o l e t h y l a m i n e N-methyl T r a n s f e r a s e s of P h a l a r i s t u b e r o s a : P u r i f i c a t i o n and P r o p e r t i e s . P h y t o c h e m i s t r y 18:1921-5  f  Psychotomimetic Agents, chapter Psychopharmacological Agents V.  4 in IV.  53  22.  B a r k e r , S. A . , J . A . M o n t i , and S. T . C h r i s t i a n (1980) M e t a b o l i s m of the H a l l u c i n o g e n N , N - d i m e t h y l t r y p t a m i n e in Rat B r a i n Homogenates. B i o c h e m i c a l P h a r m a c o l o g y 2 9 : 1 0 4 9 - 5 7  23.  R. B. B a r l o w . (1961) E f f e c t s on Amine O x i d a s e of S u b s t a n c e s Which A n t a g o n i z e 5 - h y d r o x y t r y p t a m i n e More Than T r y p t a m i n e on t h e Rat Fundus S t r i p . B r i t i s h J o u r n a l of P h a r m a c o l o g y 16:153-162.  24.  B. T . Ho, W. M. M c l s a a c , R. A n , R. T . H a r r i s , K. E. W a l k e r , & P. M. K r a l i k . (1970) B i o l o g i c a l A c t i v i t i e s of Some 5Substituted N,N-dimethyltryptamines, a-methyltryptamines, and G r a m i n e s . P s y c h o p h a r m a c o l o g i a 1 6 : 3 8 5 - 3 9 4 .  25.  S z a r a , S. & J . demethylation 15:216-17  26.  Kalberer,  27.  H o r i t a , A . and L. J . Weber (1961) The E n z y m i c D e p h o s p h o r y l a t i o n and O x i d a t i o n of P s i l o c y b i n and P s i l o c i n by Mammalian T i s s u e H o m o g e n a t e s . B i o c h e m i c a l P h a r m a c o l o g y 7 : 47-54  28.  Weber, L. J . & A . H o r i t a (1963) O x i d a t i o n of 4- and 5h y d r o x y i n d o l e D e r i v a t i v e s by Mammalian C y t o c h r o m e O x i d a s e . L i f e S c i e n c e s 1: 44-49  29.  L e s s i n , A . W., R. F. L o n g , & M. W. P a r k e s (1967) The C e n t r a l S t i m u l a n t P r o p e r t i e s of some S u b s t i t u t e d Indolylalkylamines ' a n d /3-carbol i n e s and T h e i r A c t i v i t i e s as I n h i b i t o r s of Monoamine O x i d a s e and t h e U p t a k e of 5 - h y d r o x y t r y p t a m i n e . B r i t i s h J o u r n a l of P h a r m a c o l o g y and Chemotherapy 2 9 : 7 0 - 7 9  30.  S a i - H a l a s z , A . (1963) The E f f e c t of MAO I n h i b i t i o n on t h e E x p e r i m e n t a l P s y c h o s i s I n d u c e d by D i m e t h y l t r y p t a m i n e . P s y c h o p h a r m a c o l o g i a 4:385-88  31.  S a i - H a l a s z , A . (1962) The E f f e c t of A n t i s e r o t o n i n on t h e E x p e r i m e n t a l P s y c h o s i s I n d u c e d by D i m e t h y l t r y p t a m i n e . E x p e r i e n t i a 18:137-138  Psilocin  F., in  A x e l r o d . (1959) H y d r o x y l a t i o n and Nof N , N - d i m e t h y l t r y p t a m i n e . Experientia  W.  Kreis  the R a t .  & J.  Rutschmann  Biochemical  (1962)  Pharmacology  Fate  of  11:261-69  54  3 2 . M o o r e , R. H. S. K. D e m e t r i o u & E. F. Domino (1975) Effects of I p r o n i a z i d , C h l o r o p r o m a z i n e and M e t h i o t h e p i n on DMTi n d u c e d Changes i n Body T e m p e r a t u r e , P u p i l l a r y D i l a t a t i o n , B l o o d P r e s s u r e and EEG i n the R a b b i t . A r c h i v e s I n t e r n a t i o n e l s de pharmacodynamic e t de t h e r a p i e 213:64-72 33.  Wang L u , L. J . , & E. F. Domino (1976) E f f e c t s of I p r o n i a z i d and T r a n y l c y p r o m i n e on t h e H a l f - L i f e of N,Nd i m e t h y l t r y p t a m i n e i n Rat B r a i n and L i v e r . Biochemical Pharmacology 25:1521-27  34.  S h a h , N. S . , & M. P. Hedden (1977) B e h a v i o u r a l E f f e c t s and M e t a b o l i c F a t e of N , N - d i m e t h y l t r y p t a m i n e i n M i c e P r e t r e a t e d w i t h / 3 - d i e t h y l a m i n o e t h y l - d i p h e n y l p r o p y l a c e t a t e (SKF-525-A) , I p r o n i a z i d , and C h l o r p r o m a z i n e . P h a r m a c o l o g y , B i o c h e m i s t r y and B e h a v i o u r 8:351-56  35.  H o l m s t e d t , B. (1982) / 3 - c a r b o l i n e s and T e t r a h y d r o i s o q u i n o l i n e s : H i s t o r i c a l and E t h n o p h a r m a c o l o g i c a l B a c k g r o u n d , i n F. B l o o m , (eds.) op. c i t .  et  al.,  36.  U d e n f r i e n d , S . , B. W i t k o p , B. G . R e d f i e l d , (1958) S t u d i e s w i t h R e v e r s i b l e I n h i b i t o r s O x i d a s e : H a r m a l i n e and R e l a t e d Compounds. P h a r m a c o l o g y 1:160-165  & H. W e i s s b a c h of Monoamine Biochemical  37.  H o , B. T . (1977) P h a r m a c o l o g i c a l and B i o c h e m i c a l S t u d i e s w i t h / ? - c a r b o l i n e A n a l o g s , c h a p t e r VI i n W. B. Essman & L. V a z e l l i , ( e d s . ) C u r r e n t Developments in Psychopharmacoloqy V . 4. S p e c t r u m P u b l i c a t i o n s , Inc.  38.  M c l s a a c , W. M. & V . E s t e v e z ( 1 9 6 6 ) Structure-action R e l a t i o n s h i p s of / 3 - c a r b o l i n e s a s Mono-amine O x i d a s e I n h i b i t o r s . B i o c h e m i c a l Pharmacology 26:1625-27  39.  H o , B. T . , W. M. M c l s a a c , K. E. W a l k e r , & V . E s t e v e z (1968) I n h i b i t i o n of Monoamine O x i d a s e : I n f l u e n c e of M e t h y l S u b s t i t u t i o n on the I n h i b i t o r y A c t i v i t y of / 3 - c a r b o l i n e s . J o u r n a l of P h a r m a c e u t i c a l S c i e n c e s 5 7 : 2 6 9 - 7 4  40.  B u c k h o l t z , N. S . , and W. O . Boggan (1976) E f f e c t s of T e t r a h y d r o - / 3 - c a r b o l i n e s on Monoamine O x i d a s e and S e r o t o n i n U p t a k e i n Mouse B r a i n . B i o c h e m i c a l P h a r m a c o l o g y 2 5 : 2 3 1 9 2321  55  41.  B u c k h o l t z , N. S. £ W. 0 . Boggan (1977) Monoamine O x i d a s e I n h i b i t i o n i n B r a i n and L i v e r P r o d u c e d by / 3 - c a r b o l i n e s : Structure-activity R e l a t i o n s h i p s and S u b s t r a t e Specificity. B i o c h e m i c a l Pharmacology 26:1991-96  42.  F u l l e r , R. W., B. J . W a r r e n , & B. B. M o l l o y (1970) Selective I n h i b i t i o n of Monoamine O x i d a s e i n Rat B r a i n M i t o c h o n d r i a . B i o c h e m i c a l P h a r m a c o l o g y 19:2934-2936  43.  D o n n e l l y , C . H . , E. R i c h e l s o n & D. L. Murphy (1976) P r o p e r t i e s of Monoamine O x i d a s e i n Mouse N e u r o b l a s t o m a 115 C e l l s . B i o c h e m i c a l P h a r m a c o l o g y 2 5 : 1 6 2 9 - 1 6 4 3  44.  D o n n e l l y , C . H . , & D. L. murphy (1977) S u b s t r a t e - and I n h i b i t o r - r e l a t e d C h a r a c t e r i s t i c s of Human P l a t e l e t Monoamine O x i d a s e . B i o c h e m i c a l P h a r m a c o l o g y 2 6 : 8 5 3 - 8 5 8  45.  H o u s l a y , M. D. £ K. F. T i p t o n (1974) A K i n e t i c E v a l u a t i o n of Monoamine O x i d a s e A c t i v i t y i n Rat L i v e r M i t o c h o n d r i a l O u t e r Membranes. B i o c h e m i c a l J o u r n a l 139:645-652  46.  N e f f , N. H. and H.-Y. T . Yang (1974) A n o t h e r Look a t t h e Monoamine O x i d a s e s and t h e Monoamine O x i d a s e I n h i b i t o r D r u g s . L i f e S c i e n c e s 14:2061-2074  47.  P e n n e s , H. H. & P. H. Hoch (1957) P s y c h o t o m i m e t i c s , C l i n i c a l and T h e o r e t i c a l C o n s i d e r a t i o n s : H a r m i n e , WIN-299 and N a l l i n e . A m e r i c a n J o u r n a l of P s y c h i a t r y 113:887-92  48.  N a r a n j o , C . (1967) P s y c h o t r o p i c P r o p e r t i e s o f t h e H a r m a l a A l k a l o i d s , p p . 385-391 i n D. H. E f r . o n , B. H o l m s t e d t , & N. S. K l i n e ( e d s . ) E t h n o p h a r m a c o l o g i c S e a r c h f o r P s y c h o a c t i v e D r u g s . U. S. P u b l i c H e a l t h S e r v i c e P u b l i c a t i o n #1645  49.  S l o t k i n , T . A . , . V . D i S t e f a n o & W. Y. W. Yu (1970) B l o o d L e v e l s and U r i n a r y E x c r e t i o n of Harmine and I t s Metabolites i n Man and R a t s . The J o u r n a l of P h a r m a c o l o g y and E x p e r i m e n t a l T h e r a p e u t i c s 173:26-30  50.  N a r a n j o , C . (1969) Fantasy-enhancing  51.  Osmund, H . , and J . R. A p p r o a c h . J o u r n a l of  NIE-  P s y c h o t h e r a p e u t i c P o s s i b i l i t i e s of New D r u g s . C I i n i c a l T o x i c o l o g y 2:209-224 S m y t h i e s (1952) Mental Sciences  S c h i z o p h r e n i a : A New 98:309-315  56  5 2 . M c l s a a c , W. M. (1961) A B i o c h e m i c a l C o n c e p t of D i s e a s e . Postgraduate Medicine 30:111-118  Mental  53.  M c l s a a c , W. M. (1961) F o r m a t i o n of 1-methyl-6-methoxy1 , 2 , 3 , 4 - t e t r a - h y d r o - 0 - c a r b o l i n e under P h y s i o l o g i c a l C o n d i t i o n s . B i o c h i m i c a et B i o p h y s i c a Acta 52:604-606  54.  F a r r e l l , G . & W. M. M c l s a a c (1961) A d r e n o g l o m e r u l o t r o p i n . A r c h i v e s of B i o c h e m i s t r y & B i o p h y s i c s 9 4 : 5 4 3 - 4 4  55.  F a r r e l l , G . , W. M. M c l s a a c , & A . N. T a y l o r (1964) N e u r o h u m o r a l F a c t o r s from t h e B r a i n s t e m E p i p h y s i s . pp. 141-47 i n L. M a r t i n i & A . P e c i l e ( e d s . ) Hormonal S t e r i o d s ^ B i o c h e m i s t r y , P h a r m a c o l o g y , and T h e r a p e u t i c s V. I. Academic Press.  56.  K a r i , I. (1 98 1 ) 6-methoxy-1 , 2 , 3 , 4 - t e t r a h y d r o - / 3 - c a r b o l i n e i n P i n e a l G l a n d of C h i c k e n and C o c k . FEBS L e t t e r s 127:277-280  57.  H s u , L. L . , & A . J . M a n d e l l (1975) E n z y m a t i c F o r m a t i o n of T e t r a h y d r o - 0 - c a r b o l i n e s from T r y p t a m i n e and 5M e t h y l t e t r a h y d r o f o l i c A c i d i n Rat B r a i n F r a c t i o n s : R e g i o n a l and S u b c e l l u l a r D i s t r i b u t i o n . J o u r n a l of N e u r o c h e m i s t r y 24:631-36  58.  R o m m e l s p a c h e r , H . , H. Caper & S. S t r a u s s (1976) On t h e Mode of F o r m a t i o n of T e t r a h y d r o - / 3 - c a r b o l i n e s . L i f e S c i e n c e s 18:81-88  59.  Rahwan, R. G . (1975) T o x i c E f f e c t s of E t h a n o l - P o s s i b l e R o l e of A c e t a l d e h y d e , T e t r a h y d r o i s o q u i n o l i n e s , & T e t r a h y d r o - / 3 - c a r b o l i n e s . T o x i c o l o g y and A p p l i e d Pharmacology 34:3-27  60.  D a v i s , V . E. and M. A . Walsh (1970) A l c o h o l , A m i n e s , and A l k a l o i d s : A Possible Biochemical Basis for Alcohol A d d i c t i o n . S c i e n c e 167:1005-7  61.  R o m m e l s p a c h e r , H . , S. S t r a u s s & J . Lindemann (1980) E x c r e t i o n of T e t r a h y d r o h a r m a n e and Harmane i n t o t h e U r i n e of Man and Rat A f t e r a Load w i t h E t h a n o l . FEBS L e t t e r s 109:209-12  57  6 2 . M e n n i n i , T . , S. C o t e c c h i a , S. G a r a t t i n i ( 1982) Does Ethyl-/3c a r b o l i n e - 3 - c a r b o x y l a t e I n t e r a c t w i t h Mouse B r a i n B e n z o d i a z e p i n e R e c e p t o r s i n V i v o ? J o u r n a l of Pharmacy and Pharmacology 34:394-5 63.  L a p i n , I. P. (1983) S t r u c t u r e / A c t i v i t y R e l a t i o n s h i p s i n K y n u r e n i n e , Diazepam and Some P u t a t i v e Endogenous L i g a n d s of t h e B e n z o d i a z e p i n e R e c e p t o r s . N e u r o s c i e n c e s and B i o b e h a v i o u r a l R e v i e w s 7:107-118  64.  C a n e s s a , M . , E. J a i m o v i c h , & M. de l a F u e n t e (1972) The E f f e c t of Harmane D e r i v a t i v e s on t h e Na-dependent P h o s p h o r y l a t i o n from t h e Membrane ATPase S y s t e m , p. 2 8 f f V t h I n t e r n a t i o n a l C o n g r e s s of N e p h r o l o g y . M e x i c o C i t y  65.  de S o u s a , R. C , & A . G r o s s o (1978) V a s o p r e s s i n - l i k e E f f e c t s of a H a l l u c i n o g e n i c Drug - H a r m a l i n e - on Sodium and Water T r a n s p o r t . J o u r n a l of Membrane B i o l o g y 4 0 : 7 7 - 9 4  66.  H o p p , K. H. , L. V . C u n n i n g h a m , M. C . B r o m e l , L. J. S c h e r m e i s t e r and S. K. W. K a h l i l (1976) In V i t r o A n t i t r y p a n o s o m a l A c t i v i t y of C e r t a i n A l k a l o i d s A g a i n s t Trypanosoma l e w i s i . L l o y d i a 3 9 : 3 7 5 - 7 7  67.  Umezawa, K., A . S h i r a i , T . M a t s u s h i m a , & T . S u g i m u r a C o m u t a g e n i c E f f e c t of Norharman and Harman w i t h 2A c e t y l a m i n o f l u o r e n e D e r i v a t i v e s . P r o c e e d i n g s of t h e N a t i o n a l Academy of S c i e n c e s 7 5 : 9 2 8 - 3 0  68.  Remson, J . F. & P. A . C e r u t t i (1979) I n h i b i t i o n of DNA R e p a i r and DNA S y n t h e s i s by Harman i n Human A l v e o l a r Tumor C e l l s . B i o c h e m i c a l and B i o p h y s i c a l R e s e a r c h C o m m u n i c a t i o n s 86:124-129  69.  H a y a s h i , K., M. N a g a o , & T . Sugimura (1977) I n t e r a c t i o n s Harman and Norharman w i t h DNA. N u c l e i c Ac i d s R e s e a r c h 4:3679-85  70.  T o w e r s , G. H. N . , & Z. Abramowsky. (1983) U V - m e d i a t e d G e n o t o x i c i t y of F u r a n o q u i n o l i n e s and of C e r t a i n T r y p t o p h a n D e r i v e d A l k a l o i d s . J o u r n a l of N a t u r a l P r o d u c t s 4 6 : 5 7 6 - 8 1  (1978)  of  58  PART I I :  ETHNOBIOLOGICAL  INVESTIGATIONS  MYRISTICACEOUS  OF MALPIGHIACEOUS  HALLUCINOGENS  AND  59  CHAPTER  I.  III:  ETHNOBOTANICAL COLLECTIONS AND ETHNOGRAPHIC OBSERVATIONS  Ethnobotanical  A.  Collections  C o l l e c t i o n and I d e n t i f i c a t i o n  of  Herbarium Voucher  Spec imens D u r i n g the research, plant  field-work  conducted in connection with  herbarium voucher  species  indicated  properties  or  other  Particular  efforts  source-plants  by  s p e c i m e n s were c o l l e c t e d informants  ethnobotanically were made t o  t h e M a l p i g h i a c e o u s and M y r i s t i c a c e o u s in  this  totally  successful,  collect  only  example,  study.  i.e.  in  or  manufacture  a particular  instances locality  of  plants  the  of  actual  the  were c o l l e c t e d  for  sample were not  numbers of  McKenna and a r e  Plowman  var.  "cielo")  were k i n d l y of  Natural  gift  6040  to the  refer  (Diplopterys  and Plowman  History author  to  the  cabrerana), (Virola  Ernesto M i g l i a z z a ,  these  general  collection  ).  of  In  Collection  Plowman  T i m o t h y Plowman  an  the  "DMK-".  i n C h i c a g o . Yanomamo s n u f f by D r .  of  same  spp.  to  for  available.  personal  of  always  (as,  plot  all  have  possible  purposes.  prefaced with  12,218  s u p p l i e d by D r .  was  from the  comparative  throughout  are  it  for  preparation  s o u r c e - p l a n t s used in  numbers c i t e d D.  specimens  were not  cultivated  all  uses.  voucher m a t e r i a l  same s p e c i e s  for  drug samples which  some i n s t a n c e s  from t h e  ayahuasquero),  the  These e f f o r t s  l i m i t e d amounts of  when c o l l e c t i n g  voucher  used in  m  medicinal  significant  secure  and a d m i x t u r e p l a n t s  been a n a l y z e d  t o have  this  Exceptions  6041 These  the  (B.  caapi  samples  F i e l d Museum  s a m p l e s were a formerly  of  the  60  Department  of  Anthropology, University  Park;  no a c c o m p a n y i n g v o u c h e r  snuff  samples.  Authenticated  of  Maryland,  specimens are  College  available  herbarium vouchers  for  for  all  the  "DMK-"  collection  numbers have been d e p o s i t e d i n t h e H e r b a r i u m of  Department  of  vouchers Museum;  for  Botany,  most c o l l e c t i o n s  other  duplicates  herbaria  of  collections  of  ethnobotanical  Collection  work a r e  of  of  are  also  significance listed  Plant Material  Analysis  Bark and l e a f  samples used in  preserved  in  of  air-dried  100% m e t h a n o l a t  plant the  Details  of  the  samples f o r and M e t h o d s "  11.  available)  of  preparation  phytochemical sections  Ethnographic  of  of  analysis  have  voucher  or of  samples,  cited  Most  the the  of  of  orallyin  samples. and d r u g  in the  "Materials  chapters.  Observat ions  The e t h n o g r a p h i c a s p e c t s  of  time  (collected  materials  the a p p r o p r i a t e  analyses  material  Yanomamo s n u f f  are  for  collection.  Colombia  in  II.  in methanol at  the p l a n t  Field  w h i c h were made  material  time  and t h e  the  phytochemical  sample f r o m La C h o r r e r a ,  1971—no v o u c h e r  All  Duplicate  and D r u g Samples  e x c e p t i o n s were two a y a h u a s c a  ingested paste  at  in Appendix  the  t h e d r u g s a m p l e s were a l s o p r e s e r v e d collection;  on d e p o s i t  collections.  Phytochemical  consisted either  B r i t i s h Columbia.  i n N o r t h and S o u t h A m e r i c a  some but n o t a l l  connection with t h i s  B.  University  the  the M a l p i g h i a c e o u s  and  61  Myristicaceous  h a l l u c i n o g e n s have been t h e  anthropologists, before of  the  these  than  of  native  the  these  turn  botanical,  years.  subject  was  personal  A.  the  begun t o  ayahuasqueros ayahuasca  of  Iquitos,  (persons folk  Pucallpa,  practitioners  alkaloid  a.)  collect  whether  out  for in  the  were c o n t a c t e d  ayahuasca  samples  ayahuasca  in  terms  In  practitioners  s a m p l e s of  different  collected.  The p h y t o c h e m i c a l  IV.  In  batches  some i n s t a n c e s ,  superficial,  the  various  the  and  of  types  of  all,  ayahuasca  was made  alkaloids elements  to  p r e p a r e d by t h e  contact  are  with the  and c o n s i s t e d e i t h e r  of  or  attempt in  the  different found,  of  or  ayahuasca  from one  s a m p l e s p r e p a r e d by  were c o l l e c t e d ,  results  use  vicinities  differences  from one r e g i o n t o a n o t h e r ,  different  study,  s a m p l e s p r e p a r e d by  whether e t h n o g r a p h i c  to another.  last  from as many  use a r e  six  on  as  fieldwork.  in  An e f f o r t  b.)  practitioner  the  preparation  in concentration, different  facets,  documents  of  this  t h e r e were s i g n i f i c a n t  either  documented  as p o s s i b l e . T h i s was done i n an  c o m p o s i t i o n of  practitioners,  literature  course  since  ethnography  within  chapter  by  ayahuasca  and T a r a p o t o .  different learn  this  who s p e c i a l i z e  and t o  the  or p h a r m a c o l o g i c a l  I;  carried  medicine)  study  much more t h o r o u g h l y  ethnobotanical  A s p e c t s of  interview  to  some r e s p e c t s  made, d u r i n g t h e  fieldwork  in  is  in chapter  observations  D u r i n g the  In  of  and e x p l o r e r s  receive c l a r i f i c a t i o n  The r e l e v a n t  Ethnographic  scholars  phytochemical,  reviewed  of  century.  hallucinogens  have o n l y  thirty  ethnobotanists,  subject  and i n  some c a s e s ,  same p e r s o n were  d i s c u s s e d in ayahuasquero  attending  the  Chapter was  weekly  62  ayahuasca  s e s s i o n as a p a y i n g p a r t i c i p a n t  home t o p u r c h a s e repeated v i s i t s detailed  the  small  the  remarks  ayahuasca;*  were made and i t  interviews.  became b e s t  Of  the  several  village  of  which  ayahuasca  Jose Olaya,  follow  Don F i d e l  and o t h e r  visiting  in other  was p o s s i b l e  his  instances,  to conduct  more  ayahuasqueros c o n t a c t e d ,  a c q u a i n t e d w i t h Don F i d e l  conversations. of  s a m p l e s of  or of  not  Mosambite, far  who l i v e d  from P u c a l l p a .  have been d e r i v e d  from our  was q u i t e  to  willing  medicinal plants.  talk  about  and seemed  i m p r e s s e d by t h e  fact  Don F i d e l  look  are  tradition;  he was q u i t e  c a u s e d by m i c r o b e s or d i e t a r y  treated  with a n t i b i o t i c s  patients if  we were b o t a n i c o s .  upon W e s t e r n m e d i c i n e as c o m p l e m e n t a r y  ethnomedical  to  seek  antibiotics  treatment  for,  them w i t h v i t a m i n s  himself.  that  illness  amenable plants  to  treatment  the  incorporated given  the  to the p a t i e n t ;  ayahuasca, the  treatment into  patient  in order  In  of  familiar. himself.  treatment, at  times  it  In  it  illness, In  his  practitioners, he would  however,  cases  he  supply  he or  felt were  would  usually  was not  o n l y Don F i d e l  as w e l l .  send  hundred m e d i c i n a l  these  although  seemed  own  in o r i g i n  A y a h u a s c a was  to diagnose the  would r e c e i v e  instances,  several  use  and c o u l d be  and o c c a s i o n a l l y most  the  diseases  He would o f t e n  were s u p e r n a t u r a l  w i t h any  w i t h w h i c h he was  undertake  deficiencies  some  from W e s t e r n m e d i c a l  were c a l l e d  the causes of  to h i s  aware t h a t  or v i t a m i n s .  of  He had some  W e s t e r n m e d i c i n e and s c i e n c e  to  in  Most  u n d e r s t a n d i n g of  that  I  always  consumed and a t  other  other  cases,  times  the  •Although the m a s c u l i n e pronoun i s used in t h i s d e s c r i p t i o n , a y a h u a s q u e r o s can be (and f r e q u e n t l y a r e ) women.  63  treatment neither cases  involved medicinal  Don F i d e l  that  I  or  the  plants  patient  o b s e r v e d , however,  botanical  remedy,  poultice,  or  w h i c h might  tincture,  other  than ayahuasca  would t a k e a y a h u a s c a . the  administration  take the  form of  of  a tea,  was a c c o m p a n i e d by m a g i c a l  potion,  songs,  were l i b e r a l l y  c e n s e d w i t h t o b a c c o smoke w h i c h Don F i d e l  p i p e w h i c h he had made h i m s e l f .  make p a s s e s o v e r in  the  order,  patient's  patient  Fidel  such a r a t t l e ,  affected  part  of  of m a l e v o l e n t  common e l e m e n t the  of  in  shaman.  the  Luna  objects, practices  body of [1]  elements, south.  that  remarkably  older,  the  t h o u g h he l i v e d b a s e d on two the m a g i c a l consistent  this  samples  been  symbols,  Although Luna's  hardly  a  shamanic  in  field  Iquitos, the  hundred m i l e s  is  with a  to  same the  conclusive,  but  c o s m o l o g y s h a r e d among a y a h u a s q u e r o s  from r e g i o n  may mean t h a t  geographically  several  the  malevolent  m a g i c a l cosmology c o n t a i n e d e s s e n t i a l l y  even  individuals;  or  the m a g i c a l to  is  w h i c h has  by a s o r c e r e r  intrinsic  or  t h e p u r p o s e of  object  has d e s c r i b e d i n d e t a i l  dried  saw Don  This  were c o n d u c t e d among a y a h u a s q u e r o s  Evidence  indicates  the p a t i e n t  area.  burned  spirits  never  everywhere,  the m e s t i z o a y a h u a s q u e r o s .  investigations Don F i d e l ' s  affected  vicinity  made of  out e v i l I  chants,  ayahuasqueros  and accompany t h i s  a magical  and powers w h i c h a r e of  body, the  out  Some  he would o f t e n massage  shamanic p r a c t i c e  s u c k i n g b e i n g t o draw  placed  is  s u c k i n g of  to d r i v e  influences.  however,  the p a t i e n t ' s  v i g o r o u s and n o i s y  general  body w i t h a r a t t l e  presumably,  purge the use  and t h e  all  the  The p a t i e n t ,  palm f r o n d s  remedy,  In  and w h i s t l i n g .  in a s p e c i a l  the  and  it  is  and c u l t u r a l l y  to  r e g i o n and  derived  between  from some much  restricted,  tribal  64  tradition  that  has g r a d u a l l y  been a s s i m i l a t e d  into mestizo  folk  frequently  during  medicine. Although I my f i e l d the  studies  actual  Fidel  visited the  preparation  u s e d was  Coumari,  in  I  house of  to  see  w i t h the  the  viridis),  the  in a large  Juan's cooking shed. process, several the  involving c h a n g e s of  fractions  fraction  of  photographic ayahuasca. initially all  vary  content (cf.  spp.  for  possess  cut  aluminum pot Preparation  set of  f r e s h water,  original  The l e n g t h of  an  On one  occasion  over  volume.  Luna  the  the  and t h e d e g r e e since  is  finally a low  [2]  a  multistage material  to a excellent  the p r e p a r a t i o n  final  with  by c o m b i n i n g  has p r o v i d e d  in  along  i n Don  fire  amount of  of  to b o i l ,  fire  the p l a n t  steps  boiling,  the  ayahuasca  them o v e r  and was  (Psychotria  plant  of  material  concentration,  considerable variation  f o u n d i n brews p r e p a r e d by d i f f e r e n t  in  must  alkaloid  ayahuasqueros  IV).  the  interesting  identification  Some P s y c h o t r i a  tiny  Salas  as  up and s e t  followed  of  spine-like  aspect  the  use as a d m i x t u r e s came t o  fieldwork.  witness  which Don  Juan  repute  "chacruna" admixture  An e t h n o b o t a n i c a l l y to  already  d o c u m e n t a t i o n of  Chapter  related  uncle,  to  Don Juan a c c o m p a n i e d by Don F i d e l  significantly, is  The a y a h u a s c a  p r o l o n g e d b o i l i n g of  extracted,  was u n a b l e  km from P u c a l l p a .  and c o n c e n t r a t i n g  the  I  considerable  twenty  ayahuasca,  l e a v e s of  area,  ayahuasca.  man of  who l i v e d  able  Don F i d e l  p r e p a r e d by h i s  ayahuasquero, the  Pucallpa of  usually  a much o l d e r  visited  t h e house of  species,  extensions  of  "proper"  light  folk  Psychotria  d u r i n g the  i n c l u d i n g P. of  taxonomy  course  of  viridis,  t h e m i d - r i b on t h e  abaxial  65  surface  of  glandular found  in  the  leaf.  These appear  structures  w h i c h may be e q u i v a l e n t  some P s y c h o t r i a  domatium i s  a part  that  is  like  structures  of  a leaf,  the  but may be i n h a b i t e d  1983).  These t i n y  the ayahuasqueros identify  the  "Chacruna"  them e s p i n a s  I  false  v a l u e as a d m i x t u r e s . w h i c h were a n a l y z e d and a l l  This  for  key  carthagenensis  Jacq.,  identification  therefore  identification  by the  all  of  single  DMT i n P s y c h o t r i a  any  visible  pers.  comm.,  used  by  to  spp. A l l  of  the  structures—termed plants  the  P.  lacking  by  espinas  viridis  collections  possessed these  structures,  specimen which  a l t h o u g h the  further  Rivier  carthagenensis,  lacked  or o t h e r  these  alkaloids.  Psychotria  collection  tentative; that  examined  admixtures.  may c o r r e s p o n d t o  fact  part  and were c o n s i d e r e d t o have no  T a b l e VI)  (DMCK #109)  of  feature  these  a l s o c o n t a i n e d no t r y p t a m i n e s  specimen  plant  The d o m a t i a -  G. T . ,  Psychotr ia  t o be p r e s e n t ;  Indeed,  other  1981). A  were p o i n t e d out  use as  that  chacrunas  (cf.  the  comm.,  insects.  (Prance,  term f o r  insisted  c o n t a i n e d DMT; t h e  structures  as  "domatia"  specimens I  structures  suitable  (spines)--had  the  pers.  or o t h e r viridis  swollen  t o accomodate a n t s  interviewed  save one  were r e g a r d e d as  stem or  by m i t e s  the v e r n a c u l a r  ayahuasqueros  petiole,  domatia-like  chacrunas  is  A.,  mites,  small  to  (Gentry,  Psychotr ia  a p p e a r e d t o be much t o o size,  spp.  i n h a b i t e d by a n t s , of  t o be s l i g h t l y  is  sterile  doubt  & Lindgren  is [3]  cast  and  the  on  the  reported  w h i l e none was d e t e c t e d  in  .DMCK #109. I Fidel's night,  attended  the  weekly  house on s e v e r a l  ayahuasca  s e s s i o n s h e l d at  Don  o c c a s i o n s . They were a l w a y s h e l d  and would commence soon a f t e r  dark.  Various  people  at from  66  the  neighborhood attended,  Fidel's took  trickling  d o o r y a r d , murmuring g r e e t i n g s  up p o s i t i o n s  in h i s  "living  veranda  open on one s i d e  around,  smoking and t a l k i n g  waited  by ones and twos i n t o Don  for  the  to  stragglers  to  their  room"--actually  quietly  to a r r i v e .  th'e. s e s s i o n s ; p e o p l e were o f t e n  of  only  participants  a single  those a t t e n d i n g  were p a t i e n t s  two men were a p p a r e n t l y learn  the  ayahuasca  participants  it.  take ayahuasca; Don F i d e l , by a b o u t  9:30.  ayahuasca,  Not e v e r y o n e  merely  Don F i d e l  w h i c h by t h i s  w i t h s o n g s and w h i s t l i n g and pour a b o u t into  medicines;  Usually  would u n c o r k time  there still  brown,  had  in  one  g r i m a c i n g as  they  libation.  taking  handed i t  Don F i d e l  d r a i n e d the  back  took  so Don F i d e l  the  two c u p f u l s t o e v e r y o n e  had been c o n s u m e d , c o n v e r s a t i o n  cup at  last  else's fell  draught  from  of blessed tobacco,  bitter  participants  Everyone  other  arrived  fumigated with  the  turn.  to  treatment  everyone  intensely  liquid  gulp,  c o u l d pour  the  himself,  often  one. A f t e r  or  necessarily  had been a p p r o p r i a t e l y  dark  Some  merely  t h e wine b o t t l e  and t h o r o u g h l y  others  w h i l e one  or were  form of  society;  week;  of Don F i d e l ' s ,  some o t h e r  attending  treatment.  who a t t e n d e d would  watched.  the  mestizo  g o u r d c u p w h i c h he p a s s e d t o e a c h of  next  a small  70 ml of  local  "recreationally",  some r e c e i v e d  others  Those  seeking treatment,  songs and t h e p l a n t  distances  late.  some s p e c i f i c  apprentices  used ayahuasca  c u r i o u s about  for  they  desiring  who showed up e v e r y  session  sat  while  come from c o n s i d e r a b l e  c r o s s - s e c t i o n of  they  Everyone  Some p a t i e n t s  to attend  attended  might  as  thatched  among t h e m s e l v e s  from Don F i d e l  some were r e g u l a r  a  the c o o l evening a i r .  treatment  a p p e a r e d t o be a t y p i c a l  friends  the  ayahuasca  t o a minimum. E v e r y o n e  sat  67  quietly,  waiting  Don F i d e l  for  the  would e x t i n g u i s h t h e  blackness.  Not  and c h a n t s  would b e g i n ,  night.  initial  long a f t e r ,  A few o f  these  the  effects  oil  of  lamp,  first  of  and c o n t i n u e  r e m i n d i n g me of  visions  c h a n t s which  and h a l l u c i n a t i o n s  and seemed t o be keyed  singing.  The v i s i o n s  a  visions  is  difficult  intense,  hard-edge,  imagery;  rather  greens, forest  floor,  or  enormous l e a v e s , bony-plated  of  hypnagogic  the  sorts  in ancient twining  fishes  p e r s u a d e d Don F i d e l  e x p e r i e n c e more t h a n  were f u n c t i o n s  of  hard to determine. weight,  may i n f l u e n c e  the  achieve  threshold effects.  soft  whenever  effects.  ayahuasca the  the  the  browns, on  the  with large  always  allotment,  did  How much of  response to  one's d i e t ,  Certainly  of  occasions,  and p s y c h o l o g i c a l  amount of  trigger  s c e n e s of  on two  the  the  The d r u g d i d not  and t h e d e g r e e of  that  in  The  "psychedelic"  Jungle plants  t o d o u b l e my u s u a l  suspect  of  and  Russian  as  The n a t u r e  rich  i n me; o n l y  my own p h y s i c a l I  interesting  and u n d e r w a t e r  the v e r y m i l d e s t  visions,  the  and  one m i g h t e n c o u n t e r  were common m o t i f s .  when I  the  colors  lianas,  profound mental changes  same t i m e  typical  tapestries.  elicit  c o n t e n t , of  the  They d i d not have  were m u t e d , of  some m e d i e v a l  imagery.  geometrical quality colors  tenor  t h e n a new song would  to c h a r a c t e r i z e .  their  and r e d s ,  about  f a d e d or became l e s s  renewed e x f o l i a t i o n  Their  i n t o and s u s t a i n e d by  c h a n t i n g and s i n g i n g s t o p p e d ;  songs  had h e a r d y e a r s b e f o r e .  began a t  singing,  the  languages.  I  into  most were i n Q u e c h u a ,  tempo was  liturgical  room  and on t h r o u g h o u t  the  Orthodox  Presently  t h e many a y a h u a s c a  some were a c o m b i n a t i o n of low and s t a t e l y ,  two  p l u n g i n g the  off  were i n S p a n i s h ,  the d r u g .  the  required  ayahuasqueros  to  the drug,  state,  as w e l l as  I  is  body  68  themselves  all  was h e a v i e r typical  insist  that  diet  is  a major  t h a n most p a r t i c i p a n t s ,  mestizo diet  of  yuco,  factor  and u n a c c u s t o m e d t o  plantains,  t h e d r u g may have been  and t h u s  dose.  nausea  required a higher  or v o m i t i n g t h a t  usually  ayahuasca  experience  excellent  p u r g e . Most of  themselves sessions;  and w h i c h the  t o go have t h e i r  demeanor of  calm d u r i n g the  negative  fearful  or  ayahuasca  is  the  Don F i d e l other that  through his  ritual  mystery  of  until  had a p o s i t i v e  would t a k e t i m e present  for  more s i n g i n g , sucking,  to minister  treatment).  out  [1].  Eventually, of  the  given set  and by  tobacco-blowing, he was a b l e  the  initial  noisy  every  dose  assistants (if  and  poisonous  the  The  singing,  his  and  insure  from  and  invariably  after  to  renewal.  the p a t i e n t s  the m a g i c a l  t o and t h e e f f e c t s  is  and c o n t r o l l e d  and one of  t o one of  any  in C a t h o l i c i s m ,  t o o k more t h a n  This ministration  d e s i g n e d t o draw  been a t t e n d e d  observe  and came away  t o b a c c o - b l o w i n g , and u s u a l l y  d i s c u s s e d above and i n  d i d not  p u n c t u a t e d by c h a n t s  Don F i d e l  the  outward  p e r s o n a l and s p i r i t u a l  Occasionally  an  an  experience  means,  the  excused  kept  orchestrated  this  as  and p s y c h o l o g i c a l  experience  dawn. No one e v e r  ayahuasca.  the  songs, chants, By  of  backyard during  the h o s t  but  social  use of  s e s s i o n s would c o n t i n u e , almost  the  Everyone  Like  carefully  s e s s i o n w i t h a s e n s e of  in  the  part  a reputation  s e s s i o n s , and I  manipulations.  everyone  it  intrinsic  my  different  experienced  participants  times.  c o h e r e n c e and meaning by t h e s e t t i n g . ^This was v e r y  gives  other  reactions.  central  never  forms an  purge  some went s e v e r a l  I  I  the  and smoked f i s h ,  a b s o r p t i o n and m e t a b o l i s m of I  Since  [1].  any  were  involved vigorous object patient  d r u g had begun t o  had  wane,  69  the  s e s s i o n would draw  file  out  in  and d a i l y  B.  the  to a c l o s e ,  c o o l predawn  and t h e p a r t i c i p a n t s  hours to  return  to t h e i r  would  own homes  lives.  Ethnographic  A s p e c t s of O r a l l y  Active  Myristicaceous  Pastes A l t h o u g h m e s t i z o f o l k m e d i c i n e has c h a n g e d a s tribal  elements  nevertheless is  an  have been s y n c r e t i c a l l y  it  remains a v i t a l  intrinsic  danger  that  part  its  The s i t u a t i o n  of  use w i l l  is  tribal  the lore  cultures  orally which  a c t i v e Vi rola is  rapidly  become i n c r e a s i n g l y  Western c u l t u r e . mestizos  disappear  pastes.  is  Unlike  Myristicaceous  groups t h e i r  u s e was a j e a l o u s l y  of  the  older  men.* It  to  Knowledge  the  pastes  tribes  H.,  of  they  the  future.  orally-  preparation  represents  [4,5,6];  impact  tribal of  use among  orally-ingested  the  Bora,  even w i t h i n  guarded s e c r e t comm.,  and  a body of  fragile  the  the  used o u t s i d e  pers.  little  whose c o n t e m p o r a r y  the M y r i s t i c a c e o u s is  is  it,  Ayahuasca  foreseeable  many t r a d i t i o n s ,  t h e Muinane  knowledge of  the  f r a g m e n t e d under  and p o s s i b l y  detailed  and t h e r e  d i s a p p e a r i n g as t h e  d r u g s were n e v e r  t h e m e d i c i n e men ( C a l l e ,  in  into  tradition.  with respect  ayahuasca,  an amalgam of  assimilated  and l i v i n g  tradition  much d i f f e r e n t  ingested Myristicaceous u s e s of  this  diverse  Witoto,  these  known o n l y  to  1 9 7 1 ) . The most drug i s  who know w h i c h of  the  possession  t h e many V i r o l a  * U n l i k e a y a h u a s c a , i n w h i c h b o t h men and women may p a r t i c i p a t e , t h e use of t h e o r a l l y - a c t i v e M y r i s t i c a c e o u s d r u g i s a p p a r e n t l y an a c t i v i t y f r o m w h i c h women a r e e x c l u d e d .  70  s p e c i e s are  suitable  who know t h e extract of  right  traditions  influences  Christianity, have l i t t l e  died,  their  industry  in  the  has been swept  jungle  impediment  to  the  to d i e ;  future.  become t h e  victims  of  they  will  to  implement  characterized  preceding  peoples remarks  necessarily  the  today,  in other reflect  documented t h e a t r o c i t i e s  the  on t h e s e  in of  brutal the  these  knowledge  and m u s i c .  They more  and an  Bora  and W i t o t o  the  have  sooner  the  way  Amazonian  that  prevails  w h i c h has  toward  the  f o r m e d as a r e s u l t  observations, the  Although  among  too  W e s t e r n E u r o p e a n man  in  have  sooner  forces  unfortunately of  little  with  past  The  the  once p r o u d  ethnomedical  poetry  my own o p i n i o n s ,  committed  tribes  r e g a r d e d as  typical of  dislocation  century—all  t i m e s and p l a c e s .  incomplete personal  Most  people  " p r o g r e s s , " along  people,  which  the a t t i t u d e s  resin.  meantime,  these  g r a n d p l a n of  is  they  to  indigenous  and economic  these  This attitude,  Americans  aboriginal  of  are  the  social,  d e c i m a t i o n of  often  impact  As a r e s u l t ,  c o m p l e t e d the  many L a t i n  of  the  a not-so-benign neglect.  contemporary h i s t o r i c a l ,  "development".  of  this  onslaught  t h a n an e m b a r a s s i n g r e m i n d e r  be c l e a r  of  cosmology,.magic, art,  a people waiting  Vi rola  the  peoples. Their  away by t h e  religion,  In  which  have had a s h a t t e r i n g  and s e l f - s u f f i c i e n t  is  p r o p e r way  and g e o g r a p h i c a l  part  it  white m e n — a l c o h o l i s m ,  exploitation  early  drug;  and w i t h them have d i e d  for  cultural  ruthless  the  and t h e  people.  b r o u g h t by t h e  resistance,  circumstances  are  of  of  tryptamine-laden  foreign diseases  o c c a s i o n e d by t h e  their  the  men have l o n g s i n c e  ethnomedical  rubber  the p r e p a r a t i o n  admixture p l a n t s ,  and c o n c e n t r a t e  these  outside  for  others  name of  [7,8]  the  of  have  rubber  71  industry  and t h e c u r r e n t  continued survival  of  less  the  than  optimistic  and W i t o t o c u l t u r e ,  remembered,  by  some of  something that  largely plants  the  town o f  the  a short  Pebas,  fairly  botanical  at  d r u g was  of  I  village  ride  of  secrets  the p r o p e r  by m o t o r b o a t of  fine  items.  an t h e  lighters  He a s k s  the  a s s u r i n g them t h a t  these  matters  are  Peruvian  The N o r t h  of  and m a l a r i a  informants fathers'  interest  shining hospitals  i m p r e s s e d by t h e  friendly  eager  attractive  they  to help out,  they  are  have b r o u g h t anxious  to  river  Amazon.  the with American  to trade;  show t h e i r  so,  and  pills, teach  fathers, white-  in America, to ask;  v i s i t o r s , .and a r e  to  to h i s  seems a s m a l l enough f a v o r  items  Rio  b r i n g i n g money and s u g a r  and t h e i r  it  arrived  r e g i o n had on  pastes.  fathers  Well,  now  is  points associated  their  Europe.  This  is  [ 5 , 6 ] have remarked on  in t h i s  and c i g a r e t t e  in t h e i r  source-  t h e A m p i y a c u and t h e  others  informants  from t h e  of  coated colleagues  been  preparation  Puco U r q u i l l o  the M y r i s t i c a c e o u s  coveted  grandfathers.  u s e d seem t o have of  are  as  e n c o u n t e r e d when our p a r t y  comes i n h i s m o t o r b o a t ,  and many o t h e r  the  so much of  men,  and  among t h e m s e l v e s .  