Medicine, Faculty of
Anesthesiology, Pharmacology and Therapeutics, Department of
DSpace
UBCV
Yau, Jade
Master of Science - MSc
University of British Columbia
Medical cannabis has been reported to improve the symptoms of various mental health conditions, such as anxiety, depression and chronic pain. Conversely, other studies have suggested that cannabis use contributes to mental health problems. Information gathered about medical cannabis users from previous studies have been mostly self-reported with limited diagnostic measures examining mental health. The goal of the present study was to expand on current research using standardized and clinical assessments to analyze the severity of mental health and any psychiatric conditions in a non-epidemiological population of medical cannabis users from a dispensary in Vancouver. We administered the Mini-International Neuropsychiatric Interview, based on criteria from the DSM-IV-TR and ICD-10. In order to obtain detailed information about the general well-being and mental health of individuals, seven standardized assessments evaluated perceived stress, fatigue, sleep disturbances, depression, somatic symptoms, pain, and nicotine dependence. This will provide high quality data that can be better compared to other studies in the literature. Most frequently diagnosed conditions were anxiety, depression, and substance dependence, but most self-reported conditions were anxiety, sleep and depression. Results showed that medical cannabis users with a depression diagnosis had higher perceived stress, but severity of depression was mostly minimal. Many participants reported using cannabis to treat depression, but only three had current depression. Participants with any anxiety disorder mostly preferred to use pure CBD, and many had experienced negative effects with cannabis use. A diagnosis of specific anxiety disorders, such as GAD, PTSD or social phobia, were more likely to have higher perceived stress. Those with substance dependence diagnoses showed earlier onset of regular cannabis use, higher frequency of cannabis use and dispensary visits. Alcohol or other non-cannabis dependence diagnoses were more likely to be diagnosed with panic disorder, social phobia, and higher perceived stress. Our population did not have severe disturbances with sleep, somatic symptoms or pain ratings. 74% used cannabis daily, and the average cannabis amount used per week was 4.29 grams of dried cannabis. Ultimately, cannabis may provide a therapeutic option for individuals with mental health conditions looking for alternative treatments.
CHARACTERIZATION OF MENTAL HEALTH IN CANNABIS DISPENSARY USERS, USING STRUCTURED CLINICAL INTERVIEWS AND STANDARDIZED ASSESSMENT INSTRUMENTS by Jade Yau B.Sc., The University of Liverpool, 2016 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Pharmacology and Therapeutics) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) April 2019 © Jade Yau, 2019 ii Committee Members The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the thesis entitled: Characterization of Mental Health in Cannabis Dispensary Users, Using Structured Clinical Interviews and Standardized Assessment Instruments Submitted by Jade Yau in partial fulfillment of the requirements for the degree of Master of Science in Pharmacology and Therapeutics. Examining Committee: Dr. Alasdair Barr Supervisor Dr. William Panenka Supervisory Committee Member Dr. Michael Walker Supervisory Committee Member iii Abstract Medical cannabis has been reported to improve the symptoms of various mental health conditions, such as anxiety, depression and chronic pain. Conversely, other studies have suggested that cannabis use contributes to mental health problems. Information gathered about medical cannabis users from previous studies have been mostly self-reported with limited diagnostic measures examining mental health. The goal of the present study was to expand on current research using standardized and clinical assessments to analyze the severity of mental health and any psychiatric conditions in a non-epidemiological population of medical cannabis users from a dispensary in Vancouver. We administered the Mini-International Neuropsychiatric Interview, based on criteria from the DSM-IV-TR and ICD-10. In order to obtain detailed information about the general well-being and mental health of individuals, seven standardized assessments evaluated perceived stress, fatigue, sleep disturbances, depression, somatic symptoms, pain, and nicotine dependence. This will provide high quality data that can be better compared to other studies in the literature. Most frequently diagnosed conditions were anxiety, depression, and substance dependence, but most self-reported conditions were anxiety, sleep and depression. Results showed that medical cannabis users with a depression diagnosis had higher perceived stress, but severity of depression was mostly minimal. Many participants reported using cannabis to treat depression, but only three had current depression. Participants with any anxiety disorder mostly preferred to use pure CBD, and many had experienced negative effects with cannabis use. A diagnosis of specific anxiety disorders, such as GAD, PTSD or social phobia, were more likely to have higher perceived stress. Those with substance dependence iv diagnoses showed earlier onset of regular cannabis use, higher frequency of cannabis use and dispensary visits. Alcohol or other non-cannabis dependence diagnoses were more likely to be diagnosed with panic disorder, social phobia, and higher perceived stress. Our population did not have severe disturbances with sleep, somatic symptoms or pain ratings. 74% used cannabis daily, and the average cannabis amount used per week was 4.29 grams of dried cannabis. Ultimately, cannabis may provide a therapeutic option for individuals with mental health conditions looking for alternative treatments. v Lay Summary Cannabis has been shown to benefit people with mental health problems, including depression and anxiety, but others argue that using cannabis may further worsen symptoms. Key goals of the present study were to gather information about people who use cannabis for medical purposes in order to gain further knowledge of their cannabis use routine, especially the type of cannabis and amount they use for specific medical conditions. Additionally, reliable and standard assessments were used for identifying mental disorders and examining the mental health status of individuals. Frequent conditions diagnosed from the study include various anxiety disorders, major depressive disorders and substance dependency, however, most medical cannabis users showed low to moderate levels of mental health issues, with only few severe cases. Therefore, the study contributes to the better understanding of the role that cannabis plays in mental health, as it becomes widely accessible and accepted as an alternative to conventional treatments. vi Preface The present study was conducted under the supervision of Dr. Alasdair Barr. The author is responsible for the design of the study and the data collected, with initial training for the clinical interviews from Hadley Pearce. The author performed the analysis of research data, with additional aid in organizing data from Kiki Yu. All proportions of writing, figures and tables were produced by the author. This study was approved by the Behavioral Research Ethics Board of the University of British Columbia (BREB), and the Certificate Number of the Ethics Certificate is H16-01830. Selected portions of the research data from all chapters of this thesis will be revised and submitted for publication. vii Table of Contents Abstract ......................................................................................................................................... iii Lay Summary .................................................................................................................................v Preface ........................................................................................................................................... vi Table of Contents ........................................................................................................................ vii List of Tables ..................................................................................................................................x List of Figures ............................................................................................................................... xi List of Abbreviations .................................................................................................................. xii Glossary ...................................................................................................................................... xiv Acknowledgements ......................................................................................................................xv Dedication ................................................................................................................................... xvi Chapter 1: Introduction ................................................................................................................1 1.1 Cannabis Pharmacology ................................................................................................. 1 1.2 Medical Cannabis ............................................................................................................1 1.3 Literature Review ............................................................................................................2 1.4 Research Objectives.........................................................................................................4 1.5 Thesis Overview ............................................................................................................ 5 Chapter 2: Materials and Methods ..............................................................................................6 2.1 Methods Overview...........................................................................................................6 2.2 Study Population ............................................................................................................. 6 2.2.1 Data Collection Procedure ......................................................................................... 7 2.2.2 Data Storage ................................................................................................................7 viii 2.3 Measures ........................................................................................................................ 8 2.3.1 Perceived Stress Scale................................................................................................. 8 2.3.2 PROMIS Scales .......................................................................................................... 