and e t h n o p h a r m a c e u t i c a l  shotgun s h e l l s  him t h e  debate  not u n i q u e ;  loose grasp  fathers  t h e method of  the c o n f l u e n c e  are  preparation  scientist  of  Witoto/Bora  just  like  a f a d i n g memory. They  identification  situation  My o b s e r v a t i o n s  salt,  the  a subject  little  Ampiyacu,  the  the  has become t e n t a t i v e ,  essentially  the  only  pastes,  t h e m i d d l e - a g e d and o l d e r  which  forgotten,  uncertain,  at  are  was once u s e d by t h e i r  The p u r p o s e s f o r  for  i n d i g e n o u s Amazonian p e o p l e s .  The o r a l l y - i n g e s t e d M y r i s t i c a c e o u s Bora  outlook  they  Canada, are  to a c q u i r e they  goodwill.  are  the  happy  Perhaps  if  72  they or  a pretty  out, to  co-operate  piece  w i t h the  best  it  two of  the  matter  will  if  been l o s t  or  scientist  will  I  the  as  home but  what does  forgotten  the  not  it  to  oral  for  Vi rola  pastes  were B o r a  Urquillo,  on t h e  Ampiyacu.  The p o p u l a t i o n of  banks of  the  the  which  set  plants,  the it  if  one or  grew,  new v i l l a g e  perhaps,  spawned by  these minor d e t a i l s omitted?  have  The A m e r i c a n  he t o  know  if  are  the  the  drug  the  Bora  who were w i l l i n g  d u r i n g our  Indians; lived  Brillo  and  part  The B o r a there  of  the  upriver  Jorge  lived  Nuevo,  a  in  small  from Puco of  while  Witoto;  the that  truce  between between  of  each group  s e p a r a t e d by  might e x i s t  in  Churay  about  i n Puco U r q u i l l o d i d  was an u n e a s y that  stay  a tributary  and h a l f  and W i t o t o  situation  in B r i l l o  village  provide  J o r g e Churay  Nuevo was B o r a  Bora  to  two-week  informants,  Yaguasyacu,  roughly half  inhabited a different  r e m i n d e d me of  used,  matter,  a day by m o t o r b o a t  well;  us t h r o u g h reconstruct  How i s  these  half  along very  if  informants  village  a kilometer.  the  been f o r g o t t e n ,  this  that  w h i l e Marcos F l o r e s  get  can  So t h e y  t h e manner p r e s c r i b e d by  Puco U r q u i l l o  half  sister.  shells,  know?  and M a r c o s Vega F l o r e s ,  was  gun  l e a d us t o  take  have  matter  in e x a c t l y  shot  l o n g dead m e d i c i n e men. What  in  R i o A m p i y a c u r e g i o n . Two of  Puco U r q u i l l o  to  or d e l i b e r a t e l y  encountered three  about  to  they  go away s a t i s f i e d .  themselves  the  world,  best  m e d i c i n e men? How,  s a m p l e s of  the  i s made,  w i f e or  w h i c h were f o r m e r l y  has been p r e p a r e d  Witoto  paste  their  a few d e t a i l s  original  the m i g r a t i o n ,  ancient  in  a few e x t r a  for  f o r m u l a of  the p l a n t s  their  receive  cloth  s t e p by s t e p ,  according to does  will  of  show us how t h e  procedure  in  they  them  not that  73  Protestants third  and C a t h o l i c s  informant,  shaman,  was  Alfredo  was by  A l f r e d o Moreno,  t h e headman of far  the  t h e most s e c r e t i v e agreed it,  in a d d i t i o n  the Witoto part  oldest  about  same B o s t o n  of  these  t h e method of  t o p r o v i d e me w i t h a sample of  but  would not a l l o w  to observe  Only a f t e r  several  after  days  the  cumaia t h a t  vernacular  term f o r  could c o l l e c t derived levels  of  he had c u t  sebifera,  tryptamines  some o r a l  activity  departing  for  was  days of  to pick time.  nearly  small  thirty  of  through,  the  dollars,  It  was  species  own b u n d l e of V i r o l a  67,68, lower  and 6 9 ) ; levels  sample.  Also,  of  however,  leaves  in  similarities  a  generic  sample,  t u r n e d out  t o have  and d e f i n i t e l y (see  s e c o n d l e g of three  exhibited  below). our  in advance,  Before  fieldwork, samples;  i n about  the  I  high  more p a s t e  back d o w n r i v e r  ten  enormous sum  f o r Don A l f r e d o was p r o b a b l y a  packet  for  of  collected  analyses  tryptamines  the  in  not e n o u g h , a p p a r e n t l y ,  banana-leaf  sample,  s p e c i m e n s . The f i r s t  samples  or  is  h i m . The s a m p l e s were w a i t i n g  each small  tree  its  first  (cumala  C h a p t e r V)  which  called  so t h a t  Nuevo on t h e  paid for  He  Peru)  them up on our way  fortune.  man out  its  I  in  was  down  a r r a n g e d w i t h Don A l f r e d o t o p u r c h a s e I  paste.  Don  d i d he t a k e me t o  (DMK-40)  (cf.  and a l s o  f i n d the  followed  in a subsequent b i o a s s a y  Brillo  Puco U r q u i l l o .  making t h e  his  local  our b a r g a i n ,  Myristicaceous  b a r k and v o u c h e r  from V .  of  informants,  he had d e l i v e r e d  The  t o b e i n g the  me t o accompany him t o  we had s t r u c k  ghetto.  " o o ' - k o e y " as he  or p h o t o g r a p h t h e p r o c e d u r e  manufacture.  visit  s h a r i n g the  of  the  V)  voucher  (DMK-  showed v e r y  than  back  a c c o m p a n i e d by  as v o u c h e r s  pastes  honest  us on our way  paste  (Chapter  these  t o make an  in  the  much first  s p e c i m e n s and  the  I  74  almost  identical  conclude that derived but  of  I  chemical p r o f i l e s had been g i v e n  from t h e  same t r e e .  c o u r s e d i d not  s a m p l e s were a n a l y z e d different samples taking  suitable  is  some e a s y  exceptionally  I  do not  Alfredo,  or whether  was p o o r  in  V)  have  plant.  the  of  until  and I  do not  after  all,  know t o  levels  fact  is  remains  immediately still  feel  that  most e x t e n s i v e feeling  is  the  levels  of  on t h e  fact  that  k i n d s of  extensive  b a s e d on h i s  to  contacted.  tryptamines; of  the  three  first  of  the  sample, oral  that  (Chapter  -  from p l a n t  to  received  «  their  oral  s a m p l e s were bioassayed) pastes  was  tradition. w h i c h had  activity,  I the  This high partly  other  "suitable"  Virola  substantial  amounts of  the  he a l s o  seemed t o have  than  the  other  a more  informants  In  fact,  Don A l f r e d o u t i l i z e d two u n u s u a l  i n making t h e  paste  w h i c h have  not  of Don  and  several  admixtures  part  q u e s t i o n of three  paste  a specimen  samples  "real"  and d i d e x h i b i t  he p o i n t e d out  knowledge  these  knowledge  specimens which proved to c o n t a i n right  three  for t o make  analyses  i n m e t h a n o l and were not  and t h e c l o s e s t  tryptamines  select  (the  paste  the  d e c e p t i o n on t h e  last  since  Don A l f r e d o ' s  partly  these  the  three  trying  considerable variation  that  when  Don A l f r e d o just  been  agreement  different  day whether  happened t o  unresolved,  preserved  three  found i n  from Don A l f r e d o were d i s a p p o i n t i n g activity  our  locating  compounds. S u b s e q u e n t  there  the  of  fault  this  to  months l a t e r  he was  deliberate  he j u s t  active  shown t h a t Despite  T h i s was c o n t r a r y  tryptamine  s a m p l e s were a r e s u l t  s a m p l e s l e d me t o  s a m p l e s w h i c h had a l l  specimens to p r e p a r e  out;  low  these  i n C a n a d a . The t a s k  way  money.  three  become c l e a r  considerable,  the easy  of  been r e p o r t e d  in  I  admixtures the  75  literature. leaves  of  infusion  One of  these  which are is  was a f e r n ,  made i n t o a t e a ;  was g r o w i n g on t h e  bark  lichen of  (Mart.  & Zucc.)Kuntze  lichen  were added t o t h e V i r o l a  (DMK-38)  J o r g e C h u r a y and h i s informants never  in  so and t h a t  ku", point  the  they  but  Bora  had watched  name f o r  some of  r e c o g n i z e d by t h e  the  its  different  manufacture samples  vernacular  Appendix Churay,  II).  One m o r n i n g we s e t  Rey,  and two o t h e r  Bora  to  Finally of  about  this  from the  lower  tree,  resin  was c l e a r  malocca  After  but  about  part  of  the  immediately  we had b r o u g h t  i n Puco U r q u i l l o ,  the  as  cumala of  (cf. Jorge  cumala  cumalas  "not  to  to  us  strong".  h i g h w i t h a DBH  removed t h e  trunk.  to  are  company of  70 f e e t  with a very  "ku'-ru-  e a c h . Not a l l  several  They  They  15 k i n d s of  for  had  had done  and a l s o  find a suitable  pavonis).  exuded a c o p i o u s r e s i n  pastes,  the  were p a s s e d o v e r  25 cm (DMK-34, V .  orange c o l o r . Bora  these  we came t o a l a r g e  long s t r i p s layer  but  fathers  they  cumalas which  in  make " k u ' - r u - k u " . The B o r a s p o i n t e d out a l o n g t h e way,  that  by a t a x o n o m i s t .  out,  Bora  t o make the  designations  this  many t i m e s .  distinguish  them would be c o n s i d e r e d d i f f e r e n t  identity, racemosa  were our  their  the  was s i m m e r i n g .  admitted  k i n d s of  The B o r a  other  Rinora  it  Rey  freely  bark  The  s c r a p i n g s of  while  the M y r i s t i c a c e o u s  Bora.  and have d i f f e r e n t  tree,  (Violaceae);  They  this  indeterminant  a small  resin  (DMK-39),  from  resin.  of  claimed that  t a k e us t o c o l l e c t  out  water  brother-in-law  Puco U r q u i l l o .  used the p a s t e s ,  agreed to  the  t h e n u s e d t o cook t h e V i r o l a  a d m i x t u r e was a g r e e n c r u s t o s e which  Anemia s p . ,  bark  in  The  inner  cambial  aromatic  spicy  odor;  o x i d i z e d to a reddish-  the Bora  bark  back  to  the  main  p r o c e e d e d t o c h i p away  76  the  outer  layer  layers  of  the  bark  w i t h t h e cambium was  u s i n g a machete.  t h e n pounded i n t o  w i t h an a x - h e a d . These were s t u f f e d and tamped down of  water--barely  and t h e n hours.  After  b o t t o m of  enough t o c o v e r  cooling,  the  rung out t o  reddish-brown  of  the  bark  the  a low  a d m i x t u r e s were added t o  and was e s s e n t i a l l y  most of Vi rola  the  spicy,  attempt  fire  for  the  further  was  added  about 3  Bora  this  paste  resulting  to a thick  equivalent  the  paste;  amount of are  also  men chew  added  The  flecked  o d o r l e s s and t a s t e l e s s ;  sifted  frequently.  sample.  reddisH-brown,  s h a r p odor which  following  evening  to determine  hallucinogen.  It  I  whether  with  it  had  lost  had c h a r a c t e r i z e d  the  "raw"  revealed  that  p r o d u c e d no e f f e c t  at  all,  despite  the  fact  t h e c o u r s e of  the  evening  this  the  any  suitable  and o v e r  recommended d o s e .  particular  alkaloids  without  sort  it  I  (Chapter  think  paste  that  V).  (DMK-34)  as  analysis  the  d i d not  contain  A s e c o n d sample made by  unavailable) their  s p e c i e s on two o c c a s i o n s  active  Subsequent  sample as w e l l  was d e r i v e d  which vouchers are  activity.  an  an o r a l l y  from w h i c h  (for  in  fact  times  it  sample  in  source-plant of  bioassayed this was  had f a s t e d p r e v i o u s l y  ingested several  Churay  bark—  amount  resin.  The  I  A minimal  same s p e c i e s  powdered c o c a w h i c h most of  strips  were removed and  l i q u i d was c o n c e n t r a t e d  the  phloem  aluminum pot  of  remove e x c e s s w a t e r ;  c o m p l e t e d " k u ' - r u - k u " was a d a r k black,  vessel.  strips  strips  C e c r o p i a s p . A s h e s of  No o t h e r  that  the  was mixed w i t h an a p p r o x i m a t e l y  ashes to  the  inner  long f i b r o u s  into a large  t h e m i x t u r e was b o i l e d o v e r  thoroughly  this  into  The  is  failure an  was a l s o to  completely  select  indication  of  Jorge  a just  how  77  much t h e  tribal  deteriorated p o i n t e d out informants contain  knowledge  over that  as  the  last  suitable  no l o n g e r  just  s p e c i e s are paste  a Bora  (I  Brillo all  Flores,  quite  hut,  to  the  of  in  the  Bora  of  He r e p e a t e d  botanical  ("el  Nuevo,  was h i g h l y  at  g r a s p of  loose.  nino")  Vega  upriver  from  o l d man  regarded  father,  Puco U r q u i l l o  amount of  from one s i d e  elongata  the  the  in  outer  of  Eugenio the  and  that  Once back a t  strips, bark  juice  layer. only  This a  he  he  few  was d i s c a r d e d .  He  t h e n d i p p e d them  into a small  three  his  with a machete,  cambial  two or  tree,  For  The t r e e was a  w i t h a wooden m a l l e t ,  wringing  paste  He e x p l a i n e d  bark  the  of  had d o n e .  from t h e  (DMK-59).  water and r u n g t h e this  die.  fibrous  The r e m a i n d e r  strips  bark only.  innermost  long f l e x i b l e  thick.  into a vessel  they  from whom he had i n h e r i t e d  chipping off  the c a m b i a l  since  from h i s  to  informants  on d r u g s , p o i s o n s , and m e d i c i n e s  t r e e would n o t  removed o n l y  millimeters  bowl.  it  also  were f o u n d not  their  Brillo  has  native  become somewhat  45 y e a r s o l d )  s p e c i m e n of V .  stripped off  beat  than  take  so t h a t  instead  carefully  of  [5,6]  a l t h o u g h not a p a r t i c u l a r l y  he took a, l e s s e r  was c a r e f u l  flowering  has  has  m e d i c i n e man. Don M a r c o s p r e p a r e d t h e  differently  was  drug,  He had l e a r n e d most o f . i t  one t h i n g ,  this  about  village  by  sample was made by M a r c o s  now i n h i s m i d - 7 0 s , of  indicated  A l t h o u g h some  the  suitable  Nuevo as an e x p e r t  sorts.  office  utilize  Don M a r c o s ,  p l a c e d him a t  Schultes  were once p r e p a r e d ,  from t h e v i l l a g e  Puco U r q u i l l o .  hallucinogen  decades.  tryptamines.  themselves  Flores,  few  oral  f o r making t h e p a s t e s  remember how t h e p a s t e s  Another  this  sometimes s p e c i e s  any a c t i v e  which  of  times  for  enamel each  78  strip,  then d i s c a r d e d  wringings thick  was  paste  T h i s was  ball. the  about  the  color  (DMK-64)  Prior  burning  to a d d i t i o n paste  and c o n s i s t e n c y  until  it  indicated  at  I  which  Four  seven  of  the  Ampiyacu area  Chorrera  was a l s o  nor was  paste  persons  "oo'-koey",  Churay at  I  into  I  tip  of  Urquillo  felt  for  oral  some d e g r e e of physiological c o n s i s t e d of closed. activity  oral  at  The s u b j e c t  have t r i g g e r e d  the  of  full  present,  La in  Jorge  inert,  appeared to  even was  Puco exhibit No  detected  imagery felt  the  as  dosage a s s a y e d .  and t h a t  spectrum of  the  supposedly required  sample  in  by  Colombia,  inactive  hypnagogic  who a s s a y e d t h e  was d e f i n i t e l y  any  either  samples-made by  symptoms were n o t e d . The a c t i v i t y the e l i c i t a t i o n  few  in a d d i t i o n ,  DMK-40) the  as  sharp,  expect  activity,  La C h o r r e r a ,  that  sebifera,  activity  into  any.  i n our p a r t y ;  times  thick  little  a  a  sample made by A l f r e d o Moreno a t  (made from V .  of  my t o n g u e ,  d i d not  Puco U r q u i l l o were c o m p l e t e l y  The f i r s t  a  husk of  d i p p e d my f i n g e r  h a l l u c i n o g e n s and a p p e a r e d t o be p h y s i o l o g i c a l l y  ingested.  syrup.  s a m p l e s w h i c h were c o l l e c t e d  The two p a s t e  t h o u g h an amount s e v e r a l  to a  fruit  consistency  immediately  there  c o l l e c t e d at  tested.  dried  t u r n e d my tongue numb f o r  were t e s t e d  by o t h e r  cambial  chocolate  fingers I  s u c h a low d o s e , h o w e v e r , activity,  or  the  the a s h e s ,  should do.  hallucinogenic  myself  of  was t h e  and p l a c e d a dab on t h e  sensation,  minutes;  of  the  l i q u i d was c o n c e n t r a t e d  and c o u l d be r o l l e d between  syrupy  1971,  the  t h e n m i x e d w i t h a s h e s made from t h e  Don M a r c o s  Rio  The bowl c o n t a i n i n g  simmered u n t i l  Theobroma b i c o l o r dough,  it.  with the  that  a larger  hallucinogenic  eyes  oral  dose m i g h t effects.  On  79  analysis,  this  sample p r o v e d t o c o n t a i n  substantial  concentrations  of DMT and 5-MeO-DMT, a l t h o u g h no  were d e t e c t e d .  The f o u r t h  V.  elongata  Nuevo.  This  of  of  any  (DMK-59)  of  the  paste  characterized  than  usually  and was made by M a r c o s F l o r e s  four a s s a y e d . O r a l  gram and a h a l f  rather  sample a s s a y e d was d e r i v e d  by the  typical  at  of  i n g e s t i o n of  elicited  by c o n s i d e r a b l e  perceptual  physiological  and p s y c h o l o g i c a l  h a l l u c i n o g e n s . The  initial  a feeling  felt  felt  dissociated  rapidity  of  uncomfortable.  and I  of  and s h a l l o w ,  steadier,  deeper  u n d e r s t o o d how i t  stress not  of  the  rest  their  I  lips,  of  breathing.  I  as an arrow p o i s o n ,  might be e f f e c t i v e  but  I  exertion,  had t h e  tongue,  My body  and f e l t way;  and t h o u g h t  that  alarmed  most  to maintain  I  a  reflecting  that  I  now  felt  that  any  further  be d a n g e r o u s  perceptual they  at  was  found myself  images,  racing  physically  on t r y i n g  in t h i s  feeling  and my  My mind was  which  and  labored.  my b o d y ,  symptoms and f e l t  T h e r e were no h y p n a g o g i c  or h a l l u c i n a t i o n s ,  quickly  extremities.  p l a c e d upon my r e s p i r a t o r y . s y s t e m - m i g h t  lethal.  c o n s i s t e d of  became somewhat  and c o n c e n t r a t e d  any p h y s i c a l  which  and b r e a t h i n g was  became c h i l l e d ,  the  rhythm of  use of V i r o l a  incapable  the  f o c u s e d on my own b r e a t h i n g ,  irregular  on t h e  in  from my b o d y .  onset I  spread over sensation  heavy and i n e r t ,  and f e l t the  a tingling  ingestion,  numbness i n  S w a l l o w i n g became d i f f i c u l t  The numbness g r a d u a l l y limbs  of  distress  effects,  t h e mouth and t h r o a t ,  into  a  disturbances  a strong burning sensation  in  active  a r a p i d and p r o f o u n d  following  throat.  Brillo  approximately  m a n i f e s t e d w i t h i n ten minutes  developing  from  sample p r o v e d t o be t h e most p h y s i o l o g i c a l l y  the  response,  0-carbolines  might  if  changes, have  80  m a n i f e s t e d had I  taken  p r o v e d t o be g r e a t l y to  the  constant  The symptoms of hour  to  easier,  heightened,  higher and I  physical  persisted  distress  than  gradually  became drowsy  and f e l l ten  or  fifteen  symptoms d i s a p p e a r e d , but  chilled  for  most of  sample was more a k i n anaesthetic  that  was not  to  the  this  sample was  were i s o l a t e d  unpublished data, the this  1982),  in  some o c c a s i o n s .  carbolines  (cf.  are  is  Gradually feel  of  the  paste  or left  activity. On  no It  later  concentration  biologically  active  (MacRae,  sample w h i c h has  in  been  or  detected with t h i s  this  to  "oo'-koey",  No h a l l u c i n o g e n i c  other sample  in  d o s e s were i n g e s t e d on  sample c o n t a i n e d  and d e t e c t a b l e  amounts of  substantial  tetrahydro-/3-  V).  l i m i t e d numbers of  not c o n c l u s i v e ,  "twilight"  however.  the La C h o r r e r a  was e v e r  Chapter  A l t h o u g h the here  paste  Interestingly,  tryptamines  became  bioassy  possess o r a l  though e x c e s s i v e  amounts of  half-  No / 3 - c a r b o l i n e s were d e t e c t e d  1971 i n C o l o m b i a . activity  one  amine  the  forest.  and t h e s e may w e l l have c o n t r i b u t e d  collected  even  but  from DMK-59 by Don MacRae  t o human b i o a s s a y  trials,  a pressor  of NMT; s e v e r a l  subjected  several  effect  found to c o n t a i n a h i g h  s a m p l e . The f i f t h  physiological  about  minutes.  or e n j o y a b l e ,  pharmacological a c t i v i t y . paste  of  sample d i d d e f i n i t e l y  5-MeO-DMT and a t r a c e  lignans  actions  pleasant  for  The o v e r - a l l  hearing  from t h e  continued to  than a h a l l u c i n o g e n ,  particularly  analysis, of  the  night.  I  of  sensitive  i n t o a s t a t e of  the  the  noises  faded. Breathing  most of  doubt  was e x t r e m e l y  insect  s l e e p w h i c h may have l a s t e d  general  dose. Acuity  b a c k g r o u n d hum of  45 m i n u t e s , and I  a slightly  they  human b i o a s s a y s  do i n d i c a t e  that  the  reported  oral  activity  81  of  these M y r i s t i c a c e o u s  other  than  the  fortuitous  and / 3 - c a r b o l i n e s . contained only not  orally  p a s t e s may be d e t e r m i n e d by c o m b i n a t i o n of  The p a s t e  active;  which d i d c o n t a i n  on the  other  the a c t i v e  c o m b i n a t i o n was c o m p l e t e l y Samples is  at  lacking alkaloids  least  consistent  determining presence  with those samples  of  these  due s i m p l y  without also  solely)  indicate to  the  profiles  the M y r i s t i c a c e o u s  turn,  /3-carbolines.  variable,  source-plants  oral  used t o p r e p a r e  would p r o b a b l y  result  the the  in  considered  oral  the  of  chemical drug  of  t h e d r u g may e x p l a i n  p u z z l e s about  these  and u s e d s e c r e t l y never  pastes,  (cf.  Chapter V ) .  This,  In  fact, of  different  ethnopharmacological they  are  by t h e m e d i c i n e men, t h e  fact  that  they  snuffs are  Bora, widely  Witoto,  in  the  that  the  the  the  in  fact  been u s e d o u t s i d e  although Vi rola  sample.  the  to  in  t h e c o m p o s i t i o n of  some of  e.g.,  not  variability  i n e x e r c i s i n g some d e g r e e over  is  the  in c o n s i d e r a b l e v a r i a t i o n  quality-control  paste  s a m p l e s has been shown  difficulties  batches  the  alkaloidal  from sample t o  pharmaceutical  of  together  activity  pharmacological a c t i v i t y encountered  those  unelucidated.  MAOI a s s a y s  fact,  paste  reflecting  remain  potentiation  In  result  factors  activity  the  in  activity.  and t h i s  The  however,  that  sample,  and / 3 - c a r b o l i n e s  still  ir\ v i t r o  activity  supposedly  physiological  oral  human t r i a l s ,  by t h e  be h i g h l y  of  alkaloids  tryptamines of  oral  is  La C h o r r e r a  had no a c t i v i t y ,  or a b s e n c e  C h a p t e r VI) (or  the  tryptamines  o b t a i n e d from the  (cf.  hand,  derivatives  greatest  5-MeO-DMT, w h i c h  with expectations.  s a m p l e s w h i c h do c o n t a i n The r e s u l t s  tryptamine  sample showing t h e  a single alkaloid,  variables  and Muinane  used i n the  made have  groups  Amazon B a s i n ;  and  82  the  fact  that  their  use even  in these  tribes  has d i m i n i s h e d or  d i s a p p e a r e d as c o n t a c t s w i t h o u t s i d e c u l t u r e s have  increased.  83  III.  Literature  Cited  1.  L u n a , L. E. (1983) The C o n c e p t of P l a n t s as T e a c h e r s Among F o u r M e s t i z o Shamans of I q u i t o s , N o r t h e a s t P e r u . Paper p r e s e n t e d a t t h e Symposium on Shamanism, X l t h I n t e r n a t i o n a l C o n g r e s s of A n t h r o p o l o g i c a l and E t h n o l o g i c a l S c i e n c e s , Phase 2. V a n c o u v e r , B. C . , A u g u s t 20-23 1983.  2.  L u n a , L. E. ( 1983) Don E m i l i o y sus D o c t o r i c i t o s . F i l m p r e s e n t e d a t X l t h I n t e r n a t i o n a l C o n g r e s s of A n t h r o p o l o g i c a l and E t h n o l o g i c a l S c i e n c e s , Phase 2. V a n c o u v e r , B. C , A u g u s t 20-23 1 9 8 3 .  3.  R i v i e r , L. & J . L i n d g r e n (1972) A y a h u a s c a , the S o u t h H a l l u c i n o g e n i c D r i n k : E t h n o b o t a n i c a l and C h e m i c a l Investigations. Economic Botany 29:101-129  4.  S c h u l t e s , R. E. Hallucinogen. 22:229-40  5.  S c h u l t e s , R. E . , T . S w a i n , & T . Plowman (1977) V i r o l a O r a l H a l l u c i n o g e n Among the B o r a s of P e r u . H a r v a r d B o t a n i c a l Museum L e a f l e t s 25:259-272  6.  S c h u l t e s , R. E. & T . Swain (1976) F u r t h e r N o t e s an O r a l H a l l u c i n o g e n . J o u r n a l of P s y c h e d e l i c D r u g s 8:317-324  7.  C o l l i e r , R i c h a r d (1968) The R i v e r t h a t God F o r g o t : of t h e Amazon Rubber Boom. E. P. D u t t o n & C o . , New Y o r k .  8.  Shoumatoff, Alex San F r a n c i s c o .  American  (1969) V i r o l a as an O r a l l y - a d m i n i s t e r e d H a r v a r d B o t a n i c a l Museum L e a f l e t s  (1978)  The R i v e r s Amazon.  as  on V i r o l a  Sierra  The  Club  an  as  Story  Books,  84  PART I I I :  PHYTOCHEMICAL AND PHARMACOLOGICAL  INVESTIGATIONS  85  CHAPTER  I.  I V : ALKALOID CONSTITUENTS OF AYAHUASCA BREWS, SOURCE-PLANTS, AND ADMIXTURE PLANTS  Introduction The h a l l u c i n o g e n i c  the  souls")  is  recreational inhabiting term f o r it  is  widely  p u r p o s e s by t h e  t h e Amazon B a s i n .  the  drug in  and p i n d e  the  the  [1],  believed  of  to  various  intensify  admixture p l a n t s or  chemically,  viridis  Ruiz  Diplopterys liana  in  plants  those  Plowman,  [4];  these  beverage, its  material  tribes  the  primary  and of  the  effect  alkaloids  the  [2].  the  of  Purus  among t h e in Peru.  method, R i v i e r harmine,  which  is  the  botanically Psychotria  Jacq.,  latter  and  is  also a  Banisteriopsis  the c h e m i s t r y  of  Rivier  Sharanahua  the  and L i n d g r e n vouchered  and C u l i n a  U s i n g GC/MS a s  and  of  admixture  s a m p l e s and  and L i n d g r e n  harmaline,  with  1980].  s t u d i e d ayahuasca  collected  of  Many of  s o u r c e - p l a n t s and that  is  Banisteriopsis  addition  known as  comm.,  is  caapi,  together  carthagenensis  to date  manufacture,  upper R i o  analytical  carboline  the  formerly  study  investigators  botanical of  liana  u s e d most commonly a r e  pers.  regions  i n c l u d i n g yage,  (Cuatrecasas)Gates;  T.,  populations  in d i f f e r e n t  jungle  of  t h e most common  (Malpighiaceae)  Psychotria  "vine  c o f f e e - c o l o r e d beverage  the  or m o d i f y  however  cabrerana  used in  names,  admixture p l a n t s ,  The most c o m p l e t e ayahuasca  and m e s t i z o is  for  and  used remain u n c h a r a c t e r i z e d e i t h e r  & Pavon,  [3,  of  Morton  the M a l p i g h i a c e a e  rusbyana  ritual,  Amazon,  The b i t t e r , bark  (Quechua  While ayahuasca  Peruvian  ( S p r u c e ex G r i s e b . )  leaves  aboriginal  vernacular  p r e p a r e d by b o i l i n g t h e caapi  ayahuasca  used f o r m e d i c i n a l ,  known by v a r i o u s  natema,  beverage  the  found t h a t  the  tetrahydroharmine,  0-  86  and DMT were t h e major Fig.  1 & 2).  caapi  [5]  constituents  The / 3 - c a r b o l i n e s a r e  spp.  Hashimoto et carboline  bases to  the  [4]  al.  as w e l l as  [7,8]  from t h e three  of  i n D.  have r e p o r t e d t h e  leaves  of  (viz.:  ketotetrahydronorharmine,  harmic  a c i d methyl  ester,  significantly  make  aspects  clarified.  it  of  DMT i s  unlikely  active  also  by  few c l i n i c a l  not  i n B.  hallucinogenic  well  oral  unequivocal  the  [13]  the  [9],  results  are  are  effects  of  h a r m i n e or  also to  (MAO).  of  probably  t h e /3-  are  relatively  to  be report  tetrahydroharmine.  approaching  12 mg/kg.  inactive  has been s u g g e s t e d of  is  / 3 - c a r b o l i n e s on  levels  properties  be  highly  and a r e  r e p o r t e d h a r m i n e was o r a l l y  the h a l l u c i n o g e n i c  to  but  known t o be  & Hoch [14]  It  now.known,  monoamine o x i d a s e  Pennes  that  ayahuasca.  4 mg/kg but c o u l d not  for  plant  p r o b a b l y due  reported harmaline  d o s e s of  the  the  hallucinogen  of MAO [ 1 0 , 1 1 , 1 2 ]  of  N-oxide,  drug remain  understood because there  Naranjo at  caapi  of  The p s y c h o t o m i m e t i c a c t i v i t y  investigations  human s u b j e c t s .  similarly  and h e p a t i c  6 /3-  contribute  ayahuasca  be a p o t e n t  inhibitors  hallucinogenic. is  of  of in  However  compounds i n they  the  amide,  harmine  acid).  when i n g e s t e d o r a l l y  intestinal  reversible  carbolines  that  alkaloids  known t o  The / 3 - c a r b o l i n e s p r e s e n t active  these  t h e p h a r m a c o l o g y of  known t o be i n a c t i v e deamination  of  caapi  harmic  to the p h a r m a c o l o g i c a l a c t i v i t y  A l t h o u g h the certain  and h a r m a l i n i c  in  [6]  isolation  Banisteriopsis  main c o n s t i t u e n t s  low c o n c e n t r a t i o n s  Banisteriopsis  cabrerana  norharmine,  ( . 0 0 7 - . 0 0 0 1 %)  of  (cf.  has been r e p o r t e d  acetyl  extremely  ayahuasca  constituents  while N,N-dimethyltryptamine  two P s y c h o t r i a  addition  active  at  [2,6,9,15,16]  the crude ayahuasca  brew  87  result  from a s y n e r g i s t i c  interaction  constituents;  specifically,  activation  t h e DMT t h r o u g h t h e  of  carbolines. blocking  that  it  T h i s mechanism would  its  degradation  mechanism i s  reasonable  monoamine o x i d a s e has not  the  presents  alkaloid  used in  its  ayahuasca  11.  C o l l e c t i o n of  kindly  Dept.  of  vouchers  Authenticated  the  active  in  the on  determined.  This  investigations  of  source-plants effect  of  VI.  and P l a n t  D. McKenna,  cabrerana) for  Timothy  this  paper  w i t h the  and Plowman  Plowman  Plowman  Materials refer  exception  6041  (B.  6040 and 6041  F i e l d Museum  herbarium vouchers  for  all  most c o l l e c t i o n s  British  are  also  on d e p o s i t  During ethnobotanical s a m p l e s of  ayahuasca  fieldwork  in  preparations  the  in  collection  H e r b a r i u m of  Columbia.  of  was  the  of  the  caapi  of  University  to  the  Duplicate at  the  Chicago  F i e l d Museum.  eight  by  this  ayahuasca  in Chapter  have been d e p o s i t e d i n t h e  Botany, of  of  throughout  Plant material  s u p p l i e d by D r .  numbers c i t e d  and t h e  Drug Samples  numbers of  6040 ( D i p l o p t e r y s  Chicago.  phytochemical  reported  numbers c i t e d  personal c o l l e c t i o n  "cielo").  of  0-  and Methods  Collection  var.  t h e DMT o r a l l y  the e f f e c t  An e v a l u a t i o n is  MAO by t h e  l o n g been a c c e p t e d  of  oral  MAO. A l t h o u g h  of a y a h u a s c a  on MAO i_n v i t r o  Field  Plowman  results  manufacture.  from an  been e x p e r i m e n t a l l y  constituents  Materials  A.  the  various  i n h i b i t i o n of render  ethnopharmacological l i t e r a t u r e ,  chapter  results  by v i s c e r a l and has  among t h e  s p r i n g of  were o b t a i n e d  1981, from  88  ayahuasqueros Iquitos,  living  Pucallpa,  qualitatively u s i n g HPLC.  on t h e  outskirts  and T a r a p o t o .  of  Identification standards.  are  in  identified  from whom t h e y  These samples  this  of  alkaloids  were  Ayahuasca  chapter  III  samples used f o r  by t h e  name of  were o b t a i n e d , and a l s o  for d e t a i l s  of  the  from t h e  for  i n f o r m a t i o n on h e r b a r i u m v o u c h e r  In  some  same p e r s o n .  the c o l l e c t i o n  phytochemical  collections  analysis  ayahuasquero  by a number.  methods u s e d i n  d r u g s a m p l e s and s o u r c e p l a n t s  quantified  was b a s e d on c o m p a r i s o n  c a s e s more t h a n one sample was o b t a i n e d Chapter  P e r u v i a n towns of  a n a l y z e d u s i n g 2 - d i m e n s i o n a l TLC and  with authentic  See  the  is  of  analysis; tabulated  in  Appendix 1 1 .  B.  Two-dimensional T h i n - l a y e r  The f l u o r e s c e n c e reactions, for  the  (Table  and Rf  II).  carboline  t h e Rf  is  1-dimensional  10 x 10 cm P o l y g r a m  lower  left  and l e f t - h a n d analyzed  the  color were  used in  tryptamine in F i g .  development  this  study  and /33;  of in  determined  Fig.  4  tryptamine solvent  1 and  2.  (Brinkmann I n s t r u m e n t s ) . the  standards  selected mixtures  Two-dimensional t h i n - l a y e r using  systems  shown g r a p h i c a l l y  v a l u e s of  following  Ehrlich's  two s o l v e n t  T w o - d i m e n s i o n a l TLC of  illustrates  solvent  in  and / 3 - c a r b o l i n e  standards  standards  characteristics,  values  tryptamine  Chromatography  Silica  (consisting  Gel G U V  The o r i g i n  hand c o r n e r edge. F i v e  c h r o m a t o g r a p h y was c a r r i e d  ul  either  of  of  "  precoated  plates  was marked w i t h p e n c i l  the p l a t e ,  aliquots  2 5  of  1.0  cm f r o m t h e  the m a t e r i a l  the crude ayahuasca  to  out  in  bottom be  s a m p l e s or  in  TABLE Compound Name  II:  HRF* VALUES OF TRYPTAMINE  Solvent  0 - c a r b o l i nes: norharman harman harma1 a n tetrahydroharman tetrahydro3-carboxy-harman harm 1ne h a r m a 1 i ne tetrahydroharmi ne harmol harma1ol 6-MeO-harman 6-MeO-harma1 a n 6-MeO-tetrahydroharman b r e v 1 c o 1 i ne mean % s t a n d a r d deviationo = T r y p t a m i nes : 1- tryptophan 5-hydroxy1-tryptophan tryptophol t r y p t a m i ne 5-hydroxyt r y p t a m i ne 5 - M e O - t r y p t a m i ne 6-MeO-tryptamine gram 1ne N-methy1 t r y p t a m i ne DMT 5-hydroxy-DMT 5-MeO-DMT ps i1oc i n ps i 1 o c y b i n melaton i n 5-MeO-di i s o p r o p y l t r y p t a m i ne mean % s t a n d a r d deviationo =  Solvent  2tt  STANDARDSt  UV f1uorescence  Ehrlich's r e a c t i onb  62 . 7 67 .9 49 . 0  84 .8 84 .8 67 . 7  b l ue dark b l u e grey-green  nt£  30 . 0  40 . 3  nf  UVA*  nt  0 .0 58 . 2 33 . 2  55 .9 82 .9 45 . 7  nf - UVA dark b l u e aqua  nt  24 35 17 66 44  .0 . 7 . 3 .0 . 3  35 . 7 8 1 .3 35 . 7 82 .7 56 .8  nf - UVA dark b l u e aqua It. blue tan  26 .0 56 . 5  34 . 1 79 . 5  nf dark  6 . 24  -  1*  AND p-CARBOLINE  -  -  It.  blue*  -  -  UVA blue  nt nt  5. 5  0. .0  51 . 5  0. .0 75 . 1 35 . 0  46 . 2 85 . 6 29 . 5 .  13. 5 29 . 4 29. 3 28 . 8  nf  - UVA  b 1 ue-gray  " "  blue-gray grey b1ue-gray  18 . 9 25. 0 24 . 0 25. 9  " " " "  gray It. blue dk, b l u e It. violet  10. 7 4 1 .3 16 . 4 35 . 5 42. 9 0. 0 46 . 3  17 . 8 4 1 .9 28 . 7 37. 1 41 . 6 3 .2 83 . 7  II  "  blue-gray b1ue-gray It. blue It blue dk. violet It. violet It. blue  93 . 7  54 . 1  "  It.  1 .7  8.0  " " " "  "  blue  90  *  hRf =  distance  m i g r a t e d by compound  X 100 d i s t a n c e m i g r a t e d by s o l v e n t t A l l s t a n d a r d s u s e d i n TLC and i n t h e MAO a s s a y s r e p o r t e d i n C h a p t e r VI were p u r c h a s e d from Sigma C h e m i c a l C o . , S t . L o u i s , Mo, or A l d r i c h C h e m i c a l C o . , M i l w a u k e e , W i s . , w i t h t h e f o l l o w i n g e x c e p t i o n s : P s i l o c y b i n and p s i l o c i n s t a n d a r d s ( S a n d o z : l o t numbers 8001 & 5 0 0 1 , r e s p e c t i v e l y ) were g i f t s of t h e C h i e f of S c i e n t i f i c S e r v i c e s , H e a l t h and W e l f a r e C a n a d a , O t t a w a , O n t a r i o ; 5 - M e O - d i i s o p r o p y l t r y p t a m i n e and 3 - [ 2 - ( 2 , 5 dimethyl)pyrrolylethyl]-indole were g i f t s of D r . B. A b e y s e k a r a , R a d i o p h a r m a c e u t i c a l s , I n c . , V a n c o u v e r , B. C ; 6-MeO-MTH/3B was a g i f t of D r . Bo H o l m s t e d t , K a r o l i n s k a I n s t i t u t e , S t o c k h o l m ; b r e v i c o l i n e was a g i f t of D r . E. L e e t , D e p t . Of C h e m i s t r y , U n i v e r s i t y of M i n n e s o t a , M i n n e a p o l i s , M i n n . ; t e t r a h y d r o h a r m i n e was s y n t h e s i z e d from 6-MeO-tryptamine (Sigma) and a c e t a l d e h y d e , a c c o r d i n g t o t h e method of A k a b o r i and S a i t o [ 2 9 ] . $ S o l v e n t 1: e t h e r / 2 - b u t a n o n e / c o n c . NH«OH 5:4:1 (upper p h a s e ) # S o l v e n t 2: n - p r o p a n o l / 1 . 5 % NH«OH 9:2 b r e a c t i o n to E h r l i c h ' s reagent ( c f . [20]) $ nt= not t e s t e d 4> nf - UVA = n o t f l u o r e s c e n t ; v i s i b l e as U V - a b s o r b i n g s p o t under s h o r t wave UV ii Slow c o l o r - r e a c t i o n v i s i b l e a f t e r 24 h o u r s mean s t a n d a r d d e v i a t i o n CJ mean % s t a n d a r d d e v i a t i o n = X 100 mean hRf  91  30X  9Qf  BQ-  o o  17X  7Q.  2+ 11 + 1+  a:  14+  5Q;  3+  29X  12+  Ld  6+  4Qf  > _J  18X  o  20 21*X22  3Qf  9+  26X  7+ 4+  13+ 8+ 25X  10+  19X 23X  iQ;  QMt-  16 -K  10-  so.  30-  40<  SOLVENT Figure +  50-  2  G0>  70-  BO.  90 <  100-  RF X 1 0 0  3 - P o s i t i o n s of T r y p t a m i n e and 0 - c a r b o l i n e S t a n d a r d s i n Two D i m e n s i o n a l T h i n L a y e r C h r o m a t o g r a p h y  = 0-carbolines  1. Norharman 2. Harman 3. H a r m a l a n 4. T e t r a h y d r o h a r m a n 5. T e t r a h y d r o h a r m a n 3-carboxylate 6. Harmine 7. H a r m a l i n e 8. T e t r a h y d r o h a r m i n e 9. Harmol 10 . H a r m a l o l 1 1. 12 . 13 . 14 .  15 rK—  6-Me0-harman 6-Me0-harmalan 6-Me0-tetrahydroharman Brevicoline  X = Tryptamines 15. 16. 17. 18. 19. 20. 21 . 22. 23. 24. 25. N,N 26. 27. 28. 29. 30.  L-tryptophan 5-hydroxy-l-tryptophan Tryptophol Tryptamine ' 5-hydroxy-tryptamine 5- M e O - t r y p t a m i n e 6- M e O - t r y p t a m i n e Gramine N-methyl-tryptamine N,N-dimethyltryptamine 5-hydroxy-dimethyltryptamine 5-MeO-N,N-dimethyltryptamine Psilocin Psilocybin Melatonin 5-MeO-di i s o p r o p y l t r y p t a m i n e  30+  9Qr  o o  •c-l  92  BQ.  17+  X  7Q;  L_  Ol  BQ.  •<H  5Q>  r 1 • 1  '  1  1  _ J >  4Q.  24+  24+  18+  26+  29+  IJt  24+  24+  24+  18+  3Qr  + 20+ 20+21  D  22+  2Qf  25+ 23+  iQ-  19 +  23+  19+  28.  Q-  -15.  4.  3'  I V  B«  5-  B«  7»  9«  10-  5TANDARD COMBINATIONS 100-  9Q; O O r-i  17+  X  7Q:  L_ C£  £Q-  5Q  1  L.l i  _>l  D  LD  1  30+  15+  r  r -  1  29+  BQ.  24+  4Q..  16+  27+24  24 +  24+  24+  24 +  26+ 3Q?  18+  18+ 20 20 +  25+ »*  EQ.  23+  22+  19+  23+  19 +  lQr  28+  Q-  H-  0*  1'  2-  3'  4.  5.  G •  7.  8-  9-  lO-  l l -  5TANDARD COMBINATIONS  F i g u r e 4 - One D i m e n s i o n a l TLC o f M i x t u r e s of T r y p t a m i n e S t a n d a r d s C o m p o s i t i o n of s t a n d a r d m i x t u r e s : * 1. T r y p t a m i n e + NMT + DMT 2. DMT + 5-MeO-DMT + NMT 3. DMT + 5-HO-DMT + p s i l o c i n + p s i l o c y b i n 4. 5 - M e O - t r y p t a m i n e + 6 - M e O - t r y p t a m i n e 5. T r y p t a m i n e + 5 - M e O - t r y p t a m i n e + 5HT 6. L - t r y p t o p h a n + t r y p t o p h o l 7. 5 - h y d r o x y - l - t r y p t o p h a n + 5HT 8. DMT + g r a m i n e 9 DMT + m e l a t o n i n 10. DMT + 5 - M e O - d i i s o p r o p y l t r y p t a m i n e * Numbering of i n d i v i d u a l c o n s t i t u e n t s i s a c c o r d i n g t o key i n F i g . 3.  93  the  case  of  the admixture p l a n t s  purified alkaloid  fraction)  Microcap a p p l i c a t o r . s t r e a m of  air,  collected plates  for  plates  in  in a separatory  the  any  solvent  with respect  Solvent  solvent sealed  2,  was  free  the  first 1).  to a i r  Solvent  1,  in  Following  short-  laboratory  and long-wave  short-wave  Duplicate gives  development  to v i s u a l i z e  are  visible  strong fluorescent  plates  blue  derivatives  following  tank  in  the  kept in  in  both an  c o n t a i n i n g 50 2,  plates  30-60 min or  a l k a l o i d s . DMT  as d a r k  spots  colors  e x p o s u r e t o HCI react  under  and d i h y d r o - / 3 - c a r b o l i n e s under  long-wave  reagent  c o l o r s w i t h DMT and o t h e r  d i h y d r o - / 3 - c a r b o l i n e s do not  to  this  if  Solvent  the  were s p r a y e d w i t h E h r l i c h ' s  to v i o l e t  the  b e n c h . P l a t e s were examined under  UV w h i l e t h e a r o m a t i c  characteristic  the  and d e v e l o p e d  temperature  i n a fume hood f o r  UV l i g h t  and t e t r a h y d r o - / 3 - c a r b o l i n e s  ambient  was  the  90°  Development  10 x 30 x 26 cm g l a s s c h r o m a t o g r a p h i c  were removed and a i r - d r i e d  1,  room t e m p e r a t u r e  unlined  on t h e  1,  rotated  Solvent  1 & 2 was c a r r i e d  overnight  upper phase  i n d i c a t e d by  Solvent  solvent.  out a t  using 1 was  n - p r o p a n o l / 1 . 5 % NH„OH 9 : 2 ;  2-3 d a y s a t  gentle  i n a fume h o o d .  P l a t e s were t h e n  position  c o n s i s t i n g of for  of  in a ground-glass stoppered f l a s k .  ml ± 5 ml of  Solvent  in Solvent  dry  the  using a  direction  f u n n e l and t h e  development  odor.  to t h e i r  stable  origin  s e c o n d d i m e n s i o n was commenced when  were c o m p l e t e l y  absence of left  in  the  (Solvent  a  were removed and a l l o w e d  Development  in  NH OH 5:4:1  TLC. Following  s o l u t i o n of  sample was d r i e d under a  and t h e n d e v e l o p e d  prepared  a methanol  were a p p l i e d t o  The a p p l i e d  ether/2-butanone/conc. freshly  of  vapors.  give UV.  [17]  which  tryptamine Aromatic  with E h r l i c h ' s  and  reagent  however  94  tetrahydroharmine  gives  which d e v e l o p s over distinguish and a l s o that  a characteristic  24 h r .  T h i s slow  tetrahydroharmine  from the  30 min of  containing aliquots  of  from i t s  more a r o m a t i c darker  e x p o s u r e t o HCI  known / 3 - c a r b o l i n e and  in the  samples c o r r e s p o n d i n g to  c o u l d t h u s be r e a d i l y plates  w i t h the  (cf.  reactions  v a p o r s . A TLC  plate  tryptamine sample  known  i d e n t i f i e d by c o m p a r i s o n of  "standard" plate  to  analogues  blue  s t a n d a r d s was d e v e l o p e d s i m u l t a n e o u s l y w i t h t h e constituents  color  r e a c t i o n c a n be u s e d  t r y p t a m i n e s which g i v e  appear w i t h i n  r o b i n ' s egg b l u e  plates;  standards the  sample  "ayahuasca analogue",  Fig.  6).  C.  High Pressure  L i q u i d Chromatography  1. A n a l y t i c a l  (HPLC)  conditions  A V a r i a n model 5000 HPLC i n t e r f a c e d w i t h a model SP4100 c o m p u t i n g i n t e g r a t o r analysis  of  cultivars,  the ayahuasca  samples,  was u s e d f o r the  and t h e D M T - c o n t a i n i n g a d m i x t u r e p l a n t s  model 634 v a r i a b l e  spectrophotometer. reverse  wavelength  methanol/water  caapi  (Fig.  5).  260 nm w i t h a  Column c o n s i s t e d of a V a r i a n M i c r o p a k MCH-10 Solvents  c o n t a i n i n g 0.05% t r i e t h y l a m i n e .  e l u t i o n p r o g r a m was u s e d f o r  the a n a l y s i s ,  at  flow  of  quantitative  UV/visible  p h a s e c o l u m n , 30 cm x 4 mm i . d .  a rate  the  Banisteriopsis  C o n s t i t u e n t s were d e t e c t e d by UV a b s o r p t i o n a t Varian  Spectra-physics  1%/min.  Solvent  were  A gradient  f r o m 60-90 % m e t h a n o l  r a t e was 2 m l / m i n .  Samples  were a p p l i e d t o t h e column v i a  a Rheodyne model 7125 s y r i n g e  l o a d i n g sample  w i t h a 20 ul  injector  fitted  sample l o o p .  Samples  95  B  Figure  5 - HPLC E l u t i o n P r o f i l e o f P e r u v i a n A.) A l k a l o i d s t a n d a r d s . B.) A y a h u a s c a  Ayahuasca sample.  Analytical Conditions: S o l v e n t : m e t h a n o l / H 0 c o n t a i n i n g 0.05% t r i e t h y l a m i n e Column: V a r i a n M i c r o p a k MCH-10, 30 cm x 4 mm i . d . Program: 60 - 90 % m e t h a n o l , 1%/min; f l o w r a t e = 2 ml/min D e t e c t i o n : 260 nm, V a r i a n M o d e l 634 U V / v i s i b l e spectrophotometer 2  96  were l o a d e d o n t o the microliter  syringe  2.  sample  fitted  Quantitative  Quantitative  injector  w i t h a #22 gauge 9 0 °  this  method,  analyses  were c a r r i e d  t h e column i s  known c o n c e n t r a t i o n s  integrator  program c a l c u l a t e s  calibration  Calibration  at  to generate  the  in  calculate subsequent  with a  needle.  coefficients  of  peak a r e a  a linear  t o peak a r e a .  concentration  of  of  integrator.  mixture  of  each  response enables  integrator  components of  sample r u n s by c o m p a r i s o n of  the  standards  integrator  relating data  and i s  interest  the  is  used  to  in  peak a r e a s of in  in  factor.  the  equation  The  standard  This calibration  the  components w i t h t h e peak a r e a s of  external  s t a n d a r d compounds.  two or more c o n c e n t r a t i o n s  t h e memory c i r c u i t s the  of  the  u s i n g the  SP4100 c o m p u t i n g  m i x t u r e and n o r m a l i z e s t h e  sample c o n c e n t r a t i o n stored  out  calibrated  containing  the  beveled  methods  s t a n d a r d program s u p p l i e d w i t h the In  u s i n g a 25 ul H a m i l t o n #702  sample  calibration  mix. Stock  s o l u t i o n s of  harmine,  harmaline,  and DMT s t a n d a r d s were made up t o a p r e c i s e mg/ml.  Equal  aliquots  giving a calibration 1:1  dilution  mixture  of  stock  0.25 mg/ml of  this  every  level.  five  1  each component;  the c o n c e n t r a t i o n  of  integrator  was  the c a l i b r a t i o n  The i n t e g r a t o r  sample  of  m i x t u r e w i t h m e t h a n o l gave a  in which  20 ul i n j e c t i o n s  each c o n c e n t r a t i o n  concentration  s o l u t i o n s were c o m b i n e d ,  0.125 mg/ml. The SP4100  by making s i n g l e  following  mixture  o f . a p o r t i o n of  second c a l i b r a t i o n component was  from t h e  tetrahydroharmine  injections.  was  of  each  calibrated mixture  recalibrated  at  97  3. a.  Sample  preparation  Ayahuasca  s a m p l e s . The a y a h u a s c a  been d i l u t e d w i t h m e t h a n o l on c o l l e c t i o n analysis  so t h a t  concentration aliquot  of  the a l k a l o i d s  range  the  of  present  c h i l l e d m e t h a n o l and a w h i t e ,  flocculent,  which  filtration.  This diluted preparation,  into  pipette  the HPLC.  prepared, separate  plugged with g l a s s Two r e p l i c a t e s  following  these  four  replicate  of  reported  injections.  v a l u e measured s i n c e  the  concentration  undiluted  of  the  The a y a h u a s c a in  the  weight diluted  field of  lyophilized. a  fine  A p o r t i o n of  Ten ml  was e x t r a c t e d  over  was  directly  sample were twice  integrator  in Table  III  given  alkaloids  are are  during using  10x t h e  1/10  filtered  the  t h e means of actual  the  terms  ml of  the  of  transferred  pipette  for  to a  frozen,  100 ml  was added and t h e  mg/g d r y  then ground  solution was  through glass  u s i n g a s e c o n d t e n ml a l i q u o t  extracts  to  round  5 m i n . The m e t h a n o l  and f i l t e r e d  methanol  methanol-  f r e e z e - d r i e d r e s i d u e was  a steam b a t h  repeated  in  on a steam b a t h ,  100% m e t h a n o l  removed w i t h a P a s t e u r The e x t r a c t i o n  injected  brew.  for  the  100 mg was  bottom f l a s k .  The  the  l y o p h i l i z e d sample. F i f t e e n  powder and  methanol.  was  through a  s a m p l e s w h i c h had been d i l u t e d w i t h  sample was e v a p o r a t e d  ml  with  filtration  injected  Values  A 1.5  removed by  s a m p l e s measured were  were q u a n t i f i e d  the  of  the  15 ml  each ayahuasca  sample was  for  proteinaceous  after  wool,  calibration  standard mixtures. Values  to  from s o l u t i o n was  and e a c h r e p l i c a t e runs  standards.  was d i l u t e d  precipitate  Pasteur  separated  were d i l u t e d  were w i t h i n  the c a l i b r a t i o n  crude p r e p a r a t i o n  s a m p l e s w h i c h had not  were c o m b i n e d , and t h e  wool. of  final  98  volume was a d j u s t e d  to  10 m l . Twenty  s o l u t i o n were i n j e c t e d samples,  average  was  of  b. alkaloid carried  injected  these  four  Figures  replicate  in Table  IV  cultivars.  Quantitation  dryer.  24 h r s  The a i r - d r i e d  on a r o t a r y  directly  to  shaker.  Four  replicate  replicate  given  extracts wool  sample c o n s i s t e d of  injections  decanted  All  of  material  was  freeze-dried leaves of  Plowman  frozen,  then  (10-20 m l / g d .  directly  of the  the  Psychotr ia  derived 6040.  cabrerana from a  The m e t h a n o l  wt.).  overnight The D.  and t h e  was  remaining  same manner as  the  were f i l t e r e d ,  combined w i t h the  on a r o t a r y  cabrerana  w i t h m e t h a n o l and o t h e r w i s e Psychotria  leaf  l y o p h i l i z e d . The f r e e z e - d r i e d  was powdered and e x t r a c t e d  w i t h methanol extracted  the D i p l o p t e r y s  from t h e m e t h a n o l - p r e s e r v e d m a t e r i a l  s o l i d matter  were  injections.  field;  greenhouse propagated clone  and  aliquots  s a m p l e s were a n a l y z e d u s i n g m e t h a n o l - p r e s e r v e d i n the  to  in Table V r e f l e c t  DMT-containing admixture p l a n t s .  collected  heat  100 ml  through glass  25 ml w i t h m e t h a n o l . Ten y l  o n t o t h e HPLC.  four  w i t h 2x  The c o m b i n e d  filtered  e a c h sample were made, and f i g u r e s these  the  the  stems were g r o u n d  and 5 g was e x t r a c t e d  under vacuum,  volume•adjusted  caapi  of  low  for  material  are  on stem s a m p l e s w h i c h had been d r i e d under  were c o n c e n t r a t e d  viridis  given  each  was  in a Wiley m i l l  c.  previous  cultivars  powder  mean of  As w i t h t h e  this  injections.  Banisteriopsis  the  in a p l a n t  injected  twice.  content  of  of  e a c h sample were p r e p a r e d , and  caapi  out  methanol  of  Banisteriopsis  (<60°)  the  o n t o t h e HPLC.  two r e p l i c a t e s  replicate  M1 a l i q u o t s  treated  s a m p l e s . The m e t h a n o l original  leaves  methanol  in  leaf  shaker were the  extracts used  to  99  preserve  the  samples,  a known v o l u m e . stored a t . 4 ° aliquot the  of  C. For  The r e s i d u e  layer  material  was  was  further  1 N HCI  an  g dry  2  2  The o r g a n i c  evaporator.  anhydrous N a S O „ , 2  methanol,  evaporated  organic  t o pH 8-9  with  w i t h 3 x 5 ml C H C 1 . 2  2  It  was  and f i l t e r e d  through glass  purified alkaloid  Concentration  of  were c o m b i n e d , d r i e d  to d r y n e s s ,  fraction  into  c o n s t r u c t e d by  DMT s t a n d a r d .  given  in  ul a l i q u o t s the  of  HPLC.  injecting  i n T a b l e VI  are  known amounts  means ± s . e .  of  of 2 to  injections.  GC/MS  t h e major  The i n s t r u m e n t interfaced  indole  base d e t e c t e d was  u s e d was a F i n n i g a n model  with a Perkin-Elmer  Sigma  capillary  column  temperature-programmed  (J&W  1020 a u t o m a t e d GC/MS  3B gas c h r o m a t o g r a p h .  Scientific).  from an  confirm  N,N-dimethyItryptamine.  c h r o m a t o g r a p h was e q u i p p e d w i t h a 30 m x .25mm SE-54 silica  with 2  over  D M T - c o n t a i n i n g a d m i x t u r e s were s c r e e n e d by GC/MS t o that  then  was d e t e r m i n e d by c o m p a r i s o n  with a standard curve  5 replicate  Twenty  were i n j e c t e d  the DMT p r e s e n t  Figures  redissolved  wool.  The  and t h e  2  was b a s i f i e d  of  round-  and f i l t e r e d . 2  layers  wt  t o a 50 ml  on a r o t a r y  to  and  b a s i f i e d t o pH 11-12 w i t h 2 N NaOH and e x t r a c t e d  x 5 ml C H C 1 .  D.  2.0  1 x 5 ml C H C 1 ,  d i s c a r d e d . The a q u e o u s l a y e r and e x t r a c t e d  to  transferred  to dryness  was washed w i t h  3  were s e a l e d  equivalent  shaken w i t h 5 ml of  filtrate  evaporator  alkaloid quantitation,  extract  and e v a p o r a t e d  s a t u r a t e d NaHC0  this  p u r p o s e s of  the m e t h a n o l i c  bottom f l a s k  in a r o t a r y  The c r u d e m e t h a n o l e x t r a c t s  freeze-dried leaf  acidic  and c o n c e n t r a t e d  initial  fused  The c h r o m a t o g r a p h  temperature  of  The  was  180° t o a  100  final  temperature  of  min a f t e r  injection  was  detector  250°,  helium.  250°. of  the  extracts  of  system.  (RIC)  Under  the  10 m i n , base peak Diplopterys  260°  the  cabrerana  up i n a manner Psychotria with  reagent.  positive  time  traces  of  Martello reagents,  A p p e a r a n c e of  then  that  the  of  the  NaHC0  of  the  [19].  [18].  After  Valser's,  or  was  the  was  for  used  worked  the were  tested  Dragendorff's or a  heavy  indicated  reagents  testing  alkaloids  interpreted  turbidity  and and e x t r a c t e d  layers  the  Plants  filtrate  as a possible  used i s  w i t h the  given  t o pH 8-9  w i t h 3 x 5 ml C H C 1 ;  were e v a p o r a t e d  in  precipitation  were b a s i f i e d  b a s i f i e d t o pH 11-12 and e x t r a c t e d  The c o m b i n e d o r g a n i c  in  9.5-  had a mass  and t h i s  acidic  reagent  slight  of  Material  aqueous s o l u t i o n s 3  time  & Euler  a marked t u r b i d i t y  C o m p o s i t i o n of  acidic  data  for  d e s c r i b e d above  Meyer's,  reaction;  & Farnsworth  ion  were s c r e e n e d  in methanol,  either  on a d d i t i o n  with saturated was  either  alkaloid.  Eluted  standard.  Uncommon A d m i x t u r e  Farnsworth  to  extracts  w i t h the  was  purified  reconstructed  leaf  identical  & TLC of  identical  alkaloid  the  188. The i n d o l e base p r e s e n t  samples. A l i q u o t s  precipitate  gas  by t h e mass s p e c t r o m e t e r  was p r e s e r v e d  1-2 d r o p s of  the  and P s y c h o t r i a  t h e method of  analysis  or of  3  temperature  C . The c a r r i e r  in  The uncommon a d m i x t u r e p l a n t s  in  block  initiated  s a m p l e s were i n j e c t e d .  as p e a k s  5 8 , M*  A l k a l o i d Tests  following  3°/min  c o n d i t i o n s , DMT had a r e t e n t i o n  s p e c t r u m and r e t e n t i o n  E.  leaf  generated  these  Injector  of DMT s t a n d a r d ,  compounds were d e t e c t e d chromatogram  sample.  temperature  One M1 a l i q u o t s  alkaloid  The ramp r a t e was  2  w i t h 2 x 5ml to dryness  2  it  CH C1 . 2  under  2  101  vacuum,  and the  aliquots  of  residue  this  final  p r e c o a t e d Polygram  taken  up i n  methanol  silica  gel  2.0 ml m e t h a n o l .  fraction  plates  UV  were a p p l i e d 2 5  ",  and t h e  developed  i n one d i r e c t i o n  in butanol/acetic  Following  development,  plates  s h o r t - and long-wave m o d i f i e d reagent  III.  Results  A.  shows t h a t  and s p r a y e d w i t h  t h e TLC p r o f i l e s  t h e major  Fidel  # 1 & 2,  there  is  also  of  constituents  vary  b a t c h e s made by t h e  and Don J u a n , little  ayahuasqueros.  in  are  the c o n s t i t u e n t s  Harmine,  harmol,  of  samples,  s a m p l e s save one  significant constituents  samples except Ehrlich-positive were i d e n t i f i e d  authentic  standards  T r a c e s of  other  samples;  it  is  fluorescent assumed t h a t  is  significant,  Don  similar,  and  of  brews made and  /3-carbolines was not  detected  Dimethyltryptamine  Known  by c o m p a r i s o n w i t h a m i x t u r e "analogue",  upper  left  these  represent  Absence of this  DMT i n is  the  of  in F i g .  compounds were a l s o d e t e c t e d  since  was  from T a r a p o t o . No o t h e r  s p o t s were d e t e c t e d .  (ayahuasca  undetermined s t r u c t u r e . Tarapoto  that  # 1).  to  (cf.  harmaline,  while harmalol  (Don M i l t o n  (Fig.  f r o m sample  generally  the  in a l l  samples  little  present  in a l l  examined under  Dragendorff's  eight  were f o u n d t o be t h e major  found  4:1:1.  same a y a h u a s q u e r o  # 1 & 2)  variation  the  tetrahydroharmine  i n any  was  Brews  different  by d i f f e r e n t  plate  and D i s c u s s i o n  Ayahuasca  sample;  UV l i g h t ,  to  acid/water  were a i r - d r i e d ,  M1  [20].  C o m p a r i s o n of 6)  the  Five  6)  i n most  / 3 - c a r b o l i n e s of  the  sample  only  from  sample  in  which  102 AYAHUASCA  "ANALOGUE"  DON FIDEL - SAMPLE ;? 1 PUCALLPA  DON FIDEL - SAMPLE PUCALLPA  2  e  ©  DON JUAN - SAMPLE- if 1 PUCALLPA  e  ®  DON JUAN - SAMPLE ? 2 PUCALLPA  *  DONA RIOS - SAMPLE // 1 IQUITOS  ® ©  DON WILFREDO - SAMPLE # 1 TARAPOTO  0  0 Cs)  (9  9  0  ®  DOM MILTON - SAMPLE // 1 IQUITOS  DOM SOLON -- SAMPLE » 1 IQUITOS  9  A  $  <E+)  ®  3 •  CP (§0  <9  F i g u r e 6 - TLC A n a l y s i s o f P e r u v i a n A y a h u a s c a Samples A • • D O T •  Dimethyltryptamine(DMT) Harmine Harmaline Harmol Tetrahydroharmine Harmalol Unknown  Solvents: I. e t h e r / 2 - b u t a n o r . e / 28% NH OH 5:4:1 (upper phase) I I . n-propanol/1.5% NH„OH 9:2 Plates: 0  Polygram s i l i c a g e l G F " (Brinkmann I n s t r u m e n t s ) (E+) = p o s i t i v e t o E h r l i c h ' s Reagent 25  1 03  Psychotria than  carthaqenensis  was e m p l o y e d as t h e a d m i x t u r e  t h e more commonly u s e d P. The q u a n t i t a t i v e  from b a t c h t o b a t c h , proportions  of  viridis.  HPLC a n a l y s i s  p r e p a r e d by two a y a h u a s q u e r o s either  total  (Table  weight  differences wt).  basis  in a l k a l o i d  The sample  content  (Table  content  and 7.6%  and T a r a p o t o g e n e r a l l y differed  in  for  the the  cultivar  in  the  employed to p r e p a r e  the  cultivar  exposure  to  however,  that  sunlight,  consistently harmine that B.  all  caapi  to of  all  of  is  the  tetrahydroharmine these  cultivar  collaborate  total  total  alkaloid  to  the  drink,  type  of  or t o  or d i f f e r e n t be i n v o l v e d .  in the  10.6% was  from  Iquitos  levels,  and  is  the  B.  the  Table  harmine  preparation  of  of  their  other  caapi  type  III  of  soil  of  shows,  p r o p o r t i o n s of  T h i s may  indicate  from t h e  same c u l t i v a r . uncle  from  and  Pucallpa  same r e l a t i v e  the  also  The  conditions  s a m p l e s from  the  dry  t h e method of  such as  to harmaline.  of  compared on  constituents.  s a m p l e s were p r e p a r e d e i t h e r or c l o n e s  the  alkaloid  s a m p l e s and t h o s e  ayahuasca  show a p p r o x i m a t e l y  in  considerable  76% was h a r m i n e ,  variables,  be s u r p r i s i n g s i n c e Don J u a n often  the  may a l s o  or  contents  r e l a t i v e p r o p o r t i o n of  grown,  variation  methanol-diluted  highest  different  P e r u c o u l d be r e l a t e d  in which  alkaloid  which  Pucallpa  Environmental  The  was DMT. The s a m p l e s  in  preparation.  little  ( e x p r e s s e d as mg a l k a l o i d / g  had l o w e r  difference  shows  samples  a l k a l o i d content  had t h e  p r o p o r t i o n s of  tetrahydroharmine r e g i o n s of  of  undiluted  T h e s e s a m p l e s showed  from P u c a l l p a  tetrahydroharmine,  reason  IV).  ( 7 5 . 7 mg/g d w t . )  five  III).  s a m p l e s were l y o p h i l i z e d and t h e i r a dry  of  in Pucallpa  in  constituents  rather  same  T h i s would  Don F i d e l brews.  and  not  they  HPLC QUANTITATION Name of Sample  harmol  harm 1ne  Don Fide101  tr tr  3 .85 ( .01 )  Don Fidel#2  tr  4 .64 ( .3)  Don F1del*3  tr  Don Juan#1 Don Juan#2 Average Alkaloid contentt  TABLE I I I OF UNDILUTED  AYAHUASCA  SAMPLES  A1ka1o i d C o n c e n t r a t i on ( m g / m l ) *  %  %  DMT  0 .3 (. 1 )  5  0 .61 ( .01)  10  5 . 85 ( . 19)  24  0 . 45 (. 1 )  6  0 .6 ( . 1)  8  7 . 48 ( • 16)  1 .94 ( .06)  30  0. 34 ( 2)  5  0.. 7 ( .2)  1 1  6 . 38 ( . 1 )  66  1 . 73 (. 1 )  21  0. 51 (. 16)  6  0. 51 (. 16)  6  8.05 ( .36)  5 .51 . ( .26)  67  1 .67 ( .07)  20  0. 4 1 (. 14)  5  0. 6 (. 2)  7  8 . 19 ( . 28)  4 .67 ( .2) .  65  1 .60 ( .08)  22  0. 4 1 (.06)  6  0. 6 (.06 )  8  7 . 28 ( .23)  THH  %  66  1 .06 ( .05)  18  62  1 . 77 ( . 1)  3.4 ( 2)  53  tr  5. 3 .36) (-.  tr  •  harma11ne  * f i g u r e s g i v e n a r e mg a l k a l o i d / m l o f u n d i l u t e d parentheses: percentages a r e % total a l k a l o i d , t a v e r a g e b a s e d o n n=18 r e p l i c a t e injections.  sample,  total  ± s. e . . shown i n  TABLE IV HPLC QUANTITATION OF LYOPHILIZED AlkaloidI  Sample & Origin  harmine  %  AYAHUASCA  Concentration  SAMPLES  (mg/g d.wt. ).*  harmaline  %  DMT  %  total  1 1  4. 2 ( .22)  5  5.8 ( .5)  8  75 . 6 (3.3)  7. 2 (1.7)  1 1  66.8 (3.4)  THH  Don Fldel/M Pucallpa  57 .6 ( .33)  76  Don Sol on Iqu i t o s  28 . 3 (1.3)  42  25.5 (1.4)  38  5.8 ( .9)  9  Don Wi 1 f r e d o Tarapoto  14 . 4 ( .44)  50  10.5 (1.2)  36  4. 2 ( .3)  14  n.d. t -  Don Ml 1 t o n Iqu1tos  10. 2 ( .32)  33  Dona R los Iqui tos  8.6 ( .3)  27  Average Alkaloid Content*  23 .8 (4.2)  51  8.0 ( .53)  10. 2 (1.7)  9.6 (1.8)  11.1 (1.9)  29 . 1 ( 1  33  5.2 ( 1.7)  16  5. 7 18 ( 1 .6)  31.3 (5.6)  31  6.3 ( 1.8)  20  7 .O (2.1)  22  31.5 (5.6)  24  5. 1 ( .5)  1 1  14 6.4 ( .74)  46 . 9 (4.9)  * f i g u r e s g i v e n a r e mg a l k a l o i d / g d. wt. o f l y o p h i l i z e d s a m p l e : s t a n d a r d errors (n=4) a r e g i v e n in parentheses. Percentages given are % total alkaloid. t n. d. = n o t d e t e c t e d * b a s e d o n n=16 r e p l i c a t e injections  1 06  Summarizing the Rivier  and L i n d g r e n  ayahuasca  contains  harmine,  10 mg i s  some t e n  to  carbolines Chapter  II)  [4]  of  state  a total  of  their  that  times  less  than  it  is  well within  a s MAO i n h i b i t o r s .  the  t h r e s h o l d d o s e f o r DMT when t h i s  intramuscularly be l o w e r  but  it  is  in  Rivier  & Lindgren  the  Twenty  range a t  f i v e mg i s  compound i s  possible  [4]  that  conclude:  new p h a r m a c o l o g i c a l e x p e r i m e n t s  u n d e r s t a n d i n g of  the  hallucinogenic  30 mg  which  the pure  under c o n d i t i o n s of MAO i n h i b i t i o n .  findings, results,  [21]  which  dosage a t  active  effective  of  and 25 mg, DMT. T h i s  the  are  studies,  200 ml d o s e of  65 mg a l k a l o i d ,  hallucinogenically  although  quantitative  a typical  tetrahydroharmine,  thirty are  results  for  action  of  is  t h e (3-  form, which  just  (cf. they  above  injected  the  t h r e s h o l d may  Commenting on  "In  v i e w of a  is  their  these  better ayahuasca  seem  necessary." The a l k a l o i d  levels  (Table  III)  [4]  samples c o l l e c t e d  in  order  levels  on t h e (based  samples)  a  the  contains  728 mg t o t a l  This  100 ml d o s e of  is  w e l l above  considerably carbolines. Pucallpa to  below In  the  ceremonies  of  the  of  rarely  upper Purus  Purus  typical exceeds large  for  an  five Table  harmine,  III) 160  and 60 mg i s DMT.  DMT but  ingested  75 ml and i s differences  least  the  (cf.  dose l e v e l  dose  ayahuasca  of  Pucallpa  Lindgren  by a t  467 mg i s  harmaline,  from  and  ayahuasca  which  t h r e s h o l d dose  the  samples  on t h e a v e r a g e  41 mg i s  55-60 m l . The r e l a t i v e l y  content  upper R i o  the h a l l u c i n o g e n i c  practice  five  Pucallpa  alkaloid,  tetrahydroharmine,  the  r e p o r t e d by R i v i e r  magnitude. Thus,  mg i s  of  exceed the  found in  in  is  still  for  the  in  the  usually the  /?-  closer  alkaloid  a n a l y z e d by R i v i e r  and  107  L i n d g r e n and the  Pucallpa  s t u d y may be r e a d i l y of  preparation  stems of and  in  layers  two  Banisteriopsis  packed in a of  of  The m i x t u r e  cut  metal  into  is  is  hours. water  is  boiled  for  boiled  for  batches  are  strainer  times  a much l o n g e r  during this  combined, allowed  the  has  been c o n c e n t r a t e d  six  liters  of  may be kept or  beer  B.  bottles  to c o o l ,  of  effect. based  stoppered with  of  its  on t h e  types  of  and  further  processing. but  approximately  is  the 10-15  fresh separate  through a  removed from ayahuasca  a low  fire  original  is  until  volume.  process;  refrigeration  the  it  Five  or  these in  wine  corks.  that  caapi  Cultivars  we i n t e r v i e w e d  w h i c h were c l a i m e d t o v a r y  in part  strained,  strained  Banisteriopsis  of  and  are  from t h i s  in Peru recognized s e v e r a l  The d i f f e r e n t i a t i o n  length  water  and f i l t e r e d  the  obtained  the ayahuasqueros  studies  ayahuasca  are  of  similarly  material  half  method  alternating  and r e p l a c e d w i t h  s i x months w i t h o u t  A l k a l o i d Content  All field  up t o  out  p o t and simmered o v e r  ayahuasca  for  with  b o i l i n g p r o c e s s . The  The p l a n t  to about  the  s e c t i o n s , .crushed,  time,  c o o k i n g p o t and d i s c a r d e d , and t h e n into  in  900 cm i n  t h e n consumed w i t h o u t  or c h e e s e c l o t h .  p o u r e d back  about  one h o u r ,  starts  present  upper Purus method,  together  The water may be d r a i n e d o f f several  the  s p p . Ten l i t e r s  The method employed i n P u c a l l p a mixture  In  short  vessel  in the  differences  totaling  Psychotria  a d d e d and t h e m i x t u r e cooled.  regions.  caapi  are  15 l i t e r  leaves  analyzed  e x p l a i n e d by t h e  the  1-4 cm d i a m e t e r  ayahuasca  these  different  in t h e i r varieties  admixture p l a n t s  d u r i n g our "kinds"  of  psychological of  ayahuasca  was  w h i c h were a d d e d ,  1 08  and i n p a r t types  of  on t h e  type  Banisteriopsis  of  B.  caapi  caapi  w h i c h was u t i l i z e d .  were g e n e r a l l y  r e c o g n i z e d by  practitioners  and were d i s t i n g u i s h e d by d i f f e r e n t  e.g.,  ayahuasca,  "cielo"  Some c l a i m e d  vine  applied either  to  (the  the  B.  Presumably  these  cultivars,  races,  Banisteriopsis  caapi  collected,  and t h e  d e t e r m i n e d as  stems of  that  for  there  The l o w e s t total  is  of  the  level  was  two or  caapi  are  beverage  three  to  or  four  voucher caapi  k i n d s of  by t a x o n o m i c  A n d e r s o n & B. of  the  Gates,  alkaloid  vernacular  B.  name i s  in  the  unknown has samples  correlation  recognized c u l t i v a r s ,  light,  water,  and o t h e r  growth  of  amounts of  alkaloids  are  in  same g e n e r a l  caapi  the  in  of  dried  specimen shown  (Table  f o u n d i n DMK#126 which c o n t a i n e d  t o be no c o n s i s t e n t  we  been  specialists  p l u s one  between  which  University  levels  the  B.  of  caapi  s p e c i m e n s have' a l l  affecting  i n the  from  different  or m o r p h o l o g i c a l v a r i e t i e s  w h i l e DMK#125 c o n t a i n e d t h e h i g h e s t  soil,  made  kinds.  referable  conditions  detected  of  of  V).  1.7 mg/g  level,  however.  o b s e r v e d p r o b a b l y has more t o do w i t h t h e  and t h e  ayahuasca.  indiscriminately the  recognized v a r i e t i e s  with p a r t i c u l a r  variation  or t o  considerable variation  mg/g. T h e r e a p p e a r s  plant,  R.  which the  alkaloid,  content  three  relevant  HPLC a n a l y s i s  three  (DMK#125)  the  (W.  is  adjectives,  "rumi"  kinds  these  T h e r e were no o u t s t a n d i n g m o r p h o l o g i c a l  Banisteriopsis  the M a l p i g h i a c e a e Michigan).  B.  or c h e m i c a l  between  vine  with only  " k i n d s " of  caapi.  ten  term a y a h u a s c a  but most were f a m i l i a r  differences  ayahuasca,  t o d i s t i n g u i s h as many as  Banisteriopsis  it)  "lucero"  Several  13.6  alkaloid The  age of  the  environmental  the p a r t i c u l a r  s p e c i m e n . The  range as  s a m p l e s a n a l y z e d by R i v i e r  those  & Lindgren  HPLC QUANTITATION Col l e c t i o n Name. & Origin'  #.  DMK #110 "c 1 e 1 o" Tarapoto  DMK #124 "Pucahuasca" Tarapoto  TABLE V OF BANISTERIOPSIS CAAPI DMK  .#125  CULTIVARS  DMK #126 "c i e1 o" Iqu i t o s  Iqu1tos  A1ka1o1ds Detected (mg/g d wt)  Plowman 604 1 " c i e 1 o" Tarapoto-1976 (UBC-1982)  DMK #128 " rum i " Iqu i t o s  ' .  Harm i ne  5.3  72%  5.9  47%  6.35  47%  0.57  34%  4 . 4  51%  THH  0.95  13%  3.3  26%  1.95  14%  0.25  15%  1 . 45  17%  1.3  47%  harma11ne  1.1  15%  3.2  26%  3.8  28%  0.75  44%  2 .07  24%  .5  18%  harmo1  0.05  .7%  0.06  .5%  1. 2  9%  0 . 1  6% 0.65  -  . 35  2%  n.d.  n.d.  1 .7  8.6  harma1ol  n .d. +  trace  7.4  12.5  1 .0  8%  .01  -  n.d.  total a 1ka1o1ds  * n.d.  = not detected  13.6  2. 8  35%  .3%  1 10  [4],  Further  clarification  of  or m o r p h o l o g i c a l d i f f e r e n c e s B.  caapi  cultivars  many d i f f e r e n t edaphic,  of  q u e s t i o n of  between  would r e q u i r e  individuals  and o t h e r  this  possible  recognized types  a systematic  each  environmental  type  of  s a m p l i n g of  as p o s s i b l e ;  factors  chemical  as  climatic,  should a l s o  be  considered. In  most of  the  B.  caapi  cultivars  constituted a greater  p r o p o r t i o n of  the  than  brews.  B.  in the  harmaline  ayahuasca  consistently  alkaloids,  while  the  that  p r o c e s s of  the  brews the  total  may r e s u l t  harmaline  C.  the  represented  in the  5 - 1 5 % of  In  ayahuasca  alkaloids  examined, total  the  it  o x i d a t i o n of  t o t h e more a r o m a t i c  A l k a l o i d Content  of  total  was  approximately  samples. T h i s  b o i l i n g and c o n c e n t r a t i o n  i n the  content  cultivars,  25-50% of  i n most  alkaloid  caapi  samples,  harmaline  of  indicates  the  a significant  derivative,  ayahuasca  fraction  of  harmine.  Ayahuasca Admixture  Plants  1. D M T - c o n t a i n i n g A d m i x t u r e s In  Peru,the admixture plant  preparation P.  of  ayahuasca  We e n c o u n t e r e d o n l y  preferred  Psychotria  alkaloids  of  any  Tarapoto)  however,  frequently  t o be P s y c h o t r i a  viridis  one a y a h u a s q u e r o d u r i n g o u r  t o use a n o t h e r  i d e n t i f i e d as  appears  e m p l o y e d most  species  of  Psychotria,  carthaqenensis  k i n d were d e t e c t e d  in  Jacq. this  all  of  the  P.  viridis  N,N-dimethyltryptamine  as  the  s i n g l e major  in R.  fieldwork  collection  collections  compound was c o n f i r m e d by GC/MS and c o m p a r i s o n of  & who  tentatively  Interestingly,  base.  the  (DMK#109,  contained  Identity its  no  HPLC  of  the  OMT CONTAINING  C o l 1 e c t i o n <* . Name. & Origin  TABLE VI ADMIXTURE PLANTS: ANALYSIS BY T L C . HPLC. 8. GC/MS  DMK#21 Psychotr ia viridis "chacruna" Iqu i t o s  DMK#108 Psychotr i a viridis "su i j a" Tarapoto  DMK#109 Psychotr ia carthagenens i s "yage-chacruna" Tarapoto  DMK#139 Psychot r i a viridis "chacruna" Pucallpa  Plowman 6040 D ipiopterys cabrerana "chagro-panga" Tarapoto  n.d.t  38  42  4 1.3  1  DMT S tandard  TLC: solvent  1 hRf*  42  42  solvent  2 hRff  23  24  27  25  25  +(blue)  -M b 1 u e )  +(blue)  +(violet )  ••(blue)  18.4( . 1)b  18.3(.03)  18.7(.05)  18.4(15)  19 . 1  mg/g d wt .  1.58(.3)  1 .02( .04 )  1. 2( . 17)  1 .74( .4 )  GC/MS: trace constituents  n.d.  n.d.  2-MeTHpC  5-H0DMT  reaction to E h r l i c h ' s reagent  HPLC : Ret.  t i me ( m i n )  * S o l v e n t 1: e t h e r / 2 - b u t a n o n e / c o n c N H » 0 H 5:4:1 ( u p p e r hRf= Rf x 100 t S o l v e n t 2: n - p r o p a n o 1 / 1 . 5 % N H « O H 9:2 $ n.d.= n o t d e t e c t e d b Figures i n parentheses are standard errors  n.d.  phase):  M' = 188 m/z 58=1007,  1 12  retention of  time,  TLC hRf  an a u t h e n t i c  standard  analyzed contained and  1.6  and E h r l i c h ' s  mg/g d r y  fairly  wt.  fruits  or  stems of  i n any  of  the  (Table  in  P.  leaves.  viridis.  to  that  reported  detected. 6040),  [4]  A single  for  also  leaves  of  the  P.  terms  viridis  (1976)  of  higher  admixture, uncommon;  this this  species  C o l o m b i a and E c u a d o r originally Pastaza viridis,  brought  in Ecuador or  cabrerana  collection  less  this  of  were f a m i l i a r  w i t h D.  in  of  the  T.,  was  for  analysis with a  Plowman  6040 had an  to  dried  leaf  extracts 6040  fact  6040 was  Plowman  pers.  P e r u and few  in Peru in  collected  is  Southern  6040 was  cutting  comm.,  from t h e  1980).  Rio  Psychotria  carthagenensis  its  in-  ayahuasca  of my i n f o r m a n t s  under  than  indistinguishable  cabrerana  Psychotria  cabrerana  (Plowman  of  usual admixture  and i n  was  s p e c i m e n . Plowman  A l t h o u g h Plowman  (Plowman,  choice  DMK #139,  DMT (1.74, mg/g d w t . )  otherwise  frequently,  oco-yage.  of  Diplopterys  [22]  in  extract  b e i n g u t i l i z e d as an  is  1  detected  together  identical  t o T a r a p o t o as a l i v e  a d m i x t u r e s of  panga or  but  was  use of  were  e x c e p t i o n of  The a l k a l o i d  levels  alkaloid content.  i n T a r a p o t o where i t  was d e t e c t e d  was a v a i l a b l e  was e s s e n t i a l l y  samples,  DMT, between  alkaloids  Diplopterys  greenhouse propagated c l o n e s  contained s l i g h t l y  that  samples  2-methyl-tetrahydro-/3-carboline  5-hydroxy-DMT.  original  with  w i t h a mass s p e c t r u m c o r r e s p o n d i n g  sample of  i o n chromatogram t h a t  the  No o t h e r  contained N,N-dimethyltryptamine  t r a c e amount of  of  No a l k a l o i d  the M a l p i g h i a c e o u s a d m i x t u r e ,  and t h i s  viridis  amounts of  samples w i t h the  in which a t r a c e c o n s t i t u e n t  reaction  The P.  substantial  the  Psychotria  VI).  color  are in  common names,  the  Peru chagro-  11 3  2.  Uncommon A d m i x t u r e  Ayahuasca containing cabrerana  is  usually  admixture  plants  are  utilized,  tryptamine-containing these  admixtures  literature chemical appear  p r e p a r e d u s i n g one of  or a P s y c h o t r i a  admixtures  mentioned above,  sp.;  less  either  admixtures,  have been  properties,  be a p r o m i s i n g a r e a  collections  were made of  in place  identified  biodynamic  plants  (cf.  which  to ayahuasca  Teliostachya  has  an a d m i x t u r e ,  but  (Menispermaceae) previously these  using a l k a l o i d  characterization.  species  palmatine,  has  recently  a typical  benzylisoquinoline Menispermaceae. alkaloids  Abuta  odorata  their  Appendix I).  This  research.  tests  and TLC  to permit  which  reported of  [24] the  is  one of  surprisingly  sparse.  One s t u d y  found that  of  epinephrine  (DMK  #74).  contain  the  of  effect  an  the  investigations [25]  its  further  bis-  characterizes  Although palmatine  for  (Table  giving  to  not  from  were s c r e e n e d  collection  base  these,  [23]  have  Plant material  nature,  the  informants  One of  (Verbenaceae)  in  inhibited  Three  by  VII).  was A b u t a g r a n d i f o l i a  been  of  would  qrandifolia  was a v a i l a b l e  quaternary  family  them. Many  known of  in methanol,  The o n l y  test  the  ethnobotanical  (Table  precipitation  material  unambiguously p o s i t i v e This  two,  preserved  of  were s t a t e d  r e p o r t e d as a d m i x t u r e s .  Insufficient  chemical  other  with  other  been d i s c u s s e d by S c h u l t e s  and C o r n u t i a  collections,  alkaloids VII).  been  the  the  further  t o be u s e d as a d m i x t u r e s lanceolata,  in  l i t t l e * is  for  Diplopterys  commonly, h o w e v e r ,  or  although  t h e DMT—  either  in conjunction  [2,4,22,23,]  or  to  Plants  commonest  pharmacology palmatine  on b l o o d p r e s s u r e  of  are  as  TEST FOR ALKALOIDS C o l 1 .H Genus: species: fam i 1 y : Part ext'd(g)  TABLE V I I IN UNCOMMON ADMIXTURE  PLANTS  DMK*74 Abuta grand 1 f o l i a Men 1 s p e r m a c e a e  DMK#22 Teliostachya 1anceolata Acanthaceae  DMK0 119 Cornut i a odorata Verbenaceae  DMK# 1 Just i d a pectora1i s Acanthaceae  bark(2 )  1eaves(2.7)  1 eaves(5 . 7 )  1eaves(1.2)  React i on t o : Meyer's Va1ser's  rgt.  ++  -  +  -  rgt  ++  -  +  -  Dragendorff's  ++  TLC: Dragendorff's*  ++  F1uorescent Spots  detected:  L o n g wave UV  +  Short  +  wave UV  * modified  f o r TLC a c c o r d i n g  t o Stahl [21]  1 1  rabbits,  on t h e  isolated  seminal v e s i c l e  hind-leg;  its  effect  5-hydroxytryptamine  of  stomach.  derivative  rat  Palmatine  Both a l k a l o i d s  also  dl-tetrahydropalmatine on i s o l a t e d  rat  had ACTH and b a c t e r i c i d a l  carbolines  w h i l e o t h e r s may be s y n e r g i s t i c .  brain,  causes  an  increase  w h i l e harmine causes  acetylcholine inhibits  in b r a i n ;  the ATP-Mg  isolated adrenal of  of  0-carbolines,  the  the  bark  effect.  palmitine  of  VII.  is  to  other  there  effects  of  are  the  whole  in strongly  the  to  doubt t h a t  action  addition  c o u l d modify  needed i n o r d e r  into  overall  the  t h e p h a r m a c o l o g y of  Justicia  pectoralis  var.  its  this  suggested that  (cf. it  is  stenophylla  Chapter VI,  and [ 2 7 ] )  may be u s e d by  itself  No t r y p t a m i n e s  or a l k a l o i d s  detected  i n our c o l l e c t i o n  extracts  of  this  Just ic ia p e c t o r a l i s  coumarin d e r i v a t i v e derivative  of  betaine  their  also  included in  Table  is  not  u s e d as  of  and t h e s e  a s an  an  any  other  species.  indicate  Chapter VI,  & [28]).  authors  type  the have  were  GC/MS a n a l y s i s  that  to  hallucinogenic  it  contains  u m b e l l i f e r o n e and t h e q u a t e r n a r y (cf.  and  to c l a r i f y  a d m i x t u r e but has been r e p o r t e d as an a d m i x t u r e  snuffs,  of  ayahuasca.  (Acanthaceae)  snuff.  0-  in  Whether  to ayahuasca  these  instance'  or a n t a g o n i s t i c  pectoralis  Virola  For  and  activity.  norepinephrine  [26].  Just ic ia  ayahuasca  colon,  the  decrease  of  seems l i t t l e  of  of  hand, harmine  vesicles.  investigations  the  effects  the  Some of  5HT c o n c e n t r a t i o n  agonistic  admixture p l a n t s  contribution  the  a significant  Abuta q r a n d i f o l i a  Further  many o t h e r  in  on t h e  medullary  effect  to  dependent uptake  ++  uteri,  activity.  may be a n t a g o n i s t i c  toad  inhibited  exhibited anticholinesterase  properties  harmaline  and on t h e  c  of the  nitrogen  11 6  IV.  Summary  The a l k a l o i d a l cultivars  of  B.  qualitatively dimensional  constituents  caapi  of  and a v a r i e t y  and q u a n t i t a t i v e l y  thin-layer  l i q u i d chromatography  a number o f of  (HPLC)  admixture p l a n t s  investigated  chromatography as  (TLC)  for  alkaloids  /3-carbolines to account  (GC/MS).  the  doses t y p i c a l l y  however  threshold level  is  for  assuming that visceral  it  of  total  alkaloids  batches  different B.  caapi  environmental  of  Variation  admixtures;  only  DMT was traces  of  at  the  ayahuasca,  both  blockade  p r e p a r e d by  the  i n terms of  amount  in a l k a l o i d  constituents.  content  genetic  concentrations viridis,  to differences  and i n one in  in  collection  Psychotria  base d e t e c t e d  alkaloids  of  of DMT were f o u n d  detected  s i n g l e major other  of  s a m p l e s p r e p a r e d by  but was not  the  of  individual  than a c t u a l  Psychotr ia  Diplopterys cabrerana,  of  o f DMT would be  f o u n d but may be due  rather  of  ayahuasca  by t h e  ayahuasca  found in  Substantial  collections  carthagenensis.  action  consistent,  was a l s o  factors  between c l o n e s . several  was  practitioners. cultivars  of  and p r o p o r t i o n s of  Considerable variation  screened  i n most s a m p l e s ; a p p a r e n t l y DMT  can be o r a l l y - a c t i v a t e d  same p e r s o n were r e m a r k a b l y  of  concentration  the h a l l u c i n o g e n i c  MAO. D i f f e r e n t  were  samples were, i n s u f f i c i e n t  properties  the  w e l l above t h e responsible  chromatography/  t e s t s and T L C . The l e v e l s  hallucinogenic  used,  methods.  Some a d m i x t u r e p l a n t s  f o u n d i n most a y a h u a s c a  for  were  and h i g h - p r e s s u r e  the a n a l y t i c a l  using p r e c i p i t a t i o n  brews,  u s i n g 2-  A d m i x t u r e s a m p l e s were a l s o a n a l y z e d u s i n g gas mass s p e c t r o m e t r y  ayahuasca  in  were p r e s e n t .  these Of  1 1 7  several  uncommon a d m i x t u r e  alkaloids, reaction.  only  Abuta  p l a n t s which  were s c r e e n e d  for  g r a n d i f o l i a gave an u n a m b i g u o u s l y  positive  1 18  V.  Literature  Cited  1.  S c h u l t e s , R. E. (1957) The I d e n t i t y of t h e M a i i p i g h i a c e o u s N a r c o t i c s of S o u t h A m e r i c a . H a r v a r d B o t a n i c a l Museum L e a f l e t s 18:1-56  2.  S c h u l t e s , R. E. (1972) E t h n o t o x i c o l o g i c a l S i g n i f i c a n c e A d d i t i v e s t o New W o r l d H a l l u c i n o g e n s . P l a n t S c i e n c e Bulletin 18:34-41  3.  G a t e s , B. (1979) New Names i n B a n i s t e r i o p s i s and D i p l o p t e r y s (Malpighiaceae) of the Guayana H i g h l a n d . B r i t t o n i a 3 1 : 1 0 8 - 9  4.  