9 2.3.3 Beck Depression Inventory ....................................................................................... 10 2.3.4 Patient Health Questionnaire .................................................................................... 10 2.3.5 Brief Pain Inventory .................................................................................................. 11 2.3.6 Fagerström Test for Nicotine Dependence .............................................................. 11 2.3.7 Mini-International Neuropsychiatric Interview ........................................................ 12 2.4 Data Analysis ............................................................................................................... 12 Chapter 3: Results ...................................................................................................................... 13 3.1 Demographics .............................................................................................................. 13 3.2 Psychopathology ......................................................................................................... 13 3.3 Mental and General Health ......................................................................................... 15 3.4 Cannabis Characteristics ............................................................................................. 20 3.5 Further Analysis .......................................................................................................... 26 Chapter 4: Discussion ..................................................................................................................30 4.1 Cannabis and Mood Disorders ...................................................................................... 31 4.1.1 The Relationship Between Cannabis and Depression ............................................ 32 4.1.2 Cannabis and Bipolar Disorder .............................................................................. 34 4.1.3 Cannabis and Suicide ............................................................................................. 34 4.2 Cannabis and Anxiety Disorders .................................................................................. 35 4.2.1 The Relationship Between Cannabis and Anxiety ................................................. 35 4.2.2 Anxiety and Depression ......................................................................................... 38 ix 4.2.3 Cannabis for Post-Traumatic Stress Disorder ........................................................ 38 4.3 Cannabis and Substance Dependence and Abuse ........................................................ 39 4.3.1 Excluding Cannabis Dependence or Abuse ............................................................ 40 4.4 Cannabis and Sleep Issues ........................................................................................... 43 4.4.1 Sleep Issues or Fatigue in Depression .................................................................... 44 4.4.2 Self-Reported Sleep Issues ..................................................................................... 45 4.5 Cannabis for Pain ......................................................................................................... 46 4.5.1 Gender Differences in Pain .................................................................................... 47 4.5.2 Cannabis for Pain Treatment .................................................................................. 48 4.6 Cannabis Use Characteristics ....................................................................................... 49 4.6.1 Amount of Cannabis Use ....................................................................................... 49 4.6.2 Smoking .................................................................................................................. 50 4.6.3 Other Methods of Cannabis Consumption ............................................................. 51 4.6.4 Risks for Cannabis Dependence or Abuse ............................................................. 51 4.6.5 The "Entourage Effect" .......................................................................................... 52 Chapter 5: Conclusions ..............................................................................................................54 5.1 Summary ....................................................................................................................... 54 5.2 Limitations .................................................................................................................... 55 5.3 Future Work ................................................................................................................. 56 Bibliography .................................................................................................................................57 x List of Tables Table 3.1 Conditions reported to treat using medical cannabis .................................................... 17 Table 3.2 Demographic characteristics of medical cannabis users............................................... 18 Table 3.3 Psychopathology of medical cannabis users ................................................................. 18 Table 3.4 PSS10, PHQ-15, BDI and PROMIS fatigue and sleep disturbance scores .........................19 Table 3.5 FTND and BPI scores ..........................................................................................................19 Table 3.6 Negative effects experienced from medical cannabis .........................................................23 Table 3.7 Ages of first and regular cannabis use, and reasons for medical cannabis use ...................24 Table 3.8 Preference for cannabis method, product, use and frequency .............................................25 Table 3.9 Comparison of the most frequently diagnosed psychiatric conditions ................................27 xi List of Figures Figure 3.1 Frequency of cannabis dispensary visits ..........................................................................22 Figure 3.2 Usual time of day for medical cannabis use .......................................................................22 xii List of Abbreviations ADHD: Attention Deficit Hyperactivity Disorder ASPD: Anti-Social Personality Disorder BCCHRI: British Columbia Children’s Hospital Research Institute BDI: Beck Depression Inventory BPI: Brief Pain Inventory CB1R: Cannabinoid-1 receptor CB2R: Cannabinoid-2 receptor CBD: Cannabidiol DSM: Diagnostic and Statistical Manual of Mental Disorders FTND: Fagerström Test for Nicotine Dependence GAD: Generalized Anxiety Disorder ICD: International Classification of Diseases MDD: Major Depressive Disorder MDE: Major Depressive Episode MINI: Mini-International Neuropsychiatric Interview OCD: Obsessive-Compulsive Disorder PHQ-15: Patient Health Questionnaire (15 items) PROMIS: Patient-Reported Outcomes Measurement Information System PSS10: Perceived Stress Scale (10 items) PTSD: Post-Traumatic Stress Disorder REDCap: Research Electronic Data Capture xiii SPSS: Statistical Package for Social Sciences THC: Delta 9-tetrahydrocannabinol UBC: University of British Columbia xiv Glossary Cannabinoid: natural lipophilic products found in cannabis sativa extracts. Cannabinoid receptors: G protein-coupled receptors that bind to cannabinoids, such as THC, as well as natural endocannabinoids produced in the body. Epilepsy: a chronic neurological disorder characterized by sudden convulsions or episodes of unconsciousness. Fibromyalgia: a chronic disorder characterized by fatigue and intense pain or tenderness within large areas of the body. Psychosis: a range of mental disorders that affect the mind, thoughts and emotions, and usually involves a loss of contact with reality. xv Acknowledgements First and foremost, I offer my sincere gratitude and appreciation to my supervisor Dr. Alasdair Barr. Without his support and guidance, this study would not have been possible to complete. Thank you for inspiring me and providing me with further confidence to achieve my goals. I would like to extend my gratitude to MITACs, for financial and motivational support for this research study. I would also like to thank all the staff at the Evergreen dispensary, who always made the time to further educate me on cannabis products and experiences they have observed, in support of this study. With special thanks to Mike Babins, Maria Babins, Stephen Lebovits, Marco Renna and John Baxter, who were accommodating throughout the data collection phase of the research. In addition to this, I would like to express my appreciation for the technical support from Hadley Pearce, who always found solutions to my questions and provided valuable feedback. I owe particular thanks to Kiki Yu, who worked diligently on tasks and offered plentiful support for this research. I am most grateful for my family and their constant support throughout my life, as I would not be here in Canada, if it were not for their encouragement. Lastly, I would like to thank my close friends who are always there to provide motivation and emotional support during any hardships. xvi Dedication To my mother, who continues to inspire passion and determination. 1 Chapter 1: Introduction 1.1 Cannabis Pharmacology Cannabis has many different components, however, the most studied components within cannabis are cannabinoids, such as delta 9-tetrahydrocannabinol (THC) and cannabidiol (CBD), which are chemical compounds that act on cannabinoid receptors within our bodies (Sadhir, 2016). There are two main cannabinoid receptors, identified as CB1R and CB2R, that are located in various locations around the body, with CB1R mostly present within the central and peripheral nervous systems (Sadhir, 2016). High CB1R density regions include brain regions associated with cognition, pain perception, movement and memory (Mackie, 2008), while CB2Rs are mostly present on immune cells within the spleen or macrophages (Pertwee, 2006). THC is known for its psychoactive and euphoric effects (Mehmedic et al., 2010), however, CBD does not produce this “high” feeling, but has other actions including anxiolytic properties (Crippa et al., 2009). 1.2 Medical Cannabis These cannabinoids have been described to improve a wide range of different health conditions and symptoms, for example, both THC and CBD may be an effective treatment for epilepsy (Friedman and Devinsky, 2015), multiple sclerosis (Corey-Bloom et al., 2012), fibromyalgia (Habib and Artul, 2018), and other treatment-resistant conditions (Russo, 2016). Other studies have indicated that CBD may also reduce negative effects produced from high doses of THC, particularly possible psychosis (Gururajan & Malone, 2016; Niesink & van Laar, 2013), as they suggest that a sufficient amount of CBD can counteract these effects (Wycroff et 2 al., 2018). Despite these medical benefits, cannabis has been repeatedly stated as one of the most frequently used illicit drugs worldwide (United Nations Office on Drugs and Crime, 2014; United Nations Office on Drugs and Crime, 2016; United Nations Office on Drugs and Crime, 2018). Canadian statistics showed that 14.7% of the population, aged 15-year olds and older, reported using cannabis within the past year in 2015 (Health Canada, 2015). However, one in five Canadians aged 25 years and older reported cannabis use for medical reasons, with 49.7% reporting to treat chronic pain caused by migraines, back pain, or arthritis, and 50.3% of medical cannabis users primarily using cannabis for anxiety, depression or insomnia (Health, Canada, 2015). 