R i v i e r , L. & J . L i n d g r e n (1972) A y a h u a s c a , the S o u t h H a l l u c i n o g e n i c D r i n k : E t h n o b o t a n i c a l and C h e m i c a l Investigations. Economic Botany 2 9 : 1 0 1 - 1 2 9  5.  D e u l o f e u , V . (1967) C h e m i c a l Compounds I s o l a t e d from B a n i s t e r i o p s i s and R e l a t e d S p e c i e s p p . 393-402 i n D. H. E f r o n , B. H o l m s t e d t , & N. S. K l i n e ( e d s . ) E t h n o p h a r m a c o l o g i c S e a r c h f o r P s y c h o a c t i v e D r u g s U. S. P u b l i c H e a l t h S e r v i c e P u b l i c a t i o n #1645  6.  A g u r e l l , S . , B. H o l m s t e d t , & J . E. L i n d g r e n (1968) A l k a l o i d C o n t e n t of B a n i s t e r i o p s i s r u s b y a n a . A m e r i c a n J o u r n a l of Pharmacy 140:148-151  7.  H a s h i m o t o , Y. & K. K a w a n i s h i (1975) New O r g a n i c B a s e s from Amazonian B a n i s t e r i o p s i s c a a p i . P h y t o c h e m i s t r y 14:1633-35  8.  H a s h i m o t o , Y. & K. K a w a n i s h i (1976) New A l k a l o i d s B a n i s t e r i o p s i s c a a p i . P h y t o c h e m i s t r y 15:1559-60  9.  S h u l g i n , A . T . (1976) P s y c h o t o m i m e t i c A g e n t s . C h . 4 i n M a x w e l l Gordon ( e d . ) P s y c h o p h a r m a c o l o q i c a l A g e n t s V o l . Academic P r e s s  of  American  from  IV.  1 19  10. U d e n f r i e n d , S . , B. W i t k o p , B. G . R e d f i e l d , & H. W e i s s b a c h (1958) S t u d i e s w i t h R e v e r s i b l e I n h i b i t o r s of Monoamine O x i d a s e : H a r m a l i n e and R e l a t e d Compounds. B i o c h e m i c a l P h a r m a c o l o g y 1:160-165 11.  B u c k h o l t z , N. S. & W. 0 . Boggan (1977) Monoamine O x i d a s e I n h i b i t i o n i n B r a i n and L i v e r P r o d u c e d by / 3 - c a r b o l i n e s : Structure-activity R e l a t i o n s h i p s and S u b s t r a t e Specificity B i o c h e m i c a l Pharmacology 26:1991-96  12. M c l s a a c , W. M. & V . E s t e v e z (1966) Structure-action R e l a t i o n s h i p s of / 3 - c a r b o l i n e s a s Mono-amine O x i d a s e I n h i b i t o r s B i o c h e m i c a l Pharmacology 26:1625-27 13. N a r a n j o , C . (1967) P s y c h o t r o p i c A l k a l o i d s p p . 385-391 i n D. H. op. c i t . 14.  P r o p e r t i e s of t h e Harmala E f r o n , e t al., (eds.)  P e n n e s , H. H. & P. H. Hoch (1957) P s y c h o t o m i m e t i c s , C l i n i c a l and T h e o r e t i c a l C o n s i d e r a t i o n s : H a r m i n e , WIN-299 and N a l l i n e . A m e r i c a n J o u r n a l of P s y c h i a t r y 113:887-92  15. Der M a r d e r o s i a n , A . H . , H. V . P i n k l e y , & M. F. D o b b i n s IV. (1968) N a t i v e Use and O c c u r r e n c e of N , N - d i m e t h y l t r y p t a m i n e i n t h e L e a v e s of B a n i s t e r i o p s i s r u s b y a n a . A m e r i c a n J o u r n a l of Pharmacy 140:137^147 16. A g u r e l l , S . , B. H o l m s t e d t , J . E. L i n d g r e n , & R. E. S c h u l t e s . (1968) I d e n t i f i c a t i o n of Two New / 3 - c a r b o l i n e A l k a l o i d s i n South American H a l l u c i n o g e n i c P l a n t s . Biochemical P h a r m a c o l o g y 17:2487-88 17.  R e p k e , D. B., D. T . L e s l i e & G . Guzman (1977) B a e o c y s t i n P s i l o c y b e , C o n o c y b e , and P a n a e o l u s . L l o y d i a 4 0 : 5 6 6 - 7 8  18.  F a r n s w o r t h , N. R. & K. L. E u l e r Procedure U t i l i z i n g T h i n - l a y e r 186-195  (1962) An A l k a l o i d - s c r e e n i n g Chromatography L l o y d i a 25:  19. M a r t e l l o , R. & N. R. F a r n s w o r t h (1962) O b s e r v a t i o n s on S e n s i t i v i t y of S e v e r a l Common A l k a l o i d P r e c i p i t a t i n g R e a g e n t s . L l o y d i a 25:176-185 20.  in  S t a h l , E., (1969) Handbook of T h i n - l a y e r 2 n d . e d . S p r i n g e r - V e r l a g , New Y o r k .  Chromatography  the  120  21.  S z a r a , S. (1957) The C o m p a r i s o n of t h e P s y c h o t i c E f f e c t of T r y p t a m i n e D e r i v a t i v e s w i t h t h e E f f e c t s of M e s c a l i n e and LSD-25 i n S e l f - e x p e r i m e n t s . p p . 460-467 i n S. G a r a t t i n i & V. G h e t t i ( e d s . ) p s y c h o t r o p i c d r u g s . E l s e v i e r , amsterdam.  22.  P i n k l e y , H. V. (1969) P l a n t A d m i x t u r e s t o A y a h u a s c a , t h e South American H a l l u c i n o g e n i c D r i n k . L l o y d i a 32:305  23.  S c h u l t e s , R. E . , (1979) New D a t a on t h e M a l p i g h i a c e o u s N a r c o t i c s of S o u t h A m e r i c a . H a r v a r d B o t a n i c a l Museum L e a f l e t s 23:137ff  24.  S e t o r de F i t o q u i m i c a , INPA', Manaus, Amazonas, B r a z i l . (1971) C h e m i c a l C o m p o s i t i o n of Amazonian P l a n t s . A c t a A m a z o n i c a 1:83-86  25.  C h ' e n , Mu-Ch'un & Chen-Yu C h ' i (1965) C o m p a r a t i v e P h a r m a c o l o g y of P a l m a t i n e and d l - t e t r a h y d r o p a l m a t i n e . Y a l Hseuh Hseuh Pao 1 2 : 1 8 5 - 9 2 . C i t e d i n C h e m i c a l A b s t r a c t s 6 3 : 3 4 9 2 g (19657  26.  Ho, B. T . (1977) P h a r m a c o l o g i c a l and B i o c h e m i c a l S t u d i e s with 0 - c a r b o l i n e A n a l o g s . C u r r e n t Developments in Psychopharmacoloqy V o l . 4:153-177  27.  C h a g n o n , N . , P. L e Q u e s n e , & J . M. Cook (1971) Yanomamo H a l l u c i n o g e n s : A n t h r o p o l o g i c a l , B o t a n i c a l , and C h e m i c a l F i n d i n g s . C u r r e n t A n t h r o p o l o g y 1: 2-74  28.  MacRae, D. & G . H. N. Towers (1984) J u s t i c i a p e c t o r a l i s - A S t u d y of t h e B a s i s f o r i t s Use as a V i r o l a S n u f f A d m i x t u r e . J o u r n a l of E t h n o p h a r m a c o l o g y . S u b m i t t e d .  29.  A k a b o r i , S. & K. S a i t o (1930) S y n t h e t i s c h e V e r s u c h e i n I n d o l - G r u p p e , V I I I . : S y n t h e s e von Harman und H a r m i n . Chemische B e r i c h t e 63:2245-2248  der  121  CHAPTER V :  I.  ALKALOID CONSTITUENTS OF ORALLY-ACTIVE MYRISTICACEOUS HALLUCINOGENS  Introduction  Various  species  of  the  genus V i r o l a  been e m p l o y e d by Amazon I n d i a n t r i b e s hallucinogenic Virola  trees  colorless  preparations  is  to  in a l l  resin  and g r o u n d i n t o  a snuff.  cases  The e x a c t  is  prepared without  the  [2],  the  use of  few  tribes  and t h e r e spp.  also  investigations  and r e l a t e d  genera  constituents  of  indole  related  bases  resin  ingested varies  that  and t h e  of  in  Vi rola the  snuff  form of  is in  are  added  the  widest  has  t h e Amazon B a s i n ,  of  effects. out  certain  [l], Vi r o l a  Extensive  on many  Virola  hallucinogenic  s n u f f s have been d e t e r m i n e d t o  tryptamine,  e.g.,  T r a c e amounts o f [6],  be u s e d as an h a l l u c i n o g e n ,  be  N,N-  [5,6].  from some s p e c i e s  to  while  related  known t o  low  from r e g i o n  5-methoxy-N,N-dimethyltryptamine,  been r e p o r t e d  a  the  dimethyltryptamine, derivatives  bark.  preparations  bark  active  the  over in  the  the  plants  as a s n u f f  have been c a r r i e d [4]  the  other  distribution  [3]  from  ingredients,  of  hallucinogenic  the V i r o l a to  is  or a s h e s  Virola  reports  layer  have  of  "resin",  to dryness  other  orally-ingested  may be smoked f o r  chemical spp.  are  utilize  which  of  g e o g r a p h i c a l and e t h n o l o g i c a l a  cambial  some i n s t a n c e s  addition  powdered l e a v e s  A l t h o u g h the  the  preparation  in  basis  from t h e  evaporated  method of  to t r i b e ;  others,  of  a powder,  r e g i o n and t r i b e  as t h e  The d r u g o b t a i n e d  derived  r e d d i s h exudate  Most commonly, t h e fire  [1].  (Myristicaceae)  and  /3-carbolines  and i n one s p e c i e s , /3-carbolines are  the  have not major  1 22  alkaloids  present  orally-ingested been  investigated.  Myristicaceous In leaf  the  several six  four  II.  and GC/MS.  native  In  McKenna  voucher  of  A m p i y a c u r e g i o n of  the a l k a l o i d  TLC,  constituents these  in  of  consisted  collected  La C h o r r e r a , C o l o m b i a , collected  and  tests,  in  1981; one o r a l l y - i n g e s t e d  the  Virola  1971; and  in Venezuela  work r e f e r  (cf.  to  A p p e n d i x II  for  relevant  the  R i o A m p i y a c u , however paste  all  of  sample or  the M y r i s t i c a c e o u s the  in M y r i s t i c a c e o u s  numbers of M y r i s t i c a c e o u s  available  from the  P e r u were  Alkaloids  collections  methanol at  I.  the Rio  spring,  are  Chorrera  the  bark  addition,  at  of  in  1972.  and Methods  Collection this  the  a number of M y r i s t i c a c e o u s  o r a l l y - i n g e s t e d Vi r o l a paste in  the previously  and p h a r m a c o l o g i c a l a s p e c t s  Yanomama s n u f f  Detection  in  d i s c u s s i o n of  using a l k a l o i d p r e c i p i t a t i o n  sample c o l l e c t e d  Materials  have not  d r u g s a m p l e s were i n v e s t i g a t e d ;  s a m p l e s of  cited  in  alkaloids  s a m p l e s of  A.  D.  study  Ampiyacu r e g i o n  paste  of  h a l l u c i n o g e n s may be f o u n d i n C h a p t e r  present  for  HPLC,  Rio  chemical,  constituents  preparations  A more d e t a i l e d  samples c o l l e c t e d  screened  of  The a l k a l o i d a l  Myristicaceous  ethnobotanical,  GC,  [7].  bark  time  of  the  personal c o l l e c t i o n  for  a complete  to  this  list  work).  of  herbarium  pastes  available  t h e Yanomama s n u f f  vouchers  collected for  and t h e  The m e t h a n o l was remainder  the  samples.  s a m p l e s were p r e s e r v e d  collection.  samples  numbers of  Herbarium  orally-ingested  and l e a f  preserved material  and l e a f  the  no v o u c h e r s a r e for  bark  Samples  was  La  All in  on  of  100%  decanted  frozen,  then  123  lyophilized. extracted extracts  overnight  the  wt were e v a p o r a t e d  The r e s i d u e was  of  shaken w i t h 5 ml  for  alkaloid precipitation  acidic  1 x 5 ml C H C 1 2  aqueous l a y e r  2  filtrate  and t h e  was b a s i f i e d  extracted with  the  to dryness  of  with  (10-20 m l / g d r y  (ca.  organic  the  aqueous  Meyer's  fraction  reagent.  2  2  methanol.  no l o n g e r  The o r g a n i c  anhydrous N a S O „ ,  evaporated  A m p i y a c u were a l s o p r e s e r v e d  sample was  the  frozen,  (20 m l / g d r y  wt).  powdered p l a n t  procedure.  gave  paste  was  removed and u s e d  was  until  materials;  these the  was  The  NaHC0  basified  acidified  aliquots  reaction  [8];  all  samples c o l l e c t e d  s a m p l e s were  were e x t r a c t e d  in  these  3 ml  in  Rio the  paste  methanol  dried,  other out on  alkaloid Meyer's,  reagents  over  on t h e  directly  the  were c a r r i e d  d u r i n g the  of  to  were c o m b i n e d , d r i e d  same manner as  filtrate  and  3  further  a positive  T e s t s were made w i t h V a l s e r ' s , reagent  washed  s a m p l e s . The La C h o r r e r a  tests  flask.  A small  i n m e t h a n o l and were t r e a t e d  The Yanomama s n u f f  the a c i d i c  Dragendorff's  3 g  l y o p h i l i z e d , and t h e n e x t r a c t e d w i t h  Alkaloid precipitation of  to  t o d r y n e s s and r e d i s s o l v e d  b a r k and l e a f  m e t h a n o l and p r e p a r e d i n  aliquots  equivalent  discarded.  it  2  fractions  The o r a l l y - i n g e s t e d  same manner a s  For  t o pH 8-9 w i t h s a t u r a t e d CH C1 ;  known  C.  The r e m a i n d e r layer  used  4°  and f i l t e r e d .  0.5 ml)  tests.  The  methanol  i n a 50 ml r o u n d b o t t o m 1 N HCI,  15 ml p o r t i o n s of  wt).  under vacuum t o a  extracts  t o pH 10-12 w i t h 2 N NaOH and e x t r a c t e d of  original  were s e a l e d and s t o r e d a t  aliquot the  shaker  s a m p l e , and c o n c e n t r a t e d  screening, aliquots  the  was powdered and  combined with the  The c r u d e e x t r a c t s  alkaloid dry  on a r o t a r y  were f i l t e r e d ,  to preserve volume.  The f r e e z e - d r i e d m a t e r i a l  with  samples. small  isolation and  form  124  precipitates  or  turbid  solutions  in  while  turbidity  indicates  p o s s i b l e t r a c e s of  slight  Valser's  reagent  sensitive  than  is  approximately  the other  two.  UV  2 5  "  Three  /il a l i q u o t s  p r e c o a t e d TLC p l a t e s  cm f r o m t h e  bottom edge.  d r i e d under a s t r e a m of  prepared for  T L C . Development  an u n l i n e d ± 5 ml of in  carbolines  appear  while aromatic fluorescences UV,  plates  blue  reactions 4,  Chapter  carboline  b a s e s and  UV.  IV  for  standards  detected  For  was  of  9 cm  freshly  collected in  containing were  long-  and  s h o r t - w a v e UV  characteristic examination [9]  under  which  s a m p l e s c o u l d be  of  the  Table the  50  air-dried  gives  b a s e s upon e x p o s u r e t o  some s a m p l e s ,  Rfs II  and c o l o r  and F i g s .  tryptamine  identities  were i d e n t i c a l  to  HCI  tentatively  and  of  u s i n g TLC were c o n f i r m e d by GC/MS.  t h e GC/MS a n a l y s i s  1.0  tetrahydro-/3-  reagent  (cf.  c o m p l e t e TLC d a t a  standards).  for  tank  plates  Following  i n the  Gel  temperature  t h e n examined under  from TLC b a s e d on c o m p a r i s o n of  constituents Conditions  ambient  development,  with tryptamine  with authentic  Silica  s a m p l e s were  U V - a b s o r b i n g s p o t s under  long-wave  colors  the  in  a point  upper p h a s e  chromatographic  Tryptamine  Tryptamines detected  identified  out a t  were s p r a y e d w i t h E h r l i c h ' s  to v i o l e t  vapors.  f u n n e l and t h e  and d i h y d r o - / 3 ~ c a r b o l i n e s have under  conducted  at  The s o l v e n t  a  30-60 m i n ,  as d a r k  application  NH OH 5 : 4 : 1 .  was c a r r i e d  s h o r t - w a v e UV l i g h t .  s a m p l e s was  and d e v e l o p e d t o a d i s t a n c e  Following  a fume hood f o r  alkaloid.  m a g n i t u d e more  (Brinkmann I n t r u m e n t s )  10x23x26 cm g l a s s solvent.  alkaloids,  were a p p l i e d t o P o l y g r a m  air,  in a separatory  the  of  of  w h i c h were r e d i s s o l v e d  Following  in ether/2-butanone/conc.  presence  an o r d e r  TLC of  w i t h t h e p u r i f i e d base e x t r a c t s methanol.  the  those  3 and 0-  125  described  in Chapter  c o n f i r m the  IV.  identities  of  on c o m p a r i s o n w i t h t h e Conditions those  of  For the  tryptamine  retention  t h e GC a n a l y s e s  times  are  s a m p l e s w h i c h were p o s i t i v e  to dryness  B.  Quantitative  Analysis  were q u a n t i f i e d  with a hydrogen  flame  inlet  pressure  was  0.67.  attenuation  c h r o m a t o g r a p h was  for  of  the  was h e l d f o r  VIII).  standards  chart  a rate  of  times,  The  instrument  of  the  The c o l u m n was a (J  & W  15 M  Scientific).  the c a r r i e r  gas  was  was  30 p s i ;  t h e GC d e t e c t o r  was  1x4 mv  recorder  was  1x5 mv.  temperature  of  The  initial  200°  injection  C.  and  Initial then  l0°/min. heights,  and peak h e i g h t  ratios  were d e t e r m i n e d u s i n g s t a n d a r d s  10 i n j e c t i o n s .  were u s e d t o c o n s t r u c t analyses  equipped  h y d r o g e n and a i r  t i m e s were c a l c u l a t e d  a minimum of  C o n c e n t r a t i o n of  (GC).  for  3 min f o l l o w i n g  peak  derivatives  quantitative  evaporated  alkaloid-positive  programmed, from an  120° C t o a f i n a l  Retention of  both the  temperature  temperature  tryptamine  were  TLC  Standards  column  pressure  Attenuation  of  Retention  capillary  inlet  temperature  i n c r e a s e d at  Following  C.  s a m p l e s w h i c h were  fused' s i l i c a  18 p s i ;  and t h e  Tryptamine  ionization detector.  gas was h e l i u m ;  ratio  -20°  based  standards.  3B Gas C h r o m a t o g r a p h ( P e r k i n E l m e r )  Carrier  split  alkaloids  u s i n g gas c h r o m a t o g r a p h y  u s e d was a Sigma  x 0.25mm SE-30  of  authentic  d e s c r i b e d below. for  to  bases d e t e c t e d ,  of  under n i t r o g e n and s t o r e d a t  Those M y r i s t i c a c e o u s  error  some s a m p l e s , GC was u s e d  of  as  (Table  t h e mean ± s t a n d a r d  Mixtures  calibration  the M y r i s t i c a c e o u s  tryptamine  of  calibration  of  tryptamine  curves  used in  the  samples. mixtures  ranged  from  TABLE  tryptamine standard  height  - TRYPTAMINE STANDARDS: GC ANALYTICAL  retention time (min)  tryptamine peak  VIII  (cm)  n.d.*  7.5  6  2.8  n.d  n.d  2.1  9.3  -  -  -  .8  3.5  n.d  . 42  1. 7  3. 2  n.d.  phr  peak  height  phr  peak  . 43  .82  7.3+.13 height  5-MeO-DMT  phr  -  .1 1  phr  peak  n.d.  7. 1+.21  DMT  height  1.0  9.3±.15  height  NMT  .5  1.6  -  5-MeO-T  c o n c e n t r a t i o n (mg/ml) .125 .25  6.6+.15  phrt  peak  .0625  DATA  .94  2.9  6.7  17.7  .24  .74  1.7  4.5  .65  1.9  4.3  10.3  .16  .48  1.1  2.6  9.7±. 13  * n.d.= n o t d e t e c t e d t p h r - peak h e i g h t r a t i o . h e i g h t o f s t a n d a r d peak a t c o n c e n t r a t i o n X phr= h e i g h t o f g r a m i n e peak a t 0.25 mg/ml v a l u e o f d e n o m i n a t o r was 3.91 f o r n=42 i n j e c t i o n s .  1 27  Figure  7 - GC Q u a n t i t a t i o n  of Tryptamine  Standards  1 28  0.0625 t o to  0.5 mg/ml f o r  1.0 mg/ml f o r  DMT, 5-MeO-DMT, and NMT, and from  tryptamine  and 5 - m e t h o x y - t r y p t a m i n e .  were d i s s o l v e d  in methanol/pyridine  were i n j e c t e d .  Tryptamine  readily less polar  250 ng was  methylated  Ten r e p l i c a t e at  injected;  tryptamines  injections  each c o n c e n t r a t i o n  standard  in a l l  concentration s t a n d a r d at standard, was  of  of  level.  the  Gramine was  calibration  was d e t e r m i n e d the  Preparation  ranges  at  to  however.  were made internal  ratio  the  stated,  Samples  if  constant for  each  internal  A linear  concentration*  of M y r i s t i c a c e o u s  a  height  with respect  Table V I I I ) .  was p l o t t e d a g a i n s t  mixture  and  less  i n c l u d e d a s an  mixtures,  concentration  the  be d e t e c t e d ,  The mean peak  (cf.  detected  50 ng of  each c a l i b r a t i o n  each c o n c e n t r a t i o n ,  ratio  C.  of  w e l l below  1 nl  of  being polar  be r e l i a b l y  could easily  0.25 mg/ml.  observed over  height  c o u l d not  Standards  and a l i q u o t s  and 5 - M e O - t r y p t a m i n e ,  i o n i z e d compounds,  than  9:1  0.25  relationship when t h e  (Fig.  peak  7).  f o r GC  Quantitation The base  fractions  of  the M y r i s t i c a c e o u s  s a m p l e s had been p r e v i o u s l y -20°  C.  Each  sample r e p r e s e n t e d  known amount of ml of heated  dry weight  methanol/pyridine briefly  over  plugged Pasteur  m e t h a n o l and t h e An a l i q u o t  of  9:1  the a l k a l o i d s  plant  material,  was added t o  The f i l t r a t e  the p i p e t t e  equivalent  to  1.0  the  usually samples,  to a f i n a l wt was  at  from a  3.0  g.  which  through a  was c o l l e c t e d  g dry  leaf  extracted  was washed w i t h  sample was a d j u s t e d  and  t o d r y n e s s and s t o r e d  a steam b a t h and f i l t e r e d  pipette.  graduated c y l i n d e r ,  ml.  evaporated  bark  One were  cotton  in a  small  additional volume of  removed and  1.5  129  adjusted further  to  0.5 ml w i t h a d d i t i o n a l  diluted  gramine at  to  1.0  of  0.5 mg/ml.  concentration  of  the  sample was  concentration  of  the  gramine  injections  of  tryptamines height  ratios  gave t h e mg/ml,  the  of  known d r y  g dry  to dryness w e i g h t s of  approximately  over  plugged Pasteur  point  dilution  the  calibration of  mg/ml)  and s n u f f  and t h e r e f o r e plant  standard,  peak  using  the  standards.  samples since  the  in  This  terms  of  sample  s a m p l e s had not  the a l k a l o i d  material  a steam b a t h ,  been  fractions  were d i s s o l v e d  the  from  in  curves.  wt/ml,  dry  wt  of  the  of m e t h a n o l / p y r i d i n e  ratios  to  the  sample  could  "2.0 g in  4 ml".  into  t h e GC t o  estimate  sample w i t h i n representing  the an  range  At  of  appropriate  sample was d i l u t e d w i t h an 9:1  concentration  with respect  of  with  e.g.,  injected  An a l i q u o t  through a cotton-  t o a known volume  concentration  g dry  sample was  total  filtered  and b r o u g h t  terms of  to give a f i n a l  Peak h e i g h t  paste  r e q u i r e d to b r i n g the  equal a l i q u o t  b a s e d on t h e i r  the wt,  of  wt/ml..  pipette  1 ul of  the  portion  t o mg/g d r y  m e t h a n o l . Thus t h e  be e x p r e s s e d i n this  in  mg/ml.  replicate  Concentrations  internal  0.25  final  known v o l u m e s of m e t h a n o l . T h e s e s a m p l e s were  briefly  additional  the GC. F i v e  tryptamines  w h i c h was e q u i v a l e n t 1.0  and t h e  s t a n d a r d was  was  containing  wt/ml,  constructed using tryptamine  The M y r i s t i c a c e o u s  heated  to the  solvent  final  s a m p l e s were c a l c u l a t e d  concentration  evaporated  into  sample  Thus t h e  g dry  internal  injected  with respect  curves  c o n s i s t e d of  1.0  e a c h sample were r u n .  in  calibration  were  this  ml by a d d i n g 0.5 ml of  a concentration  One ul a l i q u o t s  solvent;  of  the  containing gramine of internal  gramine 0.25  (0.5  mg/ml.  s t a n d a r d were  1 30  calculated,  and t h e  concentrations  of  were e s t i m a t e d as d e s c r i b e d a b o v e . M D  were made f o r  each sample;  tryptamines  Five  for  the  in  replicate paste  the  samples  injections  samples,  s a m p l e s were p r e p a r e d as d e s c r i b e d and 5 r e p l i c a t e  (1  duplicate  injections  of  and F i g s .  8,  e a c h were made.  III.  Results  and D i s c u s s i o n  The r e s u l t s 9,  are  presented  Detection  and I d e n t i f i c a t i o n  Myristicaceous  1.  X,  XI,  Bark and l e a f  samples v a r i e s  collections  consistent  species the  [6]  of  in  negative  for  the  whose a u t h o r s  (0.013%)  et of  the  al.  [6],  of  recent  in  5-MeO-DMT i n  the p r e s e n t  of  leaf  observed  and  to  observations  Myristicaceous  study,  collections  (I_.  ulei)  was  species  The V .  in  of V .  were  were  pavonis,  examined i n the  detected a pavonis  found  alkaloids  included in  investigators ulei.  and a l s o  Among t h o s e w h i c h  Iryanthera  I_.  These  plants  the  These  and  variation  same p l a n t ,  survey  different In  bark  r e m a r k e d upon t h e v a r i a t i o n  were s e v e r a l  one  the  the  27 c o l l e c t i o n s .  s p p . Of only  IX);  same s p e c i e s .  also  plants.  alkaloids  survey,  Holmstedt  of  13 of  and 6 I r y a n t h e r a present  (Table  with a s i m i l a r  parts  detected  the M y r i s t i c a c e o u s  parts  base c o m p o s i t i o n of  different  Alkaloids  samples  considerably  extends both to d i f f e r e n t different  of  Samples  The b a s e c o m p o s i t i o n of  in  IX,  10 and 1 1 .  A.  are  in Tables  the  survey  trace  samples,  of  of  131  which  4 collections  alkaloids level  w i t h the  (0.07  the  as V .  of  of  p a v o n i s on t h e DMT t e n d s  An i n d e t e r m i n a t e bark  wt)  which  additive  to  negative  for  DMT i n t h e  has been t e n t a t i v e l y  presence of  Vi rola  is  Six  tryptamine  methyltryptamine, position  of  this  biosynthesis  the  the voucher  V.  material  represent  elongata, traces  TLC.  The major to  V.  of  the  in  these  of  the  lesser  association  also  were these  reflects  step of  samples  amounts of  in  the  DMT or NMT  collected  base c o m p o s i t i o n ; is  sterile,  although they  profile;  compounds c o u l d be d e t e c t e d  of  by  compounds  constituents the  at  as  anomalous a l k a l o i d  fluorescent  N-  the  either  37 were a l l  and mass s p e c t r a  were  while  All  DMK-45, d e t e r m i n e d  apparently  however.  was  F i v e of  the  an  elongata  three.  penultimate  / 3 - c a r b o l i n e s . The f l u o r e s c e n t  standards,  12,218)  DMT, 5-MeO-DMT, NMT;  collections  elongata.  bases are  determination.  1983)  which p r o b a b l y  had a s i m i l a r  for  however  some c o l l e c t i o n s  DMK-35, 3 6 ,  Ehrlich-positive  d i d not match t h e R f s carboline  viz.,  possessed a completely  only  similar  and a l l  of V .  also contained  compound as  found.  comm.,  tips.  Rodrigues  (Plowman  alkaloids.  two out  of DMT. No s i m i l a r  same s i t e ,  probably  for  an o b s e r v a t i o n  w i t h 5-MeO-DMT was  pers.  bases,  one or  i n w h i c h DMT was d e t e c t e d  (W.  material,  from B r a z i l  compounds were d e t e c t e d  contained only  sterile  low  and s h o o t  determined  collections  found to c o n t a i n  others  leaves  d o u b t on t h i s  T.,  were p o s i t i v e  three  for  smoked by w i t c h d o c t o r s as  (Plowman,  alkaloids.  of  to c a s t  species  reportedly  tobacco  basis  a n a l y z e d and a l l  all  negative  e x c e p t i o n of DMK-30 w h i c h c o n t a i n e d a  mg/g d r y  This c o l l e c t i o n 1983)  were e x a m i n e d , were a l l  available  The l i m i t e d amount of  detected /3-  plant  TABLE IX - DETECTION OF ALKALOIDS IN MYRISTICACEOUS BARK AND LEAF SAMPLES name & Col 1ect ion  a l k a l o i d reagent tests:* D M V  H  DMK-30 V i r o l a pavonis leaves (3.0 g d wt.) twigs (3.0 g)  ++ + +  DMK-32 V. pavonis leaves (3.0 g) twigs (3.0 g)  _ .  +/+  ++ ++  +/-  +/-  v-  +  + 4-  -  4-  + (2)  DMT.NMT  -  4-  + (2)  DMT.NMT  4-4-  -  4-  + (2)  DMT,NMT  + 4-  +( 1 ) + (3)  NMT DMT.NMT.5Me0--DMT  -  4-  + (2)  NMT.DMT  -  4-  -  -  + 4-  +  + /-( 1 )  -  -  4-  + (3)  -  -  4-  -  -  _  -  4-  -  -  DMK-36 V i r o l a sp. leaves (3.0 g) DMK-37 V i r o l a sp. leaves (3.0 g)  + +  DMK-40 V. s e b i f e r a leaves (3.0 g) bark (3.0 g) DMK-41 V. elongata bark (3.0 g) longiflora  -  +  -  +  4-4-  4-  + 4-  + +  +  + 4-  -  DMK-45 V. e l o n g a t a bark (3.0 g) *  + +  DMK-46 V. c a l l o p h y l l a bark (6.8 g)  4-  DMK-48 I. u l e i bark (3.0 g)  DMT.NMT DMT.NMT  V-  -  4-/-  + +  4.  .  . 4-  -  + (2 ) + (2)  +/-  -  -  4-  compounds detected^  V-  + +  macrophylla  4-  _  Ehr1 i ch's react ion:*  _ _  DMK-35 V i r o l a sp. leaves (3.0g)  DMK-47 Iryanthera bark (3.0 g)  UVabs.  _ _  DMK-34 V. pavonis leaves (3.0 g) twigs (3.0 g) bark (3.0 g)  DMK-44 Iryanthera bark (3.0 g)  TLC : t UVfluor.  .  -  -  +  NMT,5MeO-DMT,, TA  Table IX (cont'd)  D  a l k a l o i d reagent tests:* V M  DMK-49 I. c r a s s 1fol1 a bark (2.3 9)  -  -  -  -  -  -  -  DMK-50 I. j u r u e n s l s bark (3.0 g)  -  -  -  -  +  -  -  OMK-51 I. p a r a e n s i s bark (3.0 g)  -  -  -  -  -  -  -  OMK-52 V i r o l a m u l t i n e r v i a bark (3.0 g)  _  _  _  DMK-56 V . c a l l o p h y l l a seeds & f r u i t s (3.0 g)  ++  ++  -  +  + (2)  DMT,NMT  DMK-59 V. elongata bark (3.0 9) leaves (3 0 g)  ++ +  +  ++ +  + +  + (2) + (1)  NMT.5-MeO-DMT NMT,DMT  DMK-63 V. pavon i s bark (3.0 9)  -  -  -  -  +  -  DMK-67 V. e l o n g a t a leaves (3 0 g) bark (3.0 g)  ++ +/-  +  +  + /-  + (1)  5MeO-DMT  ++  +  +  +( 1 )  5MeO-DMT  ++  +  +  +(D  5-MeO-DMT  name & Col 1ectIon H  TLC : t UVfluor.  UVabs.  Ehr1 i ch's react ion:1  DMK-68 V. elongata leaves (3 0 g) bark (3.0 9)  ++  +  DMK-69 V. elongata leaves (3 0 g) bark (3.0 9)  ++ + /-  +  DMK-75 V. 1oretens i s leaves (3. 0 g)  -  -  -  -  -  -  +  ++  -  +  + (1)  DMK-78 Osteophloem leaves (3.0 g)  platyspermum ++  compounds detected^  -  */-  -  N-methyltryptophan methyl e s t e r  Table  IX  (cont'd)  name & CollectIon  #  a 1ka1o i d r e a g e n t tests:* M D  TLC : t UVfluor.  UVabs.  V  Ehr1i ch's r e a c t i on:$  DMK-82 V. a l b i d i f l o r a bark (3.0 g)  -  -  -  .  .  _  Plowman 12218 V i r o l a s p . bark (2.0 g)  -  -  -  -  +  -  compounds detected))  -  * r e a c t i o n t o a l k a l o i d p r e c i p i t a t i o n reagents. D=Dragendorff's r e a g e n t ; M=Meyer's r e a g e n t : V = V a l s e r ' s r e a g e n t . C o m p o s i t i o n reagents i s a c c o r d i n g to Farnsworth [ 8 ] , t R e s u l t s o f TLC o f b a s i c f r a c t i o n s : p r e s e n c e / a b s e n c e o f U V - f 1 u o r e s c e n t o r U V - a b s o r b i n g s p o t s i s i n d i c a t e d . $ P r e s e n c e / a b s e n c e o f E h r 1 1 c h - p o s i t 1 v e s p o t s ( d i a g n o s t i c f o r t r y p t a m i n e s ) o n TLC p l a t e i s i n d i c a t e d . Numbers i n parentheses i n d i c a t e n of E h r 1 i c h - p o s i t i v e spots detected. b I n d i c a t e s m a j o r compounds i d e n t i f i e d i n s a m p l e , u s i n g a c o m b i n a t i o n o f m e t h o d s i n c l u d i n g T L C , GC, HPLC, a n d i n some c a s e s GC/MS.  TABLE X - DETECTION OF ALKALOIDS name & Collection # of s o u r c e p l a n t A.  Orally  Active  amt. extracted ( g d wt. ) Paste  a l k a l o i d reagent test:* D M V  IN MYRISTICACEOUS PASTE AND SNUFF  SAMPLES  TLC: t UV  f1uor .  UVabs.  Ehrlich's react ion:i  compounds detected))  Samples:* ++  1. DMK-40 V. s e b i f e r a 2.0 +++ A l f r e d o M o r e n o n\ - P u c o U r q u i l l o 2. DMK-67 V. e l o n g a t a 2.0 +++ A l f r e d o M o r e n o *2 - P u c o U r q u i l l o  +++  -  +  + (2)  NMT.DMT, 5-MeO-DMT 5-MeO-NMT  +++  -  +  +( 1 )  NMT.DMT, MTHpC (GC/MS)  3. DMK-68 V. e l o n g a t a 2.0 +++ A l f r e d o M o r e n o *3 - P u c o U r q u i l l o  ++  +++  -  +  +( 1 )  NMT  4. DMK-69 V. e l o n g a t a 2.0 +++ A l f r e d o M o r e n o #4 - P u c o U r q u i l l o  ++  4- + +  -  +  +( 1 )  NMT  -  -  -  5. DMK-34 V. p a v o n i s 2.0 J o r g e Churay - Puco U r q u i l l o  -  6. DMK-59 V. e l o n g a t a 5.4 M a r c o s F l o r e s - B r i l l o Nuevo  +++  ++  +++  -  +  + (2)  5MeO-DMT. 5Me0-NMT  ++  +++  -  +  + (2)  DMT. NMT. MTHpC. DMTHpC (GC/MS)  ++ + 1.7 ++ = J u s t i c i a p e c t o r a l i s + unknown s p e c i e s ?  +  -  c o u m a r i n . umbel 1 i f e r o n e (TLC.GC/MS)  +  + (3)  DMT. 5-MeO-DMT. NMT. umbe11iferone. coumarin (TLC.GC/MS)  +  + (2)  DMT,5MeO-DMT  + (2)  NMT, 5Me0-DMT  7. no v o u c h e r 2.0 "oo'-koey" La C h o r r e r a . Colombia B.  Yanomamo s n u f f s  (Venezuela.  1. no v o u c h e r "buhenak + m a s h a h a r a "  4. no v o u c h e r "yakuana-sagona"  +  +  (1971)  1972).•  ++  ++  ++ 3.0 ++ sp. c a r b o n i z e d resin?  ++  2. no v o u c h e r "mashahari" = J u s t i c i a  3. no v o u c h e r "caraknak" = V i r o l a  +  3.0 ++ pectoralis  4.0 +++ + = V i r o l a sp. or complete snuff +  +  +  +  +  +  * r e a c t i o n to a l k a l o i d p r e c i p i t a t i o n reagents. D=Oragendorff's r e a g e n t ; M=Meyer's r e a g e n t ; V = V a l s e r ' s r e a g e n t . Composition of reagents a c c o r d i n g to Farnsworth [ 8 ] . t R e s u l t s o f TLC o f b a s i c f r a c t i o n s . U V f l u o r . I n d i c a t e s p r e s e n c e / a b s e n c e o f f l u o r e s c e n t s p o t s : UVabs. I n d i c a t e s presence/absence of UV-absorbant s p o t s . * Presence/absence of E h r 1 i c h - p o s i t i v e spots ( d i a g n o s t i c f o r tryptamines) o n T L C . Numbers i n p a r e n t h e s e s i n d i c a t e P o f Ehr 1 1 c h - p o s i t i v e s p o t s d e t e c t e d b I n d i c a t e s m a j o r compounds i d e n t i f i e d i n s a m p l e , u s i n g c o m b i n a t i o n o f m e t h o d s i n c l u d i n g TLC, GC. HPLC. & GC/MS. H F i r s t l i n e i n d i c a t e s c o l l e c t i o n n a n d i d e n t i t y o f s o u r c e - p l a n t , where known; s e c o n d l i n e i n d i c a t e s name o f p e r s o n m a n u f a c t u r i n g sample and v i l l a g e o f o r i g i n * No v o u c h e r s a v a i l a b l e f o r Yanomama s n u f f s a m p l e s . S e c o n d l i n e l i s t s Yanomama name o f s a m p l e a n d p r o b a b l e b o t a n i c a l i d e n t i t y b a s e d on names c i t e d i n S c h u l t e s [ 2 1 .  1 37  material genetic  precluded further variant  of V .  has been r e - d i r e c t e d represent [7]  harmalan,  the  [10]  The most  d o e s not  is  not  phytochemical  of  ill-defined  theiodora  Rodrigues V.  [10]  contains  and 2 e n t r i e s is  for  the  genus  the  b i n o m i a l V.  Table reported  in  IX  all  the  of  these  Rodrigues,  have been  examined t h r e e c o l l e c t i o n s  refer  if  is  to  not  the  use of  elongata  cited  in  for V.  properly  species  differences  and  or  [6] elongata,  revision  of  d e s i g n a t e d by  the m a j o r i t y  examined i n  snuffs  r e c o g n i z e d by  to V.  list  result  Virola.  Rodrigues'  are  the  as a  arisen  of  the  the p r e s e n t  study  concepts  followed.  other  which d e s e r v e  genus  legitimate  genus  5 entries  Inasmuch as  collections  in  the  hallucinogenic  species  al.  elongata.  as e q u i v a l e n t  the  of  tryptamines  literature  species  theiodora;  shows s e v e r a l  [6]  in  may  6-MeO-  i n w h i c h c o n f u s i o n has  cuspidata,  elongata.  [10]  this  treated  Vi r o l a  voucher  in  yet  it  of V i r o l a  c u s p i d a t a as a to V.  or  Cassady et  t a x o n o m i c monograph of  preparation  f o r V.  were d e t e r m i n e d by D r . established  bases  d i d not d e t e c t  concepts  instance  followed,  Myristicaceous  t h e major  [1,2,3,5,6,11,12]  pastes;  0-carbolines,  collection.  and e t h n o b o t a n i c a l  in the  2 entries  of  a  biosynthesis  6-MeO-tetrahydroharman,  instance  species  For  the  equivalent  only  and i s  calophylla.  recent  it  Numerous p u b l i c a t i o n s  orally-ingested  of  r e c o g n i z e V.  the  in the  Virola  synthesis  of  DMK-45 may r e p r e s e n t  in which t r y p t a m i n e  investigators  considering  This  the  the  isolation  these  species.  species,  to  and 6-MeO-harman as  cuspidata;  Virola  elongata  a misidentification  reported  this  investigation.  from the  comment. H o l m s t e d t  of V i r o l a m u l t i n e r v i a ,  et  survey  al.,  2 of  which  1 38  c o n t a i n e d DMT i n t h e  bark  while the  A single  this  species  survey  s p e c i m e n of  and was a l k a l o i d  detected tissue  in the  examined;  substantial the  leaves  bark  species  (DMK-40)  this  T a b l e XI)  NMT i n  was t h e  [6],  the  and t h i s species  of  samples o b t a i n e d a t  for  V.  sebi f e r a .  Holmstedt  et  collections  of  Osteophloem platyspermum  of  [6]  others in  survey  Ehrlich  t o any of  the  available  Rf=0.6  the  TLC s o l v e n t  in  GC r e t e n t i o n  time  compound was  isolated  spectral  analysis  of  was  [6]  Materials  peaks  9)  and t h e p a r e n t  methyl  the  corresponding  and a  stated.  The  from HPLC r u n s .  unsubstituted  matched t h a t  and  represented  indoles  (Fig.  2 8 9 , 2 7 9 , and 273 nm and minima  (Fig.  in  and M e t h o d s )  the  of  cited  T h i s compound gave  by c o l l e c t i n g typical  from  (DMK-78)  base not  conditions  was  base  while  leaves  standards.  (cf.  and  DMT, 5-MeO-DMT,  the  N,N-dimethy1-L-tryptophan however  sample of  this  examined 3  samples,  positive  N-methyl-L-tryptophan  130 mass u n i t s  sole  (incorrectly  the  of  Corothie  10.1 min under  The mass s p e c t r u m  base p e a k ,  used  only  orally-  p l a t y s p e r m u m was  tryptamine  w i t h a b s o r p t i o n maxima a t  s p e c t r u m of  0.  by a s i n g l e  which c o n t a i n e d a s i n g l e  286.  i n one of  were a l k a l o i d - n e g a t i v e .  the p r e s e n t  al.,  the  as O s t e o p h l o e m p l a t y p h y l l u m ) .  5-hydroxy-DMT were d e t e c t e d  the  Puco U r q u i l l o .  of  I  the  were  contained  one of  of DMT as  Table  present  Our c o l l e c t i o n  isolation  bark  was  negative.  DMT, 5-MeO-DMT, and NMT i n  leaves.  source-plant  the  no a l k a l o i d s  r e p o r t e d the  the  [13]  of  In  sebi fera  survey,  (cf.  and t r a c e s  ingested paste Nakano  i n our  amounts  was examined i n  negative. of V .  t h i r d was a l k a l o i d  of  ester;  a  UV 8)  at  reference  the  base  peak  i o n was m/z 2 3 2 . The compound  has an i d e n t i c a l  N-methyl-L-tryptophan  molecular  methyl  ester  weight can  be  and  DMK 78  rrNH 3  130  100-1  BASE M/ 130 M+232  CH  f  •  r  COOCH  H  102  173  [ *T  1  f  '  1 1' t  1  1  U—r—i—| r !—• |-l i i—r—i—i— r  m/e  3  232 ' > ••—r  ' l' •—1—i—|—i—l—i—l—'—l—'—i—'—1—•—l—i—l—'—r  F i g u r e 9 - Mass Spectrum of N - m e t h y l - t r y p t o p h a n m e t h y l e s t e r from l e a v e s of O s t e o p h l o e m p l a t y s p e r m u m  140  distinguished units  which  fragment  from i t  by t h e  represents  (COOMe)  the  from t h e  at  m/z  in 0.  reported several  in  cordifolia sample  is  (Malvaceae) consistent  Identification is  that  ion  ester.  the  [16].  in a l l  it  the  that  respects  tryptophan  in  fact  N-  been  found  in  Sida for  our  reported  in a  in  [16].  Myristicaceous  standpoint in  absent  The  is  data  with that  tryptamines  side  it  and i n  The mass s p e c t r a l  to  is  shows an M-59 peak  has been  [14,15]  from a b i o s y n t h e t i c  of  carboxylate  T h i s compound has not  Leguminosae  pathway  methylation  173 mass  (M-59). T h i s peak  although  an N - m e t h y l a t e d  interesting  indicates involve  of  the methyl  strong evidence  methyl  in the  a peak a t  platyspermum c l e a r l y  the M y r i s t i c a c e a e  species  of  of  N,N-dimethyl-L-tryptophan.  173, t h u s p r o v i d i n g  methyl-l-tryptophan  genus  loss parent  from t h e mass s p e c t r u m of compound d e t e c t e d  presence  this  as  it  family  chain nitrogen p r i o r  may  to  decarboxylat ion. 2.  Snuff  The a l k a l o i d Myristicaceous X).  and p a s t e  constituents  La C h o r r e r a ,  collected  1981 a t  Vi rola  but  substantial cases  the  were a l s o  Colombia,  in  the W i t o t o / B o r a  one of  the M y r i s t i c a c e o u s  concentrations  of  b a s e c o m p o s i t i o n of  c o m p o s i t i o n of  the  alkaloid the  source p l a n t s  of (Table  orally-ingested  1971, and 6 p a s t e  villages  from V e n e z e u l a were a l s o  samples  investigated  Nuevo on t h e R i o A m p i y a c u i n P e r u .  snuff  All  a number of  i n c l u d e d one sample of  c o l l e c t e d at  and B r i l l o  of  drug p r e p a r a t i o n s  These samples  in  samples  of  Puco  Four  paste samples  Urquillo  samples  of  screened. paste (Table  pastes  samples  contained  X and X I ) .  reflected  used to p r e p a r e  the  them;  In base the  most  141  concentrations orders plant  of  of  tryptamines  magnitude g r e a t e r  material.  in  than  )3-carbolines  capable Moreno  of  (DMK-67, V .  were p r e s e n t  In  this  elongata)  limit the  of  that  contained high levels one of  [5]  (M =186,  115,  77)  while  +  +  144,  129,  similar  to  mass u n i t s  2  loss  w h i c h no v o u c h e r  143=100%,  w i t h the  of  immediately  2-Me-THp"C, t h i s  represents  the  a stabilized  loss  intermediate  The p r o m i n e n t peak a t  t h e p i p e r i d i n e N and t h e  fragmentation  of  pattern  for  loss  m/z  2-Me-  m/z 157, pattern 14 t o  of  is 15  shows a the C H 3  from C , and  with p o s i t i v e  adjacent  130,  185 (M-15)  a methyl  m/z  as  m/z  after  peaks are  c o r r e s p o n d i n g to the  facile  However available,  compound a l s o  b a s e peak at  the  two j3-  and s t r o n g p e a k s a t  major  to  p e a k s at  all  a l t h o u g h the  closely  established  that  M-43,  of  p u b l i s h e d mass  additional  eluting  is  2-Me-TH0C e x c e p t  p i p e r i d i n e N. of  so c l o s e  The f r a g m e n t a t i o n  f o r m a t i o n of the  w i t h a mass s p e c t r u m  identity  185=100%,  Like  Alfredo  2-methyl-tetrahydro-j3-carbol ine.  for  other,  m/z  higher.  method  low c o n c e n t r a t i o n s  10).  fragment,  probably  only  77 ( F i g .  p r o m i n e n t peak a t N=CH  the  118, 9 2 ,  the  c o u l d be u n e q u i v o c a l l y  m/z  crude  the  low  of NMT and DMT, and t r a c e s  these  spectrum  TH/3C, had M = 2 0 0 ,  two of  a p o o r s p e c t r u m was o b t a i n e d .  £-methyl-TH/3C b a s e d on i t s  89,  for  from La C h o r r e r a ,  carbolines;  the  such  was  / 3 - c a r b o l i n e component was  detection  sample  analysis  contained  p u b l i s h e d [5]  sample t h e  in  in  1 to 2  them. The s e c o n d sample p r e p a r e d by  DMT, NMT and a t r a c e c o n s t i t u e n t matching that  were u s u a l l y  the c o n c e n t r a t i o n  t h a t mass s p e c t r a l  detecting  pastes  were f o u n d i n o n l y  s a m p l e s and i n b o t h i n s t a n c e s concentrations  the  157 i s  carbon  tetrahydro-/3-carbolines  charge  the on  p r o d u c e d by  3,  a  [17].  typical A  BASE M/Z 143  M*186  rlOO  3  H  -50  I S  42 SI  n  SB M  I li i |l> i nl  89  iljlj,, lmil|ll  Figure  h. ,  a23  .Mi..  ,|i  m  Me  10 - Mass S p e c t r u m of MTH/3C f r o m La C h o r r e r a O o ' - k o e y  BASE M/Z 185  M+200  -100  Figure  1 1 - Mass S p e c t r u m o f DMTH/3C La C h o r r e r a O o ' - k o e y  from  143  reasonable  structure  1,2-dimethyl  can be p o s t u l a t e d  tetrahydro-/3-carboline.  1 , 2 - d i m e t h y l - T H j 3 C , was from t h e  isolated  s e e d s of A n a d e n a n t h e r a  The f a i l u r e s a m p l e s and t h e  to detect extremely  some i n t e r e s t i n g mechanism of activity  of  low  activity  they  contain,  intestinal effective  yet  these  the  present  sufficient  compounds a r e  in  the  pastes,  concentration  activity  of  the M y r i s t i c a c e o u s  does f o r a y a h u a s c a aromatic (cf.  /3-carbolines  Chapter  inhibitors Vi rola paste  (cf.  IV)  than  pastes  are the  (cf.  Chapter VI,  them  also  less  effective that  pharmacological  significance the p a s t e s .  In  these in  were  i n h i b i t MAO.  to account  as  it  for  probably  [18,19,20]).  [21]).  in  The ayahuasca  a s MAO  detected S i n c e not  constituents of  orally  the  also  in  the  all  of  c o u l d have potentiating  t h e q u e s t i o n of  the  contain  tetrahydro-/3-carbolines,  terms  fact,  from  p r o v i d e d they  pastes  by  orally  to e f f e c t i v e l y  also  active  are  / 3 - c a r b o l i n e s , and t h o s e w h i c h do  unlikely  in  orally  found in h i g h c o n c e n t r a t i o n  seems e x t r e m e l y  tryptamines  IV  results  tryptamines  could  tetrahydro-/3-carbolines  the  not  [11,12,6]  raises  hallucinogenic  certainly  c o n s i d e r a b l y more e f f e c t i v e  samples c o n t a i n  t r a c e amounts of  Chapter  paste  samples  to p r o t e c t  and t h e o r e t i c a l l y  tryptamines  6-MeO-  postulated  The  almost  the  two  psychotomimetic  T h i s mechanism has been p o s t u l a t e d oral  the  of  d e g r a d a t i o n . The j 3 - c a r b o l i n e s  MAO i n h i b i t o r s  potentiate  compound,  in a l l  pastes.  pastes  of  viz.,  (Leguminoseae).  found in  r e q u i r i n g an MAO i n h i b i t o r and h e p a t i c  in  these  the M y r i s t i c a c e o u s  themselves,  peregrina  levels  of  compound,  by A u g u r e l l and c o w o r k e r s [ 1 8 ]  questions with regard to  oral  this  A similar  /3-carbolines  from t h e h i g h c o n c e n t r a t i o n s which  for  whether  it any the the  144  Myristicaceous remains  open  pastes  are  orally  (cf.-Chapter  In  their  oral  activity,  other  than  /3-carboline mediated  levels  of  /3-carbolines  to detect drugs,  if  III).  similar  also  present,  detected  compounds i n  either  Virola  or d u r i n g t h e  resin  d u r i n g the  has a l s o  aldehyde  to  the  of  the  followed  orally-ingested  precipitation  tests.  All  these  (viz..:  Rinora  (DMK-38), 43),  Anemia s p .  T\ b i c o l o r H_;_ &  (Schult. pastes In  addition  t o the  four M y r i s t i c a c e o u s  the  pastes,  and the  source-plants that  used f o r  they  the  alkaloid  type  et  by c y c l i z a t i o n  samples  [22].  were s c r e e n e d f o r  admixtures  alkaloids  & Zucc. )Kuntze,  and P h i l o d e n d r o n  (DMK-  nervosum  as a d m i x t u r e s t o the  Virola  III.  orally-ingested Myristicaceous  snuff  using  The use of  Theobroma s u b i n a c u m M a r t .  in Chapter  This  s u c h as NMT by  u t i l i z e d as  (Mart.  the  [6].  paste  derivatives  of  extract.  al.  found in the  the  may be formed  c o o k i n g and c o n c e n t r a t i o n  (DMK-64)),  samples,  s a m p l e s c o l l e c t e d among the Yanomama  V e n e z e u l a were a n a l y z e d . T h e s e s a m p l e s  various  components used i n  are  not  a c c o m p a n i e d by v o u c h e r  Dr.  Ernesto Migliazza,  research  the  racemosa  d i s c u s s e d more f u l l y  I n d i a n s of  failure  (DMK-65),  & Schult.)Kunth  is  in  were a l k a l o i d - n e g a t i v e .  (DMK-39),  that  low  collections  pastes  appears  i n h i b i t i o n of MAO. The  work-up of  non-Myristicaceous  species  it  must depend on some mechanism  formed from t r y p t a m i n e  condensation  Four  hallucinogens  been r a i s e d by H o l m s t e d t  Tetrahydro-/3-carbolines can be r e a d i l y  as  any c a s e ,  l e a v e s open t h e p o s s i b i l i t y  as a r t i f a c t s  possibility  effective  the m a n u f a c t u r e  of  the  represent snuffs,  but  s p e c i m e n s . They were c o l l e c t e d  an e t h n o l i n g u i s t  who c o n d u c t e d  on Yanomama l a n g u a g e and grammar  field  f r o m 1970-72.  They  by  1 45  were g i v e n time  was  of  samples  faculty  Maryland,  analyses the  identity  which  Var.  stenophylla  is  "mashahari" Schultes  almost  each  states  to J u s t i c i a  other  that  term  is  probably  Justicia  is  analyses  have  ( hanak means  sufficiently  "leaf")  close  different  samples  The sample  no a l k a l o i d s  (cf.  found the  in  terms support  labelled  T a b l e X)  but  Peruvian  (DMK-1,  is  [23]);  their  the  while  labelled  name  "buhenak"  k i n d or v a r i e t y  to t h i s  the  this terms  the of  Justicia  Chemical  latter  + buhenak"  contained  benzopyran  T h e s e compounds were  Just ic ia  identity  ; the  that  to each t y p e .  the  pectoralis:  that  is  mashahari  I n d i a n s of  Justicia  did contain  of  Two  a Yanomama  "mashahara  collections  chemical  + mashahara".  possibility one  the  Jacq.  and boo-hanak  c o u m a r i n and u m b e l l i f e r o n e .  the  author  lends  to  at  "buhenak  stenophylla, two names f o r  names  herbaceous  pectoralis  apply  supposition.  derivatives  an  in B r a z i l ,  synonymous. A n o t h e r  the  of  Cauaburi var.  of  identifications.  Indians,  and a p p l y  of  Subsequent  samples  labelled  Yanomama may r e c o g n i z e more t h a n pectoralis  these  to a r r i v e  Karauetari  Brazil,  masha-hara-hanak  sample.  the  each  By c o m p a r i n g t h e s e was a b l e  '  although  name of  the  pectoralis  Tototobi,  I  that  collected  studies;  native  powdered l e a v e s  certainly  the  Migliazza  tentative  L e o n a r d . One of  while  [2]  aromatic  s u b g r o u p on t h e R i o  latter  [2],  who a t  Anthropology at  liguistic  Migliazza.  of  of  Dr.  the c o r r e c t  tended to c o n f i r m these  plant  are  College Park.  r e p o r t e d by S c h u l t e s  samples are  Migliazza,  the Department  were c o l l e c t e d ,  probable botanical  Rio  of  1974 by D r .  s a m p l e s was n o t e d by D r .  with those  of  in  in connection with h i s  no v o u c h e r s the  the author  on t h e  University the  to  p e c t o r a l i s made by  has been e s t a b l i s h e d  by  146  c o m p a r i s o n of authentic to  their  mass s p e c t r a  standards.  speculate  that  B a s e d on t h i s  the  sample  powdered J u s t i c i a  admixtures.  The s i t u a t i o n  only  this  (Table  sample  account  for  explanation samples,  Just ic ia  the  absence  that  if  this  a p p l i e d to another  in  which  [24,  is  as  of  is  reasonable  + mashahara" without  label  any  to  the  indicates  present,  that  chemical  Prance,  the  sole  but  pectoralis  cannot  s p e c i m e n s . One  is  really  two  "buhenak  ingredient  "buhenak"  i n s t e a d may be a species,  is  that  this  or a r e l a t e d  comm.,  intoxicating  ingredient;  snuff  these  ethnobotanical  investigations.  sample c o n s i s t s material,  1983]  that using  reports  and of  term  which  of sample species,  as w e l l as c o u m a r i n s . T h e r e  pers.  c h a r r e d and c a r b o n i z e d p l a n t  issue  the manufacture  explanation  Justicia  Yanomama t e r m " c a r a k n a k " .  the  used i n  c o r r o b o r a t e d by f u r t h e r A third  the  probably a Vi r o l a  and i s  an  then  p e c t o r a l i s,  G. T . ,  e x p l a n a t i o n s may  voucher  "mashahari"  case,  tryptamines  Several  have been e x c h a n g e d on t h e  ingredient,  represent  derivatives  unfortunately  botanical  the  Just ic ia  Yanomama do p r e p a r e  pectoralis  but  An a l t e r n a t i v e  synthesizes  reports the  fact  pectoral is.  labels  tryptamines  Yanomama s n u f f . does  the  coumarin  sample l a b e l l e d  represent  does c o n t a i n  seems  with respect  pectoralis)  to the  difference  and t h e  + mashahara"; may not  of  is  clear  with  X & XI ) has d e t e c t e d DMT, 5-MeO-DMT, and NMT i n  this  be d e c i d e d i n  "buhenak  A l t h o u g h the  (Justicia  in addition  characteristic  it  p e c t o r a l i s leaves less  "mashahari".  one i n g r e d i e n t  analysis  is  values  evidence,  labelled  c o n s i s t s of  sample l a b e l l e d  and TLC Rf  exist  occasionally Justicia  need t o  be  chemical black,  labelled  T h i s t e r m d o e s not  partially  with  the  correspond to  any  1 47  of  those  r e p o r t e d by S c h u l t e s  carbonized Vi rola  resin.  snuff  on t h e  the  resin  becomes c a r b o n i z e d i n  rest of  this  of  the  the  to  which  produce the  of  snuff.  the p a r t l y  this  t h e p r o c e s s of is  Both i t s  Table X I )  make i t  either  powdered,  of  Based  resin.  dark  virtually  and i t s  the  Tototobi  nyakwana,  which  the  equivalence  exact  c o m p l i c a t e d by t h e i n c l u d e s at dialects; [25].  In  v i e w of for  term a p p l i e d to  fact  that  f o u r major  many of  by M i g l i a z z a closely  least  these this the  with those  that  it  is  various  labelled  resin  of  of  "yakuanabark  sample or o f  the  snuff  the  on t h e  close  these  to  native  languages,  mutually  remarkable snuff  r e c o r d e d by  each w i t h  that  finished  According Rio  yakuana. terms  is  family  numerous  unintelligible  the  names  recorded  components can be matched  Schultes.  (cf.  consists  t h e Yanomama l i n g u i s t i c  are  DMT and  support  admixtures.  reasonably  dialects is  levels  this  plus other  [2],  seems  high a l k a l o i d content  concentrated V i r o l a resin  to  "caraknak"  r e d d i s h brown powdered  certain  remainder  it  Table X I )  sample'is  the  coffee-colored  labeled  (cf.  of  from  The  description,  The low  of  the  carbonized material  on t h i s  to S c h u l t e s  Determining  boiling  powdered s e p a r a t e l y  charred material  appearance  containing Vi rola  is  a portion  ground i n t o a l i g h t  The f o u r t h  and c o n s i s t s  material.  snuff  mentions that  sample c o n t a i n e d  identification.  of  [2],  carbonized Vi rola  5-MeO-DMT w h i c h  sagona"  is  partially  d e s c r i b i n g the p r e p a r a t i o n  then mixed w i t h t h e  final  probable that consists  is  of  form a b l a c k i s h brown p o w d e r .  uncarbonized resin  powder,  this  Tototobi  carbonized material resin  but may c o n s i s t  Schultes,  the  resin;  Rio  [2],  so  1 48  B.  Quantitative  Analyses  The q u a n t i t a t i v e various Virola  Myristicaceous snuff  contain  data  of M y r i s t i c a c e o u s  for  the  similar  amounts of  snuff  sample c o n t a i n e d  order  of m a g n i t u d e as  tryptamines  drug samples  ("yakuana-sagona")  (Table  and t h e  alkaloids  Cauaburi.  snuff  nyakwana et  al.  [5]  DMT and 5-MeO-DMT, or more t h a n quantitative  [5,6], error of  this  is  sample,  The o t h e r contain  or  in  levels  in  compared t o  the  found in  were g e n e r a l l y  of  koey  For  instance,  in Witoto)  contained second,  derived  same o r d e r the  first  batch  this  [5]  who  Rio  of  It  is  of the  of  the  studies  possible  the  was  110 mg/g  light  and o t h e r  that  alkaloid  experimental  sample.  low  an  content data.  contained  m a g n i t u d e as of  70% of  levels  elongata.  and t h e q u a l i t a t i v e  to  quite  Tryptamine  paste  those  in  (designated  from A l f r e d o Moreno a t  from DMK-67,68, and 6 9 ,  specimens,  of  and f o u r t h b a t c h e s  been d e t e r m i n e d as V .  al.  the o r a l l y - i n g e s t e d M y r i s t i c a c e o u s  obtained  contained anomalously  same  Tototobi  In  and " c a r a k n a k " )  "yakuana"  18.8 mg/g a l k a l o i d ,  third,  the  Yanomama s n u f f s w h i c h were f o u n d  ("mashahari"  concentrations  snuff.  in  calculation the  Rio  The  of  from t h e  11% a l k a l o i d s .  t h e measurement  the  the  basis.  et  the  samples  t o c o n t a i n more t h a n  reported  components of  tryptamines  paste  wt  from the  open t o q u e s t i o n .  was made e i t h e r  the  low  work  figure  various  snuff  the  show t h a t  r e p o r t e d by H o l m s t e d t "epena"  other  XI)  on a d r y  f o u n d 7.15 mg/g i n a sample of  r e p o r t e d by H o l m s t e d t  found in  19.7 mg/g 5-MeO-DMT, a f i g u r e that  A sample of  Samples  w h i c h was  Puco  drugs the oo'-  Urquillo,  5-MeO-DMT.  The  o b t a i n e d from A l f r e d o Moreno of  alkaloid.  These batches  respectively,  all  of  C o m p a r i s o n of  the  voucher  and q u a n t i t a t i v e  which  were have  similarities  of  TABLE  XI - QUANTITATIVE  S a m p l e name & origin A. O r a l l y  ANALYSIS  OF TRYPTAMINES  Species & C o l l e c t i o n .#  active  Myristicaceous  a 1ka1o i d s detec ted  IN MYRISTICACEOUS  mg/g  SAMPLES  %  d wt.  pastes:  "oo'-koey" La C h o r r e r a . Colombia  no v o u c h e r  DMT NMT Total:  1 .58 9 . 43 1 1.01  14 86  "oo'-koey" Puco Urqu i 1 1 o A l f r e d o M o r e n o #1  DMK-40 V. s e b i f e r a  DMT 5-MeO-DMT NMT Total:  3 .8 13 . 2 1 . 78 18 . 78  20 70 10  "oo'-koey" Puco Urqu i11o A l f r e d o M o r e n o #2  DMK-67 V. e l o n g a t a  DMT NMT Total :  0 .065 0 . 86 0 .92  7 93  "oo'-koey" Puco U r q u i 1 1 o A l f r e d o Moreno #3  DMK-68 V. e l o n g a t a  DMT NMT Total:  0 . 25 2. 2 2 . 45  10 90  "oo'-koey" Puco U r q u i 1 l o A l f r e d o M o r e n o #4  DMK-69 V. e l o n g a t a  DMT NMT Total:  0 . 164 1 .43 1 59  10 90  "ku' - r u - k u " B r i l l o Nuevo M a r c o s F l o r e s #1  DMK-59 V. e l o n g a t a  5-MeO-DMT  15 . 72  100  B. Yanomama s n u f f s 8> s n u f f  admixtures:  "mashahar i " Venezuela  =  Justicia pectoralis (no v o u c h e r )  DMT 5-MeO-DMT Total:  0. 09 0. 52 0. 61  15 85  "caraknak" Venezuela  =  V i r o l a sp. carbonized resin (no v o u c h e r )  DMT 5-MeO-DMT Total:  0. 064' 0. 32 0. 384  17 83  = V i r o l a sp. (snuff) (no voucher)  5-MeO-DMT  "yakuana-sagona" Venezuela  19.7  100  Table  XI ( c o n t ' d )  Sample name S or i g i n C. V i r o l a  bark  Species & Co 1 1 e c t i o n # & leaf  V i r o l a sp.  V i r o l a sp.  Virola sp.  Virola  Virola  Virola  Virola  Virola  sebifera  elongata  callophylla  callophylla  elongata  mg/g  %  d wt.  samples:  DMK-30 1 eaves twigs  V i r o l a sp.  a 1ka1o i d s detected  DMK-35 1 eaves  DMK-36 1 eaves  DMK-37 1 eaves  DMK-40 1 eaves bark  DMK-41 bark  DMK-46 bark DMK-56 seeds &  DMK-59 bark 1 eaves  fruit  DMT NMT DMT NMT  0.08 trace 0.085 trace  DMT NMT  0.097 trace  100  DMT , NMT  0. 106 trace  100  DMT NMT  0.097 trace  100  NMT DMT 5-MeO-DMT NMT Total:  trace 0.078 0.181 trace 0.259  DMT NMT Total :  0.063 0. 102 0. 165  DMT  0. 56  100  DMT NMT  0. 185 trace  100  5-MeO-DMT NMT DMT NMT  0. 23 t race 0.17 trace  100  100 100  30 70  38 62  100  151  the  alkaloid  profiles  of  the  bark,  leaf  obtained  from t h e s e  three  specimens  it  clear  that  these  three  same  tree.  quite  from t h e  The v a r i a t i o n i n g e s t e d samples substantial  seen  in  (Table  XI)  For  in  the  example t h e  levels  Generally  the  involves  alkaloid  (e.g.  at  least for  than  technology  of  extracting,  in  from " r a w "  the the  that  for  their  IX  the  & X).  of  source-  The  were u s u a l l y  Therefore  which  it  60 -  seems  basically the  resin,  does  base c o m p o s i t i o n compared  of  the  compounds have a l s o bark a r g u e s  against  t h e moment t h e q u e s t i o n of  activity,  Similar  that  where t h e  minor c o n s t i t u e n t s ,  orally-ingested Myristicaceous potentiate  in  measurable  samples.  reflected  prepared pastes  may be a r t i f a c t s  these  present.  quantity.  snuff  instances (Table  #1).  p r e p a r e d from DMK-  and c o n c e n t r a t i n g  however  untreated V i r o l a  Disregarding  those  orally  to  bases  significant  source p l a n t s .  change  tetrahydro-/3-carbol i n e s , The f a c t  in  cooking,  source-plants;  process.  that  the p a s t e s  make  derived  the  from DMK-40 c o n t a i n e d  p r e p a r i n g the d r u g ,  in a d r a s t i c  in  XI)  considerable  tryptamine  examination  in  X,  A l f r e d o Moreno  a c c o m p a n i e d by  base c o m p o s i t i o n of  greater  result the  is  5-MeO-DMT i n any  concentrations  200 t i m e s  to  alkaloid  sample p r e p a r e d  were a v a i l a b l e  alkaloid  not  of  i n c o m p o s i t i o n were f o u n d - i n t h e  the  IX,  s a m p l e s were a l l  levels  k i n d and number of  source-plants,  that  paste  Tables  of DMT, 5-MeO-DMT, and NMT, w h i l e  differences  plants  of  variation  59 c o n t a i n e d o n l y  the  (cf.  samples  r a n g e d from no a l k a l o i d  concentrations  This quantitative variation  the  and p a s t e  drugs r e q u i r e  s u c h as  the  cooking been  isolated  this,  however.  whether  the  a MAOI i n o r d e r  we can use t h e q u a n t i t a t i v e  data  to from  1 52  T a b l e XI  to estimate  to e l i c i t [26] for  psychotomimetic  reported  in  require  the  typical that  reached at  i n g e s t i o n of  somewhat  less  much p l a n t I).  plant  major  material.-  constituent  material  would not  Virola  snuff  several  be a p r o b l e m but  some m e c h a n i c a l  of  bioassays  that  5-MeO-DMT; c e r t a i n l y  two p a s t e  samples which  (cf.  Chapter  III  pharmacological a c t i v i t y  of  the  the  showed t h e  these  one-tenth  as  (cf.  4 grams of  nose and  throat  active  a relatively  greater  was a c h a r a c t e r i s t i c greatest In  activity  fact,  preparations  is  the  of  in  the  actual  probably  d e t e r m i n e d by more than a s i m p l e d o s e - r e s p o n s e r e l a t i o n s h i p ; p r e s e n c e o r a b s e n c e of MAO i n h i b i t o r s , the  diet,  body w e i g h t ,  i n g e s t i n g the tolerance  is  physiological w h i c h was  drug,  and g e n e r a l  the  frequency  developed, are action  observed  in  of  all  these  the  health of  route of  the  of  the  ingestion,  person  use and whether  factors  of  orally-ingested  The most  contain this  or  i n g e s t i o n of 4  a b s o r p t i o n of  and T a b l e X I ) . of  the  would  paste  t h r e s h o l d dose  difficulties.  and s n u f f s may be t h o s e  for  5-MeO-DMT i n s t e a d  grams of the  i.e,,  that  1 gram of  then a p p r o x i m a t e l y  t h r o u g h t h e mucous l i n i n g  might p r e s e n t  if  would be an a d e q u a t e  i n g e s t i o n of  pastes  proportion  than  However  a 75 kg  mg/kg,  clear  dose  a t h r e s h o l d dose  " o p t i m a l " dose would r e q u i r e  of  The  1.0 is  Szara  threshold  15 mg f o r  0.7 -  content  DMT were t h e  lower  it  required  tryptamines.  0.2mg/kg, i . e . ,  alkaloid  wt  of  the  highest  w h i l e an  - 5 g dry  pastes  was  d r u g w h i c h would be  50 and 75 mg. Thus from T a b l e XI  samples w i t h the  Table  i.m.  with optimal e f f e c t s  between  snuff,  effects  self-experiments  DMT a d m i n i s t e r e d  adult,  the  t h e amount of  or  not  which c o u l d a f f e c t  d r u g s . The v a r i a b i l i t y  in  s e l f - e x p e r i m e n t s w i t h some s a m p l e s  the  response  1 53  examined i n indicate  the p r e s e n t  that  preparations  (cf.  Chapter  the a c t i v i t y / i n a c t i v i t y is  them b o t a n i c a l  IV.  study  of  III)  these  also  of  numerous v a r i a b l e s ,  or c h e m i c a l  in  nature.  not  all  of  Summary  s a m p l e s and i n p u r p o r t e d l y from M y r i s t i c a c e o u s quantitatively tests  in M y r i s t i c a c e o u s hallucinogenic  major  Sixteen  of  the  twenty  b a s e s were DMT a n d / o r  levels  of  samples.  and  eight  precipitation  bark  amounts of  / 3 - c a r b o l i n e s were not Considerable variation  usually  and  the  in a l k a l o i d  bark  samples c o n t a i n e d a l k a l o i d s ;  species  had d e t e c t a b l e  identified  as N - m e t h y l - t r y p t o p h a n  UV and mass s p e c t r a l orally-ingested except types  characteristics.  d r u g made from V i r o l a  one c o n t a i n e d  substantial  and p r o p o r t i o n s of  between s a m p l e s .  methyl  Samples  of V i r o l a  a d m i x t u r e s were a n a l y z e d and a l l  indolic ester  spp.  present  snuff  found, Fourteen  none of  A single  sample  on t h e  basis  tryptamines, varied  including one  of  an  were a n a l y z e d .  components but  the  base,  Seven s a m p l e s of  amounts of  tryptamines  was  same s p e c i e s .  alkaloids.  O s t e o p h l o e m p l a t y s p e r m u m c o n t a i n e d an  leaf  profiles  of  Iryanthera  amounts of  or  collections  eighteen V i r o l a  the  The  Detectable  extending to d i f f e r e n t the  of  leaf  alkaloids.  present.  found in  derived  and  5-MeO-DMT; much s m a l l e r  a n d / o r NMT were a l s o  leaf  preparations  a n a l y z e d u s i n g T L C , GC, a l k a l o i d  and GC/MS.  tryptamine  bark  s o u r c e s were q u a l i t a t i v e l y  samples a n a l y z e d c o n t a i n e d d e t e c t a b l e  of  to  Myristicaceous  a function  Alkaloid constituents  six  tends  All  but  greatly various contained  the  1 54  detectable highest while  levels  of  tryptamines.  concentrations  of  the M y r i s t i c a c e o u s  concentrations  ranging  The d r u g s a m p l e s h a v i n g  alkaloids bark  contained  and l e a f  from 0.05  to  the M y r i s t i c a c e o u s  of  / 3 - c a r b o l i n e s w h i c h had mass s p e c t r a  by  results  indicate  /3-carbolines i s  the M y r i s t i c a c e o u s probably  not  s a m p l e s had much wt.  that  unlikely pastes,  the  since  pharmacologically  the  two  amounts  c o r r e s p o n d i n g t o MTH/3C constituents,  inactivation  to account  wt  lower  Only  drug samples c o n t a i n e d d e t e c t a b l e  and DMTH/3C. The / 3 - c a r b o l i n e s were t r a c e These  15-20 mg/g d r y  0.26 mg/g d r y  of  the  for  of  the  p e r i p h e r a l MAO oral  activity  amounts d e t e c t e d  significant.  however.  are  of  155  V.  Literature  1.  R.  E. S c h u l t e s . (1979) E v o l u t i o n of t h e I d e n t i f i c a t i o n of the M y r i s t i c a c e o u s H a l l u c i n o g e n s of S o u t h A m e r i c a . J o u r n a l of E t h n o p h a r m a c o l o g y 1:211-239  2.  R.  E. S c h u l t e s , £< B. H o l m s t e d t of t h e M y r i s t i c a c e o u s S n u f f s Rhodora '70:11 3-160  3.  R.  E. S c h u l t e s & A . Hofmann. (1980) The Botany and C h e m i s t r y of H a l l u c i n o q e n s (2nd E d . ) C h a r l e s C . Thomas, P u b l i s h e r s . S p r i n g f i e l d , 111  4.  0.  R. G o t t l i e b . Myristicaceae 1:309-323  5.  S.  A g u r e l l , B. H o l m s t e d t , & J . E. L i n d g r e n . (1969) A l k a l o i d s i n C e r t a i n S p e c i e s of V i r o l a and O t h e r S o u t h A m e r i c a n P l a n t s of E t h n o p h a r m a c o l o g i c I n t e r e s t . A c t a Chemica S c a n d i n a v i c a 23:903-916  6.  B.  H o l m s t e d t , J . E. L i n d g r e n , T . Plowman, L. R i v i e r , R. E. S c h u l t e s & O. T o v a r . (1980) I n d o l e A l k a l o i d s i n Amazonian M y r i s t i c a c e a e : F i e l d and L a b o r a t o r y R e s e a r c h . H a r v a r d B o t a n i c a l Museum L e a f l e t s 2 8 : 2 1 5 - 2 3 4  7.  J.  M. C a s s a d y , G . E. B l a i r , R. F. R a f f a u f & V . E. T y l e r . (1971) The I s o l a t i o n of 6-methoxyharmalan and 6methoxyharman from V i r o l a c u s p i d a t a . L l o y d i a 3 4 : 1 6 1 - 1 6 2  8.  R.  M a r t e l l o & N. F a r n s w o r t h . (1962) O b s e r v a t i o n s on t h e S e n s i t i v i t y of S e v e r a l Common A l k a l o i d P r e c i p i t a t i n g Reagents. L l o y d i a 25:176-185  9. D.  Cited  B. R e p k e , Psilocybe,  (1968) The V e g e t a l Ingredients of t h e N o r t h w e s t Amazon.  (1979) C h e m i c a l S t u d i e s on M e d i c i n a l from A m a z o n i a . J o u r n a l of E t h n o p h a r m a c o l o g y  D. T . L e s l i e & G . Guzman. (1977) C o n o c y b e , and P a n a e o l u s . L l o y d i a  Baeocystin 40:566-78  in  10. W. A . R o d r i g u e s . (1980) R e v i s a o T a x o n o m i c a d a s E s p e c i e s de V i r o l a Aublet (Myristicaceae) do B r a s i l . A c t a A m a z o n i c a 1:1-123  1 56  11.  R.  E.  Schultes  12.  R. E. S c h u l t e s & T . S w a i n . (1976) an O r a l H a l l u c i n o g e n . J o u r n a l of 324.  13.  E. C o r o t h i e & T . N a k a n o . V i r o l a s e b i f e r a . Planta  14.  S. R. J o h n s , J . A . L a m b e r t o n , & A . A. S i o u m i s . (1971) The M a j o r A l k a l o i d of A o t u s s u b g l a u c a ( L e g u m i n o s e a e ) , S-(+)-N m e t h y l t r y p t o p h a n m e t h y l e s t e r . A u s t r a l i a n J o u r n a l of C h e m i s t r y 24:439-40  Hallucinogen.  (1969)  Harvard  Virola  as  an  Botanical  (1969) Medica  Orally-administered  Museum L e a f l e t s  22:229-40.  F u r t h e r N o t e s on V i r o l a as P s y c h e d e l i c Drugs 8:317-  Constituents 17:184-88  of  the  Bark  of  15. N. Mandava, J . D. A n d e r s o n & S. R. D u t k y . (1974) I n d o l e P l a n t - g r o w t h I n h i b i t o r from A b r u s p r e c a t o r i u s S e e d s . P h y t o c h e m i s t r y 13:2853-2856 16.  S.  Ghosal,  17.  R. T . C o u t i s , R. A . L o c o c k & G . W. A. S l y w k a . (1970) S p e c t r a of S e l e c t e d /3-carbol i n e s [ /3-9H-pyr i d o ( 3 , 4b ) i n d o l e s ] . O r g a n i c Mass S p e c t r o m e t r y 3:879-889  18.  S. A g u r e l l , B. H o l m s t e d t , J . E. L i n d g r e n , & R. E. Schultes. (1968) I d e n t i f i c a t i o n of Two New / 3 - c a r b o l i n e A l k a l o i d s i n South American H a l l u c i n o g e n i c P l a n t s . Biochemical P h a r m a c o l o g y 17:2487-88  19.  S c h u l t e s , R. E. (1972) E t h n o t o x i c o l o g i c a l S i g n i f i c a n c e A d d i t i v e s t o New W o r l d H a l l u c i n o g e n s . P l a n t S c i e n c e B u l l e t i n 18: 34-41  20.  Der M a r d e r o s i a n , A . H . , H. V . P i n k l e y , & M. F. D o b b i n s IV. 91968) N a t i v e Use and O c c u r r e n c e of N,N-dimethyltryptamine i n the L e a v e s of B a n i s t e r i o p s i s r u s b y a n a . A m e r i c a n J o u r n a l o f Pharmacy 140:137-147  21.  N. S. B u c k h o l t z & W. 0 . B o g g a n . (1976) E f f e c t s of T e t r a h y d r o - / 3 - c a r b o l i n e s on Monoamine O x i d a s e and S e r o t o n i n U p t a k e i n Mouse B r a i n . B i o c h e m i c a l P h a r m a c o l o g y 2 5 : 2 3 1 9 2321 1976  Alkaloids  R.  of  Ballav, Sida  P.  S.  Chauhan k R.  cordi f o l i a .  Mehta.  Phytochemistry  (1975)  14:830-832 Mass  of <  157  22.  R. G. T a b o r s k y & W. M. M c l s a a c . (1964) The S y n t h e s i s and P r e l i m i n a r y P h a r m a c o l o g y of Some 9 H - P y r i d o [ 3 , 4 - b ] i n d o l e s ( / 3 - c a r b o l i n e s ) and T r y p t a m i n e s R e l a t e d t o S e r o t o n i n and M e l a t o n i n . J o u r n a l of M e d i c i n a l C h e m i s t r y 7:135-141  23.  D. MacRae & G . H. N. Towers (1984) J u s t i c i a p e c t o r a l i s , a Study of t h e B a s i s f o r i t s Use as a V i r o l a S n u f f A d m i x t u r e . J o u r n a l of E t h n o p h a r m a c o l o g y . S u b m i t t e d .  24.  C h a g n o n , N . , P. L e Q u e s n e , & J . M. Cook (1971) Yanomamo H a l l u c i n o g e n s : A n t h r o p o l o g i c a l , B o t a n i c a l , and C h e m i c a l F i n d i n g s . C u r r e n t A n t h r o p o l o g y 12:72-74  25.  E.  26.  S. S z a r a (1957) The C o m p a r i s o n of the P s y c h o t i c E f f e c t of T r y p t a m i n e D e r i v a t i v e s w i t h t h e E f f e c t s of M e s c a l i n e and LSD-25 i n S e l f - e x p e r i m e n t s . p p . 460-467 i n S. G a r a t t i n i & V . G h e t t i ( e d s . ) P s y c h o t r o p i c D r u g s E l s e v i e r , Amsterdam.  C. M i g l i a z z a .  Intelligibility.  (1972) PhD.  Yanomama Grammar and  Thesis,  Indiana  University.  1 5 8  CHAPTER V I : ORALLY-ACTIVE MALPIGHIACEOUS AND MYRISTICACEOUS HALLUCINOGENS AND THEIR CONSTITUENTS AS MONOAMINE OXIDASE INHIBITORS I.  Introduction  The m i t o c h o n d r i a l l y - l o c a l i z e d enzyme monoamine (MAO)  plays  an  important  i n mammalian m e t a b o l i s m . MAO  catalyzes  the  including  tyramine,  tryptamine,  dopamine,  and o t h e r  monoamines, a c c o r d i n g t o  reaction RCH NH 2  equation + 0  2  vertebrates intestine,  to  accumulated  norepinephrine, the  widely  distributed  and i n v e r t e b r a t e s ,  3  inactivate  2  i n c l u d i n g the  function  liver,  heart,  the  diet  acid decarboxylation. and s e l e c t i v e  f u n c t i o n as CNS  indicates  related  of  that  the v i s c e r a l  systems  from t o x i c  Evidence  two  to c e r t a i n  to  species,  has  its as  been  MAO s y s t e m  biogenic  of  the  amines  aromatic  amino  specificity  MAO i n h i b i t o r s  indicates  d e s i g n a t e d MAO-A and MAO-B  Houslay  & Tipton  of  species  u s i n g mixed s u b s t r a t e  two  [ 2 ] , The  to protect  b a s e d on s u b s t r a t e  [4,5,6,7]. the  small  neurotransmitter  evidence  and formed as a r e s u l t  sensitivity  t h a t MAO c o n s i s t s  brain,  in  e n d o g e n o u s l y p r o d u c e d monoamines s u c h  n e r v o u s and c a r d i o v a s c u l a r in  tissues  and l u n g s  of MAO i s  [ 3 ] , Considerable experimental [ 2 ] which  2  throughout v a r i o u s  b l o o d p l a s m a and p l a t e l e t s , metabolic  + H 0  f u n c t i o n s a s a d e t o x i f i c a t i o n mechanism s e r v i n g  ingested  general  [1]:  s e r o t o n i n or d o p a m i n e , w h i c h substances  b i o g e n i c monoamines  serotonin,  2  significant  ability  d e a m i n a t i o n of  + H 0 --MAO—> RCHO + N H  2  The enzyme i s  most  oxidative  role  oxidase  [7] carried  out a k i n e t i c assays  evaluation  and c o n c l u d e d  159  that  the  substrates  phenylethylamines free  p-hydroxyl  species  for  species A a c t i v i t y  and 0 - p h e n y l e t h a n o l a m i n e  B activity  included substituted  derivatives,  phenylethanolamines. and t h e m-O-methyl  derivatives  aromatic  (e.g.,  adding a polar (e.g.  or  results  the  above  MAO-B s i n c e the  rule it  existence  selective  it  two  derivatives,  species  is  the  indole alkaloids 2).  that  for  substances  norepinephrine interact In  general  The  investigated,  to  form  specific but  for  if  it  conforms  b o t h MAO-A and  Further  evidence  of MAO comes from e x p e r i m e n t s  for  using  [5]. w h i c h have been t h e  investigations  which are  of four  phenylcyclopropylamine  synthetic  derivatives,  widespread  focus  b e l o n g t o one of  propargylamine,  These are  0-carboline  T h e s e compounds a r e  dopamine,  0-phenylethylamines  known t o have c o r r e s p o n d i n g a n a l o g u e s  exception  out  benzylamine).  substituents.  N-benzyl-N-methyl [9].  0-  0-  substances which  would be a s u b s t r a t e aromatic  for  substrates  s e r o t o n i n and  hydrazine d e r i v a t i v e s ,  piperidinopyrazine not  been  t h e MAO i n h i b i t o r s  viz.,  point  i n a common s u b s t r a t e .  b i o c h e m i c a l and c l i n i c a l classes,  substituted  [8]  than  group to  MAO i n h i b i t o r s  Most of  b e n z y l a m i n e and  r e m o v i n g one from s e r o t o n i n  lacks of  Substrates  dopamine a r e  al.,  rings  m e t a b o l i s m of DMT has not to  of  0-phenylethylamine,  hydroxyl  tyramine)  tryptamine  et  not  0-  having a  5-methoxytryptamine,  w i t h MAO-A s u c h as  have more p o l a r w i t h MAO-B  but  Tryptamine,  b o t h MAO-A and MAO-B. N e f f interact  derivatives  g r o u p ; and 5 - h y d r o x y t r y p t a m i n e .  phenylethylamine  which  were s u b s t i t u t e d  or  compounds w h i c h  in n a t u r e . a g r o u p of  in nature  biosynthetically  2-methyl-3-  derived  [10] from  The  are  major  tricyclic (cf.  Fig.  tryptamine  1 60  and i t s  derivatives  tryptamine first  and c a n be r e a d i l y  derivatives  to demonstrate  extremely These  potent  [11].  that  investigators  increasing  carbolines  Subsequently, harmaline  experiments  that  it  The c a p a c i t y  ayahuasca  other  orally  of  [13,14,15,16]  tryptamines  & V).  0-carbolines as  viridis,  ayahuasca  (cf.  which a r e  prepared  Chapter  contain  alkaloids;  well  harmine,  tetrahydro-/3-  MAO has  for  the for  been  oral the  from V i r o l a  activity  activity  spp.  of  [17,18,19].  hallucinogenic  psychotomimetic (DMT),  5-methoxy-N,N-  tryptamine  derivatives  (cf.  amounts of  the  the  some s a m p l e s c o n t a i n  7-  admixture  preparation Virola  various as  Chapters  and  from t h e  sap of  tryptamines  that  o f MAO-A.  harmaline,  cambial  decreased  serotonin,  The o r a l l y - i n g e s t e d  psychoactive  in a d d i t i o n  ring;  inhibit  commonly u s e d i n  from t h e  0-carbolines  showed  as DMT d e r i v e d  IV).  are  activity  al.[4]  and r e l a t e d  substantial  compounds  et  contain  0-carboline  contains  Psychotria  species,  spp.  the  however.  orally-ingested  (5-MeO-DMT)  as w e l l a s  tetrahydroharmine plant  and t h e  were  activity,  s u c h as N , N - d i m e t h y l t r y p t a m i n e  Ayahuasca  substituted  and t h a t  and p o s s i b l y a l s o  from V i r o l a  dimethyltryptamine derivatives,  to  [12]  aromatic  inhibitor  ingested drugs d e r i v e d  derived  fully  o x i d a t i o n of  0-carbolines  from  monoamine o x i d a s e .  piperidine  by F u l l e r  inhibited  of  mechanism r e s p o n s i b l e  Both ayahuasca pastes  the  was a s p e c i f i c  s u g g e s t e d t o be the of  of  showed s i g n i f i c a n t  selectively  indicating  inhibitors,  saturation  still  the  al.,  and r e l a t e d  inhibitors  showed t h a t  were t h e most e f f e c t i v e with  U d e n f r i e n d et  harmaline  reversible  synthesized  the trace  of  pastes,  Virola  major amounts  of  IV  161  tetrahydro-0-carbolines tryptamines not MAO;  orally in  the  this  activity  of  ayahuasca  and t h e V i r o l a  of MAO by t h e s e been  investigated.  of  composition  mixtures of  the  exhibit  synergistic  A.  compounds may  of  the  oral the  fractions  as  specific  of  various  inhibitors  relationships  of  MAO-A was  of  a  selected  were d e t e r m i n e d .  Activity  the  alkaloid  fractions  pastes.  to determine activity  was a l s o  of  ayahuasca  The m i x t u r e s of whether  The a c t i v i t y  of  of  of  Vi rola  one V i r o l a  lignan  investigated  three  were  alkaloids  The MAOI a c t i v i t y  fractions  and a c r u d e  the  standards  c o m b i n a t i o n s of  as MAOI.  basic  and  fraction  two paste  paste isolated  [26].  and Methods  Preparation  Rat-liver,  has  0-carboline  compounds w h i c h a p p r o x i m a t e d  lacking alkaloids elongata  active.  preparations, alkaloid  are  peripheral  the  s a m p l e s and t h e  Materials  the  but  compounds was compared w i t h  s a m p l e s were i n v e s t i g a t e d .  II.  their  from e a c h c l a s s  individual  in order  from V .  by  rendered o r a l l y  paste  The s t r u c t u r e / a c t i v i t y  assayed  sample  however,  the a c t i v i t y  derivatives  o r a l l y - i n g e s t e d Vi rola  ayahuasca  d r u g s or  study,  derivatives  measured w i t h  hallucinogens,  investigated.  present  and t r y p t a m i n e  activity  0-carbolines,  The  mechanism has been p r o p o s e d t o u n d e r l y  not p r e v i o u s l y  sample of  of  from d e a m i n a t i o n and t h u s  Although  the  potent  [16,19]).  p r e s u m a b l y due t o d e a m i n a t i o n  presence  be p r o t e c t e d  In  C h a p t e r V and  DMT and 5-MeO-DMT a r e active,  inhibition  (cf.  of  rat-liver  obtained  cytosol  from mature  female W i s t a r  rats,  was  162  u s e d as  the  s o u r c e of monoamine o x i d a s e  were s a c r i f i c e d  by s t u n n i n g f o l l o w e d  The a b d o m i n a l c a v i t y p e r i t o n e u m and t h e phosphate b u f f e r , with a beveled was  was opened by r e m o v a l  liver pH 7.2  of  injection  steel  liver  was  sonicated  fraction  was  kept  was  used without  B.  1:1  fragments.  with b u f f e r .  for  10 s e c .  for  further  of  hepatic  to a  the  vein  placed  was.  cytosol  T h i s d i l u t e d whole the  (±  3000 x  The s u p e r n a t a n t  of  in  glass  t o a smooth p a s t e  The d i l u t e d  duration  and  liver  The homogenate was c e n t r i f u g e d a t  on i c e  Preparation  skin  The p e r f u s e d  were t r a n s f e r r e d  remove n u c l e a r  fraction  belly  and i m m e d i a t e l y  ml b u f f e r ) .  and d i l u t e d  into  syringe.  1 g liver/3  collected  the  the  by  rats  dislocation.  [20]  and h o m o g e n i z e d i n c o l d b u f f e r  20 min t o  of  The  M sodium  homogenizer  g for  assays.  p e r f u s e d w i t h c o l d 0.1  #22 s t a i n l e s s  Portions  the  by c e r v i c a l  removed from t h e a b d o m i n a l c a v i t y  cold buffer.  for  cytosol  experiment,  and  centrifugation.  reaction  m i x t u r e and a d d i t i o n  of  labelled  substrate The a s s a y disposable ml.  was c o n d u c t e d a t  test  C o m p o s i t i o n of  added i n h i b i t o r cytosol, of  t u b e s . Volume of the  reaction  c o n s i s t e d of  and 25 ul l a b e l l e d  5-hydroxytryptamine  (Amersham).  concentration  of  ul a l i q u o t  the  to  the  C in  13 x 100 mm  reaction  mixture  in c o n t r o l s  375 ul b u f f e r , substrate.  m i x t u r e was  100 ul  whole  The s u b s t r a t e 1  substrate  activity 2 x 10~  3  reaction  of  0.5  lacking  (side-chain-2- "Ocreatinine  The l a b e l l e d  5HT t o a s p e c i f i c  37.5°  consisted sulfate  was d i l u t e d w i t h c o l d  carrier  0.835 mCi/mmole and a  M. At  this  mixture  dilution,  results  addition  in a f i n a l  of  a 25  volume  of  1 63  500 M1 and a 5HT c o n c e n t r a t i o n of  vCi  0.04  except  of  the  labelled labelled  5HT. A l l substrate  w h i c h were m a i n t a i n e d a t control  blanks,  were p r e p a r e d by min.  Prior  to  0.1  components of  reaction  mixture  were added t o t h e  reaction  tubes  ice  of  tubes  C water  a s s a y was  initiated  by a d d i n g a 25 nl  substrate  to  and r e p l a c i n g substrate After  the assay  M citrate.  to the  separate  lower  was  the  reaction  products are  were c o u n t e d f o r  Scintillation  C.  (New  soluble  the 37.5°  0.5 ml  T u b e s were  In in  this the  various  d i s s o l v e d i n 0.1  1.0  then 10 min  method,  [21]  organic  remains a  C.  saturated  1.0  England N u c l e a r ) .  in  the  ml  aliquot  vial  Scintillation  I s o c a p 300 L i q u i d  Counter.  s o l u t i o n s of  derivatives,  mixer,  1.0 ml of  to a s c i n t i l l a t i o n  10 min i n a S e a r l e  Assays using tryptamine  Stock  diluted  2000 rpm f o r  the p r o t o n a t e d s u b s t r a t e  9.0 ml A q u a s o l - 2  the  5 m i n . The  30 min a t  t o each t u b e .  10  t u b e s were  F o l l o w i n g a d d i t i o n of  upper p h a s e was t r a n s f e r r e d  containing  for  for  t e r m i n a t e d by a d d i n g  acetate  controls,  sec on a v o r t e x  o r g a n i c and a q u e o u s l a y e r s .  phase while  of  aqueous p h a s e . F o l l o w i n g c e n t r i f u g a t i o n ,  the  vials  bath.  1-2  aliquot  5 sec e a c h and c e n t r i f u g e d at  labelled  (upper)  of  for  reaction  f o l l o w e d by t h e a d d i t i o n of  and 2.0 ml e t h y l  vortexed  the  t u b e s were i n c u b a t e d f o r  reaction  T h i s was  the a c t i v e  b a t h and e q u i l i b r a t e d  mixing for  i n t h e water  30 min t h e  NaCl,  tubes,  Inactivated  i n b o i l i n g water  the a s s a y ,  immersed i n a 3 7 . 5 °  the  bath.  in c o m p o s i t i o n to  immersing the  initiation  of  the  0 ° C i n an  identical  mM, c o n t a i n i n g a t o t a l  and 0 - c a r b o l i n e  standards  0 - c a r b o l i n e and  tryptamine  N H C l , were p r e p a r e d so  that  1 64  addition i n an  of  a 50  inhibitor  500 u l .  soluble  from  i n 0.1 Stock  10~  c o n s i s t e d of  N HCI  3  to  10"  the  Boiled  of  were a l s o  addition controls assayed  with b u f f e r ,  HCI).  no a p p r e c i a b l e  T h e r e was  which b u f f e r  r e p l a c e d the  10% Tween-80  represented  relative  reaction  recovered  represented (usually  plus  a  cytosol,  warm water inhibitor  inhibitor  and 25 ul  before  bath, at  were  50 ul  concentration, added j u s t  in  concentration  containing  the  so t h a t  the  3 7 . 5 ° C was 5  difference  concentrations  to these  controls,  products recovered from t h e  control  200-300 cpm) counts.  was  subtracted  in which  and t h e  0.1  N  in N HCI  lacking  % inhibition  inhibitor  the  amount by  the  The b a c k g r o u n d c o u n t the  boiled  of  was  (measured as cpm)  in  no  was  controls  by d i v i d i n g  tubes.  detected  between  The c o n t r o l s  of  in  or w i t h 50 ul 0.1  and t h o s e  inhibitor.  enzyme but  (inhibitor  10% Tween-80,  0% MAO i n h i b i t i o n ;  by t h e a c t i v i t y  and i n h i b i t o r  containing active  inhibitor  r e p l a c e d the  tubes c o n t a i n i n g v a r i e d  amount  over  simultaneously  replaced either  labelled  the  were  concentrations  dilutions,  s o l u t i o n was to  of  b l a n k s c o n t a i n i n g d e n a t u r e d enzyme were i n c l u d e d  inhibitor  calculated  lower  100 ul whole  the c y t o s o l  In  inhibitor  volume  compounds were d i s s o l v e d  appropriate  t u b e s were t r a n s f e r r e d  each r u n .  or  result  5-Methoxy-diisopropyl  M. A s s a y m i x t u r e s  1 0  325 ul b u f f e r ,  time  for  1:10  The i n h i b i t o r  incubation min.  would  M and a t o t a l  3  so t h e s e  solutions  s o l u t i o n of  substrate. assay  10~  derivatives  p r e p a r e d by making s e r i a l  inhibitor  of  mixture  and 3 - [ 2 - ( 2 , 5 - d i m e t h y l ) p y r r o l y l e t h y l ] - i n d o l e  10% Tween-80.  range  to a r e a c t i o n  concentration  The t r y p t a m i n e  tryptamine poorly  aliquot  blanks  from b o t h c o n t r o l  counts  of  165  D.  Preparation  and q u a n t i t a t i o n  of  ayahuasca  samples  for  MAO a s s a y The a y a h u a s c a and Don Juan #2.  samples used in  F i v e ml a l i q u o t s  w i t h c h i l l e d m e t h a n o l and the removed by f i l t r a t i o n . to dryness N HCl to this  under  reconstituted in  Chapter  IV.  to c o n t a i n Serial 0 to  1:10  the  original  showed t h e  dilutions  of  the  the  assays  relative  a.  Equimolar  the  tetrahydroharmine; stock b.  solution:  Equimolar  2.16 mg/ml ( 1 0 ~ "ayahuasca  the  harmaline,  total  alkaloid  concentration  of  3  harmine,  harmaline,  b a s e d on a v e r a g e  analogue  26% t e t r a h y d r o h a r m i n e ;  in  #1"  ranging  from  of  the  the and %  of  ayahuasca. assayed:  and of  undiluted MW).  tetrahydroharmine,  undiluted  solution:  MW).  - 69% h a r m i n e ,  overall  samples  respectively.  M, b a s e d on a v e r a g e  of  of  controls.  c o m p o s i t i o n s were  (10"  0.01  alkaloids  inhibitors,  c o m p o s i t i o n of  alkaloid concentration M,  the  M1 a l i q u o t s  harmine,  2.115 mg/ml  3  dilution  samples,  of  mixture  and DMT; t o t a l  c.  following  mixture  5 ml  were a l s o c o n d u c t e d u s i n g m i x t u r e s  s t a n d a r d s which a p p r o x i m a t e d the Mixtures having  to  the  50 ml  evaporated  s o l u t i o n s were added t o  same manner as  was c a l c u l a t e d  Inhibitor  then  reconstituted  N HCl. Fifty  d i l u t e d ayahuasca in  A 1:1  #1  precipitate  alkaloid,  reconstituted  7  inhibition  volume.  mg/ml and 4.8 mg/ml t o t a l  mixture  to  u s i n g t h e HPLC method d e s c r i b e d  1 0 ~ , were made u s i n g 0.01  reaction  s o l u t i o n was  s o l u t i o n was u s e d t o q u a n t i f y  This quantification  appropriately  e a c h were d i l u t e d  white n o n a l k a l o i d a l  The f i l t e r e d  the m i x t u r e  3.5  of  were Don F i d e l  r e d u c e d p r e s s u r e and r e s o l u b i l i z e d i n  reconstitute  present  the assay  4.6% h a r m a l i n e ,  concentration  equivalent  to  and the  1 66  equimolar d.  mixture.  "ayahuasca  analogue  tetrahydroharmine, to  the•equimolar  E.  and q u a n t i t a t i o n  Don M a r c o s  paste  from La C h o r r e r a ,  wt  of  the  of  in  (V.  Colombia  the  from V i r o l a  elongata,  each paste  original  resolubilized  sebifera,  DMK-59)  (no v o u c h e r ) .  and t h e  Aliquots  sample e q u i v a l e n t  sample were e v a p o r a t e d  conditions  quantitative  diluted  to q u a n t i t a t i v e l y  identical  samples  tryptamines  this  s a m p l e . The q u a n t i t a t i v e  were  the ayahuasca of  ul a l i q u o t s  in order  the  (cf  to  those  Chapter  determine  used i n the IV).  (Table  XII).  An " a n a l o g u e "  of  c o n s i s t e d of  tryptamine  standards  a mixture of  p r o p o r t i o n s and c o n c e n t r a t i o n s  the  Each paste  paste  t h e monoamine o x i d a s e sample and t h e  analogue  If  alkaloid  analytical of  e a c h sample  was  "analogue" in  a n a l o g u e were  system.  injected  the  the  a s were measured i n  sample and i t s  1:1  concentration  from  Each p a s t e  in  and  quantitation  The m o l a r  i n e a c h sample was c a l c u l a t e d  data  the  methods and  standards.  assayed  the  Pasteur  sample were  prepared using tryptamine  samples.  "oo-'-  2 ml m e t h a n o l . One ml was r e m o v e d , d i l u t e d  of  o n t o t h e HPLC  (DMK-  of  to dryness  pipette.  Twenty  were  to 0.2-0.4 g  through a cotton-plugged  of  paste  assay  w i t h m e t h a n o l , and f i l t e r e d  content  equivalent  of M y r i s t i c a c e o u s  samples used f o r  prepared  sample #1,  methanol e x t r a c t s dry  concentration  22%  f o r MAO a s s a y  A l f r e d o Moreno sample #1,  koey"  6% h a r m a l i n e ,  mixture.  The M y r i s t i c a c e o u s  40),  - 65% h a r m i n e ,  and 7% DMT; o v e r a l l  Preparation  samples  #2"  same  the  paste  simultaneously  t h e MAOI a c t i v i t y  were e q u i v a l e n t ,  this  would  of  Table  XII: Alkaloid Concentration in Myristicaceous A s s a y e d f o r MAOI A c t i v i t y *  Sample Name  Alkaloids Detected  Alkaloid Concentration  (mg/ml)  Paste  Samples  Mo 1 a r Concentration  NMT  1 . 38  7.9 x 1 0 "  "oo'-koey"  DMT  0. 1  0.53  (no  Total  1 . 48  8 . 43 x 1 0 "  5-MeO-DMT  2 .03  9.3  5-MeO-DMT  1.19  5 . 48 x 1 0 "  DMT  0.3  1 .54 x 1 0 "  Total  1.49  7.02  La  Chorrera  voucher)  Don M a r c o s #1  x 10"  x 10"  (DMK-59)  Alfredo (DMK-40)  M o r e n o *'1  * HPLC q u a n t i t a t i o n c a r r i e d o u t o n s a m p l e s r e s o l u b i 1 i z e d M a t e r i a l s and Methods.  x 10"  i n 10% Tween-80. C f  (M)  168  indicate solely  that  to  enzyme i n h i b i t i o n  the  tryptamines,  5HT f o r MAO-A. activity  of  If  which are  the MAOI a c t i v i t y  the a n a l o g u e ,  constituents  _in a d d i t i o n  the  over-all  inhibitory  the  paste  however, to  the  its  80. V.  additional  of  substrates  the p a s t e  this  would  exceeded  indicate  tryptamine  pavonis)  and the  undiluted stock  paste  lignan in  sample  amount of  dissolved  from V .  e a c h was  3.0  to  in  10%  If  the  sample  to  from  10% Tween-  f r o m DMK-34, elongata  10% Tween-80. C o n c e n t r a t i o n s  s o l u t i o n s of  some  quantitation,  restore  (derived  fraction  the  that  " a n a l o g u e s " were p r e p a r e d standards  of  were c o n t r i b u t i n g  F o l l o w i n g HPLC  Tween-80 was added t o  The a l k a l o i d - f r e e  were a l s o p r e p a r e d  III.  competitive  attributable  removed under n i t r o g e n .  v o l u m e . The p a s t e  s o l u t i o n s of  mg/ml,  was  s a m p l e s were d i l u t e d w i t h an e q u i v a l e n t  original  stock  pastes  tryptamines  activity.  Tween-80 and t h e m e t h a n o l was necessary  by t h e  g dry  (DMK-59)  of  the  wt/ml and 10  respectively.  Results  A.  and D i s c u s s i o n  0 - c a r b o l i n e s and T r y p t a m i n e s a s MAOI:  Structure/Activity  Relationships  1. In the  0-carbolines  order  to assess  the  /3-carboline s k e l e t o n  activity (Table  of  XIII)  fraction  as  influence  (cf.  Fig.  of  2)  structural  on the MAO i n h i b i t o r y  t h e s e compounds, a s e l e c t e d g r o u p of were a s s a y e d the  s o u r c e of  i_n v i t r o  u s i n g the  enzyme and  variation  1  standards  rat-liver  "C-labelled  5-  cytosol  of  169  hydroxytryptamine lists the  1 5 0 values  values  al.,  creatinine  sulfate  f o r the present  r e p o r t e d by M c l s a a c  of i n h i b i t o r  i n h i b i t e d with respect Estevez  to controls  as s u b s t r a t e ,  Since  and a l s o  enzyme, values  enzyme a c t i v i t y lacking  while Buckholtz 1  and p a r t i a l l y reported  in Table XIII  general,  however,  fraction  and  reported  studies.  as s u b s t r a t e .  substrate  study  inhibitors  Thus,  relationships  a r e i n agreement  f o r example,  the f u l l y  potent. potent this  Estevez  the p i p e r i d i n e  harmaline,  analogues  The 7 - s u b s t i t u t e d than  s t u d y and t h a t  is fully  saturated  Inhibitory  harmine and h a r m a l i n e ,  the f u l l y  aromatic  but of  more  the corresponding 6-substituted  [ 2 2 ] f o u n d 6-methoxy-harman  fully  compound i s more  / 3 - c a r b o l i n e s were g e n e r a l l y  of Buckholtz  study  inhibitors  between t h e 7 - m e t h o x y l a t e d  and d i h y d r o d e r i v a t i v e s  inhibitors  In  aromatic and  and t e t r a h y d r o h a r m i n e ) .  i s roughly equivalent  6-methoxylated  are not  with the  ring  i n which  so  of /3-carbolines  than analogues  aromatic  of the  the I  i n [22] and [23].  more p o t e n t  potency  is  used,  dihydro-/3-carbolines a r e s i g n i f i c a n t l y  harmine,  C  t h e c o n c l u s i o n s s u g g e s t e d by t h e p r e s e n t  a s monoamine o x i d a s e previous  1 a  s o u r c e and p r e p a r a t i o n  f o r the present  regarding the s t r u c t u r e / a c t i v i t y  in  Mclsaac &  e t a l . [23] u t i l i z e d  by t h e p a r t i c u l a r  comparable t o those  the  i s 50%  inhibitor.  "C-tryptamine  d e t e r m i n e d by t h e t i s s u e  directly  (cf.  includes  t h e d e g r e e o f MAO i n h i b i t i o n m e a s u r a b l e _in v i t r o  partially  XIII  [ 2 2 ] and B u c k h o l t z , e t  mitochondrial  mouse whole b r a i n homogenate and  Table  v a l u e c o r r e s p o n d s t o t h e molar  50  a t which  [22] used a c a l f - l i v e r  tyramine  experiment Estevez  [ 2 3 ] f o r c o m p a r i s o n . The I  concentration  as s u b s t r a t e .  analogues  e t a l . [23] but Mclsaac & was e q u i p o t e n t  with  harmine  170  TABLE STRUCTURE/ACTIVITY Inhibi tor  XIII  RELATIONSHIPS OF /3-CARBOLINES AS MAO INHIBITORS  I 50*  Iso  Mclsaac et al.t  Iso  Buckhol et a l . *  Harmine  1 .26 X  10"  8  1.5  X  1 o-  8  8.0  X  10"  Harmaline  1 .58 X  10"  8  1.0  X  1 o-  6  6.0  X  10"  THH  1 . 77 X  10-  6  not  tested  1 .4 X  10"  6MeO-harmalan  1 .20 X  10"  6  4.5 X  10-  1.8  X  10-  6MeO~harman  7.08 X  10"  7  1 .5 X  10"  3.1  X  10"  Harmol  5.00  X  10-  7  2.7  X  1 o-  5.8  X  10"  Harman  4.47  X  10"  7  5.0  X  10'  3.3  X  10-  Norharman  3.55 X  10"  6  7.5 X  10'  2.0  X  10"  6-MeO-MTH/3C  3.98 X  10-  7  not  not  tested  7  8  8  9  1 0  tested  8  8  5  5  5  6  6  5  * I = m o l a r c o n c e n t r a t i o n of i n h i b i t o r e q u a l t o 50% i n h i b i t i o n of a c t i v i t y w i t h r e s p e c t t o c o n t r o l s ( p r e s e n t e x p e r i m e n t ) . V a l u e s g i v e n a r e means of a t l e a s t t h r e e s e p a r a t e d e t e r m i n a t i o n s , t R e s u l t s r e p o r t e d by M c l s a a c e t a l . [22] u s i n g c a l f - l i v e r m i t o c h o n d r i a & t y r a m i n e as s u b s t r a t e . $ R e s u l t s r e p o r t e d by B u c k h o l t z e t a l . [23] u s i n g mouse whole b r a i n homogenate and t r y p t a m i n e as s u b s t r a t e . 50  171  TABLE XIV  - MAOI ACTIVITY OF AYAHUASCA SAMPLES AND MIXTURES OF /3-CARBOLINES  Inhibitor 5 0  % inhibition 1 0" M 3  Harmine + THH + Harmalinee q u i m o l a r mix #1  3.16  x 10'  94  Harmine + THH + Harmaline e q u i m o l a r mix #2  2.51  x 10  99.6  Harmine + THH + DMT + Harmaline e q u i m o l a r mix #3  7.1  ayahuasca "analogue"  #1*  3.98  x  10'  7  99.3  ayahuasca "analogue"  #2+  2.82  x  10"  B  99.3  ayahuasca samples:$ Don F i d e l #1  1.58  x 10-  5  Don J u a n  #2  - 8  x 10-  99.2  8  <1.0 x 1 0 '  7  * M i x t u r e of / 3 - c a r b o l i n e s a p p r o x i m a t i n g p r o p o r t i o n s f o u n d i n a y a h u a s c a , v i z . , 69% h a r m i n e , 26% THH, and 4.6% h a r m a l i n e . t M i x t u r e of 0 - c a r b o l i n e s + DMT a p p r o x i m a t i n g p r o p o r t i o n s f o u n d i n a y a h u a s c a , v i z . , 65% h a r m i n e , 6% h a r m a l i n e , 22% THH, and 7% DMT. $ F i g u r e s given for ayahuasca represent d i l u t i o n f a c t o r with respect to u n d i l u t e d samples.  at  1 72  while  6-methoxy-harmalan  harmaline. a  less  Hydroxyl  was a more a c t i v e  substitution  a c t i v e compound t h a n t h e  s u b s t i t u t e d compound ( c f . study less  harmane, active  equipotent  lacking  than  the  t o the  which agree  Mclsaac  et  than at  al.,  either  C i (cf  in these Mclsaac  [22]  substituents  7-methoxylated  and i n  and E s t e v e z  those  t o be i n  the  of  any  of  was a p p r o x i m a t e l y The g r e a t e r other  the  activity  6-methoxylated  methylation  of  by e i t h e r  al.[23];  former  of  the  the  piperidine  inhibitory the  basicity  structural  of  Lack  authors,  a methyl  et  al.  somewhat  of  for  spp.,  a s harman  greatest  and  inhibitory  /3-carbolines t e s t e d ,  [22]  reported  or  and  t h a n THH. t o THH and  6-MeO-MTH/3C was  & Estevez  however,  to  the  not  Buckholtz,  that  et  acetylation  i n a compound l a c k i n g  substitution  f o r MAOI  but  activity  from V i r o l a  potency  nitrogen.  resulted  group  activity  [23]  greater  active  6-methoxy-2-methyl-  would c o m p l e t e l y  the p i p e r i d i n e n i t r o g e n ,  requirement  of  more  Buckholtz,  range  Mclsaac  This  [23].  a n a l o g u e s may be due p r i m a r i l y  nitrogen  activity.  al.  compound w i t h r e s p e c t  the p i p e r i d i n e  investigated  et  of m a g n i t u d e more a c t i v e  this  was  approximately  reduced  6-methoxylated  of  ring,  t o be somewhat  a compound r e p o r t e d  an o r d e r  in  present  in  found  same g e n e r a l  the  but  Buckholtz,  Thus 6-MeO-MTH(3C e x h i b i t e d t h e  activity  the  I  In  resulted  reported  harmane.  tetrahydro-/3-carbol i n e ,  harmol.  of  of  results  a r o m a t i c compounds,  6-methoxy-harman.  [22]  for  analogue  fully  harmine and norharmane) assays  ring  on t h e a r o m a t i c  r e p o r t e d harmane or  than  c o r r e s p o n d i n g methoxy-  h a r m i n e and h a r m o l ) .  with those  harmine  norharmane t h a n  [16]  on t h e a r o m a t i c  6-methoxylated  results  inhibitor  activity.  which  is  abolish  probably a  173  2.  Tryptamines  A l t h o u g h the carboline  derivatives  investigated of  structure/activity  investigated tryptamines  as MAO i n h i b i t o r s has been  [22,23]  tryptamine  similar  derivatives the  as  effects  investigations  have of  inhibitors  was t h e  DMT and s e v e r a l  of  amine o x i d a s e  and 5HT were u s e d as substrate.  5-substituted  In  degree  of  substrates  a more r e c e n t  dimethyltryptamines,  electronic  of  inhibitory  DMT d e r i v a t i v e s  of  were more a c t i v e  MAOI and b o t h were g e n e r a l l y methyltryptamines. inhibitory giving molar  of  the a l k y l  Presumably also  the  was  50% i n h i b i t i o n ;  influence of  Of  activity  basis.  the  t h a n when  active  5-MeO-DMT was  activity  a reflection  of  MAO i n h i b i t i o n by  ring  and  the  as  a-  tested,  times  substituents  activity  The  greatest  1 mM c o n c e n t r a t i o n  of  e x h i b i t e d by t h e  their  and  substituents.  than  3.4  s i d e - c h a i n on t h e a c t i o n  the  when  less  active  s t u d y was u n d e r t a k e n t o a s s e s s  indole  liver  gramine d e r i v a t i v e s  4 DMT d e r i v a t i v e s  shown by DMT, a  The p r e s e n t various  less  methylated  tryptamine  steric  5-position the  [24]  c o u l d f i n d no  w i t h the  than  activity  Barlow  a-methyltryptamines,  activity  characteristics  t h e MAOI  related  [25]  0-  systematically  inhibition  study  the  in guinea-pig  g r a m i n e s was e x a m i n e d . T h e s e i n v e s t i g a t o r s correlation  of  of  not been c o n d u c t e d .  homogenates and f o u n d a g r e a t e r tyramine  relationships  on a  the  and m o d i f i c a t i o n s  tryptamines various  as  MAOI.  derivatives  as c o m p e t i t i v e  substrates  is of  MAO-A. C o m p a r i s o n of (Table  XV)  indicates  w i t h the that  the I  50  most of  I  50  values  values the  of  for  the  the  g-carbolines  (Table  XIII)  assayed are  one t o  two  tryptamines  tryptamine  derivatives  TABLE  Compound Assayed  XV - MAOI A C T I V I T Y OF TRYPTAMINE D E R I V A T I V E S AND MYRISTICACEOUS PASTES  o r sample  Tryptamine  150*  % I n h i b i t i o n at 1 x 10~ ' M  derivatives:  5-hydroxy-tryptophan  6 .31 x  10" '  56  Tryptam1ne  2 .82 x  10-  89  5 - M e 0 - 1 r y p t a m i ne  3 .98 x  10- '  89  ( m e i a t o n i n)  3 .98 x  10- •  70  N-methy1 - t r y p t a m i ne  2 .24 x  10"  s  90  N,N-d i methy 1 t r y p t a m i ne  1 .58 x  10"  !  99  5 - M e 0 - N , N - d i m e t h y l t r y p t a m i ne  4 .47 x  10-  2 .82 x  10" '  5  5-MeO-N-acety1-tryptamine  98  5  4-hydroxy-N.N-dimethy 1 tryptamine  (psilocin)  96  4-phosphoryl-N,N-dimethyl> 1 .00 x  10" '  35  tryptamine  >1 .00 x  10"  40  3-{2(2.5d1methyl )pyrro1y1-ethy1]-i ndole)  2 .51 x  tryptamine  (psilocybin)  5-Me0-N,N-d i i s o p r o p y 1 1  10-  5  91  Table  XV  (cont'd)  Compound o r Assayed  Myristicaceous La La  Chorrera Chorrera  Iso*  sample  pastes  Jorge  tt\  F l o r e s s a m p l e #1 F l o r e s analogue  Non-alkaloidal Churay  (DMK-34. V.  paste  analogues: 1 .51 1 .90  "oo'-koey" analogue  A l f r e d o Moreno s a m p l e A. M o r e n o a n a l o g u e Marcos Marcos  and  % I n h i b i t i o n at highest concentration  X X  10' 10"  5 5  96 94  (8 . 43 X (8..43 X  10" ' M)t 10" ' M)  8 .91 X 6 . 30 X  10" * 10"  96 97  (7 .02 (7 .02  X  10" * M) M) 10"  2 .95 X 2 . 34 X  10" 10"  92 92  (9 . 30 X (9 . 30 X  10" ' M) 10" * M)  88  (15  6  5 5  X  1  samples:  sample Pavonis)  #1 1200  „g  d wt/ml*  x  10  1  „g  d  Crude l i g n a n f r a c t i o n (DMK-59. V. E l o n g a t a ) 20 „g d wt/ml 64 (50 „g d w t / m l ) * M o l a r c o n c e n t r a t i o n a t 5 0 % i n h i b i t i o n o f enzyme a c t i v i t y t F i g u r e s g i v e n are % i n h i b i t i o n at h i g h e s t molar c o n c e n t r a t i o n of t r y p t a m i n e s i n sample or a n a l o g u e s . t F i g u r e s g i v e n a r e c o n c e n t r a t i o n s e x p r e s s e d as ^g d r y w e i g h t / m l .  wt/ml)  176  orders  of  magnitude  inhibitors  of  less  effective  MAO. The major  dimethyltryptamine;  w i t h the  derivatives  this  tested,  tetrahydroharmine tryptamine less  may be r e l a t e d side-chain c h a i n N.  are  to  the  relative  activity  at  ring  active  the h i g h e s t  is  psilocin  shows r e d u c e d but  compared t o DMT, but (psilocybin)  effect  of  various  more complex t h a n  well  essentially  largest of  the  alkyl-N  as  may p e r m i t  with l i p o p h i l i c  A certain  in  d e g r e e of  appears  t o be a r e q u i r e m e n t  because  t h e p r o t o n a t e d amine  even  of  the  and side-  orders  MAOI  of  MAOI  of  large  of  activity phosphoryl  the a c t i v i t y .  for  The  appears  instance  though i t the  the  the  to  the  same  has by f a r  lipophilic degree  side chain  the  nature  of  enzyme d e s p i t e  f o r MAOI a c t i v i t y ,  be  3-[2-(2,5-  approximately  case  interacts  ring  s u b s t i t u t e d compound  size;  of  of  by c o m p a r i s o n of  a considerable  basicity  activity  The i n f l u e n c e  substituents  residues  in  significant  w i t h the  this  magnitude  without  exhibits  tryptamine,  other  c o r r e s p o n d i n g 5-  abolishes  relative  to  and t h e  significant  side-chain  substituent;  N-substituent  interaction size.  activity  of  basicity  illustrated  still  tryptamine  All  reduction  used.  4-hydroxy  dimethyl)-pyrrolylethyl]-indole inhibitory  the  essentially  the  simply  orders  s i z e and p o l a r i t y  substitution  alkyl  XIII).  some one and o n e - h a l f  is  and p s i l o c y b i n ;  all  comparable  50  several  to  as  N,N-  (Table  concentration  substituents  B-carbolines  v a l u e of  50  t h a n DMT as MAOI,  psilocin  ester  I  is  and t h i s  and a l s o  MeO-diisopropyl analogue  bulky  one t o  than DMT as MAOI,  substituents  less  lowest  the  compound has an I  Thus 5-MeO-DMT i s  magnitude  exception  and 6-MeO-harmalan  derivatives  effective  than  its  nitrogen  presumably  w i t h an a n i o n i c  moiety  at  177  the a c t i v e basic  site  of  character,  e.g.  the N - a c e t y l a t e d MAOI a c t i v i t y .  the  this  tryptamine homologs, factors  B.  Presence  even  activity  of  0-carbolines  ayahuasca harmine,  standard mixtures  determine inhibition  by the  it  + DMT a t  included in  interfered  /3-carbolines.  contained approximately  representative  of  system,  appropriately  e x h i b i t e d by  the  shown by m i x t u r e s which a r e Four  of  known t o be  types  of  the  an  while  the  second  equimolar  the m i x t u r e  in order  The t h i r d and f o u r t h  same m o l a r c o n c e n t r a t i o n  as  the e q u i m o l a r m i x t u r e s ,  reflected  the p r o p o r t i o n s found in  from a n a l o g u e m i x t u r e  of  to  w i t h o r e n h a n c e d t h e MAO  alkaloids  omitted  activity  and t e t r a h y d r o h a r m i n e  DMT was  whether  a  i n our a s s a y  found i n a y a h u a s c a .  3 /3-carbolines  concentration;  steric  were c o m p a r e d . One was an e q u i m o l a r m i x t u r e  harmaline,  c o n t a i n e d the  than  a n a l o g u e s as MAOI of  and t e t r a h y d r o h a r m i n e ,  /3-carbolines  basic  non-polar.  activity  samples was compared t o t h a t  t h e major  harmine,  are  had been e v a l u a t e d the  the  d i i s o p r o p y l and h i g h e r  and a y a h u a s c a  inhibitory  and  lipophilic  a more a c t i v e MAOI  s a m p l e s . The a c t i v i t y  harmaline,  on t h e  with a secondary  the  this  to abolish  substituents  substituents  s t e p was t o e v a l u a t e  d i l u t e d ayahuasca  also  may be d i m i n i s h e d due t o  ayahuasca  relative  of  which a b o l i s h  5-hydroxy-tryptophan,  appear  non-polar  the case  t h o u g h the  Activity  next  of  interactions  o r NMT. In  Once t h e  the  zwitterionic  would e x p l a i n why DMT i s  however,  sample of  the  compound m e l a t o n i n ,  n i t r o g e n may enhance site;  enzyme. S u b s t i t u t i o n s  #3,  but  the  was  of  proportions  the ayahuasca but  mixtures  brews;  included  in  DMT was  analogue  178  mixture  #4 (cf.  Two of  the  Materials  and M e t h o d s ) .  ayahuasca  samples  # 2 and Don F i d e l HPLC  in order  sample  # 1 , were a n a l y z e d u s i n g  to determine  undiluted samples. T o t a l  the  concentration  subjected  s o l u t i o n was 50  that  of  the  system  both ayahuasca  enzyme a t  Don F i d e l ' s  even at  many o r d e r s first  magnitude.  empirical  properties  evidence of  preparation.  for  ayahuasca  It  study  oral  in v i t r o  action fully  of  the are  7  due t o  only  are  sample  effect  its  the  constitute of  the  required, particularly in both animals  the pharmacology of  that  on MAO  visceral  the  present  toward Further  i_n v i v o  and humans, this  by  hallucinogenic  the  ayahuasca.  of  the  ayahuasca  t h e DMT i n  step  the  that  of  first  of  concentration  inactivation  of  clearly  when d i l u t e d  that  rat-  MAO  indicate  even  hypothesis  potentiation  represents  sample.  # 2 exceeded 5 0 %  the  (10~ )  results  the  dilute  1 2 shows  effective  s h o u l d be e m p h a s i z e d , h o w e v e r ,  ayahuasca  elucidate  from each  These o b s e r v a t i o n s  u n d e r s t a n d i n g t h e p h a r m a c o l o g y of investigations  undiluted  w h i l e Don J u a n ' s  d e m o n s t r a t i o n of  MAO and c o n s e q u e n t  in v i t r o  These  were  t h e most  Fig.  the  determined  showed > 4 0 % i n h i b i t i o n  a c t i v e as an MAO i n h i b i t o r of  and p r o v i d e  #1 s t i l l  in  u s i n g t h e j_n v i t r o  extremely  one t e n - m i l l i o n t h  u n d i l u t e d brew. is  dilutions  1 2 , Table XIV).  strength,  5  ayahuasca  (Fig.  was  The s a m p l e s  as the  sample  alkaloids  so t h a t  activity  samples are  1 0 " full  inhibition  appropriate  f o r MAO i n h i b i t o r y  cytosol  inhibitors;  1:10 dilutions  7  M1 a l i q u o t s  liver  serial  1 x 1 0 " as c o n c e n t r a t e d  were a s s a y e d  the  to  of  respectively.  Don J u a n  quantitative  alkaloid concentration  t o be 4 . 8 mg/ml and 3 . 5 mg/ml, then  from P u c a l l p a ,  studies  in order  Amazonian d r u g .  of  the  to Another  1  !  0-  1 1<  1 E-  1 3-  1  1  4.  5*  1 £•  7*  NEGATIVE LOG DILUTION FACTOR Figure  12 - M A O I  Activity  + = Don J u a n x = Don F i d e l  of A y a h u a s c a  Sample Sample  #2 #1  180  point  worth mentioning  prepared  from B.  admixture the  to  caapi  plants;  preparation.  presumably the  the  is  in  the  that  alone without  these  T h i s would a l t e r  hallucinogenic  considerably  greater  s a m p l e s would be r e q u i r e d  its  this  if  a d d i t i o n of  pharmacology if  case  than  from  and  present,  would be due  concentrations  t h o s e measured  a nonsynergistic  is  any  DMT would be a b s e n t  effects,  In  on o c c a s i o n a y a h u a s c a  the  instances,  |3-carbolines a l o n e .  carbolines  fact  of  in  0-  our  mechanism  is  assumed. It  is  informative  by t h e m i x t u r e s elicited Figs.  of  by s i n g l e  13 & 1 4 ) .  In  harmine,  harmaline,  parallel  with  concentration  0-carboline  the  first  as  the mixture  assay,  analogue  equimolar  enzyme a c t i v i t y  at  a concentration  is  between  constituent the  least  of  the m i x t u r e  active  indicating  that  lower a  than  result  is  (harmaline,  with respect  I  50  to  would  value  not o b s e r v e d ,  of  of  I  x 10~  = 1.77  50  I  50  that  the  found  in  50% of  x 10"  rather  the value  6  8  M)  and  M) than  of MAO. A  values  any one c o n s t i t u e n t  indicating  individual  x 10~  inhibition in  overall  active  = 1.58  50  of  M. T h i s  7  t h e most  additively  their  result  I  XIV,  and 26%  inhibited  3.16  value  50  compounds a c t  interaction the  I  &  in  same  proportions  mixture of  the  but w i t h t h e  the  (tetrahydroharmine, these  synergistically synergistic  the  XIII  was a s s a y e d  4.6% h a r m a l i n e ,  The e q u i m o l a r  inhibition  (Table  - having  mixture  in approximately  69% h a r m i n e ,  produced  an e q u i m o l a r m i x t u r e  #1"  tetrahydroharmine.  intermediate  with the  and t e t r a h y d r o h a r m i n e  the  viz.:  % MAO i n h i b i t i o n  standards  components of  "ayahuasca  components p r e s e n t ayahuasca,  t o compare t h e  by  considerably itself;  inhibitory  such  100.  -ID*  . _ 5-  r E G A T I V E LOG  ••rCENTRATIQN  CM)  F i g u r e 13 - MAOI A c t i v i t y /3-carboline M i x t u r e s  of  harmine + h a r m a l i n e  + THH: E q u i m o l a r  Mixture  x = " A y a h u a s c a a n a l o g u e #1" - 69% h a r m i n e , 4 . 6 % h a r m a l i n e , 26% THH  182  activity  of  the  three  compounds c o l l e c t i v e l y  the  activity  of  I  value  "analogue  50  of  equimolar  the most e f f e c t i v e  mixture  respectively)  (3.98  that  essentially  slightly  a trace  contribute  significantly  which  drug  this In  the  to  second assay  parallel  w i t h an e q u i m o l a r  the  (Table  XIV)  in v i t r o  MAOI.  activity  of  less  in  close,  the  to expect  higher  value.  50  harmaline,  value  is  it  is  and p r o b a b l y d o e s  of  not  inhibition  it  that  the in  value  of  measured in  mixture  the of  x 10"  /3-carbolines it  is slightly  65% h a r m i n e ,  8  as  equimolar  and 7% DMT - was a l s o 2.82  this  /3-carbolines  w i t h DMT t o have a - containing  DMT would  that  equimolar  concentration  22% t e t r a h y d r o h a r m i n e ,  measured w i t h t h e  of  of  values  50  appears  the  in  determine  l a c k i n g DMT; t h e r e f o r e  " A n a l o g u e #2"  50  to  The I  of  /3-carbolines  concentrations  DMT i n  total  three  in order  however  the m i x t u r e  and f o u n d t o have an I the  out  effectiveness  the m i x t u r e  reasonable I  and  inhibitory  was a s s a y e d  the  g-carbolines.  the p r e s e n c e  mitigate  of  must be remembered, h o w e v e r ,  than  the  an e q u i m o l a r m i x t u r e  significant  m i x t u r e c o n t a i n i n g DMT t h e is  14)  mixture  the  were f a i r l y  system,  It  the  harmine  the monoamine o x i d a s e  was c a r r i e d  p r e s e n c e of  may s l i g h t l y  The  M,  7  than harmine,  and t e t r a h y d r o h a r m i n e  p l u s DMT. T h i s a s s a y  affect  with  f o r most of  in ayahuasca  (Fig.  harmaline,  the  group.  than  elicits.  harmine,  whether  greater  Although harmaline  stronger  component  identical  t h e c o m b i n a t i o n of  alone can account  t o or  not the  M and 3.16 x 1 0 '  7  e x h i b i t e d by a y a h u a s c a .  equivalent  compound of  was n e a r l y  x 10"  indicating  tetrahydroharmine activity  #1"  is  M, q u i t e  6%  assayed close  equimolar mixture c o n t a i n i n g  3-  to  2.  3.  A.  S>  B*  7-  B-  9-  IO-  11>  NEGATIVE LDD CONCENTRATION (M) F i g u r e 14 - MAOI A c t i v i t y of 0-carboline/DMT Mixtures + = harmine  + harmaline  x = harmine+ h a r m a l i n e = "Ayahuasca analogue  + THH: E q u i m o l a r  Mixture  + THH + DMT: E q u i m o l a r #2"  - 65% h a r m i n e ,  22% THH, 7% DMT  6%  Mixture  harmaline,  184  carbolines g r o u p of first  alone.  assays  group;  of  the  I  the  discrepancy in  Activity  the  values  50  were somewhat  batch v a r i a b i l i t y  C.  All  lower is  measured  than  in  this  t h o s e measured  probably  related  second in  to batch  rat-liver  enzyme  preparations.  of M y r i s t i c a c e o u s  pastes  and p a s t e  the to  "analogues"  as MAOI The t h r e e GC a n a l y s i s  Myristicaceous  had p r e v i o u s l y  concentrations activity  in  of  samples which  shown t o have  tryptamines  t h e _i_n v i t r o  concentrations  paste  (Table  rat-liver  and p r o p o r t i o n s of  XI)  for  mixtures  of  proportions  use  as  assays  in  (Table  by t h e  tryptamines. close  to  activity  trace in, of  of  the  tryptamines;  it  amounts of  e.g.,  the  pastes  XV,  (cf.  all the  themselves  15-17,)  paste  cases,  the  I  pastes  is  due s o l e l y  seems u n l i k e l y ,  tryptamines  is  the  to  the  has any  the  pastes  present.  to  the  almost  sample that  the  is  only quite  t h e MAOI of  the  presence  tryptamines  significance or  of  The r e l a t i v e  of  activity  containing  presence that  and  The r e s u l t s  paralleled  paste  of  simultaneously  t h e MAOI  indicating  addition  sample) of  were run  therefore,  /3-carbolines in  consisting  same c o n c e n t r a t i o n s  analogues,  analogue mixture  paste  s a m p l e s had been  show t h a t  of  50  the  & Methods).  pastes  the  La C h o r r e r a  the  the  of  e n h a n c i n g t h e MAOI a c t i o n  potentiating  in  the  in  f o r MAOI  The  "analogues",  Materials  Fig.  were a s s a y e d  tryptamines  Paste  orally-ingested  activity  In  that of  the  assay.  standards  sample  e x h i b i t e d by t h e exactly  the  tryptamine  w i t h each paste these  in  highest  enzyme s y s t e m .  s a m p l e s were d e t e r m i n e d by HPLC a f t e r prepared  the  quantitative  in  of (as  terms  orally MAOI  activity  185  10Q.  £•  3-  4.  E*  5-  7-  NEGATIVE LOG CONCENTRATION (M) Figure  15 - MAOI A c t i v i t y of M y r i s t i c a c e o u s P a s t e s : La C h o r r e r a O o ' - k o e y  + = La C h o r r e r a O o ' - k o e y x = La C h o r r e r a  "analogue"  (no  voucher)  (cf.Tables  XII  & XV)  186  of  the  of  tryptamines  only  pastes  appears  slightly  t o be a f u n c t i o n  present, lower  e.g.,  the  value this of  is  the  the  three,  which  DMT, t h e most e f f e c t i v e tested.  A l t h o u g h ijn v i v o  r e q u i r e d to confirm these indicates what  is  pastes  that  these  due t o are  the  orally  their  pastes  effective  oral  addition  the  investigate  DMK-34, V .  pavonis)  C h a p t e r VI) obtained of  inhibition  significant sample, the of  lignan the  was  t h e j_n v i t r o exhibit  the p a s t e  lignan  50  since  concentration  would be evidence  MAOI a c t i v i t y Therefore it  beyond  if  these  appears  of  s a m p l e s may a l s o  that to  and t r a c e s  the  a paste  system;  (DMK-59)  the  highest  the  highest  fraction.  in  o f /3-carbolines. sample  w h i c h was a l k a l o i d - f r e e in  be  n o n - n i t r o g e n o u s MAOI  a crude  Table lignan  assayed. (Fig.  concentrations.  For  By c o n t r a s t ,  was  the  order  from  X, fraction  Some  18)  but  the  crude e x t r a c t ,  concentration  In  (derived  (cf.  was a l s o  15000 ^g d r y wt/ml of  sample,  crude  experiments  bases a l o n e .  possibility,  elongata  at  I  tryptamine  was o b s e r v e d w i t h b o t h s a m p l e s  only  this  of  presence  was a s s a y e d  from V.  lowest  highest  as h a l l u c i n o g e n s ,  tryptamines this  t h e Don  activity.  due t o t h e to  in  t h a n MAO i n h i b i t i o n must be s o u g h t  The MAOI a c t i v i t y partially  do not  tryptamine  some mechanism o t h e r explain  results,  50  more a c t i v e MAOI  with expectations  the  I  former  tryptamine  the  MAOI of a l l  the  #1 had t h e  consistent  sample c o n t a i n e d p r o p o r t i o n a t e l y  derivatives  to  is  sample  and amount  sample had an  which are  s i n g l e major  sample. A l f r e d o Moreno's of  types  t h a n t h e Don M a r c o s s a m p l e ;  5-MeO-DMT w h i c h  Marcos  the  La C h o r r e r a  s a m p l e c o n t a i n e d NMT + DMT, b o t h of than  of  degree was  paste  and  50 /ig d r y  tryptamine-  for wt/ml  187  10Q*  9Qf  BQ-  m  7Q;  EQr  D 5Q:  4Qr  LJ  CK bJ Q_  3Q;  SQr  I Q r  NEGATIVE LOG CONCENTRATION (M) F i g u r e 16 - MAOI A c t i v i t y of M y r i s t i c a c e o u s P a s t e s : A l f r e d o Moreno O o ' - k o e y Sample #1 x = A l f r e d o Moreno O o ' - k o e y Sample + = A l f r e d o Moreno Sample  #1  #1 " a n a l o g u e "  (DMK-40, (cf.  V.  sebifera)  T a b l e s XII  & XV)  188 100_i  5Q.  •  S'  1  1  3-  1  A'  1  5*  E>  1  7.  B-  NEGATIVE LOG CONCENTRATION (M) F i g u r e 17 - MAOI A c t i v i t y of M y r i s t i c a c e o u s P a s t e s : M a r c o s F l o r e s K u ' - r u - k u Sample #1 x = Marcos F l o r e s + = Marcos F l o r e s  K u ' - r u - k u Sample#l Sample  #1  "analogue"  (DMK-59, V. (cf.  elongata)  T a b l e s XII  & XV)  F i g u r e 18 - MAOI A c t i v i t y of N o n - a l k a l o i d C o n s t i t u e n t s of M y r i s t i c a c e o u s P a s t e s non-alkaloidal paste x = lignan  fraction  sample  (DMK-34, V .  (DMK-59, V .  pavonis)  elongata)  190  containing paste at  dry  crude  wt  concentrations  extract.  therefore  s a m p l e s showed c o m p a r a b l e amounts o f  The  appears  to a general  possibility  that  specific  the  the  of  order  of  3 to  shown by t h e  be f a i r l y  denaturing due t o  highly  inhibition to  preparation  on t h e  the  4 ug  inhibition  dry  wt/ml  alkaloid-free  nonspecific  and p r o b a b l y  proteins  the  high phenolic  Myristicaceous  in  content pastes  of  samples is  due  enzyme  of  the  samples.  may c o n t a i n  n o n - n i t r o g e n o u s MAO i n h i b i t o r  seems  The  some  somewhat  remote.  IV.  Summary The a c t i v i t y  derivatives assay  of  a number of  as MAOI was  tryptamine  investigated  and 5 - h y d r o x y - " C - t r y p t a m i n e  u s i n g an  as  1  and  j3-carboline  iji v i t r o  substrate.  Activity  measured u s i n g s i n g l e compounds and m i x t u r e s  of  the  samples  results  ayahuasca  were compared t o  and s a m p l e s of of  several  magnitude  of  with tryptamine significantly  derivatives.  more e f f e c t i v e  the  mixture,  synergistic  mechanism o f  MAOI a c t i v i t y  carbolines.  greater  of  than  Mixtures  of  as MAOI t h a n  indicating action.  were f o u n d f o r  Samples  of  0-carboline derivatives  compound i n  for  activity  ayahuasca  both the  the  similar  that  to  were most  of  active  than a  and 0 -  be h i g h l y magnitude,  measured  and p r o p o r t i o n s of  not  correlations  tryptamines  were f o u n d t o  be  measured  rather  Some s t r u c t u r a l  orders  comparable c o n c e n t r a t i o n s  single  an a d d i t i v e  pastes.  found to  activity  the  by s e v e r a l  o b s e r v e d was  of  j3-carbolines  as MAOI even when d i l u t e d activity  was  the  was  compounds and  orally-ingested Myristicaceous  The MAOI a c t i v i t y orders  the  enzyme  for  0-carboline  active and  191  mixtures.  Based on t h i s  ayahuasca  could function effectively  orally  potentiate  hallucinogenic  evidence  t h e DMT w h i c h  action  of  the  was m e a s u r e d when s a m p l e s of pastes  were a s s a y e d .  s a m p l e s were c l o s e l y  it  appears  likely  as MAOI i_n v i v o  due m a i n l y of  indicate  probably  responsible  drug.  A lesser  degree  orally-ingested  The i n h i b i t i o n  by t h e  /3-carbolines  pastes  unlikely is  inhibition  due t o  significantly that  the  oral  total  activity  of  the p o t e n t i a t i o n  of MAO by / 3 - c a r b o l i n e s ;  of  are,  in  fact,  the  pastes  activity orally  of  the  for  traces  probably it  Myristicaceous  tryptamines  the  is  i n h i b i t i o n . Thus  the  the M y r i s t i c a c e o u s  active.  