1.3 Literature Review Similarly, physicians from a study evaluating medical cannabis patients, using the international classification of diseases (ICD-9), found that the most frequently coded conditions to treat with cannabis were for pain from back and neck injuries, sleep disorders, anxiety, depression, and muscle spasms (Reinarman et al., 2011). Authors of the study reported that information about the potential therapeutic benefits of cannabis were most likely spread through informal recommendations, suggesting a broad and widening patient population of medical cannabis users (Reinarman et al., 2011), thus, mental health conditions are the most common conditions reported for medical cannabis use. Other studies that explore medical use of cannabis for mental health conditions report that many chronic pain patients describe improved health and reduced pain upon starting cannabis use (Boehnke et al., 2019), and also improve problems with sleep caused by the chronic pain (Babson, Sottile, and Morabito, 2017). Moreover, cannabis could reduce post-traumatic stress disorder (PTSD) symptoms by decreasing associated 3 nightmares, while CBD has potential to regulate excessive daytime sleepiness and issues with REM sleep disorders (Babson, Sottile, and Morabito, 2017). Meanwhile, cannabis strains containing higher THC levels are recommended to medical cannabis users suffering from pain, insomnia and depression (Sinclair, 2016). In any given year, one in five Canadians may experience a mental health condition (Smetanin et al., 2011), and for many people, cannabis provides a more effective therapeutic option with minimal or no side effects compared to conventional medications, especially for pain relief (Carter et al., 2015), as a medical cannabis replacement could eliminate the chance of opioid addiction or a possible overdose (Reiman, Welty, and Soloman, 2017). Although this may be true, other studies propose that cannabis may contribute to the development of depression or anxiety. Lev-Ran et al. (2014) suggested that higher depression rates were found in weekly cannabis users compared to non-users, while Crippa et al. (2009) reported a number of risks associated with cannabis use in their critical review, stating that a high dose may cause intense fear or anxiety, or even panic and phobia attacks with higher dosing. Conversely, Denson and Earleywine (2006) resulted with fewer depressive participants and less physical symptom complaints from daily medical cannabis users compared to non-users. CBD clinical studies show a reduction of anxiety and reduced cognitive impairment in groups after receiving 600 mg of CBD, while placebo groups displayed higher levels of anxiety, discomfort and higher alert levels in comparison to a control group (Bergamaschi et al., 2011). The profiles of medical cannabis users have therefore been previously studied, and patients have self-reported that cannabis relieves pain, anxiety, depression, headaches, and also improves sleep, relaxation, appetite and concentration (Reinarman et al., 2011; Zaller et al., 2015, Walsh et al., 2013; Bonn-Miller et al., 2014; Nunberg et al., 2013; Pledger, Martin & 4 Cumming, 2016). Meanwhile, a recent guided systematic review emphasized that mental health conditions were one of the most important reasons for medical cannabis use, specifically for possible PTSD treatment and substitution for other addicting substances (Walsh et al., 2017). These studies have been beneficial and useful to better understand the people that use cannabis medically, however, the information collected from past studies have been self-reported with limited evidence-based research and diagnostic tools investigating mental health. 1.4 Research Objectives With this in mind, the role of cannabis for medical purposes must be further clarified as cannabis gains further interest as an alternative treatment, especially for neuropsychiatric problems (National Academies, 2017), and becomes decriminalized in many parts of the world (Grucza et al., 2018; Baum, 2016). After examining previous literature, the objectives of our study involve expanding on current research using standardized and clinical measures to investigate whether medical cannabis users meet diagnostic criteria for any psychiatric disorder, and to explore any associations between mental health and cannabis characteristics. This will provide high quality data that can be better compared to other studies in the literature. The goal of the present study was to analyze the severity of mental health and any psychiatric conditions in a non-epidemiological population of medical cannabis users from a dispensary in Vancouver and nearby cities of Canada. A neuropsychiatric structured clinical interview was completed to determine whether participants met criteria for a current or lifetime diagnosis of a major psychiatric disorder. In addition, subjects completed seven standardized questionnaires to measure symptom severity of stress, fatigue, insomnia, pain, depression, somatic symptoms and nicotine dependence. These findings were combined with information on 5 cannabis use routine to provide a detailed description of mental health in the dispensary population. 1.5 Thesis Overview This thesis consists of five chapters focusing on the present study of cannabis use and mental health states within medical cannabis users. Chapter 1 provides background information on cannabis pharmacology, with a general overview of medical cannabis use for certain medical conditions, especially for psychiatric conditions. Research objectives are also identified in chapter 1. Chapter 2 includes the methodology of the research study, with detailed information on participant eligibility, and a description of the tests, questionnaires and interviews used for the study. Chapter 3 displays the results from the study, along with tables and figures, while Chapter 4 discusses these results in depth. Specifically focusing on psychiatric disorders and their relationships with cannabis. Chapter 5 provides a summary of the study, with any strengths or limitations and future work for further research in the area. 6 Chapter 2: Materials and Methods 2.1 Methods Overview A hundred people who self-medicate with medical cannabis for mental health purposes were recruited from a specific cannabis dispensary. Participants completed a series of questionnaires that includes demographic information and their medical cannabis use, as well as a structured diagnostic interview and disorder-specific tests that measure how severely affected people are by mental health conditions. Data was stored electronically, and statistical analysis was completed using SPSS. 2.2 Study Population Participants (n = 100) were healthy individuals who use medical cannabis for any mental health symptoms, recruited from the Vancouver metropolitan area. These participants were considered low-risk for major psychiatric conditions, as they were not being given any treatment or invasive intervention from the study, only a series of surveys and an interview. Participants were recruited exclusively from the Evergreen Cannabis Society compassion club and were able to take flyers about the study, which included contact information of the research coordinator. Participants were eligible for the study if they were 19 years old or older, a current member of the Evergreen Cannabis Society compassion club, use medical cannabis for managing mental health symptoms, and are able to give informed consent without assistance. The research coordinator would then schedule a session with participants to complete the questionnaires and neuropsychiatric interview, either at Evergreen or at the Detwiller Pavilion building, around UBC hospital. 7 2.2.1 Data Collection Procedure During the session, the study coordinator would firstly ensure that participants understood all expectations from the study, before signing the study consent form. All participants were assigned unique study numbers and a unique record number in a secure web-based survey platform “REDCap”, to ensure that all information collected was de-identified and anonymous. All seven questionnaires were administered through the REDCap server, while the research coordinator would conduct the neuropsychiatric interview on paper. The average time taken to complete a single study session was forty-five minutes, and participants were given an honorarium of $50 for their time. 2.2.2 Data Storage Paper documents, such as the neuropsychiatric interview, the signed consent form and the payment invoice form are kept in separate folders so that names on the consent form are not linked to the neuropsychiatric interview, and these are placed within a locked drawer in a locked office at UBC hospital. Participant names and contact information linking them to their study number are kept encrypted in a Master list and only accessible by the co-investigators and research coordinators. All data will be kept stored securely for twenty years at the British Columbia Children’s Hospital Research Institute (BCCHRI), and after twenty years, all electronic data will be deleted and destroyed from the REDCap web-platform, while all paper documents will be shredded. Information for participants who select to be contacted for future research on the informed consent form will be kept in an encrypted excel file on a secure 8 computer at the BCCHRI. Only the date of consent, name and telephone number or email address of participants were collected and will be stored for twenty years after which it will be electronically destroyed. 2.3 Measures Detailed demographic information were collected, including age, gender, marital status, living status, education, and current employment. Specific questions regarding cannabis characteristics was also inquired, for example, age they first used cannabis, conditions or symptoms for using cannabis medically, preferred consumption method, frequency of cannabis use, time of day they usually use cannabis, amount of cannabis used, preferred cannabinoid content and any negative experiences from using cannabis. Participants could type in their own answers if options available were inadequate. Meanwhile, participants who selected that they currently smoke cigarettes would have also completed the Fagerström test for nicotine dependence. Six other self-report questionnaires were also incorporated, in order to obtain more detail around the individual’s general well-being and mental health characteristics. These include the perceived stress scale (PSS10), PROMIS fatigue scale, PROMIS sleep disturbance scale, Beck depression inventory, the patient health questionnaire (PHQ-15) and the brief pain inventory (BPI). 