the  via  some mechanism o t h e r  i n h i b i t i o n must be i n v o k e d t o a c c o u n t hallucinogenic  of  standards  These  tryptamines;  t o the  the  paste  or n o n - n i t r o g e n o u s i n h i b i t o r s p r e s e n t  do not c o n t r i b u t e appears  of  for  inhibition  tryptamine  the MAOI a c t i v i t y  t o the h i g h c o n c e n t r a t i o n s  of  thus  Myristicaceous  elicited  matched by m i x t u r e s of  that  and  is  h a v i n g c o m p a r a b l e p r o p o r t i o n s and c o n c e n t r a t i o n s . observations  that  t h a n MAO  oral pastes  if  they  192  V.  Literature  Cited  1.  Y a s u n o b u , K. T . , H. I s h i z a k i , & N. M i n a m i u r a (1976) The M o l e c u l a r , M e c h a n i s t i c and I m m u n o l o g i c a l P r o p e r t i e s of Amine O x i d a s e s . M o l e c u l a r and C e l l u l a r B i o c h e m i s t r y 13:3-29  2.  M a r l e y , E . , & B. B l a c k w e l l (1970) I n t e r a c t i o n s of Monoamine Oxidase I n h i b i t o r s , Amines, & F o o d s t u f f s . Advances in P h a r m a c o l o g y & Chemotherapy 8 : 1 8 5 - 2 3 9  3.  I v e r s o n , L. L . , (1979) The C h e m i s t r y a m e r i c a n S e p t . 1979:134-149  4.  F u l l e r , R. W., B. J . W a r r e n , & B. B. M o l l o y (1970) Selective I n h i b i t i o n of Monoamine O x i d a s e i n Rat B r a i M m i t o c h o n d r i a . B i o c h e m i c a l P h a r m a c o l o g y 19:2934-2936  5.  D o n n e l l y , C. H . , E. R i c h e l s o n & D. L. Murphy (1976) P r o p e r t i e s of Monoamine O x i d a s e i n Mouse N e u r o b l a s t o m a 115 C e l l s . B i o c h e m i c a l P h a r m a c o l o g y 2 5 : 1 6 2 9 - 1 6 4 3  6.  D o n n e l l y , C . H . , & D. L. Murphy (1977) S u b s t r a t e - and I n h i b i t o r - r e l a t e d C h a r a c t e r i s t i c s of Human P l a t e l e t Monoamine O x i d a s e . B i o c h e m i c a l P h a r m a c o l o g y 2 6 : 8 5 3 - 8 5 8  7.  H o u s l a y , M. D. & K. F. T i p t o n (1974) A K i n e t i c E v a l u a t i o n of Monoamine O x i d a s e A c t i v i t y i n Rat L i v e r M i t o c h o n d r i a l O u t e r Membranes. B i o c h e m i c a l J o u r n a l 139:645-652  8.  N e f f , N. H. And H.-Y. T . Yang (1974) A n o t h e r Look a t t h e Monoamine O x i d a s e s and t h e Monoamine O x i d a s e I n h i b i t o r D r u g s . L i f e S c i e n c e s 14:2061-2074  9.  P l e t s c h e r , A . (1966) Monoamine O x i d a s e P h a r m a c o l o g i c a l Reviews 18:121-129  of  the  Brain.  Sc i e n t i f i c  NIE-  Inhibitors.  10. A l l e n , J . R. F . , & B. H o l m s t e d t (1980) The S i m p l e /3c a r b o l i n e A l k a l o i d s . P h y t o c h e m i s t r y 19:1573-1582 11.  R. G . T a b o r s k y & W. M. M c l s a a c . The S y n t h e s i s and P r e l i m i n a r y P h a r m a c o l o g y of Some 9 H - P y r i d o [ 3 , 4 - b ] i n d o l e s ( / 3 - c a r b o l i n e s ) R e l a t e d t o S e r o t o n i n and M e l a t o n i n . J o u r n a l of M e d i c i n a l C h e m i s t r y 7:135-141 1964  193  12. U d e n f r i e n d , S . , B. W i t k o p , B. G . R e d f i e l d , & H. W e i s s b a c h (1958) S t u d i e s W i t h R e v e r s i b l e I n h i b i t o r s of Monoamine O x i d a s e : H a r m a l i n e and R e l a t e d Compounds. B i o c h e m i c a l P h a r m a c o l o g y 1:160-165 13.  S c h u l t e s , R. E. (1972) E t h n o t o x i c o l o g i c a l S i g n i f i c a n c e A d d i t i v e s t o New W o r l d H a l l u c i n o g e n s . P l a n t Sc i e n c e B u l l e t i n 18: 34-41  of  14.  S h u l g i n , A . T . (1976) M a x w e l l Gordon ( e d . ) Academic P r e s s .  15.  Der M a r d e r o s i a n , A . H . , H. V . P i n k l e y , & M. F. D o b b i n s IV. (1968) N a t i v e Use and O c c u r r e n c e of N,N-dimethyItryptamine i n t h e L e a v e s of B a n i s t e r i o p s i s r u s b y a n a . A m e r i c a n J o u r n a l of Pharmacy 140:137-147  Psychotomimetic A g e n t s . Ch. 4 in Psychopharmacological Agents V o l .  IV.  16. A g u r e l l , S . , B. H o l m s t e d t , J . E. L i n d g r e n , & R. E. Schultes. (1968) I d e n t i f i c a t i o n of Two New / 3 - c a r b o l i n e A l k a l o i d s i n South American H a l l u c i n o g e n i c P l a n t s . Biochemical P h a r m a c o l o g y 17:2487-88 17.  Schultes,  R.  E.  18.  S c h u l t e s , R. E. & T . Swain (1976) an O r a l H a l l u c i n o g e n . J o u r n a l o f 324  19.  S c h u l t e s , R. E . , T . S w a i n , & T . Plowman (1977) V i r o l a O r a l H a l l u c i n o g e n Among t h e B o r a s of P e r u . H a r v a r d B o t a n i c a l Museum L e a f l e t s 2 5 : 2 5 9 - 2 7 2  20.  Dawson, R. M. C , D. C . E l l i o t , W. H. E l l i o t , ( e d s . ) (1969) D a t a f o r B i o c h e m i c a l R e s e a r c h , U n i v e r s i t y P r e s s , L o n d o n ; p. 484  21.  T i p t o n , K. F. & M. B. H. Youdim (1976) A s s a y of Monoamine O x i d a s e . In Monoamine O x i d a s e And I t s I n h i b i t i o n . C i b a F o u n d a t i o n Symposium 39 ( N . S . ) . E l s e v i e r , A m s t e r d a m .  Hallucinogen.  (1969)  Harvard  Vi rola  as an  Botanical  Orally-administered  Museum L e a f l e t s  22:229-40  F u r t h e r N o t e s on V i r o l a as P s y c h e d e l i c Drugs 8:317-  as  an  K. M. J o n e s 2nd e d . O x f o r d  1 94  22.  M c l s a a c , W. M. & V . E s t e v e z (1966) Structure-action R e l a t i o n s h i p s of 0 - c a r b o l i n e s a s Mono-amine O x i d a s e I n h i b i t o r s . B i o c h e m i c a l Pharmacology 26:1625-27  23.  B u c k h o l t z , N. S. & W. 0 . Boggan (1977) Monoamine O x i d a s e I n h i b i t i o n i n B r a i n and L i v e r P r o d u c e d by 0 - c a r b o l i n e s : S t r u c t u r e - a c t i v i t y R e l a t i o n s h i p s and S u b s t r a t e Specificity. B i o c h e m i c a l Pharmacology 26:1991-96  24.  R. B. B a r l o w . (1961) E f f e c t s on Amine O x i d a s e o f S u b s t a n c e s Which A n t a g o n i z e 5 - h y d r o x y t r y p t a m i n e More t h a n T r y p t a m i n e on t h e Rat Fundus S t r i p . B r i t i s h J o u r n a l o f P h a r m a c o l o g y 16:153-162.  25.  B. T . H o , W. M. M c l s a a c , R. A n , R. T . H a r r i s , K. E. W a l k e r , & P. M. K r a l i k (1970) B i o l o g i c a l A c t i v i t i e s o f Some 5S u b s t i t u t e d N , N - d i m e t h y l t r y p t a m i n e s , a- m e t h y l t r y p t a m i n e s , and G r a m i n e s . P s y c h o p h a r m a c o l o g i a 16:385-394  26.  D. MacRae. (1984) E t h n o b i o l o g i c a l and C h e m i c a l I n v e s t i g a t i o n s of S e l e c t e d Amazonian P l a n t s . PhD U n i v e r s i t y of B r i t i s h C o l u m b i a , V a n c o u v e r , B. C .  thesis,  195  CHAPTER V I I : COMPARATIVE ETHNOPHARMACOLOGY OF MALPIGHIACEOUS AND MYRISTICACEOUS HALLUCINOGENS: SUMMARY AND CONCLUSION I.  Introduction This  thesis  ethnobotanical,  presents  the  results  phytochemical, of  hallucinogenic  drink  ayahuasca  Banisteriopsis  caapi  (Malpighiaceae)  spp.  notably  two Amazonian h a l l u c i n o g e n s .  Diplopterys  The c a m b i a l  resin  of  orally-ingested  hallucinogenic from e n t i r e l y  alkaloids--tryptamines  constituents the  of  o r a l l y - i n g e s t e d Vi rola  peripheral  investigations  activity—involving constituents thesis.  tryptamines  Other  Jjn v i t r o  objectives data  mestizo populations, for  alkaloidal  the  d r u g s a m p l e s . Most of  these  sources,  has been s u g g e s t e d the  of  the  it  their this  oral  ayahuasca  and  that  deamination  by  activity.  p o s t u l a t e d mechanism of  evaluations the  use of  active  /3-carbolines--protects  from o x i d a t i v e  collection  in  tribes.  the  to  case  and  In  phytochemical a n a l y s i s ,  constituents  snuffs  botanical  of  t h e d r u g s and  primary  were t h e c o l l e c t i o n  on t h e  genus V i r o l a  and / 3 - c a r b o l i n e s — a r e  a s MAOI--were one of  and e t h n o g r a p h i c  material  of  the  Psychotr ia  u s e d by some  different  pastes,  MAO and t h u s p e r m i t s  Experimental  pastes  liana  admixture  and v a r i o u s  hallucinogenic  inhibition--due  psychotomimetic  and s u n d r y  members of  both p r e p a r a t i o n s .  monoamine o x i d a s e the  s o u r c e of  The  p r e p a r e d from t h e  certain  is  similar  the  is  cabrerana  (Myristicaceae)  Although derived  ethnographic,  and p h a r m a c o l o g i c a l  investigations  plants,  of  these of  of  voucher  source-plants,  their of  this  ethnobotanical  d r u g s among I n d i a n  and t h e  objectives  objectives  oral  and  s p e c i m e n s and  analysis  of  admixture p l a n t s ,  have been m e t ,  and i t  and is  1 96  now a p p r o p r i a t e for  ayahuasca  to  summarize and compare t h e  with those  found f o r  the  results  obtained  Myristicaceous  halluc inogens.  Ayahuasca  11•  The c o n t e m p o r a r y primarily  within  c o m p r i s e d of  an amalgam of  these  tribes  of  their  ethnomedical  and  the  ranging  ayahuasquero's  has  from m e n t a l  skills  acquired.  the  plants with  it  enables  and t h e he  is  able  of  illness,  across  distances.  any  these  Whether  or  an  many of  w h i c h do c o n t a i n  can be)  used i n c o n j u n c t i o n  ayahuasca  to  brews c o n t a i n  N,N-dimethyltryptamine.  there  impressive  highly  to  to h i s the  The major  and l e s s e r  it  is  also  p r o f e s s i o n can  be  medicinal  of  the h e a l i n g divine  uses  ceremonies;  the  supernatural  and see and communicate is  a rational  basis  p h a r m a c o p o e i a of  The  plants(or  phytochemical  most m e s t i z o  amounts of  / 3 - c a r b o l i n e s and  /3-carbolines are  amounts of  for  constituents—are  found that  substantial  it  supernatural  biodynamic  have  is  many  to p a r a s i t e s ,  with ayahuasca.  reported here  tetrahydroharmine,  of  used in  not  central  treatment  learn  future  occupies a  Not o n l y  to diagnose d i s e a s e s ,  practices,  investigations  the  intrinsic  the  is  A l t h o u g h most  medicine.  passport  healer  predict  which  and been a d o p t e d among  and i t  illness  songs and c h a n t s  causes  of  for  or h e a l e r ' s  occurs  f r a g m e n t e d o r d i s a p p e a r e d , much survived  cure-all  medicine,  traditions.  in mestizo folk  d i m e n s i o n s where the It  mestizo folk  among t h e s e ,  position  in South America  many t r i b a l  lore  is  e m p l o y e d as a g e n e r a l disorders  of  have l o n g s i n c e  Ayahuasca  important  ayahuasca  the c o n t e x t  of  mestizos.  use of  harmaline;  harmine only  and  traces  197  of  other  /3-carbolines  in  these  s a m p l e s were s e v e r a l  those  reported  tribes  were d e t e c t e d .  i n an e a r l i e r  i n h a b i t i n g the  A "typical"  study  of  ayahuasca  Purfis  in  are  effective  threshold  level  for  however.  Therefore  activity  of  activated  MAOI;  it  is  hallucinogenic these  ayahuasca  is  data  the  activity  indicate  hypothesis  is  s u p p o r t e d by t h e  of  inhibitor  of MAO jjn v i t r o  o r d e r s of  m a g n i t u d e . A number o f  different  practitioners  analyzed.  The same a l k a l o i d s  parts  differences  concentration  cultivars.  It  ayahuasqueros  is all  remarkable  all  of  except  plant  that,  are  the ayahuasca  very  use of  extracted  and  Proportional different  and p r o p o r t i o n a l in t h i s  the  since  f a c e d w i t h so many  samples a n a l y z e d  by  expected  pharmacological consistency  for concentration  a  and p r o p o r t i o n s of  material  procedure.  to the  found;  a c r o s s P e r u manage t o m a n u f a c t u r e  h a v i n g a h i g h d e g r e e of to batch;  preparation  is  were  Peru,  were c o n s i s t e n t l y  may be a t t r i b u t a b l e  This  of  dependent  i n the  orally  brewed  this  variables  is  samples,  components. C o n c e n t r a t i o n d i f f e r e n c e s  other  the  even when d i l u t e d by many  ayahuasca  amount of  /3-  the MAO i n h i b i t i o n  various  on t h e  the  hallucinogenic  /3-carbolines.  in d i f f e r e n t  in the  above  /3-carbolines,  f i n d i n g that ayahuasca  effective  is  below the  the  well  which  p r o b a b l y due t o DMT, w h i c h  high concentration  samples d i f f e r e d mainly  of  that  by some mechanism, p r e s u m a b l y  i n d u c e d by the  well  [1].  between  is  range a t  still  Peru  contains  and 40-80 mg DMT; t h i s  t h r e s h o l d dose f o r DMT and w i t h i n  than  p r e p a r e d by  southwestern  100 ml dose of m e s t i z o a y a h u a s c a  carbolines  /3-carbolines  o r d e r s of m a g n i t u d e g r e a t e r  upper R i o  500 and 800 mg / 3 - c a r b o l i n e s the  The amounts of  B.  caapi  variables, a drug from  batch  differences  s t u d y c o u l d have  198  been t a k e n admixture single  from t h e plants  major  wt.  in a l l  several  caapi  mg/g d wt  differences than  to  of  of  the  them; o n l y  The c o n c e n t r a t i o n Similar  cultivars  same c o n s t i t u e n t s 1.7  in a l l  samples.  B.  All  DMT-containing  w h i c h were a n a l y z e d were s i m i l a r ;  base  were d e t e c t e d .  same p o t .  genetically  was not  1-2 mg/g d r y  found in  but c o n c e n t r a t i o n s to  13.6 mg/g d r y  due t o e n v i r o n m e n t a l  the less  ranged wt.  the  from  These  factors  based b i o c h e m i c a l d i f f e r e n c e s  the  alkaloids  w h i c h were a n a l y z e d . More or  alkaloids)  probably are  other  DMT was between  consistency  were p r e s e n t  (total  of  t r a c e s of  DMT was  rather  between  cult ivars.  III.  Myristicaceous Unlike  derived  never the  the  spp.  become i n t e g r a t e d  into  ingested Myristicaceous hallucinogen snuff;  it  possibly groups.  is  Myristicaceous  mestizo folk  tribal  This  is  societies  more e t h n o l o g i c a l l y  t h e Maku and a p p a r e n t l y  specialized  knowledge o f  most members of  the  have true  Bora,  usage of  the the  of  the  a has  result in  some  its  Witoto,  source-plants,  Another c o m p l i c a t i n g  oral  use as a  Muinane,  outside  Virola  to  orallyas an  than  t h e m e d i c i n e men and a r e  tribe.  and  As a  spp.  occur  oral  is  f r a g m e n t e d due  restricted  d o e s not  tribes,  and modes of  medicine.  Use of V i r o l a  h a s been r e p o r t e d among t h e  preparation,  genera  d r u g s has d i m i n i s h e d or  particularly  pastes.  Even w i t h i n t h e s e  preparations  i n d i g e n o u s Amazonian t r i b e s  these M y r i s t i c a c e o u s  influences.  hallucinogenic  or o t h e r  d i s a p p e a r e d as t h e  outside  use of  c o n f i n e d t o a few  use of  cases  ayahuasca,  from V i r o l a  practice  Hallucinogens  and  these  methods of  drug are not  factor  known is  the to  that  199  the  Bora  region,  and W i t o t o p o p u l a t i o n s where t h e  fieldwork  not  indigenous to that  Rio  Putumayo  of  the  not  in  the e a r l y  traditions  t o the  n o r any  knowledge  some c a s e s , that  there  amount of  this  was c a r r i e d  but m i g r a t e d  of  the  rather is  tribal  oral  inexact.  a high degree  species.  The c o m p o s i t i o n o f in  this  The work of  not  the  reflection  the c h e m i c a l  while a l l  of  same c o n s t i t u e n t s which  Psychotria  Vi rola pastes Large  is  concentration  s a m p l e s were a l s o  found.  Either  or  criteria  which  "best"  (i.e.,  strongest)  (e.g.,  taste,  s m e l l , and/or  been  this  has a l w a y s been a f e a t u r e the  largely  If  the  of  the  has  the  of  the  is  species  visual  Vi rola  samples  this  both  is  a  source-plants.  these  the  d e p e n d i n g on  one of  the  other  alkaloids  in  of  oral  one.  various  chemical  orally-ingested  used to  to prepare of  select the  the  is  true,  the  paste  resin)  has now become a  former p o s s i b i l i t y  in  and  variable,  not  appearance  selection  that  same  paste  high degree of  has  shown  type  or absent  were f o r m e r l y  Vi rola  f o r g o t t e n and t h e  haphazard p r o c e s s .  result  same base c o m p o s i t i o n a s any  in the  pastes,  This  among d i f f e r e n t  u s e d as a d m i x t u r e ) ,  differences  variability  result  s a m p l e s had e s s e n t i a l l y  ( w i t h DMT b e i n g p r e s e n t  had t h e  in  and p r e s u m a b l y of  the  d r u g s has become,  similarly  variability  the ayahuasca  s p . was  the  collections  study  as a  reported here  only  are  ethnomedical  orally-ingested  and q u a n t i t a t i v e l y ,  Thus,  their  out,  f r o m n o r t h of  industry.  variability  qualitatively of  of  Ampiyacu  century,  Myristicaceous  even among d i f f e r e n t  were a n a l y z e d  this  institutions;  alkaloid constituents, but  there  rubber  preservation  other  study  d e c a d e s of  species,  which  the Rio  d i s l o c a t i o n s p r o d u c e d by t h e  contributed  local  area  for  inhabiting  this  have fairly may  200  e x p l a i n why they or  the  usually  four  was  consumed i t  kept  faith  from t h e  in  the  restricted alone:  samples a c t u a l l y  probably their  paste  if  only  i_s o r a l l y  people at  efficacy  of  to the  one out  active,  large,  m e d i c i n e men and why of  this  every  three  information  in order  to  was  preserve  t h e m e d i c i n e man and  his  medic i n e s . Another the  objective  mechanism f o r  Myristicaceous activation of  of  visceral  some of  the  the  even  in  it  this  ones.  In  the  found as c o n s t i t u e n t s the  two  compared t o  the  carbolines.  A further  point  paste oral  instance all  type,  which  are  d i h y d r o - and f u l l y is  that  activity  or  typical  of  and  paste  aromatic  only  active  of  of  or  0-  nothing in  which c o n t a i n e d inactive  5-MeO-DMT i n  a l t h o u g h the  the  which  base  activity  of MAO i n h i b i t i o n ,  the  in  ku'-ru-ku,  A l t h o u g h the M y r i s t i c a c e o u s  some d e g r e e  0-  as d e t e r m i n e d  while Marcos F l o r e s '  orally  hallucinogens.  samples d i d e x h i b i t  the  had l i t t l e  inactivity  La C h o r r e r a o o ' - k o e y ,  high concentrations  was h i g h l y  new  presence or absence  samples a p p a r e n t l y  self-experiments  fraction,  answering  p o o r MAO  0 - c a r b o l i n e s , was c o m p l e t e l y  contained only  inhibition  /3-carbolines,  highest repeated  oral  0 - c a r b o l i n e s were of  the  of  the  has c r e a t e d  self-experiments; levels  to  T h o s e / 3 - c a r b o l i n e s w h i c h were f o u n d b e l o n g  inhibitors  t o do w i t h t h e i r  examine  these  p r o c e s s of  of  to  t h r o u g h the  samples c o n t a i n i n g  tetrahydro-/3-carboline  the  the  first  of  ayahuasca,  investigation  to  in  like  In  was  activity  constituents  were d e t e c t e d .  carbolines  oral  due,  traces the  investigations  0-carbolines?  questions  consistently  samples;  is  tryptamine  e v e n more p u z z l i n g not  these  (presumed)  pastes;  MAO by  these  of  was  paste  this  was  not  201  shown t o  be p r i m a r i l y  constituents; showed o n l y the  synthetic  several  the  pastes,  tryptamine  orders  of  tryptamine the  when t h e y  or  are  other  orally  of  such as oral  activity  orally  tryptamines (including  pastes  Certainly  It  is  differ  active,  is  in  I  for  the  0-carboline of  was c o m p a r a b l e  50  the  All  of  to  this  Myristicaceous  must owe t h e i r whether  basically  activity  to  due t o |3-  is  equally  the  bioassay,  that  not due t o  two  possibilities  the  oral  experimental  the  oral  activity  tryptamines  active  in  their That  does c o n t a i n but  whether  not  that  effects Virola  biological  the  for  tryptamines  from resin  biologically  these  at  constituents,  was a t y p i c a l  p o s s i b l e , however,  s p e c t r u m of is  the  would h e l p t o e x p l a i n why  significantly  of  for  further  self-experiments  capable  the  its  biologically  sample a s s a y e d )  eliciting  of  usually  0-carbol ines.  administered parenterally. the  were  those  suggests that  this  has been e s t a b l i s h e d ;  in  the  There are  lignans  observed  of  b o t h would r e q u i r e  observed  hallucinogens. taken  than  tested;  t o some o t h e r  lignans.  values  50  t o c o n f i r m . The f i r s t  rather  i n h i b i t i o n . Most  mechanism might a c c o u n t  consideration;  but  samples  constituents.  the M y r i s t i c a c e o u s  all,  from t h e  w h i c h were a s s a y e d as MAOI  t h a n MAO i n h i b i t i o n ,  some s a m p l e s ?  investigations  I  tryptamine  DMT showed t h e most MAOI a c t i v i t y  active  What a l t e r n a t i v e of  the  lower  considered together  carbolines  worth  but  the  non-specific  derivatives  least  due t o  constituents  derivatives  magnitude  some mechanism o t h e r  activity  entirely  of  Interestingly,  THH,' one of evidence  degree  some a c t i v i t y  derivatives. all  not  non-alkaloidal  a slight  did exhibit  if  lignans  active are  responses  known. The s e c o n d  possibility,  202  which a l s o c a l l s that  the  oral  derivatives  f o r much f u r t h e r  inactivation  is  in  metabolic  B o t h j_n v i t r o  [2,3]  Chapter  (cf.  oxidation  peripheral  tissues  compounds a r e  but a p p a r e n t l y  inactive  pattern  be c o m p l e t e l y  of  for  studies  of  i_n v i v o  MAO i n h i b i t o r s  inhibitors  [6]  have  support  for  the  the  reported  in  i.p.  rather  circulation  is  than o r a l l y ;  shunt" metabolism. the  that  directly It  from i t s  i_n v i v o  thus  but  if  Little it  is  known of  follows  [5]  it  the  would less  w h i l e t h e MAOI of  either active  the oxidase  iproniazid  DMT, t h e MFO these  studies  of  in  related  inhibitor  results  the  a d m i n i s t e r e d to  t h e compound r e a c h e s  and a v o i d s is  [4].  interpret  t h e DMT i s  as by MAO  type the  animal  the  "intestinal/hepatic-portal  p o s s i b l e that  intestinal/hepatic-portal  respects  of DMT and  t h a t DMT i s m e t a b o l i z e d m a i n l y  A p r o b l e m w i t h most  than  [2,3];  DMT m e t a b o l i s m i n  half-life  in v i v o .  [6],  tissues  and m i c r o s o m a l m i x e d f u n c t i o n  authors  hypothesis  a n d / o r N-  t o one h u n d r e d t i m e s  found t h a t  p r o l o n g s p l a s m a and t i s s u e SKF-525A d o e s n o t ;  in b r a i n  amine N - o x i d e s ,  ten  of DMT m e t a b o l i s m  in p e r i p h e r a l  not  or  the  has been shown t o o c c u r  of DMT-NO,  tertiary  inactive,  t h a n DMT. O t h e r  (MFO)  studies  as h a l l u c i n o g e n s  action  more  compounds i n  6-hydroxylation  6-hydroxy d e r i v a t i v e s  hallucinogenic  presence  that  by MAO. 6 - h y d r o x y l a t i o n  significantly,  general  these  and j_n v i v o  suggest  peripheral  may be r e l a t i v e l y  of DMT o c c u r s more r e a d i l y  deamination  the  II)  of  is  related  d e a m i n a t i o n by  pathways  the d e g r a d a t i o n  periphery.  investigation,  DMT, 5-MeO-DMT, and  not due t o o x i d a t i v e  MAO; a l t e r n a t i v e significant  of  experimental  t h e m e t a b o l i s m of DMT v i a  s h u n t may d i f f e r  in  important  m e t a b o l i s m when i n t r o d u c e d d i r e c t l y  into  the  203  b l o o d s t r e a m or  body c a v i t y .  hydroxylation,  and/or N - o x i d a t i o n ,  important event,  In  t h a n MAO as a c a t a b o l i c  _in v i v o  parenteral  metabolic  routes  of  studies  our u n d e r s t a n d i n g of  related  compounds i s  certain  is  involved. of  that  far  may be r e l a t i v e l y route  i n the  both the  for  of  involved  in  possibly  even more i m p o r t a n t .  i.p.  or  shed l i t t l e  all  that  oxidative  is  for  the  for  if  pastes as  some of  lack  a s MAOI. the  presence  of  inhibitors  m i c r o s o m a l MFOs. of  of  it  In  In  the  latter  case,  r e s i n may s p e c i f i c a l l y  inhibit  block  of  case  the the  oxidation(s)  and a r e  in  the activity  former  oxygen  from  case,  in  the for  and 6 -  in  the  Virola  m i c r o s o m a l MFO and  DMT c a u s e d by t h e s e  compound c o u l d be p r o t e c t e d  not  as c o - s u b s t r a t e  constituents  hepatic  some  anti-oxidants  t h e m i c r o s o m a l enzymes c a t a l y z i n g DMT N - o x i d a t i o n hydroxylation.  of  exhibit  the m o l e c u l a r  available  then a  mechanism  the  non-specific  a h i g h p r o p o r t i o n of  t h u s making l e s s  and/or  are  are  activity  This alternative  activity  high concentrations  scavange  vicinity,  of  oral  non-alkaloid constituents  may p o s s e s s a n t i - o x i d a n t  specific  could  effective  that  degradation  microsomal o x i d a s e s ,  /3-carbolines  postulates  is  orally-  Vi rola  significantly  for  but m i c r o s o m a l MFOs, w h i c h  Interestingly,  though they  is  known  reaction  the  even  light  The f a c t  mechanism c a n be p r o p o s e d t o e x p l a i n pastes,  any  other  6 - h y d r o x y l and N-oxide p a t h w a y s ,  a d m i n i s t e r e d DMT i_s a s u b s t r a t e  In  m e t a b o l i s m of DMT and  responsible  periphery,  more  compound.  administration.  from c o m p l e t e ; type  the  actually  the p e r i p h e r a l  more t h a n  shunt 6 -  involving  oral  MAO may be p a r t i a l l y  tryptamines  hepatic  administration  on DMT m e t a b o l i s m f o l l o w i n g that  the  enzymes.  oxidative  In  thus either  204  transformation up i n t o  the  intestinal/hepatic  t h e CNS i n t h e  number of  lignans  protective hepatic  in  form of  the  shunt  and t h u s  unchanged t e r t i a r y  have been c h a r a c t e r i z e d w h i c h  activity  against  hepatotoxins  MFO has been p r o p o s e d as  the  [7];  lacking  hepatoprotective been  implicated  responsible  exhibit  inhibition  properties. in other  constituents  genera V i r o l a  (V.  sample;  activity  in  compounds,  this  the  sample  g r o u p has  are  [8],  neolignans,  novel  both r i c h  bark  source-plant  showed t h e  and  this  of DMK-59  f o r Marcos  greatest  Flores'  degree  of  A number of  other  including flavans,  flavanoids,  isoflavonoids,  number of V i r o l a  and n e o l i g n a n s , and I r y a n t h e r a  as a n t i o x i d a n t s  inactivation  of MFOs v i a  s p p . ; some of  these to  from a compounds  the  n o n s p e c i f i c m e c h a n i s m . In  the p e r i p h e r a l  m e t a b o l i s m of DMT and r e l a t e d compounds,  following  administration,  oral  the presence under the  these  form of  of  antioxidants  conditions the  may be s i g n i f i c a n t l y  and/or  specific  amine.  any  altered  case  in  MFO i n h i b i t o r s ;  t h e compounds might w e l l  unchanged t e r t i a r y  oral  phenolic  have been i s o l a t e d  and c o u l d c o n t r i b u t e this  in  group,  flavans,  lignans having  i n the  The  self-experiments.  diarylpropanoids,  could act  Several  w h i c h was  inhibition  methylenedioxyphenyl  were c h a r a c t e r i z e d  elongata)  paste  [9].  have  t h e main p h a r m a c o p h o r e  and I r y a n t h e r a  acid derivatives,  diarylpropanoids substitution  as  oxidase  i n c o r p o r a t i n g the  fatty  d i d not  of  moiety,  The m e t h y l e n e d i o x y p h e n y l  studies  of  p r o b a b l e mechanism. A l l  configuration  f o r mixed f u n c t i o n  Myristicaceous  including  this  taken  amine. A  t h e a c t i v e compounds p o s s e s s e d a m e t h y l e n e d i o x y p h e n y l but a n a l o g s  be  reach  Further  t h e CNS  in  jjn v i v o and _in  205  vitro this  e x p e r i m e n t s would be r e q u i r e d t o c o n f i r m or alternative  phytochemical present least  mechanism of  study,  it  appears  as p r o b a b l e ,  Myristicaceous  if  In  view of  that  this  alternative  not more p r o b a b l e , for  the  oral  in  the  the  hypothesis  is  t h a n MAO i n h i b i t i o n  activity  of  at as  the  pastes.  Conclusion Phytochemical  the  c o u r s e of  establish  vitro  the  study  has been  mechanism of however  it  oral  the  activity  original  cannot  metabolism.  activity  which  of  indicates  mechanism t h e  The a l t e r n a t i v e  active  ayahuasca,  necessary  mechanism f o r  ayahuasca.  Myristicaceous indicate  In  not  the case  preparations,  constituents—is  of  however,  responsible  for  traces  their of  oral  almost  /3-carbolines,  the  the  to  due t o  contains  above of  invoke  this  reported  here  /3-carbolines not  The p a s t e s  they  the  degradative the  the  or  mechanism  do not  in  case  orally-ingested  data  certainly  activity.  the  hallucinogenic  the pharmacology  t h a t MAO i n h i b i t i o n - - w h e t h e r  some o t h e r  more t h a n  is  in  and  effectively  mechanism p r o p o s e d i n in  it  that  from p e r i p h e r a l  d i s c u s s i o n may a l s o be i m p l i c a t e d least  two Amazonian  ayahuasca  to  in  definitely  proposed to e x p l a i n  /3-carbolines  DMT, may be p r o t e c t e d  but a t  to  in these  be d i s p r o v e d . C e r t a i n l y  MAO and by t h i s  constituent,  insufficient  hypothesis  h i g h enough c o n c e n t r a t i o n s inhibit  information c o l l e c t e d  has p r o v i d e d p h y t o c h e m i c a l d a t a  pharmacological evidence  ayahuasca  oral  and p h a r m a c o l o g i c a l  this  hallucinogens;  of  activity.  and p h a r m a c o l o g i c a l d a t a a c c u m u l a t e d  the mechanism r e s p o n s i b l e  IV.  oral  disconfirm  contain  show p o o r a c t i v i t y  as  206  MAOI,  and t h e i r  w i t h the must  oral  presence  therefore  be  Myristicaceous is  of  activity,  0-carbolines.  pastes.  one  that  active  constituents  the  other  p e r h a p s more a t t r a c t i v e are  constituents  inhibit  enzymes r e s p o n s i b l e tryptamine  for  derivatives.  activity  than  is  is  hepatic  6-hydroxylation MFO i n h i b i t o r s  and V i r o l a  excellent  this  moiety.  proven vivo to  or  Unfortunately  disproven u n t i l  m e t a b o l i s m of  start  DMT i n  the  presence  neither more has  study of  the  mechanism of  these  have been d i s c u s s e d biologically  The o t h e r the  and  active  degradation  by  and N - o x i d a t i o n require  the  s o u r c e s of  DMT and r e l a t e d  would be t o  that  correlated  mixed-function oxidases,  c o n f i g u r a t i o n as  are  not  activity  due t o  from p e r i p h e r a l  methylenedioxyphenyl spp.  oral  tryptamines.  possibility  protected  which  the  Two s u c h a l t e r n a t i v e s oral  is  Some a l t e r n a t i v e  invoked to e x p l a i n  above;  tryptamines  when p r e s e n t ,  the  active  the  of  presence  of a  pharmacophore,  compounds p o s s e s s i n g  alternative  mechanism can  been l e a r n e d ' a b o u t  the  compounds. An o b v i o u s  m e t a b o l i s m of  known MFO i n h i b i t o r s .  be  in place  orally-administered  207  V.  Literature  1.  R i v i e r , L. & J . l i n d g r e n (1972) A y a h u a s c a , t h e S o u t h H a l l u c i n o g e n i c D r i n k : E t h n o b o t a n i c a l and C h e m i c a l I n v e s t i g a t i o n s . Economic B o t a n y 2 9 : 1 0 1 - 1 2 9  2.  B a r k e r , S. A . , J . A . M o n t i , and S. T . C h r i s t i a n (1980) M e t a b o l i s m of t h e H a l l u c i n o g e n N , N - d i m e t h y l t r y p t a m i n e in Rat B r a i n H o m o g e n a t e s . B i o c h e m i c a l P h a r m a c o l o g y 2 9 : 1 0 4 9 - 5 7  3.  S z a r a , S. & J . A x e l r o d . (1959) H y d r o x y l a t i o n and Nd e m e t h y l a t i o n of N , N - d i m e t h y l t r y p t a m i n e . Experientia 15:216-17  4.  S h u l g i n , A . T . (1976) P s y c h o t o m i m e t i c A g e n t s , c h a p t e r 4 i n M a x w e l l Gordon ( e d . ) P s y c h o p h a r m a c o l o g i c a l A g e n t s V . IV. Academic P r e s s  5.  B i c k e l , M. H. (1969) The P h a r m a c o l o g y and B i o c h e m i s t r y o x i d e s . P h a r m a c o l o g i c a l Reviews 21:325-358  6.  S h a h , N. S . , & M. P. Hedden (1977) B e h a v i o u r a l E f f e c t s and M e t a b o l i c F a t e of N , N - d i m e t h y l t r y p t a m i n e i n M i c e P r e t r e a t e d with /3-diethylaminoethyl- D i p h e n y l p r o p y l a c e t a t e (SKF-525A ) , I p r o n i a z i d , and C h l o r p r o m a z i n e . P h a r m a c o l o g y , B i o c h e m i s t r y and B e h a v i o u r 8:351-56  7.  MacRae, W. D . , & G . H. N. Towers of L i g n a n s . P h y t o c h e m i s t r y . In  8.  B r a t t s t e n , L. B. (1977) B i o c h e m i c a l D e f e n s e Mechanisms i n H e r b i v o r e s A g a i n s t P l a n t A l l e l o c h e m i c a l s . C h a p t e r 5 i n G. A . R o s e n t h a l , and D. H. J a n z e n ( e d s . ) H e r b i v o r e s : T h e i r I n t e r a c t i o n s w i t h Secondary M e t a b o l i t e s . Academic P r e s s .  9.  G o t t l i e b , O. R. Myristicaceae 1:309-323  10.  Cited  (1984) B i o l o g i c a l press.  American  of  N-  Activities  (1979) C h e m i c a l S t u d i e s on M e d i c i n a l from A m a z o n i a . J o u r n a l of E t h n o p h a r m a c o l o g y  D. MacRae. (1984) E t h n o b i o l o g i c a l and C h e m i c a l I n v e s t i g a t i o n s of S e l e c t e d Amazonian P l a n t s . PhD U n i v e r s i t y of B r i t i s h C o l u m b i a , V a n c o u v e r , B. C .  thesis,  208  APPENDIX I  TABLE  XVI  - BIOLOGICALLY  ACTIVE  CONSTITUENTS  IN  AYAHUASCA  ADMIXTURES  The f o l l o w i n g l i s t o f p l a n t s p e c i e s has b e e n c o m p i l e d f r o m v a r i o u s s o u r c e s and i s i n t e n d e d as a summary o f t h e c u r r e n t s t a t e o f phytochemical k n o w l e d g e o f t h o s e g e n e r a and s p e c i e s w h i c h a r e known t o be u t i l i z e d a s a d m i x t u r e s t o a y a h u a s c a . The i n f o r m a t i o n on t h e u s e o f t h e s e s p e c i e s as a y a h u a s c a a d m i x t u r e s i s c o m p i l e d p r i m a r i l y f r o m r e f e r e n c e s 1,2,3,4,5, and 86; i n f o r m a t i o n on t h e v e r n a c u l a r names o f t h e p l a n t s u s e d i s c o m p i l e d f r o m t h e r e f e r e n c e s c i t e d a b o v e and a l s o f r o m 85. The p h y t o c h e m i c a l information is d e r i v e d p r i m a r i l y f r o m a c o m p u t e r s e a r c h o f t h e B i o l o g i c a l A b s t r a c t s D a t a B a s e and t h e A m e r i c a n C h e m i c a l S o c i e t y D a t a B a s e , c o v e r i n g t h e y e a r s 1 9 7 0 - p r e s e n t . The r e f e r e n c e s c i t e d i n t h i s a p p e n d i x a r e n o t i n t e n d e d t o be e x h a u s t i v e b u t r a t h e r a r e i n t e n d e d a s I n d i c a t o r s o f t h e e x i s t e n c e o r n o n e x i s t e n c e o f i n f o r m a t i o n r e g a r d i n g b i o d y n a m i c c o n s t i t u e n t s i n t h e s p e c i e s l i s t e d . In t h e c a s e o f c e r t a i n g e n e r a , e s p e c i a l l y T a b e r n a e m o n t a n a , T a b e b u i a . M a y t e n u s . A l c h o r n e a , Ocimum, E r y t h r i n a . F i c u s . and U n c a r i a . t h e number o f a v a i l a b l e r e f e r e n c e s r u n s w e l l i n t o t h e t h o u s a n d s ; i n t h e s e i n s t a n c e s o n l y a few key r e f e r e n c e s h a v e b e e n c i t e d . I n most i n s t a n c e s t h e r e f e r e n c e s c i t e d do n o t r e f e r s p e c i f i c a l l y t o t h e s p e c i e s u s e d as an a y a h u a s c a a d m i x t u r e , b u t t o some c l o s e l y r e l a t e d s p e c i e s i n t h e same g e n u s . O f t e n i n f o r m a t i o n i s n o t a v a i l a b l e on t h e c o n s t i t u e n t s o f t h e p a r t i c u l a r s p e c i e s u s e d i n c o n j u n c t i o n w i t h a y a h u a s c a , b u t 1s a v a i l a b l e f o r o t h e r members o f t h e g e n u s .  Fam i 1 y : Genus &  Species  Vernacular  Acanthaceae: T e l i o s t a c h y a l a n c e o l a t a Nees v a r . C r i s p a Nees 1n M a r t . Amaranthaceae: I r e s i n e s p . P. A1ternanthera  Br.  sp.  succuba  Araceae: Montrichardia  none  Constituents  References  1. 3  reported  hydroxy-cinnamic  "picurullana-quina"  none  "cuchura-caspl"  steroid  L.  "uchu-sanango"  bisindole alkaloids, c o r n a r i d i ne  (Spruce)Woods  "bellaco-caspi"  flavonoids,  "raya  none  reported  1  none  reported  1  lehmanli  Tabernaemontana  negro"  Biodynamic  -  Apocynaceae: Malouetla tamaquarina  Hlmatanthus  "toe  Name  I Heron  (Aubl.)A.  arborescens  B ignonlaceae: Mansoa a l l i a c e a e (Lem.)A. G e n t r y  DC.  Schott.  "ajo  balsa"  sacha"  acid  amides  reported  alkaloids,  2 .4.85  conopharyng1ne terpenoids,  fu1voplurnieron  Tabebuia heteropoda (DC)Sandw1th.  "tahuar1"  dibenzoxanthenes.  Tynnanthus panurensls (Bur.)Sandwi th.  "clavohuasca"  none  reported  1 , 44  napthoquinones.lapachol  2 ,26,62 1 ,2,8.9,31.76,84 .  1 ,32,43 ,  1 ,22,53,73  1  Table  XVI  Fam11y: Genus &  (cont'd)  Species  Vernacular  Bombacaceae: Celba pentandra Cavamllesla Cactaceae: Opunt1a sp. Eplphyllum  L.  hylogelton  Ulb.  Mill sp.  Haw.  Name  • Biodynamic  " 1upuna"  none  "puca  ?  1upuna"  1  reported  1 , 37  "tchai"  N-methy1 - t y r a m i n e ,  mescaline  "pokere"  none  reported  5  reported  1  Caryocaraceae: Anthodiscus pilosus  Ducke  "tahuar i"  none  Ce1astraceae: Maytenus e b e n i f o l i a  Reiss  "chuchuhuas i"  sesquiterpene alkaloids, nicotinoyl alkaloids, t n t e r p e n e s , may t e n s i n e . tingonane, ansa m a c r o l i d e s .  Cyc1anthaceae: Carludovlca dlvergens  5,40.42  1 ,20,41,49 52.78, etc.  "tamsh i"  none  "piri-piri"  quinones, saponins,  "chicorro"  none  Euphorbiaceae: Alchornea castenifolia (Wi1 I d . ) Juss.  "hi poruru"  alchornine, imadazole a l k a l o i d s , corynanthe-type alkaloids, antifeedants, etc.  1, 6 3 . 79,84,  Hura  "catahua"  tiglione diterpenes. piscicidal compounds, 1ect i ns  1 ,47.54.65  "renaco"  clusianone,  xanthochymol ,  neolignans,  sesquiterpenes,  Cyperaceae: Cyperus sp.  Cyperus  Drude  References  Constituents  L.  dlgitatus  crepitans  Gutt1 ferae: Clusia Insignis  Roxb.  L.  Mart.  Lablateae: Ocimum m i c r a n t h u m  Willd.  Lecyth i daceae: Couroupita guianensis  Aubl.  "pichana,  "ayahuma"  abaca"  1  reported  1,7,57  essential oils sesquiterpenes  86  reported  i ndo1e  a 1ka1o i ds  G4  triterpenoids  a n t i h e 1 merit i c s  70  1.25.36.66  2.  19.  1.12,60  30.  50  Table  XVI  Famlly: Genus &  (cont'd)  Species  Vernacular  Legumlnosae: Calllandra angustlfolia  Biodynamic  Constituents  "bobinsana"  imlno  "hua i racasp i "  none  P 1 t h e c e l 1 o b i urn l a e t u m (Poepp. & Endl.) Benth.  "remo  phytomitogens,  Scleroblum  "pa 1i s a n g r e " = "pa 1i s a n t o " ?  none  "amaciza"  Erythrina  Cedrllinga  Spruce  Name  catenaeformis  setiferum  Ducke  Erythrina poepplgiana ( W a l p . ) 0 . F. C o o k Voucapoua  americana  Ducke  Aubl .  caspi"  =  "amasisa"?  "huacapu"  References  1 ,33,38  acids  1  reported lupeol,  spinasterol  1 ,85  reported  alkaloids,  1 , 13,69  1 . 8 5 . 3 4 . 77  etc.  none  reported  1  Lomar1 ops 1daceae: Lomarlopsis japurensis ( M a r t . ) d . Sm.  "shoka"  none  reported  5  Loranthaceae: Phryg11anthus var. robustus  "miya"  none  reported  5  none  reported  1  Phtlrusa H . B . K.  eugenoides Glaz.  pyrifolia Elchler  Marantaceae: Calathea veitchiana V e i t c h . Ex H o o k e r Men i s p e r m a c e a e : Abuta grandlfolla ( M a r t . ) Sandwi t h . Moraceae: Coussapoa Mildbr. Ficus Ficus  tessmannli  ruiziana insipida  Pourouma sp. aff.  Standi. Willd.  Aubl. foleata  "sueIda  con  "pu1 ma"  tryptophan  "abuta", "caimit11lo", "sanango"  tropolone isoquinolines, p a 1 mat i ne  "renaco"  none  "renaco" "oje"  furocoumarins . triterpenes, bipheny1hexahydroindolizines, phenanthroxindolizines  1 , 2 8 . 2 9 , 71  none  1  "chu11achaqui McBr.  sueIda"  caspi"  2 , 75  oxo-aporph1nes,  reported  reported  1.86.15. 58,59  1  Table  XVI  Faml1y: Genus &  (cont'd)  Species  Vernacular  Myristicaceae: V i r o l a sp. Aubl.  Virola Warb.  surinamensis  Nymph i a c e a e : Cabomba a q u a t i c a  Aubl .  Polygonaceae: T r i p l a r i s surinamensis Mart, var. chamissoana Meisn. Pontedar iaceae: Pontedaria cordata  L.  Phytolaccaceae: Petiveria allIaceae  L.  Rubiaceae: C a 1 y c o p h y 1 1 urn s p r u c e a n u m (Benth.)Hooker Guettarda Standi.  ferox  linear la g u i a n e n s i s (Aubl.)Gmel  Schizaeceae: Lygodium venustum  Scrophular i aceae: Scoparia dulcis L.  Sw.  Name  Biodynamic  References  Constituents  "cumala"  d i a r y l propanoids, 2-methyl ketones tryptamines. p-carbolines, neolignans  1 .6.24.61 74  "caupur i"  neo1i gnans  1 .6  "murere"  =  "mureru"?  none  reported  1 .85  "tangarana"  none  reported  1  "amaron  none  reported  2 .3  borrachero"  "mucura"  oligo  "capirona  negro"  none  sulfides,  triterpenes,  reported  canthemine.  "garabata"  sp i r o - o x i n d o l e s . b i s - i n d o l e s . y o h i mb i n e s  "nucnu  del  monte"  pichana"  hetero-yohimbine  antfferti1ity  triterpenes,  1,16.18.39  1  "garabata"  "tachai  trithiolanes  alkaloids  1.10,48  hetero-  1 .27,67. 76,82,84  agents  S - M e O - b e n z o x a z o l i 1 i none  5.55  1 ,21 . 5 6 . 7 2  Table  XVI  Fam1 1 y : Genus &  (cont'd)  Solanaceae: Datura suaveolens (Willd.) Brechtold Brunfelsia P1owman Iochroma Meers in Juanulloa  &  Presl  chiricsanango  fuchsoides Hooker ochracea  Verbenaceae: Cornutia odorata (P.& E.) Peopp. Vitex Vahl .  Vernacular  Species  triflora  Cuatr.  Name  Biodynamic  References  Constituents  "toe"  tropane  alkaloids  1,2.3,4  "chiricsanango"  s c o p a l e t i n , CNS d e p r e s s a n t s , antiinflammatory compounds  1 . 2 , 11 ,87.88  "borrachero"  none  reported  2,3,4  "ayahuasca"  none  reported  "shi nguarana"  none  reported  " tahuar i"  diterpenes lactones, flavonoid glycosides  85,86  iridoid  glycosides,  1 , 17.23.51.68  214  References 1.  L u i s E. L u n a . The C o n c e p t of P l a n t s as T e a c h e r s Among F o u r M e s t i z o Shamans of I q u i t o s , N o r t h e a s t P e r u . Paper p r e s e n t e d a t t h e Symposium on Shamanism, X l t h I n t e r n a t i o n a l C o n g r e s s of A n t h r o p o l o g i c a l and E t h n o l o g i c a l S c i e n c e s , Phase 2. V a n c o u v e r , B. C , A u g u s t 2 0 - 2 3 , 1983.  2.  R.  E. S c h u l t e s . E t h n o t o x i c o l o g i c a l S i g n i f i c a n c e of A d d i t i v e s t o New W o r l d H a l l u c i n o g e n s . P l a n t S c i e n c e B u l l e t i n 18: 344 1 . 1972.  3.  R.  E. S c h u l t e s . New D a t a on the M a l p i g h i a c e o u s N a r c o t i c s of S o u t h A m e r i c a H a r v a r d B o t a n i c a l Museum L e a f l e t s , 23:I37ff. 1979.  4.  H.  V. P i n k l e y . P l a n t Admixtures t o A y a h u a s c a , the South A m e r i c a n H a l l u c i n o g e n i c D r i n k . L l o y d i a 3 2 : 3 0 5 . 1969.  5.  L.  R i v i e r & J . L i n d g r e n . Ayahuasca, the South American H a l l u c i n o g e n i c D r i n k : E t h n o b o t a n i c a l and C h e m i c a l Investigations. E c o n o m i c Botany 2 9 : 1 0 1 - 1 2 9 . 1972.  6.  L.  E. S. B a r a t a , P. M. N e o l i g n a n s of V i r o l a 8 6 . 1978.  7.  R.  D. A l l a n , R. J . W e l l s , R. L. C o r r e l l , & J . K, M a c L e o d . P r e s e n c e of Q u i n o n e s i n the Genus C y p e r u s as an A i d t o C l a s s i f i c a t i o n . P h y t o c h e m i s t r y 1 7 : 2 6 3 - 2 6 6 . 1978.  8.  D.  G . K i n g s t o n . P l a n t A n t i - c a n c e r A g e n t s P a r t 6: I s o l a t i o n V o a c a n g i n e , V o a c a m i n e and E p i - v o a c o r i n e from T a b e r n a e m o n t a n a a r b o r e a S a p . J o u r n a l of Pharmaceutical S c i e n c e s 6 7 : 2 7 1 - 7 2 . 1978.  9.  D.  G . K i n g s t o n , B. B. G e r h a r t , F. I o n e s c u , M. M. M a n g i n o , & S. M. S a m i . P l a n t A n t i - c a n c e r A g e n t s P a r t 5: New b i s - I n d o l e A l k a l o i d s from T a b e r n a e m o n t a n a j o h n s t o n i i Stem B a r k . J o u r n a l of P h a r m a c e u t i c a l S c i e n c e s 6 7 : 2 4 9 - 5 1 . 1978.  10. H. P. H u s s o n , S t r u c t u r e of Biosynthesis 22:1889-92.  B a k e r , 0 . R. G o t t l i e b , & E. A . R u v e d a . Surinamensis. Phytochemistry 17:783-  C . K a n - F a n , T . S e v e n e t , & J . P. V i d a l . C a t h e n a m i n e , Key I n t e r m e d i a t e i n t h e of I n d o l e A l k a l o i d s . T e t r a h e d r o n L e t t e r s 1977.  The  of  215  11. M. C h a u b a l , & R. P. I y e r . C a r b o n - 1 3 NMR S p e c t r a S c o p o l e t i n . L l o y d i a 4 0 : 6 1 8 . 1977.  of  12. J . Bergman, B. E g e s t a d , & J - O . L i n d s t r o m . The S t r u c t u r e Some I n d o l i c C o n s t i t u e n t s i n C o u r o u p i t a g u a i n e n s i s . T e t r a h e d r o n L e t t e r s 3 0 : 2 6 2 5 - 2 6 . 1977.  of  13. M. Y a d a v , V . K. C . G a n a s w a r a n . P h y t o - M i t o g e n s of T r o p i c a l Legumes P a r t I: I s o l a t i o n f r o m P a r k i a s p e c i o s a and P i t h e c e l l o b i u m j i r i n g a . M a l a y s i a n J o u r n a l of S c i e n c e 4 : 2 5 2 6 . 1976. 14. C . K. K o k a t e & K. C . V a r m a . P h a r m a c o l o g i c a l S t u d y on E s s e n t i a l O i l of C y p e r u s s c a r i o s u s P a r t I: E f f e c t on C e n t r a l N e r v o u s System p p . 189-193 i n L. D. Kapoor & R. K r i s h n a n ( e d s . ) A d v a n c e s i n E s s e n t i a l O i l I n d u s t r y . Today & T o m o r r o w ' s P r i n t e r s & P u b l i s h e r s , New D e l h i . 1977. 15.  J . V . S i l v e r t o n , C . K a b u t o , K. T . B u c k , M. P. C a v a . S t r u c t u r e of I m e r u b r i n e , a N o v e l C o n d e n s e d T r o p o l o n e I s o q u i n o l i n e A l k a l o i d . J o u r n a l of t h e A m e r i c a n C h e m i c a l S o c i e t y 9 9 : 6 7 0 8 - 1 2 . 1977.  16. C . Von S z c z e p a n s k i , J . H e i n d l , G-A. H o y e r , & E. S c h r o e d e r . B i o l o g i c a l l y A c t i v e Compounds from P l a n t s P a r t 2: S y n t h e s i s and A n t i - m i c r o b i a l A c t i v i t y of Some D i s s y m m e t r i c O l i g o S u l f i d e s . European J o u r n a l of M e d i c i n a l C h e m i s t r y 12:2798 4 . 1977. 17. R. U. K o d a n d a , R. E. V e n k a t a , R. D. V e n k a t a . P h e n o l i c C o n s t i t u e n t s of t h e Bark of V i t e x n e g u n d o . I n d i a n J o u r n a l of Pharmacy 3 9 : 4 1 . 1977. 18. F. P. S e g e l m a n , & A . B. S e g e l m a n . C o n s t i t u e n t s of P e t i v e r i a a l l i a c e a e (Phytolaccaceae) P a r t 1: I s o l a t i o n of I s o a r b o r i n o l , I s o a r b o r i n o l A c e t a t e and I s o a r b o r i n o l C i n n a m a t e from t h e L e a v e s . L l o y d i a 3 8 : 5 3 7 . 1975. 19. R. G . Roy, N. M. M a d e s a y a a , R. B. G h o s h , D. V . G o p a l k r i s h n a n , N. N. M u r t h y , T . J . D o r a i r a , & N. L. S i t a r a m a n . Study on I n h a l a t i o n T h e r a p y by an I n d i g e n o u s Compound on Plasmodium v i v a x and P l a s m o d i u m f a l c i p a r u m I n f e c t i o n s : A P r e l i m i n a r y C o m m u n i c a t i o n . I n d i a n J o u r n a l of M e d i c i n a l R e s e a r c h 1 0 : 1 4 5 1 - 5 5 . 1976.  216  20.  S. M. K u p c h a n , & R. M. S m i t h . M a y t o l i n e , M a y t i n e , and M a t o l i d i n e , N o v e l N i c o t i n o y l S e s q u i t e r p e n e A l k a l o i d s from M a y t e n u s s e r r a t a . J o u r n a l of Organ i c Chemi s t r y 4 2 : 1 1 5 - 1 1 8 . 1977.  21.  C-M. Chen & C - T . C h e n . 6-Methoxy B e n o x a z o l i n o n e and T r i t e r p e n o i d s from R o o t s of S c o p a r i a d u l c i s . Phytochemistry 1 5 : 1 9 9 7 - 9 9 . 1976.  22.  R. Y. Wong, K. J . P a l m e r , G. D. M a n n e r s , & L. J u r d . The S t r u c t u r e of G u a y a c a n i n w i t h A c e t o n e of C r y s t a l l i z a t i o n , A N a t u r a l l y O c c u r r i n g D i b e n z o x a n t h e n e from T a b e b u i a g u a y a c a n . A c t a C r y s t o l l o g r a p h i c a S e c . B 8 : 2 3 9 6 - 2 4 0 0 . 1976.  23.  H.  24.  R. B a r u f f a l d i , E. F e d e l i , & N. C o r t e s i . S t u d y of the F a t of V i r o l a s u r i n a m e n s i s P a r t 1: A c i d i c and G l y c e r i d e C o m p o s i t i o n and C h e m i c a l N a t u r e of Some of the U n s a p o n i f i a b l e C o m p o n e n t s . R e v i s t a de F a r m a c i a e B i o q u i m i c a da U n i v e r s i d a d e de Sao P a u l o 1 3 : 9 1 - 1 0 2 . 1975.  25.  L. E. M c C a n d l i s h , J . C . H a n s o n , & G. H. S t o u t . The S t r u c t u r e s of 2 D e r i v a t i v e s of B i - c y c l o - 3 , 3 , 1 - n o n a n e - 2 , 4 , 9 t i r o n e , a N a t u r a l P r o d u c t C l u s i a n o n e and T r i m e t h y l a t e d C a t e c h i n i c A c i d . A c t a C r y s t a l l o g r a p h i c a , S e c . B: Structural C r y s t a l l o g r a p h y and C r y s t a l C h e m i s t r y 3 2 : 1 7 9 3 - 1 8 0 1 . 1976.  26.  J.  27.  Y. B a n , M. S e t o , & T . O i s h i . The S y n t h e s i s of 3 S p i r o O x i n d o l e D e r i v a t i v e s P a r t 7: T o t a l S y n t h e s i s of A l k a l o i d s Racemic R h y n c h o p h y l l i n e and Racemic Isorhynchophylline. C h e m i c a l & P h a r m a c e u t i c a l B u l l e t i n 11:2605-13 1975.  28.  Y. I. E i d l e r , G. L. G e n k i n a , T . T . S h a k i r o v . Quantitative D e t e r m i n a t i o n of F u r o c o u m a r i n s i n F i c u s c a r i c a L e a v e s . K h i m i y a P r i r o d n y k h S o e d i n e n i i 3 : 3 4 9 - 5 1 . 1975.  29.  M. H. A . E l g a m a l , B. A . H. E l - t a w i l , & M. B. E. F a y e z . The T r i t e r p e n o i d C o n s t i t u e n t s of t h e L e a v e s of F i c u s n i t i d a . N a t u r w i s s e n s c h a f t e n 6 2 : 4 8 6 . 1975.  Taguchi.  Chemical  D.  Studies  & Pharmaceutical  M e d i n a & R.  Malouetia  on the  Bracho.  glandulifera.  Constituents Bulletin  7:1668-70.  Constituents  Planta  of V i t e x  Medica  of  the  cannibolia.  1976.  Bark  of  2 9 : 3 6 7 - 6 9 . 1976.  217  30.  S. J . T e r h u n e , J . W. H o f f , & R. W. L a w r e n c e . B i c y c l o s e s q u i p h e l l a n d r e n e and 1-epi B i c y c l o s e s q u i p h e l l a n d r e n e 2 New D i e n e s B a s e d on t h e C a d a l e n e S k e l e t o n . P h y t o c h e m i s t r y 1 3 : 1 1 8 3 - 8 5 . 1974.  31.  B. T a l a p a t r a , A . P a t r a , & S. K. T a l a p a t r a . T e r p e n o i d s and A l k a l o i d s of t h e L e a v e s of T a b e r n a e m o n t a n a c o r o n a r i a . P h y t o c h e m i s t r y 14: 1652-53. 1975.  32.  R. R. P a r i s , & S. D u r e t . The F l a v o n o i d s of V a r i o u s A p o c y n a c e a e . P l a n t e s M e d i c i n a l e s et P h y t o t h e r a p i e 8:318-25. 1974.  33.  G. A.  34.  K. I t o , M. H a r u n a , & H. F u r u k a . S t u d i e s on t h e E r y t h r i n a A l k a l o i d s P a r t 10: A l k a l o i d s of S e v e r a l E r y t h r i n a s p . P l a n t s from S i n g a p o r e M a l a y s i a . Yakugaku Z a s s h i 3 : 3 5 8 - 6 2 . 1975.  35.  S. R. Hemingway, & J . D. P h i l l i p s o n . A l k a l o i d s from S o u t h A m e r i c a n S p e c i e s of U n c a r i a ( R u b i a c e a e ) . J o u r n a l of Pharmacy and P h a r m a c o l o g y 2 6 ( s u p p l . ) : 1 1 3 p . 1974.  36.  D. L. D r e y e r . X a n t h o c h y m o l from C l u s i a r o s e a P h y t o c h e m i s t r y 1 3 : 2 8 8 3 - 8 4 . 1974.  37.  J . E. L o p e z G u i l l e n P e r u p a r t 5. B i o t a  & I. K. De C o r n e l i o . M e d i c i n a l 1 0 : 7 6 - 1 0 4 . 1974.  Plants  of  38.  J . E. L o p e z G u i l l e n P e r u p a r t 4. B i o t a  & I. K. De C o r n e l i o . M e d i c i n a l 1 0 : 2 8 - 5 6 . 1974.  Plants  of  39.  E. K. A d e s o g a n . T r i t h i o l a n i a c i n , a N o v e l T r i t h i o l a n e from P e t i v e r i a a l l i a c e a . J o u r n a l of t h e C h e m i c a l Soc i e t y , C h e m i c a l C o m m u n i c a t i o n s 2 1 : 9 0 6 - 7 . 1974.  40.  R. L. V a n d e r Veen & L. G . W e s t . N-methyl T y r a m i n e O p u n t i a c l a v a t a . P h y t o c h e m i s t r y 1 3 : 8 6 6 - 6 7 . 1974.  41.  M. L e b o e u f . M a y t a n s i n e and M a y t a n s i n o i d s . Plantes M e d i c i n a l e s e t P h y t o t h e r a p i e 1 2 : 5 3 - 7 0 . 1978.  D a r d e n n e . New F r e e  Phytochemistry  14:860.  Amino A c i d s  1975.  from L e g u m i n o s a e .  (Guttiferae).  from  218  42.  J . P a r d a n a n i , B. N. M e y e r , & J . L. M c L a u g h l i n . M e s c a l i n e and R e l a t e d Compounds from O p u n t i a s p i n o s i o r . L l o y d i a 4 1 : 2 8 6 8 8 . 1978.  43.  G . P. Perdue & R. N. B l o m s t e r . S o u t h A m e r i c a n P l a n t s P a r t 3: I s o l a t i o n of F u l v o p l u m i e r i n from H i m a t a n t h u s s u c u u b a ( A p o c y n a c e a e ) . J o u r n a l of P h a r m a c e u t i c a l S c i e n c e s 6 7 : 1 3 2 2 2 3 . 1978.  44.  J . M a r t i n - T a n g u y , F. C a b a n n e , E. P e r d r i z e i , & C . M a r t i n . The D i s t r i b u t i o n of H y d r o x y - c i n n a m i c A c i d Amides i n F l o w e r i n g P l a n t s . P h y t o c h e m i s t r y 1 1 : 1 9 2 7 - 8 . 1978.  45.  P. K. M e h r o t r a & V . P. K a m b o j . Hormonal P r o f i l e of C o r o n a r i d i n e H y d r o c h l o r i d e , an A n t i f e r t i l i t y Agent O r i g i n . P l a n t a M e d i c a 3 3 : 3 4 5 - 4 9 . 1978.  46.  H. Wagner & J . B u r g h a r t . S p e r m i d i n e A l k a l o i d s and T r i t e r p e n e s from Maytenus h e t e r o p h y l l a s s p . h e t e r o p h y l l a and P l e u r o s t y l a a f r i c a n a : C h e m i c a l C o n s t i t u e n t s of t h e C e l a s t r a c e a e P a r t 4. P l a n t a M e d i c a 3 2 A : 9 - 1 4 . 1977.  47.  F. J . E v a n s & C . J . S o p e r . The T i g l i a n e Daphnane and Ingenane D i t e r p e n e s : T h e i r C h e m i s t r y , D i s t r i b u t i o n , and B i o l o g i c a l A c t i v i t i e s ; A R e v i e w . L l o y d i a 4 : 1 9 3 - 2 3 3 . 1978.  48.  C . Kan-Fan & H. P. H u s s o n . S t e r e o c h e m i c a l C o n t r o l i n the B i o m i m e t i c C o n v e r s i o n of H e t e r o y o h i m b i n e A l k a l o i d P r e c u r s o r s : I s o l a t i o n of a N o v e l Key I n t e r m e d i a t e . Journal of t h e C h e m i c a l S o c i e t y , C h e m i c a l C o m m u n i c a t i o n s 1 4 : 6 1 8 - 1 9 . 1 978.  49.  H. N o z a k i , H. S u z u k i , K-H. L e e , & A . T . M c p h a i l . Structure and S t e r e o c h e m i s t r y of M a y t e n f o l i c A c i d and M a y t e n f o l i o l , 2 New A n t i - Leukemic T r i t e r p e n e s from M a y t e n u s D i v e r s i f o l i a : X-Ray C r y s t a l S t r u c t u r e s . J o u r n a l of the C h e m i c a l Soc i e t y , C h e m i c a l C o m m u n i c a t i o n s 0 : 1 0 4 8 - 5 1 . 1982.  50.  D. G . D e s a i , N. S. Ambade, & R. R. Mane. S y n t h e s i s of Ocimum a New N e o l i g n a n from Ocimum a m e r i c a n u m . I n d i a n J o u r n a l of Chemistry Section B O r g a n i c C h e m i s t r y 5 : 4 9 1 - 9 2 . 1982.  of  Plant  f  51.  C . K. S e h g a l , S. C . T a n e j a , K. L. D h a r , & C . K. A t a l . 2' p H y d r o x y b e n z o y l M u s a e n o s i d i c A c i d , a New I r i d o i d G l y c o s i d e from V i t e x n e g u n d o . ' P h y t o c h e m i s t r y 2 : 3 6 3 - 6 6 . 1982.  219  52.  J . G. G o n z a l e s , G . D e l l e Monache, F. D e l l e Manache, G . B. M a r i n i - B e t t o l o . C h u c h u h u a s h a , a Drug Used i n F o l k M e d i c i n e i n the Amazonian and Andean A r e a s of S o u t h A m e r i c a : A C h e m i c a l Study of Maytenus L a e v i s . J o u r n a l o f E t h n o p h a r m a c o l o g y 5 : 7 3 - 7 8 . 1982.  53.  D. G . K i n g s t o n & M. M. Rao. I s o l a t i o n , S t r u c t u r e Elucidation and S y n t h e s i s of 2 New C y t o t o x i c N a p t h o q u i n o n e s from T a b e b u i a c a s s i n o i d e s . P l a n t a M e d i c a 3 : 2 3 0 - 3 1 . 1980.  54.  M. P e r e , D. P e r e , & P. Rouge. I s o l a t i o n and S t u d i e s of the P h y s i c o c h e m i c a l and B i o l o g i c a l P r o p e r t i e s of L e c t i n s from Hura c r e p i t a n s . P l a n t a M e d i c a 4 1 : 3 4 4 - 5 0 . 1981.  55.  B. B. G a i t o n d e & R. T . M a h a j a n . A n t i f e r t i l i t y A c t i v i t y of L y g o d i u m f l e x u o s u m . I n d i a n J o u r n a l of M e d i c a l R e s e a r c h 7 2 : 5 9 7 - 6 0 4 . 1980.  56.  S. B. M a h a t o , M. C . D a s , & N. P. S c o p a r i a d u l c i s . Phytochemi s t r y  57.  P. N. S i n g h of C y p e r u s  58.  J . W. S k i l e s , J . M. S a a , & M. P. C a v a . S p l e n d i d i n e , a New Oxo A p o r p h i n e A l k a l o i d from A b u t a r u f e s c e n s . C a n a d i a n J o u r n a l of C h e m i s t r y 5 7 : 1 6 4 2 - 4 6 . 1979.  59.  S e t o r de F i t o q u i m i c a , INPA, M a n a u s , A m a z o n a s , B r a z i l . Chemical Composition of Amazonian P l a n t s . A c t a A m a z o n i c a 1 : 8 3 - 8 6 . 1971 .  60.  A . K. Sen 6 S. B. M a h a t o . C o u r o u p i t i n e a New A l k a l o i d Couroupita g u i a n e n s i s . Tetrahedron L e t t e r s 7:609-10.  61.  O. R. G o t t l i e b , & A . A . L o u r e i r o . D i s t r i b u t i o n of D i a r y l P r o p a n o i d s i n Amazonian V i r o l a S p e c i e s . Phytochemistry 1 2 : 1 8 3 0 . 1973.  62.  F. Khuong-Huu, & M-J. M a g d e l a i n e . S t e r i o d A l k a l o i d s from M a l o u e t i a b r a c h y l o b a and from M a l o u e t i a h e u d e l o t i i . P h y t o c h e m i s t r y 7 : 1 8 1 3 - 1 6 . 1973.  S a h u . The T e r p e n o i d s 2 0 : 1 7 1 - 7 3 . 1981.  & S. B. S i n g h . A New S a p o n i n from M a t u r e r o t u n d u s . P h y t o c h e m i s t r y 1 9 : 2 0 5 6 . 1980.  of  Tubers  from 1974.  220  63.  F. Khuong-Huu & J . P. Le F o r e s t i e r . A l c h o r n e i n e , I s o a l c h o r n e i n e and A l c h o r n e i n o n e , P r o d u c t s I s o l a t e d A l c h o r n e a f l o r i b u n d a . T e t r a h e d r o n 2 8 : 5 2 0 7 - 2 0 . 1972.  64.  H. H i k i n o , & K. A o t a . S t r u c t u r e and A b s o l u t e C o n f i g u r a t i o n of A l p h a R o t u n o l and B e t a R o t u n o l , S e s q u i t e r p e n o i d s of C y p e r u s r o t u n d u s M. T e t r a h e d r o n 2 7 : 4 8 3 1 - 3 6 . 1971.  65.  K. S a k a t a , & K. Kawazu. S t u d i e s on a P i s c i c i d a l C o n s t i t u e n t of Hura c r e p i t a n s D. P a r t 1: I s o l a t i o n and C h a r a c t e r i z a t i o n of Hura T o x i n and i t s P i s c i c i d a l A c t i v i t y . A g r i c u l t u r a l and B i o l o g i c a l C h e m i s t r y 3 5 : 1 0 8 4 - 9 1 . 1971.  66.  S. B. Mathur T r i t e r p e n o i d C o n s t i t u e n t s P h y t o c h e m i s t r y 1 1 : 1 5 1 3 - 1 4 . 1972.  67.  M. L a v a u l t , C . M o r e t t i , & J . B r u n e t o n . A l k a l o i d s g u i a n e n s i s . P l a n t a M e d i c a 4 7 : 2 4 4 - 5 . 1983.  68.  A . H. J a c k s o n , & A . S. C h a w l a . S t u d i e s of E r y t h r i n a A l k a l o i d s . P a r t IV. GC/MS I n v e s t i g a t i o n s of A l k a l o i d s t h e L e a v e s of E. p o e p p i g i a n a , E. m a c r o p h y l l a , E. b e r t e r o a n a , and E. s a l v i f l o r a . A l l e r t o n i a 3 : 3 9 - 4 5 .  of  Clusia  from  rosea  of  D.  Uncaria  in 1982.  69.  S. P. G u n a s e k e r a , G . A . C o r d e l l , & N. R. Farnsworth. C o n s t i t u e n t s of P i t h e c e l l o b i u m m u l t i f l o r u m . J o u r n a l N a t u r a l P r o d u c t s 4 5 : 6 5 1 . 1982.  70.  B. L. H. H a n k i n s o n . I n v e s t i g a t i o n of C o n s t i t u e n t s and A n t i f e e d a n t A c t i v i t y of A l c h o r n e a t r i p l i n e r v i a . D i s s e r t a t i o n A b s t r a c t s I n t e r n a t i o n a l S e c . B # DA8217228. 1 982  71.  S. R. V e n k a t a c h a l a m , & N. B. M u l c h a n d a n i . I s o l a t i o n of P h e n a n t h r o i n d o l i z i d i n e A l k a l o i d s and a N o v e l B i p h e n y l h e x a h y d r o i n d o l i z i n e A l k a l o i d from F i c u s h i s p i d a . N a t u r w i s s e n s c h a f t e n 6 9 : 2 8 7 - 8 . 1982.  72.  J . L i , Y. L i , R. N i e , & J . Z h o u . C o i x o l and B e t u l i n i c A c i d of S c o p a r i a d u l c i s L. Yun-nan C h i h Wu Yen C h i u 3 : 4 7 5 - 7 . 1981.  73.  L. P r a k a s h & R. S i n g h . C h e m i c a l E x a m i n a t i o n of t h e L e a v e s and Stem h e a r t w o o d of T a b e b u i a p e n t a p h y l l a ( L i n n ) H e m s l . (Bignoniaceae). J o u r n a l of t h e I n d i a n C h e m i c a l S o c i e t y 5 8 : 1 1 2 2 - 2 3 . 1981.  of  221  7 4 . O . R. G o t t l i e b . C h e m i c a l S t u d i e s on M e d i c i n a l M y r i s t i c a c e a e from A m a z o n i a . J o u r n a l of E t h n o p h a r m a c o l o q y 1:309-323. 1979. 7 5 . W.  of  E.  Splittstoesser  Tropical  Roots  & F.  W.  Martin.  The T r y p t o p h a n  and T u b e r s . H o r t s c i e n c e  10:23-24.  76.  G . A . C o r d e l l & J . E. S a x t o n . B i s i n d o l e i n R. H. F. Manske & R. G . A . R o d r i g o , V o l X X . A c a d e m i c P r e s s . 1981.  77.  S.  F.  Dyke  78.  D.  M.  Smith.  79.  D.  S.  Seigler.  80.  R.  L.  Clarke.  The T r o p a n e A l k a l o i d s .  Chapter  81.  J.  E.  Saxton.  Alkaloids  and R e l a t e d  82.  J.  S.  Bindra.  Oxindole A l k a l o i d s .  83.  M.  Shamma & R.  Chapter  F.  Manske  Manske,  op.  N.  Quessy.  (ed.)  Plant  and R e l a t e d  op_. c i t . ,  op_. c i t . , V o l X V I .  Chapter  of  Mitragyna  pjo. c i t . , V o l .  1973.  Castenson.  6 i n Manske,  XIV.  2 in  H,  1 in  Manske,  Species.  Manske,  Alkaloids.  Indole A l k a l o i d s  in  1 973.  84. V.  Snieckus.  85.  J.  Soukup. V o c a b u l a r i o  86.  D. McKenna, G . H. N. T o w e r s , & F. S. A b b o t t . Monoamine Oxidase I n h i b i t o r s i n South American H a l l u c i n o g e n i c Plants: T r y p t a m i n e and 0 - c a r b o l i n e C o n s t i t u e n t s of A y a h u a s c a . J o u r n a l of E t h n o p h a r m a c o l o g y . 1 0 : 1 9 5 - 2 2 3 . 1984  Chapter  Peruana  1 in Manske,  of  2 in  The O x o a p o r p h i n e  op_. c i t . , V o l . X I V .  Distribution  Chapter  1973.  Chapter  1981.  4 i n R.  1977.  and A l k a l o i d s .  1977.  3 in Manske,  L.  1977.  Alkaloids,  Vol XVIII.  Alkaloids.  Systematics  1975.  A l k a l o i d s . Chapter 1 ( e d s . ) The A l k a l o i d s  The A l k a l o i d s V o l . X V I .  c i t . , V o l XIV.  Chapter  Erythrina  & Rodrigo,  The C e l a s t r a c e a e  c i t . , Vol XVI.  Chapter  op.  & S.  1 i n Manske  Content  op. c i t . , Vol XI. de l o s  Colegio Salesiana,  1968.  Nombres V u l g a r e s  Lima.  1970.  Plants.  de l a  Flora  222  87.  Plowman, T . B r u n f e l s i a i n E t h n o m e d i c i n e . Museum L e a f l e t s 2 5 : 2 8 9 - 3 2 0 . 1977.  Harvard  Botanical  88.  I y e r , R. P., J . K. Brown, M. G . C h a u b a l & M. H. M a l o n e . B r u n f e l s i a hopeana I. H i p p o c r a t i c S c r e e n i n g and A n t i i n f l a m m a t o r y E v a l u a t i o n . J o u r n a l of N a t u r a l P r o d u c t s 40:356-60. 1c77.  223  APPENDIX  II  The f o l l o w i n g l i s t of h e r b a r i u m v o u c h e r s p e c i m e n s i n c l u d e s t h e c o l l e c t i o n d a t a on a l l of the s p e c i m e n s d i s c u s s e d i n the t e x t f o r which h e r b a r i u m v o u c h e r s are a v a i l a b l e . In a d d i t i o n A p p e n d i x II i n c l u d e s any o t h e r p l a n t c o l l e c t i o n w h i c h was s t a t e d by i n f o r m a n t s t o have a m e d i c i n a l o r e t h n o b o t a n i c a l l y s i g i f i c a n t u s e . A p p e n d i x II a l s o i n c l u d e s a l l c o l l e c t i o n s from t h e M y r i s t i c a c e a e and M a l p i g h i a c e a e , even t h o u g h t h e s e may not have been u t i l i z e d i n t h e p r e p a r a t i o n of d r u g s a m p l e s a n a l y z e d i n t h i s work or may not be u s e d i n t h i s manner. P l a n t c o l l e c t i o n s w h i c h were not known t o have e t h n o b o t a n i c a l or m e d i c i n a l s i g n i f i c a n c e have been o m i t t e d from t h i s c o l l e c t i o n l i s t . In i n s t a n c e s where m u l t i p l e c o l l e c t i o n s were made of t h e same s p e c i e s , the taxonomic a u t h o r i t y i s g i v e n i n the f i r s t c i t a t i o n ; the a u t h o r i t y i s omitted i n subsequent c i t a t i o n s .  TABLE C o l l e c t ion # (DMK-)  B1nom i a 1 & authority  DMK-1 * t  Justicia Jacq.  DMK-3  XVII  - LIST  OF HERBARIUM VOUCHER COLLECTIONS  Determined by:*  UBC H e r b a r i u m Duplicate A c c e s s * V172- V o u c h e r s :  masha-h1r i  T . P1owman(F )  175  F.USM,MO*  a d d i t i v e to V i r o l a snuff used t o t r e a t c o l d s o r e s  B a n i s t e r i o p s i s caapi (Spr.ex G r i s e b ) Morton  ayahuasca  T . P1owman(F)  177  F.USM  source  DMK-16*  Sanchezia Leonard  -  P . Mateka i t i s ( F )  189  F.USM,ECON UNAP  l e a v e s smoked o r b r e w e d a s ha 11uc i n o g e n  DMK-20*  Psychotria R. & P.  viridis  chacruna  T . P1owmanf F )  193  UBC o n l y  admixture t o ayahuasca o r i g . s t o c k f o r DMK-21  OMK-21*  Psychotria  viridis  chacruna  T . P1owmanf F )  194  F.USM,ECON. see above MICH.RVH,UNAP  DMK-22*  Teliostachya Nees  toe  T . P1owmanf F )  195  F.USM.ECON. UNAP,MO.RVH  DMK-23*  V i r o l a pavonis (A. DC. )A. C. Smi t h  cumala  W. Rodr i g u e s f I N P A )  196  F,USM.ECON. UNAP,INPA.RVH  DMK-30*  Virola  cuma1 a  W . Rodr i g u e s ( I N P A )  201  F . ECON. INPA UNAP.RVH  alkaloid  +  DMK-3 1 *  P a l i c o u r e a sp.  -  J.  203  F,USM,MO, UNAP,RVH  alkaloid  ++  DMK-32*  Virola  pavonis  cuma1 a  W . Rodrigues(INPA)  204  F.USM,ECON, alkaloid INPA.UNAP,RVH  DMK-34*  Virola  pavonis  cuma1 a : ku'-ru-ku  W . Rodr i g u e s f I N P A )  205  F,USM.ECON, UNAP,MICH. INPA,MO.RVH  alkaloid source of Bora paste a t P U .  DMK-35*  V i r o l a sp.  cuma1 a  P . Matakaitis(F)  206  UBC o n l y  alkaloid  +  DMK-36*  V i r o l a sp.  cumala  P . Matakaitis(F)  207  UBC o n l y  alkaloid  +  DMK-37*  V i r o l a sp.  cuma1 a  P . Matakaitis(F)  208  UBC o n l y  alkaloid  +  DMK-38*  R l n o r a racemosa (Mart.&Zucc.IKuntze  -  A . Gentry(MO)  209  F , USM.ECON. UNAP.MO.RVH  a l k . -; 1 i c h e n o n bark added t o Virola paste  DMK-39*  Anemia s p .  -  R . G.  210  F,USM.ECON, UNAP,RVH  alk.-;tea f r . leaves u s e d t o cook V i r o l a p a s t e  DMK-40*  Virola Aubl .  cumala r o j a ; oo'-koey; p i r i ;  211  F.USM.MICH. INPA,MO.RVH ECON.UNAP  a 1 k . + + : s o u r c e o f D.A. M o r e n o s a m p l e #1  Vernacular  pectoralis  tigrina  lanceolata  pavonis  seblfera  Name  negro  •  Ruiz(UNAP)  Stolze(F)  W. R o d r i g u e s f I N P A )  Remarks:  of ayahuasca  ayahuasca  admixture  -  Table  XVII  Col l e c t i o n (DMK-) DMK-41*  (Cont'd) #  B1nom i a 1 & authority  Vernacular  Virola elongata (Benth.)Warb.  DMK-42  P1tyrogramma c a 1 o m e 1 o s ( L . ) L i nk  DMK-43*  Theobroma s u b 1nacum  DMK-44*  Mart.  Iryanthera longlflora  Ducke  Name  cuma1 a : o o ' - k o o - n a ;  -  Determ1ned by:*  UBC H e r b a r i u m Duplicate A c c e s s H V172- V o u c h e r s :  W.  212  Rodr1gues(INPA)  R. G.  Stolze(F)  Remarks:  F,USM,ECON, UNAP, INPA, RVH  alkaloid ++ sui table for  213  F.USM,UNAP RVH  j u i c e of croz i ers used f o r c a t a r a c t s ashes of f r u i ts added t o V i r o l a p a s t e  macambo d e l monte: Bora:a'-he  P. M a t a k a l t i s ( F )  214  F.USM.ECON, UNAP,RVH  Bora : ehu-ghwa-o-oo-e  W.  2 15  F.USM ECON,UNAP  Rodrigues(INPA)  alkaloid INPA  +  DMK-45*  Virola  elongata  Bora:ugr-pah-1 aye  W. R o d r i g u e s ( I N P A )  216  INPA  DMK-46*  Virola Warb.  calophylla  Bora:kuhr'-re-ko  W.  Rodr i g u e s ( I N P A )  217  F.USM.ECON UNAP  DMK-47*  Iryanthera macrophylla  Bora:hach iurne-e  W.  Rodr i g u e s ( I N P A )  219  F .USM.ECON. alkaloid UNAP. INPA, RVH  Bora:hachi-e  W. Rodr i g u e s ( I N P A )  218  USM,INPA, RVH  Bora:ch i - c h i - c h  W. Rodr i g u e s ( I N P A )  220  F,USM.ECON a 1ka1o i d INPA, UNAP, RVH  DMK-48*  Iryanthera Warb.  DMK-49*  Iryanthera crassifolla  (Bth.)Warb. ulel  A. C. S m i t h  .alkaloid  paste  alkaloid +;suitable f o r making p a s t e  alkaloid  -  -  -  DMK-50*  Iryanthera Warb.  juruensis  Bora:pij1-hah'-eh  W.  Rodrigues(INPA)  221  F.USM.ECON, alkaloid INPA,UNAP.RVH  DMK-51*  Iryanthera Warb.  paraensls  B o r a : t i - t i-mueh  W.  Rodr i g u e s ( I N P A )  222  F.USM.ECON, alkaloid INPA.UNAP.RVH  DMK-52*  Virola Ducke  multinervia  Bora:kat'-so-eh  W. Rodr i g u e s ( I N P A )  223  F.USM.ECON, alkaloid INPA.UNAP RVH  DMK-53  Virola  calophylla  W1 t o t o : o o - k o o ' - n a  W. R o d r 1 g u e s ( I N P A )  224  F,USM,ECON. UNAP.INPA  DMK-54  V i r o l a sp.  P. M a t a k a l t i s ( F )  225  USM.ECON.UNAP,RVH  DMK-56*  Virola  W1toto:ti-ti-mueh  W. R o d r i g u e s ( I N P A )  226  F.USM.ECON INPA.UNAP. RVH  alkaloid + (seeds & f r u i t s )  DMK-57  Ban i s t e r i ops i s mur1cata(Cav.)Cuatr.  sacha-ayahuasca  B . Gates  227  F,USM.ECON, UNAP,MICH. RVH  u s e d t o make ayahuasca  calophylla  cuma1 a  (MICH)-  -  su i t a b 1e f o r  paste  ro  Table  XVII  (Cont'd)  Col l e c t i o n H (DMK-)  B1nomla1 & authority  V e r n a c u l a r Name  Determined by:*  UBC H e r b a r i u m Dup1i c a t e A c c e s s * V172- V o u c h e r s :  DMK -59*  Virola  elongata  cumala  w.  Rodr1gues(INPA)  229  F.USM,ECON. UNAP,MICH. INPA.MO,RVH  s o u r c e o f Don M a r c o s ' k u ' - r u - k u : a l k a l o i d ++  DMK -63*  Virola  pavonis  cumala b l a n c a ; Bora:ku'-ru-ku  w.  Rodrigues(INPA)  233  F.USM.ECON. UNAP,MICH  alk. -; said for paste  DMK -64*  P h i l o d e n d r o n nervosum (Schult.cV Schul t . )Kunth  -  T . Plowman!F)  234  F.USM.ECON, UNAP.MICH, MO,RVH  admixture to Virola paste; alkaloid  -  Theobroma b i c o l o r  macambo; Bora:a'-hep  T  F.USM.ECON. UNAP,M0,RVH  admixture to V i r o l a paste; a l k a l o i d  -  -  C.  Niezgoda(F)  236  F.USM.UNAP, RVH  tea used as s e d a t i v e ; admix, t o a y a h u a s c a  DMK -65  DMK  -66*  Calliandra Spruce  H.&B.  angustifolia  PIowmanfF)  235  Remarks:  suitable  DMK -67*  Virola  elongata  cuma1 a; W1 t o t o : o o ' - k o o - n a  w.  RodriguesfINPA)  237  F.USM,UNAP, INPA.RVH  a l k . + ; S o u r c e o f D.A. M o r e n o s a m p l e H2  DMK  -68*  Virola  elongata  cuma1 a; Wi toto:oo'-koo-na  w . Rodr i g u e s f I N P A )  238  F.USM.UNAP. INPA,RVH. ECON  a l k . + ; s o u r c e o f D.A. M o r e n o s a m p l e #3  DMK  -69*  Virola  elongata  cuma1 a ; Wi t o t o : o o ' - k o o ' - n a  w.  RodriguesfINPA)  239  F.USM.UNAP, INPA,ECON. RVH  a 1 k . + ; s o u r c e o f D.A. M o r e n o s a m p l e #4  DMK -70  Virola  elongata  cumala  w. R o d r i g u e s f I N P A )  240  F.USM.ECON. INPA.RVH  source  of seeds  DMK -71  Virola  elongata  cumala  w.  241  F.USM.ECON. source MO.INPA,UNAP , RVH  of seeds  DMK -73  Banisteriopsis mart i n i a n a ( A d r . J u s s . ) C u a t r . var. subenervia Cuatr.  B. G a t e s ( M I C H )  243  F.USM,MO. ECON.MICH, UNAP,RVH  DMK -74*  Abuta grandifolia (Mart.)Sandwith  a b u t a , c a 1 m i 1111o, sanango  T . P1owmanfF)  244  F.USM.ECON, UNAP,RVH  admixture to ayahuasca; a l k a l o i d  DMK -75*  Virola loretensis A.C. Smi t h  cuma1 a  W . Rodrigues(INPA)  245  F,USM.ECON. UNAP,MICH. INPA,MO.RVH  alkaloid  DMK--78*  Osteoph1oem platyspermum  -  w. Rodr i g u e s f I N P A )  248  F.USM.ECON, INPA,UNAP, RVH  a l k . +; N - M e - t r y p t o p h a n methyl-ester i n Ivs.  F.USM.UNAP. INPA,RVH  a 1ka1o i d -  DMK -82*  Virola Ducke  Rodr i g u e s ( I N P A )  (A.DC)Warb.  albidiflora  c u m a l a de 1os b r u j o s  w. Rodr i g u e s f I N P A )  251  ++  -  ho  Table  XVII ( C o n t ' d )  Col l e c t i o n (DMK-)  #  B i nom i a 1 & authority  Determined by:*  UBC H e r b a r i u m Duplicate Access V172- V o u c h e r s :  -  W.  Anderson(MICH)  252  F,USM,UNAP, MICH,MO,RVH  -  W.  Anderson(MICH)  253  F,USM.UNAP, MICH,MO,RVH  W.  A n d e r s o n ( M I C H ) 255  F,USM.UNAP, MICH,MO,RVH  -  W.  Anderson(MICH)  25G  F,USM,UNAP, MICH.MO,RVH  Vernacular  Name  DMK-83*  M a s c a g n i a s 1 n e m a r i e n s 1s (Aubl.)Griseb.  DMK-84*  Byrsonima poeppigiana Adr. J u s s .  DMK-86  Burdachia ' pr1smatocarpa Adr. Juss. var. l o r e t o e n s i s Anderson  DMK-87  Mascagnia benthamlana (Griseb.)Anderson  DMK-88  Mascagnia benthamiana  -  W.  Anderson(MICH)  257  F,USM.UNAP. MICH,MO.RVH  DMK-89  Mascagnia  -  W.  Anderson(MICH)  258  F,USM.UNAP. MICH.MO,RVH  DMK-90  Heteropterys o r i n o c e n s i s (H.B.K.)Adr. J u s s .  w.  Anderson(MICH)  259  F.UNAP.MICH, RVH  DMK-91  S t igmaphy1 Ion hypoleucum Miq  DMK-92  Byrsonima arthropoda Adr. J u s s .  DMK-93  Heteropterys or i nocens1s  DMK-94  Heteropterys or 1nocens1s  DMK-95  Heteropterys orinocensis  DMK-96  Heteropterys or 1nocens1s  DMK-97  Brunfelsia grandiflora D. Don s s p . s c h u l t e s i i P1owman  DMK-103  Byrsonima c h r y s o p h y l l a H.B.K.  DMK-104  Hyptis suaveolens (L. )Poi t.  benthamiana  Remarks:  -  w.  Anderson(MICH)  260  F,USM,UNAP. MICH.MO,RVH  -  w.  Anderson(MICH)  261  F,USM.UNAP. MICH.RVH  -  w. A n d e r s o n ( M l C H )  262  F.UNAP.MICH. USM,MO.RVH  -  w.  Anderson(MICH)  263  F.UNAP.MICH, RVH  -  w.  Anderson(MICH)  264  UNAP,MICH.RVH  -  w.  Anderson(MICH)  265  UNAP,MICH.RVH, F,USM,MO  ch1r i csanango  T . P1owman(F)  266  F,UNAP,RVH  -  W. A n d e r s o n ( M I C H )  272  F,USM,UNAP, MICH,RVH  -  C .Ni e z g o d a ( F )  273  F,USM,MO, UNAP.RVH  febrifuge;admix. ayahuasca  used  to  f o r rheumatism  Table  XVII  CollectIon (DMK- )  (Cont'd) n  Binomial & authority  V e r n a c u l a r Name  Determined by:*  Dupli cate UBC H e r b a r i u m A c c e s s # V172- V o u c h e r s :  Remarks:  DMK- 107*  Davi11a ni tIda (Vahl.)Kub.  pucahuasca  P . Mataka i t i s ( F )  276  UBC  DMK- 108*  Psychotria  yage-sem i r u c a ; chacruna:sui j a  T . P1owman(F)  277  F.USM,ECON, UNAP,MICH, M0-. RVH  a 1k. + ;adm i x . To ayahuasca  DMK- 109*  Psychotr ia carthagenens1s  yage;yagechacruna  P . Mataka i t i s ( F )  278  F.UNAP  Jacq.  a 1k. -; adm i x. t o ayahuasca  DMK- 1 10*  Banisteriopsis  caapi  cielo  T . P1owman(F )  279  F.UNAP  ayahausca  cuitivar  DMK- 1 1 1  Banisteriopsis  caapi  lucero  ayahuasca  T . P1owman(F)  280  F.UNAP  ayahuasca  cultivar  DMK- 1 12  Banisteriopsis  caapi  lucero  ayahuasca  T . Plowman(F)  281  F,UNAP  ayahuasca  cultivar  DMK- 1 13  Senna o c c i d e n t a l i s ( L. )L i nk  R. B a r n a b y ( N Y )  282  UBC  medicinal: use u n c e r t a i n  DMK- 1 15  Petiveria  mukura  P . Matakai t i s ( F )  284  F,USM.UNAP. MO,RVH  used i n t h e bath; to ayahuasca  DMK- 1 16  Piper  cordonc i11o  W . Burger(F)  285  F,UNAP,RVH  tea of l e a v e s used t o t r e a t asthma S heal bones  DMK- 1 17  Ocimum Wi1 I d .  albaca  T . P1owman(F)  286  UNAP  f o r t h e stomach; ayahuasca admixture  DMK- 1 18  H i p p e a s t r u m puniceum (Lam.)Kuntze  samangi  T . Plowman(F)  287  UNAP  for dropsy, & sore arches  DMK- 1 19  Cornutia odorata (P.& E.)Poepp.  shi nguarana  T . P1owman(F)  288  UBC  only  admixture t o ayahuasca alkaloid -  DMK- 120  Sambucus m e x i c a n a salco Presl . ssp.bipinnata(S.SC.)Schwer.  T . P1owman(F)  289  UNAP,RVH  treatment of e p i l e p s y , cough, b r o n c h i t u s  DMK- 12 1  Chenopod1um a m b r o s i o i d e s L.  T . P1owman(F)  290  F.USM.MO. RVH  used  i n bath  DMK- 122  Maranta  T . P1owman(F)  291  UNAP.RVH  used  i n bath  viridis  a l l i a c e a e L.  aduncum L.  micranthum  a r u n d i n a c e a e L.  ayahuasca  retama  buseta  s h i mpanpana  only  only  admix,  ro ro  Table  XVII  (Cont'd)  Col 1 e c t I o n f (DMK-)  Binomial & authority  DMK- 123  Alpinia Schum  DMK- 124*  Banisteriopsis  DMK- 125*  Determined by:*  UBC H e r b a r i u m Duplicate A c c e s s ff V172- V o u c h e r s :  m i sk i - p a n g a  P . J.  Maas(F)  292  F,USM,ECON. MO,UNAP,RVH  use  caapi  pucahuasca  B . Gates  (MICH)  293  UNAP.MICH, RVH  ayahuasca  cuit ivar  Banisteriopsis  caapi  ayahuasca  B . Gates  (MICH)  294  UNAP.MICH, RVH  ayahuasca  c u 1 1 i var  DMK- 126*  Banisteriopsis  caapi  cielo  ayahuasca  B . Gates  (MICH)  295  UNAP.MICH, RVH  ayahuasca  cuit ivar  DMK- 127*  Banisteriopsis  caapi  delo  ayahuasca  B . Gates  (MICH)  296  UNAP,MICH, RVH  ayahuasca  c u 1 1 i var  DMK- 128*  Banisteriopsis  caapi  rumi  T . P 1 owman ( F )  297  UBC  only  ayahuasca  c u 1 1 i var  DMK- 129  Psychotria  P . Matakai t i s ( F )  298  UBC  only  admix, t o a y a h u a s c a ; cu11 i var  P . Mataka i t i s ( F )  299  UBC  only  adm i x. t o a y a h u a s c a ; cu1t1var  UBC  only  admix, t o a y a h u a s c a ; c u 1 1 i var  DMK- 130  DMK- 131  Vernacular  speciosa  Psychotria  Psychotria  viridis  viridis  viridis  Name  ayahuasca  chacruna - ' l a hembra'  chacruna - ' l a hembra' chacruna - ' e l macho'  M.  form  form P . Matakaitis(F  ) 300  form  Remarks: uncertain  DMK- 132  Psychotria  viridis  chacruna  P . Matakaitis(F)  301  UBC  only  admix, t o a y a h u a s c a ; cuit ivar  DMK- 134  Brunfelsia D. Don  grandiflora  ch1r1csanango - 'grande' form  T . Plowman(F )  302  UBC  only  adm i x. t o a y a h u a s c a ; cu1t i var  DMK- 135  Brunfelsia grandiflora ssp. s c h u l t e s 1 i P1owman  chi r1csanango -'pequeno' form  T . P1owmanfF)  303  UBC  only  admix, t o a y a h u a s c a : cuit1var  DMK- 136  Iryanthera Ducke  cuma1 a  W.  Rodr i g u e s ( I N P A )  304  INPA  source of  large  seeds  DMK- 137  Iryanthera  cuma1 a  W.  RodriguesfINPA)  305  INPA  source of  smal1  seeds  lancifolia  juruensis  Table  XVII  Col l e c t i o n (DMK-)  (Cont'd) *  B i nom1a 1 & authority  Determined by:*  UBC Herbarium Duplicate A c c e s s It V 1 7 2 - V o u c h e r s :  -  P . Matakai t i s ( F )  306  F,USM.MO  l e a v e s chewed for toothache  chacruna  P . Matakai t i s(F )  307  UBC  admix,  Vernacular L'Her  Name  Remarks:  DMK-138*  Spllanthus  alba  DMK-139*  Psychotria  viridis  DMK-142  Trlpogandra glandulosa (Seub.)Rohw. v a r . ( v e l . sp. a f f . )  -  B . Faden(US)  308  F.USM,MO  use u n c e r t a i n ; market p l a c e s  DMK-143*  Cyperus Roxb.  ch1 c o r r o ; chlcorro-p1r1-piri  D.  309  USM  tubers used as a y a h u a s c a admix.; o r smoked a s h a l l u c i n o g e n  DMK- 144  Eleutherlne (Ml 1 1 ) U r b .  -  T . P1owman(F)  310  UBC  digitatus  bulbosa  Adams(F)  only  only  to ayahuasca sold in i n Peru  b u l b made i n t o t e a to a i d i n c h i l d b i r t h  * = Name o f t a x o n o m i s t m a k i n g d e t e r m i n a t i o n . H e r b a r i u m c o d e s a r e shown i n p a r e n t h e s e s t - * i n d i c a t e s a d d i t i o n a l m a t e r i a l was c o l l e c t e d f o r p h y t o c h e m i c a l a n a l y s i s \ - H e r b a r i a w h e r e d u p l i c a t e v o u c h e r s a r e o n d e p o s i t . H e r b a r i u m c o d e s a r e a c c o r d i n g t o Index H e r b a r i o r u m I ( 1 9 7 4 ) : F = F i e l d Museum o f N a t u r a l H i s t o r y , C h i c a g o , 111. UBC = H e r b a r i u m o f U n i v e r s i t y o f B r i t i s h C o l u m b i a ECON = O a k e s Ames E c o n o m i c H e r b a r i u m , H a r v a r d B o t a n i c a l Museum, H a r v a r d U n i v e r s i t y USM = H e r b a r l o S a n M a r c o s , Museo d e H i s t o r i a N a t u r a l , L i m a , P e r u MICH = H e r b a r i u m o f t h e U n i v e r s i t y o f M i c h i g a n . Ann A r b o r . M i c h . INPA = I n s t i t u t o N a c i o n a l d e P e s q u i s a s do A m a z o n i a , Manaus, B r a z i l MO = M i s s o u r i B o t a n i c a l G a r d e n , S t . L o u i s , Mo. US = U.S. N a t i o n a l H e r b a r i u m . S m i t h s o n i a n I n s t i t u t i o n . W a s h i n g t o n . D. C. UNAP = H e r b a r i u m o f t h e U n i v e r s i d a d N a c i o n a l d e Amazonense P e r u a n a , I q u i t o s , P e r u ( n o t l i s t e d i n Index H e r b a r i o r u m ) RVH = H e r b a r i u m o f R.V. H e r a c l i t u s , I n s t i t u t e o f E c o t e c h i c s , A i x - e n - P r o v e n c e . F r a n c e ( n o t l i s t e d i n I n d e x H e r b a r i o r u m )  

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