2.3.1 Perceived Stress Scale The perceived stress scale (PSS10) enables the participant to rate their lives in terms of unpredictability, lack of control and overload (Cohen, Kamarck & Mermelstein, 1983). The PSS-10 consists of ten items, which include six positively phrased items and four negatively phrased 9 items, that are rated on a 5-point Likert scale, 0 (never) to 4 (very often) (Cohen, Kamarck & Mermelstein, 1983). Total high scores indicate high levels of perceived stress, and the scores range from 0 to 40 (Cohen, Kamarck & Mermelstein, 1983). 2.3.2 PROMIS Scales Established in 2004, the Patient-Reported Outcomes Measurement Information System (PROMIS) is a research program that provides clinicians and researchers with dynamic tools to assess the health status of their patients, while incorporating the patient’s perspective of their physical, mental and social well-being (PROMIS Cooperative Group, 2008). During the PROMIS fatigue scale (short form 7a), participants were able to rate how tired they were over the past 7 days (PROMIS Cooperative Group, 2008). This enables us to evaluate whether they have mild feelings of tiredness to a debilitating sense of exhaustion that causes a loss of one’s ability to function normally socially or carry out daily activities. Items on the fatigue scale are split according to “experience of fatigue”, specifically the frequency, duration and intensity, as well as the physical, mental and social effect the fatigue caused (PROMIS Cooperative Group, 2008). Sleep disturbance (short form 8a) is an eight-item measure for sleep disturbance in adults aged eighteen or older, during their past seven days (PROMIS Cooperative Group, 2008). Both the PROMIS Fatigue and Sleep Disturbance scales are rated on a 5-point scale (1=never; 2=rarely; 3=sometimes; 4=often; 5= always) by participants (PROMIS Cooperative Group, 2008). Total raw scores range from 8 to 40, which are converted into t-scores using PROMIS conversion tables in order to standardize the results, meanwhile, a high total score indicates a greater severity in fatigue or sleep disturbance (PROMIS Cooperative Group, 2008). 10 2.3.3 Beck Depression Inventory The Beck Depression Inventory (BDI) is a self-report rating inventory with twenty-one items that evaluates depressive symptoms and attitudes over the past week (Beck et al., 1961). Each item would be focused on a specific category and included four statements to reflect depression severity from neutral to maximal (Beck et al., 1961). These statements are assigned numerical values from 0 to 3, and the BDI scores are a total sum of the statement values (Beck et al., 1961). Total scores are interpreted into rankings of depression, i.e. 0 to 13 = minimal; 14 to 19 = mild; 20 to 28 = moderate; and 29 to 63 = severe (Beck et al., 1961). Categories evaluated from the BDI include sadness, pessimism, past failures, loss of pleasure, guilty feelings, punishment feelings, self-dislike, self-criticalness, suicidal thoughts or wishes, crying, agitation, loss of interest, indecisiveness, worthlessness, loss of energy, changes in sleeping pattern, irritability, changes in appetite, concentration difficulty, tiredness or fatigue, and loss of interest in sex (Beck et al., 1961). 2.3.4 Patient Health Questionnaire Patient Health Questionnaire (PHQ-15) is a self-administrative form of the diagnostic tool, primary care evaluation of mental disorders (PRIME-MD), developed by Pfizer Inc. (Spitzer et al., 1994). The PHQ-15 involves fifteen somatic symptoms: stomach pain; back pain; pain in arms, legs or joints; menstrual cramps; headaches; chest pain; dizziness; fainting spells; feeling your heart race or pound; shortness of breath; pain or problems during sexual intercourse; constipation, loose bowels or diarrhea; nausea, gas or indigestion; feeling tired or having low energy; and trouble sleeping (Kroenke et al., 2002). These symptoms are scored either 0 = “not bothered at all”; 1 = “bothered a little”; or 2 = “bothered a lot”, which ultimately provides a 11 severity score ranging from 0 to 30 (Kroenke et al., 2002). Total PHQ-15 scores of five, ten, and fifteen signify cut-off points for low, medium and high severity of somatic symptoms, respectively (Kroenke et al., 2002). 2.3.5 Brief Pain Inventory Brief pain inventory (BPI) is a self-administered questionnaire used to evaluate pain severity and the impact the pain has on daily functioning (Cleeland & Ryan, 1994). During the BPI, participants would firstly select if they had any pain in specific areas of their body, and then use the 10-point scale to rate their worst, least, average and current pain intensity, as well as list current treatments for the pain and rate how effective these treatments were (Cleeland & Ryan, 1994). Participants also rate the degree of interference the pain has with general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life (Cleeland & Ryan, 1994). 2.3.6 Fagerström Test for Nicotine Dependence The Fagerström test for Nicotine Dependence (FTND) is a self-administered method of determining the physical addiction to nicotine within the tobacco in cigarette smokers (Heatherton et al., 1991). Participants that selected they currently smoke cigarettes would complete the Fagerström test, consisting of six questions relating to early morning smoking, number of cigarettes consumed daily, and difficulty restraining from smoking (Heatherton et al., 1991). Dependency levels are established from total points and divided into low (0 to 2 points), average (3 to 5 points), strong (6 to 7 points) and very strong (8 to 10 points) (Heatherton et al., 1991). 12 2.3.7 Mini-International Neuropsychiatric Interview We administered the sixth version of the Mini-international neuropsychiatric interview (MINI), a short structured clinical interview, in order to make diagnoses of psychiatric disorders based around the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) and the International Classification of Diseases, tenth edition (ICD-10) (Sheehan et al., 1998). Psychiatric disorders in the MINI include Major Depressive Disorder (MDD), Suicidality, Bipolar Disorder, Panic Disorder, Agoraphobia, Social Phobia, Obsessive Compulsive Disorder (OCD), Post-traumatic Stress Disorder (PTSD), Alcohol Dependence, Substance Dependence, Psychotic Disorder, Anorexia Nervosa, Bulimia Nervosa, Generalized Anxiety Disorder (GAD), and Antisocial Personality Disorder (ASPD) (Sheehan et al., 1998). 2.4 Data Analysis Descriptive analysis was performed on participant demographics, cannabis characteristics, questionnaire results and MINI diagnoses. The independent samples t-test was used for continuous variables, whilst categorical data was analyzed using Chi-squared tests. We compared most frequent diagnosed conditions with cannabis characteristics and other diagnosed psychiatric disorders. The alpha level was set to 0.05. All analyses were performed using the Statistical Package for Social Sciences (SPSS) software version 25.0 (IBM Corp., 2017). 13 Chapter 3: Results 3.1 Demographics Descriptive analyses indicated that majority of participants were male (68%), were aged between 19 to 24 years (35%) or 25 to 30 years (24%), and mostly of Caucasian decent (66%) (Table 3.2). Most live with roommates/friends (45%) or spouse/significant other/children (26%), while the highest education level most participants achieved was a college degree (46%) or some college but no degree (32%). Job classification varied widely, while majority of participants work full time or over thirty hours per week (33%) (Table 3.2). 3.2 Psychopathology Examined using the MINI, 14% were diagnosed with only one current DSM-IV diagnosis and 15% with one DSM-IV diagnosis in the past and lifetime. However, more participants had multiple disorders, with 52% being diagnosed with more than one current disorder, and 65% with multiple lifetime disorders. In total, 80% of the medical cannabis population had any lifetime disorder, and 66% had any current disorder (Table 3.3). During the MINI, fifty people had experienced a Major Depressive Episode (MDE) in the past, however, only thirty-three people had MDE recurrently and only three participants also had a MDE currently (within the past two weeks). Past manic and hypomanic episodes were also examined, found in fifteen and twelve participants, respectively. From knowing MDE and manic episodes, thirty-three participants were diagnosed with a lifetime prevalence of depression, while only three were diagnosed with current depression (Table 3.1). Bipolar disorder was also measured, specifically Bipolar I disorder in their lifetime (n=12), Bipolar II disorder currently (n=2), Bipolar II disorder 14 in their lifetime (n=7) (Table 3.1). Importantly, a diagnosis for a substance dependence will automatically indicate a diagnosis for abusing the substance as well, however, some subjects could abuse a substance but may not be dependent on them. Therefore, all diagnoses of substance dependency will also indicate substance abuse, however, our results will state the total percentage of substance abuse. 30% of participants were diagnosed with a non-alcohol substance dependence while 42% abused a non-alcoholic substance. Results from Table 3.3 show that 20% had alcohol dependence and 25% abused alcohol, meanwhile, 18% were diagnosed with cannabis dependence, while 30% were abusing cannabis. Anxiety related disorders were also examined during the MINI, with a total of forty-three participants being diagnosed with any anxiety disorder, including panic disorder (23%), agoraphobia (21%), generalized anxiety disorder (16%) social phobia (7%), and post-traumatic stress disorder (PTSD) (2%) (Table 3.3). 38% of study participants had low suicidality, however participants were placed in this category if they answered “yes” to the question, “in the past month, have you felt hopeless?”. Furthermore, eight participants had moderate suicidality and one participant had a high suicidality risk. Other psychiatric disorders included anti-social personality disorder (ASPD), which 8% of our medical cannabis population were diagnosed with (Table 3.3). Table 3.1 shows the most frequent mental conditions that were self-reported to benefit from cannabis treatment, which were anxiety/stress (n=77), sleep issues (n=53) and depression (n=47). Other self-reported mental conditions included PTSD (n=14), pain (n=25), Bipolar disorder (n=5), and focus/attention (n=14). Twenty-seven people also use medical cannabis to treat other health-related conditions, scoliosis, type-1 diabetes, arthritis, concussion/post-concussion symptoms, autoimmune inflammatory response, and headaches. The primary condition to treat with medical cannabis was also noted by participants, with anxiety (n=43) 15 being the most frequently self-reported primary condition. Other common primary conditions included insomnia or sleep issues (n=18), depression (n=16) and pain (n=5). 3.3 Mental and General Health For the perceived stress scale, thirty-seven participants had low perceived stress, fifty-seven had moderate perceived stress, and five had high perceived stress (Table 3.4). From the Patient Health Questionnaire (PHQ-15) most participants ranked minimal (n=43), thirty-two people ranked low, twenty-one people ranked medium and four people ranked high (Table 3.4). While using the Brief Pain Inventory (BPI), thirty-five participants answered that they felt pain, and mean scores of pain rating and pain interference were calculated, 2.9 and 2.2, respectively (Table 3.5). “Lower back (muscle)” was a highly reported area of pain (34%), other specific regions reported included the neck, shoulder blades, wrists, stomach and spine. Ninety-eight people completed the PROMIS sleep disturbance, with an average t-score of 46.7, with scores ranging from 28.9 to 76.5, excluding partial test completion participants. Eighty-one had none to slight disturbance with sleep, fourteen had mild sleep disturbance, four had moderate sleep disturbance, and only one had severe disturbances with sleep (Table 3.4). All participants completed the PROMIS fatigue questionnaire, resulting with an average t-score of 51.1, with scores ranging from 33.4 to 72.9. Sixty-one people had none to slight fatigue, twenty-nine had mild fatigue, nine people had moderate fatigue and one person had severe fatigue (Table 3.4). Beck Depression scores were mostly minimal (n=83), with others rated as having mild depression (n=9), moderate depression (n=7) or severe depression (n=1) (Table 3.4). Only the regular smokers were eligible to complete the Fagerström test (n=21), which indicated that 48% 16 ranked low nicotine dependence, 38% ranked average dependence, 14% ranked strong dependence, and there were no scorings for very strong dependence (Table 3.5). 17 Condition Self-Reported (N) Self-reported primary benefit (N) Diagnosed (N) Current Lifetime Depression 47 16 3 33 Bipolar Disorder 5 0 2 19 Bipolar I - - 0 12 Bipolar II - - 2 7 Anxiety 77 43 43 - PTSD 14 2 2 - Sleep issues 53 18 - - Focus, attention 14 3 - - Pain 25 5 35* - Other 27 13 - - Note: Bipolar disorders include Bipolar I, Bipolar single manic episode past, Bipolar II disorders; conditions diagnosed using the MINI neuropsychiatric interview. Not all conditions listed were able to be explored in the MINI. *Pain was determined using the Brief Pain Inventory and who answered “yes” to any pain in their life. Table 3.1 Conditions reported to treat using medical cannabis, including total self-reported, primary condition treated with medical cannabis and number of conditions actually diagnosed. 18 Characteristic % Gender Male 68 Female 32 Age 19 to 24 years 35 25 to 30 years 24 31 to 35 years 10 36 to 40 years 9 41 to 45 years 2 46 to 50 years 7 51 to 55 years 8 56 years and older 5 Average current age: 33.6 years Ethnicity African, Caribbean 1 Caucasian 66 Asian 9 Hispanic 4 Middle Eastern 1 Mixed, Other 18 First Nations 1 Highest Education Level Less than high school 4 High School graduate or GED 13 Some college 32 College degree 46 Doctoral degree 1 Job Classification Human services 17 Healthcare 3 Arts, Entertainment 8 Manager 16 Professional 11 Service worker 7 Technician 3 None 25 Other 11 Employment Status Part-time (34 hours/week or less) 23 Full-time (35 hours/week or more) 33 Student 15 Unemployed 9 Retired 5 Other 10 Table 3.2 Demographic characteristics of medical cannabis users Psychiatric Disorder % Current DSM-IV diagnosis Single 14 Multiple 52 Any 66 Lifetime DSM-IV diagnoses Single 15 Multiple 65 Any 80 Any anxiety disorder 43 Alcohol dependence 20 Alcohol abuse 25 Cannabis dependence 18 Cannabis abuse 30 Other substance dependence 12 Other substance abuse 12 Antisocial personality disorder 8 Table 3.3 Psychopathology of medical cannabis users, collected using the MINI 19 Score (Rank) Questionnaire N Perceived Stress Scale 0 to 13 (Low perceived stress) 37 14 to 26 (Moderate perceived stress) 57 27 to 40 (High perceived stress) 5 Patient Health Questionnaire (PHQ-15) 0 to 4 (Minimal) 43 5 to 9 (Low) 32 10 to 14 (Medium) 21 15 to 30 (High) 4 Beck Depression Inventory 0 to 13 (Minimal depression) 83 14 to 19 (Mild depression) 9 20 to 28 (Moderate depression) 7 29 to 63 (Severe depression) 1 PROMIS fatigue Less than 55 (None to slight) 61 55.0 to 59.9 (Mild) 29 60.0 to 69.9 (Moderate) 9 70 and over (Severe) 1 Average score 51.1 PROMIS Sleep Disturbance Less than 55 (None to slight) 81 55.0 to 59.9 (Mild) 14 60.0 to 69.9 (Moderate) 4 70 and over (Severe) 1 Average score 46.7 Table 3.4 PSS10, PHQ-15, BDI, and PROMIS Fatigue and Sleep disturbance scores from medical cannabis users Score (Rank) Questionnaire N (%) Fagerström Test for nicotine dependence 0 to 2 (Low dependence) 10 (48) 3 to 5 (Average dependence) 8 (38) 6 to 7 (Strong dependence) 3 (14) 8 to 10 (Very strong) 0 (0) Brief Pain Inventory (N=35) Pain rating average score 2.9 Pain interference average score 2.2 Table 3.5 FTND scores and BPI ratings from medical cannabis users 20 3.4 Cannabis Characteristics All participants were members at the Evergreen dispensary, but twenty-one participants were also members at other dispensaries. Age of first cannabis use was collected in years, with majority of participants first using cannabis at 16 to 20 years (n=56), 15 or younger (n=31) and 21 to 25 years (n=10), and the average age of first cannabis use was 17.3 years old (Table 3.7). Majority starting using cannabis regularly around 16 to 20 years old (n=51), while others regularly started around ages 15 or younger (n=8) and 21 to 25 years (n=24), whilst four people selected that they never used cannabis regularly, and average age of onset of regular cannabis use was 20.4 years old (Table 3.7). More participants started using cannabis recreationally (n=88) than medicinally (n=11), and the average number of medicinal cannabis use was 5.5 years (Table 3.7). Reasons to start using medical cannabis included: “conventional treatments don’t work” (n=22), “wanted a natural treatment” (n=52), “doctor recommendation” (n=10), “internet search for treatments” (n=16), “hear-say from friends/family” (n=40), and “other” (n=18), such as “relieved symptoms” or “self-medication” (Table 3.7). Common reasons against using conventional treatments included that they were “not effective” (n=44), had side effects (n=54), were expensive (n=25), or other reasons (n=25) (Table 3.7), such as “strong preference against using man-made pills” or “not a long-term solution”, whereas some indicated that they use conventional treatments but also use medical cannabis to supplement their treatment. Many members of the Evergreen compassion club visited once a week (n=40), every two weeks (n=22), once a month (n=14), or more than twice a week (n=17) (Figure 3.1). Smoking was the most preferred form of cannabis consumption (n=71), while vaporizing was the next most preferred (n=43). Other consumption forms were less common, such as 21 edibles (n=20), capsules (n=17), oral tinctures (n=15), tea (n=9), and topicals (n=11) (Table 3.8). Dried cannabis (n=91) was the most commonly bought cannabis product from Evergreen, with an eighth (3.5g) of dried cannabis (n=40) being the most popular amount of product used per week. Less than 1 gram was selected by thirty-one participants, and far fewer people chose other amounts of product per week, specifically, seventeen people used 7 grams (a quarter), and six people used 14 grams (a half) and two people used 28 grams (an ounce) or more per week (Table 3.8). Meanwhile, the average cannabis amount per week was 4.29 grams for those that used dried cannabis. Most of this population used cannabis in the evening (n=67) or on an as-needed basis (n=37) (Figure 3.2), and more than three times a day (n=23), twice a day (n=25) or once a day (n=30) (Table 3.8). Preference for cannabinoid concentration was also taken into account, resulting with high THC/low CBD (n=35), equal THC/CBD (n=35), low THC/high CBD (n=21), pure THC (n=20) and pure CBD (n=18) (Table 3.8). Fourteen participants did not know what cannabinoids they prefer or what they were, while six people had no preference at all. Fifty-five participants had experienced negative effects from using medical cannabis, which included increased anxiety (n=36), paranoia (n=26), short-term memory loss (n=25) and decreased attention span (n=21) (Table 3.6). However, most people rarely feel these side effects (n=20), or only notice them during a certain cannabis type (n=19) (Table 3.6). 22 Figure 3.1 Frequency of cannabis dispensary visits from medical cannabis users. Figure 3.2 Usual time of day for medical cannabis use. 174022143 40102030405060708090100>2 times aweekOnce a week Every 2weeksOnce amonthOnce every2 months< Every 3monthsFrequencyNumber of dispensary visits913171627673510370 20 40 60 80 100Early morning (6am-9am)Mid-morning (9am-11am)Midday (10am-2pm)Mid-afternoon (2pm-4pm)Early evening (4pm-7pm)Evening (7pm-10pm)Late night (10pm-12am)Middle of the night (12am-6am)On an as-needed basisFrequencyTime of Day 23 Table 3.6 Negative effects ever experienced by participants after using medical cannabis (N=55), and the frequency of occurrence. Characteristic N Negative effects from medical cannabis Short-term memory loss 25 Dizziness 16 Decreased attention span 21 Decreased sensory perception 6 Increased anxiety 36 Paranoia 26 Impaired body movements 9 Difficulty breathing 8 Other 8 Frequency of negative effects Every time I use cannabis 2 Nearly every time 4 Sometimes 6 Rarely 20 Only during a certain cannabis type 19 Not since the first time I used cannabis 1 Other 10 24 Characteristic N Age first Cannabis use 15 years or younger 31 16 to 20 years 56 21 to 25 years 10 26 to 30 years 1 31 to 35 years 1 36 years or older 1 Average: 17.3 years Age regularly use cannabis 15 years or younger 8 16 to 20 years 51 21 to 25 years 24 26 to 30 years 5 31 to 35 years 4 36 to 40 years 1 41 to 45 years 1 46 to 50 years 1 51 years or older 1 Never used regularly 4 Average: 20.4 years Initial intention of cannabis use Medicinal 11 Recreational 88 Average years of medicinal cannabis use: 5.5 years Reason for medical cannabis use Conventional treatments unhelpful 22 Prefer natural treatment 52 Doctor recommendation 10 Internet search for treatments 16 Hear-say from peers 40 Other 18 Reasons conventional treatments not preferred Not effective 44 Side effects 54 Expensive 25 Other 25 Table 3.7 Ages of first cannabis use and regular use, with initial reasons for using medical cannabis and not conventional treatments 25 Characteristic N Preferred form of consumption Smoking 71 Vaporizer 43 Edibles 20 Capsules 17 Tinctures 15 Tea 9 Topical 11 Cannabis products usually bought Dried cannabis 91 CBD capsules 23 Edibles 17 Extracts, concentrates 9 Tea 8 Tinctures 8 Massage oil, cream 13 Preferred THC to CBD concentrations Pure THC 20 Pure CBD 18 High THC/Low CBD 35 Equal THC/CBD 35 Low THC/High CBD 21 No preference 6 Don’t know 14 Amount of product use per week Dried cannabis <1g 31 3.5g (an eighth) 40 7g (a quarter) 17 14g (a half) 6 28g (an ounce) 2 Average amount of grams used per week 4.29 Capsules (1 to 2 daily) 10 Tincture (5 drops daily) 4 Other (5 teabags, 20 oz creams, oils and bath salts) 6 Medical cannabis use frequency 3 times a day or more 23 2 times a day 25 Once a day 30 Every other day 4 3 times a week 10 Once a week 4 Every 2 weeks 3 Once a month 1 Less than once a month 2 Depends on symptoms 20 Percentage of participants using cannabis daily: 74% Table 3.8 Preference for method of consumption, cannabis product, cannabinoid concentration, frequency and amount of cannabis use by medical cannabis users. 26 3.5 Further Analysis Additionally, exploratory analyses of the research data were conducted with the most frequent lifetime psychiatric conditions, in order to identify any differences between patterns of cannabis use (Table 3.9). Psychiatric conditions included lifetime depression, any lifetime anxiety disorders and substance dependence or abuse (excluding cannabis dependence/abuse). Generally, those diagnosed with anxiety or depression showed significantly higher scores for perceived stress, fatigue, beck depression and physical symptoms severity tests than those without depression or anxiety. However, participants with a substance use disorder only had higher scores for perceived stress and beck depression compared to non-abusers (Table 3.9). Anxiety lifetime disorders group also used more CBD focused products, including capsules and tinctures, and were more likely recommended by a doctor to use medical cannabis, however, this group were also more likely to experience negative side effects. Participants with lifetime depression also were more likely to use CBD capsules, but this group had significantly more females than those without depression. The substance use disorder group were significantly younger than non-substance users and they visited the dispensary more often than non-abusers. Their reasons for medical cannabis use included the belief that conventional treatments are not effective, and they were more likely to smoke cannabis rather than using a vaporizer or tinctures. 27 Anxiety Disorders Major Depressive Disorder Substance Use Disorder (Except Cannabis) No (N=57) Yes (N=43) P-value No (N=67) Yes (N=33) P-value No (N=48) Yes (N=22) P-value Male % 70.2 65.1 0.591 77.6 48.5 0.003 64.6 63.6 0.939 Current Smoker % 19.3 23.3 0.628 23.9 15.2 0.465 12.5 36.4 0.095 Reason for Medicinal Cannabis Use % Conventional treatments don't work 15.8 25.6 0.226 16.4 27.3 0.202 14.6 40.9 0.015 My doctor recommended it to me 1.8 18.6 0.004 9.0 9.1 0.982 6.2 18.2 0.122 Internet search on treatments for my condition 8.8 23.3 0.045 11.9 21.2 0.222 12.5 22.7 0.275 Experiences Pain % 21.1 53.5 0.001 28.4 48.5 0.047 29.2 27.3 0.871 Condition % Anxiety/Stress 66.7 90.7 0.005 74.6 81.8 0.422 75.0 68.2 0.552 Depression 31.6 67.4 0.000 37.3 66.7 0.006 31.2 59.1 0.027 Insomnia/Sleep Issues 50.9 55.8 0.624 53.7 51.5 0.835 50.0 77.3 0.032 Bipolar 0.0 11.6 0.008 6.0 3.0 0.526 2.1 13.6 0.053 28 Form of Consumption % Smoking 73.7 67.4 0.496 74.6 63.6 0.255 54.2 95.5 0.001 Vaporizer 38.6 46.5 0.427 38.8 48.5 0.356 47.9 22.7 0.046 Tincture 8.8 23.3 0.045 10.4 24.2 0.069 20.8 0.0 0.021 Capsules 10.5 25.6 0.047 9.0 33.3 0.002 16.7 4.5 0.160 Cannabis Product: CBD Capsules % 8.8 41.9 0.000 16.4 36.4 0.026 18.8 18.2 0.955 Time of Use: On an as needed basis % 24.6 53.5 0.003 32.8 45.4 0.219 37.5 36.4 0.927 Concentration: Pure CBD % 10.5 27.9 0.025 13.4 27.3 0.090 20.8 9.1 0.226 Experienced Negative Effects with Cannabis Use % 42.1 69.8 0.008 50.7 60.6 0.392 37.5 59.1 0.106 Negative Effects % Short-term memory loss 17.5 34.9 0.047 25.4 24.2 0.902 14.6 36.4 0.039 Increased anxiety 28.1 46.5 0.057 35.8 36.4 0.958 25.0 50.0 0.039 Paranoia 14.0 41.9 0.002 23.9 30.3 0.491 12.5 40.9 0.007 29 Dispensary Visits Per Month (SD) 4.2 (3.5) 3.9 (3.4) 0.664 3.7 (3.3) 4.7 (3.7) 0.202 3.1 (3.1) 5.0 (3.6) 0.024 Cannabis Use Quantity, grams per week (SD) 4.5 (4.8) 4.0 (4.6) 0.598 3.9 (3.2) 5.2 (7.0) 0.358 3.4 (3.3) 4.1 (2.0) 0.347 Cannabis Use Frequency, times per month (SD) 50.2 (27.8) 42.9 (34.3) 0.267 47.7 (30.8) 45.6 (31.1) 0.766 39.5 (28.7) 59.3 (28.7) 0.011 Current Age (SD) 33.9 (12.3) 33.2 (13.9) 0.810 34.2 (13.6) 32.4 (12.1) 0.561 37.6 (13.7) 28.1 (10.3) 0.017 Age of First Cannabis Use (SD) 17.1 (3.8) 17.6 (5.8) 0.575 17.5 (5.1) 17.0 (4.2) 0.668 17.8 (4.7) 18.1 (6.5) 0.851 Age of Onset of Regular Use (SD) 20.7 (6.3) 20.0 (6.3) 0.588 20.5 (6.7) 20.1 (5.3) 0.819 21.7 (7.2) 20.4 (6.7) 0.487 Scale Test Means (SD) Perceived Stress Scale 13.7 (5.1) 19.2 (6.7) 0.000 14.8 (6.1) 18.6 (6.4) 0.006 14.2 (6.3) 19.2 (5.8) 0.002 PROMIS Fatigue 48.7 (7.7) 54.3 (6.6) 0.000 50.0 (7.8) 53.4 (6.9) 0.036 51.5 (8.4) 52.3 (4.9) 0.610 PROMIS Sleep Disturbance 46.0 (8.0) 54.3 (6.6) 0.386 46.7 (8.6) 46.3 (8.5) 0.831 47.8 (8.8) 47.4 (7.9) 0.851 Beck Depression 4.1 (3.4) 12.3 (7.6) 0.000 6.3 (5.8) 10.3 (8.3) 0.016 5.9 (5.3) 10.8 (7.5) 0.002 PHQ-15 4.6 (3.2) 8.5 (4.4) 0.000 5.5 (3.8) 7.8 (4.6) 0.009 6.1 (3.9) 7.4 (3.7) 0.174 BPI Pain Rating 13.8 (9.2) 15.3 (11.0) 0.686 11.8 (8.6) 18.2 (11.3) 0.068 14.1 (9.5) 13.2 (11.6) 0.857 BPI Pain Interference 16.6 (13.8) 14.8 (11.8) 0.696 13.1 (11.8) 18.2 (12.8) 0.231 16.3 (13.4) 13.5 (15.0) 0.685 Fagerström 2.7 (2.0) 2.9 (2.6) 0.866 2.9 (1.9) 2.4 (3.4) 0.748 1.5 (1.6) 3.5 (1.9) 0.058 Table 3.9 Comparison of the most frequently diagnosed psychiatric conditions with demographics, symptom scale tests, reasons for medical cannabis use, medical conditions diagnosed, and other patterns of cannabis use. SD = Standard Deviation; PHQ-15 = Patient Health Questionnaire, BPI = Brief Pain Inventory 30 Chapter 4: Discussion Our study is the first to administer diagnostic tests with standardized assessment questionnaires to assess the quantity and severity of the mental health problems in medical cannabis users. Our approach compared the self-reports from participants with any diagnoses they met criteria for, allowing us to analyze the accuracy of mental health perception within medical cannabis users, coupled with discovering similarities or differences between the frequency and amount of their cannabis use. The findings from our study correlate with similar medical cannabis use patterns from some studies (Reinarman et al., 2011), and provides more evidence supporting the characteristics found within medical cannabis. Almost half of our participants starting using cannabis to treat mental health conditions, because they preferred a more natural treatment, and that conventional treatments brought on unwanted side effects or they were not effective enough. Meanwhile, dispensaries can provide a welcoming, relaxed and convenient atmosphere to people suffering from medical conditions, with forty of our participants describing frequency visits as often as once a week, suggesting positive interactions with dispensary staff on a regular basis. We included the MINI neuropsychiatric interview for diagnosing mental disorders, as it incorporates criteria from both the ICD-10 and the DSM-IV for twenty-three psychiatric disorders. The MINI also provides evidence of acceptable reliability (Amorim, 2000) and value for clinical assessment, especially for depression and anxiety disorders (Pettersson et al., 2018). Those meeting criteria for multiple diagnoses, 80% lifetime and 66% current, mostly included mood disorders, different types of anxiety disorders and substance dependences. In contrast, information from the 2012 Canadian Community Health Survey indicated that only a third of the general population of Canada met criteria for at least one of the major psychiatric disorders (Pearson, Janz & Ali, 2013), similar to common psychiatric 31 disorders found in the present study. These authors also stated that younger people, around 15 to 24 years, tended to experience a mental disorder and/or a substance use disorder more than other age groups (Pearson, Janz and Ali, 2013), which was also true for our data, but results were not significant. Generally, the rates of mental disorders were relatively higher within our study population compared to data collected on the Canadian population. 4.1 Cannabis and Mood Disorders According to the World Health Organization, 300 million people worldwide were diagnosed with depression in 2015, while around 15% of adults will experience depression in their lifetime (World Health Organization, 2017). In 2012, 3.5 million or 12.6% of Canadians met criteria for a mood disorder, with 11.3% meeting criteria for a major depressive episode (MDE) (Pearson, Janz & Ali, 2013). More recently, according to Canadian Community Health Survey from 2017, 4.5% of Canadians aged between 12 and 17-years old were diagnosed by a health professional as having a mood disorder, such as depression or bipolar (Statistics Canada, 2018). While 8.9% of 18 to 34-year olds also were diagnosed with a mood disorder, and this was slightly higher for 35 to 49-year olds and 50 to 64-year olds (Statistics Canada, 2018). Previous data collected in 2012 reported higher rates of current depression within females (5.8%) compared to males (3.6%) (Pearson, Janz & Ali, 2013). Similarly, there were slightly more females than males diagnosed with depression within our study, but these results were not significant, even though previous research shows that females are generally more likely to develop depression compared to males (Piccinelli et al., 2000). 32 4.1.1 The Relation Between Cannabis and Depression Depression has become a major problem in the lives of many individuals, with some people turning away from expensive and potentially harming pharmaceuticals and towards medical cannabis as a treatment (Zaller et al., 2015). Supporting this, significantly more participants diagnosed with lifetime MDD visited the Evergreen dispensary more frequently, around two or three times a week, than participants without MDD. Conversely, there have been mixed reviews on the use of cannabis to treat depression, with multiple suggestions for possible mechanisms, for example, the act of using cannabis will eventually lead to lifestyle events that will ultimately lead to depression (Lev-Ran et al., 2014), or that individuals already suffering from a mental health condition have a higher chance of using cannabis to “self-medicate” (Hayatbakhsk et al., 2007). Lev-Ran et al. (2014) also suggest that activation of CB1 receptors is associated with decreased depression, from the observation that the CB1 receptor antagonist, Rimonabant, is related to depression development (Lev-Ran et al., 2014), while animal studies show that CB1 receptor knockout mice displayed depressive-like activities, such as reduced responses to a reward stimulus and higher sensitivity to stress exposure (Aso, Ozaita, Serra & Maldonado, 2011). Therefore, the presence and action of a CB1 receptor may be related to preventing depression from occurring. Other suggestions indicate that cannabis and a genetic vulnerability for depression triggers the onset of depressive symptoms (Lynskey et al., 2004), or that genetic and environmental factors both contribute to the development of depression (Hayatbakhsh et al., 2007), as high stressful surroundings may already be harmful enough to an individual’s well-being. Data analysis showed that participants with lifetime MDD had significantly higher perceived stress scale scores than those without MDD, 18.6 and 14.8, respectively, suggesting that depressed people from our study were also experience higher 33 amounts of stress. Moreover, many previous studies did not specify their criterion for “frequent use” and “heavy use” (Lev-Ran et al., 2014), therefore, the dose of cannabis consumption may have varied widely between analyses and may affect the reliability of conclusions from studies. Our medical cannabis population showed relatively higher percentages of mood disorders compared to the general population of Canada, as thirty-three people had experienced a major depression disorder (MDD) in their lifetime. Furthermore, sixteen people stated that depression was the primary condition for cannabis use, but only three were diagnosed with current depression, suggesting that a higher number of medical cannabis users did not have clinical depression and were still using cannabis to treat their depressive symptoms, as 39.4% of all people with MDD diagnoses stated using cannabis depending on when symptoms appear. Meanwhile, 66.7% of those with a lifetime prevalence of MDD significantly selected depression to treat with medical cannabis, implying that their medical cannabis use could prevent the transition from past lifetime MDD to current MDD. The severity of depressive symptoms, from the Beck Depression Inventory, were compared with subjects that were diagnosed with a MDD currently, or in their lifetime. Although all subjects with current depression ranked in the highest category scored in the Beck Depression by our medical cannabis population, some subjects without a diagnosis for current depression also scored “moderate depression”. However, there was no significant association found between lifetime depression and Beck Depression scores, while 60% of participants with lifetime depression scored “minimal” in the Beck Depression inventory. Moreover, other studies reported that medical cannabis is used to improve mood and general well-being (Walsh et al., 2017), which could explain the low severity of depression in medical cannabis users, and that their medical cannabis use helps to avoid a major depressive episode to occur. 34 4.1.2 Cannabis and Bipolar Disorder Findings from bipolar disorder studies, show that individuals diagnosed with bipolar disorder are more likely to “self-medicate” and use higher doses of cannabis compared to people diagnosed with depression (Bolton, Robinson & Sareen, 2009). Since people with bipolar disorder may assume a pattern of regular heavy cannabis use, harmful adverse effects may occur and research shows that high doses of cannabis may exacerbate manic symptoms and progress their bipolar disorder (Taub et al., 2018). However, this analysis was not significant in our study, as participants diagnosed with Bipolar I, Bipolar II, or having a single manic episode used cannabis 51.5 times per month on average, which was only slightly higher compared to participants with MDD that used cannabis 45.6 times per month on average. Although, our results indicated that a diagnosis of bipolar disorder was significantly related to a diagnosis of alcohol dependence or abuse, or a substance dependence, however, not for cannabis dependence or abuse. Past research also suggests a relation between bipolar disorder and anti-social personality disorder (ASPD), as the criterion for both disorders overlap for some clinical and behavioral characteristics (Fan & Hassell, 2008), therefore there is a high likelihood of comorbid ASPD and bipolar disorder occurring (Taub et al., 2018). However, our study did not show any significant associations between ASPD and bipolar disorders, as there were no diagnoses for current bipolar disorder within our population. 4.1.3 Cannabis and Suicide Suicidal behavior can be related to severe depression (Mental Health Commission of Canada, 2015), and in 2015, 14% of young Canadians (15 to 24 years) reported having suicidal 35 thoughts within their life (Findlay, 2017). Our suicide severity results showed mostly low ranks (n=38) with very minimal current suicidality. Past studies analyzing cannabis use and suicide, found that the strong relation between using cannabis and suicide was justified by severe psychological issues, and thus cannabis use is highly unlikely to directly cause a suicide risk (Price et al., 2009). 4.2 Cannabis and Anxiety Disorders 4.2.1 The Relation Between Cannabis and Anxiety Globally, anxiety disorders are estimated to occur in 3.6% of the whole population (World Health Organization, 2017), therefore, anxiety is another major mental health condition, and in 2012, 2.4 million Canadians (8.7%) reported symptoms relating to generalized anxiety disorder (GAD) (Pearson, Janz & Ali, 2013). Many variations of anxiety disorders exist, as people may develop symptoms of fear and anxiety from different circumstances, including GAD, panic disorder, agoraphobia, social anxiety phobia, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD), but they all can significantly disrupt the well-being of an individual (Blessing et al., 2015). From our study, forty-three people were diagnosed with any anxiety disorder, which was consistent with self-reports, as forty-three people chose anxiety as their primary benefit from using medical cannabis. However, seventy-seven people from our study included anxiety as one of their mental health conditions to treat with medical cannabis, since participants could select multiple conditions for medical cannabis use, showing that anxiety was the most common choice for medical conditions in general. When comparing between participants with anxiety diagnoses and without anxiety, 90.7% of all those with anxiety self-reported using cannabis to treat anxiety, which was significant compared to anxiety self-reports 36 from only 66.7% of those without anxiety. Other significant differences between a diagnosis of anxiety, showed that participants with anxiety also reported using cannabis to treat depression (67.4%) and bipolar disorder (11.6%). Nonetheless, as with depression, past literature on cannabis use and anxiety presents mixed reviews. Crippa et al. (2009) report a critical review of the association between cannabis and anxiety, discovering that high doses of cannabis may trigger anxiety, while higher doses can develop into panic attacks in new cannabis users (Tunving, 1987). Our results showed that 69.8% of participants with anxiety had experienced negative effects with cannabis use, involving memory loss (34.9%) and paranoia (41.9%). However, participants also reported that most of these negative effects rarely occur with cannabis use or happen with certain cannabis types. Other studies propose that the development of cannabis dependence produces withdrawal symptoms that include signs of anxiety (Kouri & Pope, 2000), and that cannabis could block anxiety pharmaceutical medications (Szuster, Pontius, & Campos, 1988). Other possible mechanisms of the relationship between cannabis and anxiety involve the effects of THC on various neurotransmitter systems within the brain (Crippa et al., 2009), while Tournier et al. (2003) report that agoraphobia diagnoses significantly increased the chance of cannabis use. A meta-analysis of thirty-one studies involving the general population, concluded with a positive association between anxiety and cannabis use or a cannabis use disorder, but only in studies that used criteria according to clinical assessments, such as the ICD, compared to using disorder-severity measurements (Kedzior & Laeber, 2014). Even so, it remains uncertain if cannabis use causes anxiety development or if the presence of an anxiety disorder leads to cannabis use, however, we cannot dismiss the possibility of other contributing factors as well (Tournier et al., 2003). 37 In contrast, other studies propose that long term cannabis users find cannabis to help with relaxation and to reduce anxiety symptoms (Hathaway, 2003). 18.3% of participants with anxiety were recommended to use cannabis from a doctor, while 23.3% used the internet to search for anxiety treatments and discovered medical cannabis. Moreover, daily cannabis users from a non-clinical study indicated no anxiolytic effects from regular consumption of cannabis and concluded that there was no significant association between anxiety and daily cannabis use (Tournier et al., 2003). Preclinical trials display strong evidence for CBD as a potential treatment, especially for GAD, social phobia, panic disorder, OCD and PTSD, as CBD was shown to decrease fear memories or expression and anxiety effects produced from stress (Blessing et al., 2015). Human studies also support CBD as a treatment for anxiety disorders, including social anxiety, from a study using a series of different doses (Blessing et al., 2015). Our data supports these results, as 27.9% of participants with anxiety disorders preferred to use pure CBD, while others mostly bought and used CBD capsules or CBD tinctures. Further findings from our study, revealed that participants who scored high or moderate perceived stress also met criteria for current GAD, PTSD, social phobia, current agoraphobia or panic disorder. Other participants that scored low perceived stress, were diagnosed with current agoraphobia and/or lifetime panic disorder, suggesting that those diagnosed with GAD, PTSD and social phobia had higher perceived stress compared to those diagnosed with agoraphobia or panic disorder. Moreover, all subjects with high perceived stress were also diagnosed with multiple current anxiety disorders and other psychiatric disorders, such as depression. Meanwhile, half of the people with anxiety disorders (53.5%) experience some kind of pain after completing the BPI. 38 4.2.2 Anxiety and Depression Global health estimates report that almost 50% of the population that are diagnosed with depression are likely to also be diagnosed with an anxiety disorder as well (World Health Organization, 2017). While in 2013, 11.6% of Canadians (18 years and older) reported they had a mood disorder and/or an anxiety disorder (Statistics Canada, 2013). A higher percentage was indicated within our medical cannabis population, as 44% were diagnosed with any anxiety or depression, and 20% met criteria for MDD and anxiety, while 9% were diagnosed with a Bipolar I disorder and any anxiety disorder. The development relationship between depression and anxiety is unclear, however, there is a distinct difference between comorbid anxiety and major depression compared with the development of anxiety symptoms as a result of major depression (Fava et al., 2000). Moreover, previous research also shows that a diagnosis of both mood and anxiety disorders are more common in females than males (O’Donnell et al., 2015), however, medical cannabis users from our study indicated that slightly more males had both mood and anxiety disorders over females, but this result was not significant. More importantly, the THC content within a cannabis dose has a major impact on possible anxiety effects, as research indicates that low doses are safer and more effective at reducing anxiety (Niesink & van Laar, 2013). 4.2.3 Cannabis for Post-Traumatic Stress Disorder In addition, research shows that cannabis has been implicated specifically for PTSD, since no suitable treatments have been developed for symptoms or development of PTSD (Trezza & Campolongo, 2013), despite that around two thirds of an overall population may experience a traumatizing event in their lifetime (Javidi & Yadollahie, 2012), while the lifetime 39 prevalence of PTSD in Canada is up to 9.2% (Van Ameringen et al., 2008). Current first-line PTSD medications include many different anti-depressants, anticonvulsants, or benzodiazepines (Albucher & Liberzon, 2002), however a significant number of diagnosed patients respond poorly to these pharmaceutical medications (Ipser et al., 2006), and more effective treatments need to replace current drugs. Therefore, studies have suggested targeting the endocannabinoid system, due to its wide variety of biological action on emotion and cognition, coupled with evidence from positron emission tomography (PET) scans of PTSD patients showing decreased amounts of the naturally occurring endocannabinoid, anandamide, a component of the endocannabinoid system (Neumeister, 2013). While, CBD action may disrupt fear memories and decrease anxiety symptoms of PTSD (Loflin, Babson & Bonn-Miller, 2017), increasing the concentration of CBD correlates to a decreasing level of anxiety, but different THC doses can either be anxiolytic or anxiogenic (Viveros et al., 2005), thus implying a better outcome from high CBD levels in reducing PTSD symptoms. However, lower THC doses (2.5 mg or 5 mg) were associated with decreased frequencies of nightmares and better sleep (Roitman et al., 2014), while higher THC doses (15 mg) resulted with no sleep improvement and negative moods (Nicholson et al., 2004). As a result, cannabinoid concentration of cannabis strains, especially for THC, should be considered when treating PTSD symptoms, such as anxiety. 4.3 Cannabis and Substance Dependence or Abuse Compared to the general population, people with a mental disorder have twice the chance of being diagnosed with a comorbid substance use disorder, while around 15% of people suffering with substance use problems also have a mental illness (Rush et al., 2008). In 2012, alcohol was the most popular substance for people to abuse or become dependent on, as 18.1% 40 of the Canadian population met criteria (Pearson, Janz & Ali, 2013), which was similar to our medical cannabis population. For other substances in the general population, 6.8% abused or were dependent on cannabis more, compared to other substances such as cocaine and heroin (Pearson, Janz & Ali, 2013). In contrast, more people met criteria for cannabis dependence compared to other substance dependences in medical cannabis users from our study, although fewer participants were abusing cannabis compared to abusing other substances, including cocaine and heroin. 32.7% of all substance-abusers used cannabis more than three times per day, with an average of 54.1 times per month compared to 39.5 times per month for non-abusers. Past research suggests that the potency of cannabis use, including quantity and concentration, of daily cannabis users must be properly distinguished due to huge variations of cannabinoid content within cannabis use (Zeisser et al., 2011), with a stronger potency linked to higher chances of developing cannabis dependence (van der Pol et al., 2013). 4.3.1 Excluding Cannabis Dependence or Abuse However, in order to analyze the effects from only alcohol or other recreational drugs and not cannabis, participants diagnosed with cannabis dependence or abuse were excluded from the “substance use disorder” group. Results revealed a stronger significant difference between substance use disorders and a lifetime diagnosis for panic disorder, as 40.9% of the substance use disorder group were diagnosed with a panic disorder, compared to 12.5% of non-abusers with a panic disorder. This indicates a stronger association between alcohol or other substance abuse with a diagnosis of panic disorder compared to including cannabis abusers within the group of substance abusers. Clinical studies have already established a convincing co-occurrence of substance use disorders and panic disorder, suggesting that people often abuse substances to 41 reduce anxiety effects (Grant et al., 2004). Meanwhile, research implies that cannabis may cause panic attacks and worsen panic disorder (Zvolensky et al., 2007), even though cannabis has been shown to have anxiolytic properties (Crippa et al., 2009) and our data show that medical cannabis users who use high doses may be related with lower occurrences of panic disorder. Similarly, when cannabis dependence or abuse was excluded, alcohol/other substance abusers had significantly more diagnoses of social phobia, suggesting that either those with social phobia are more likely to abuse alcohol or other drugs rather than cannabis. These support past studies on the frequent co-morbidity of social phobia and alcohol use disorders (Stewart & Conrod, 2008), and that CBD in cannabis has the potential to reduce anxiety symptoms from social phobia (Bergamaschi et al., 2011). From these results, cannabis use may play a medical role in reducing specific anxiety symptoms for people with alcohol or other substance dependency. Cannabis characteristics of all substance abusers revealed significantly higher percentages of earlier onset of regular cannabis use by ages 16 to 20-years old, compared to non-abusers. Meanwhile, for those with substance use disorders and excluding cannabis abusers, the average current age was significantly younger than non-abusers, 28.1 years and 37.6 years, respectively. Suggesting that for our population, younger age groups were more likely to meet criteria for alcohol or other substance abuse, but not for cannabis abuse. The substance use disorders group generally had a higher frequency of cannabis compared to non-abusers, specifically higher dried cannabis consumption per week, which correlates to the observation that almost all participants within the substance use disorder group preferred to smoke cannabis. Furthermore, negative effects ever experienced that were significantly more common for all substance abusers compared to non-abusers, included short-term memory loss, dizziness, decreased attention span, increased anxiety and paranoia. Fewer significant negative effects were 42 reported from the substance use disorder group, which involved only memory loss, increased anxiety and paranoia, indicating that the inclusion of cannabis abusers into the all substance abusers group, brought additional variations of possible negative effects experienced while using cannabis. Overall, those diagnosed with substance dependence or abuse significantly rated more negative effects than non-dependent cannabis users, which could be explained by their higher frequency of cannabis use or a slight preference for THC, as higher concentrations of THC compared to low levels of CBD may increase the risk for negative effects, such as memory impairment or even psychosis (Englund et al., 2013). Additionally, our results showed 66.7% of cannabis dependence diagnoses reported withdrawal symptoms, similar to previous studies that suggest paying closer attention to cannabis-dependent medical cannabis users in order to help them recognize withdrawal effects as a consequence of regular and heavy cannabis use (Perron et al., 2019). In addition, the substance use disorder group had a higher average score for perceived stress compared to non-abusers, 19.2 and 14.2, respectively. This indicates a stronger relation between non-cannabis substances/alcohol abusers and higher perceived stress compared to cannabis abusers. Consequently, substance abuse is strongly associated with anxiety and stress, especially with the abuse of alcohol, cocaine and other recreational drugs, as the mechanisms of fear and anxiety within the brain also interact with the stress response pathway (Shin & Liberzon, 2010). Moreover, further analysis showed higher Beck depression scores within all substance abusers compared to non-abusers. This significance increased when cannabis abusers were excluded, as the Beck depression average increased, implying that cannabis abusers have lower levels of depression. However, these Beck depression averages were still within the 43 “minimal” ranking, thus explains why no associations were present between substance abuse and major depression diagnoses in our medical cannabis users. 4.4 Cannabis and Sleep Issues Problems with sleeping nearly every night, or insomnia, includes difficulty falling asleep, waking up in the middle of the night, early morning wakening or sleeping excessively represents one of the criteria for a diagnosis of certain psychiatric disorders, notably depression, GAD and PTSD (American Psychiatric Association, 2000). Therefore, quality of sleep may further characterize the mental health state of an individual. 40% of Canadians will experience a sleep disorder in their lifetime, which could greatly enhance the risk of other serious health conditions (Morin et al., 2011). Reports from the Canadian Health Measures Survey (CHMS) between 2007 and 2013, indicated that a third of Canadians (ages 18 to 64 years) had less than seven hours sleep, whilst females had more sleep on average than males, 7.24 hours and seven hours, respectively (Chaput, Wong & Michaud, 2017). Although, despite having more sleep, females reported more trouble falling asleep than males (Hurst, 2008). Moreover, the number of hours slept has decreased since reports in 2005, where the average was around eight hours (Hurst, 2008), indicating increasing problems with sleep within the Canadian general population. Furthermore, previous data from 2005 showed 35% of females reported trouble falling asleep or staying asleep, rated as “sometimes”, “most of the time”, or “all the time”, while male reports were 10% lower (Hurst, 2008). Results between 2007 and 2013 also indicated a higher percentage of females having trouble sleeping compared to males, 55% and 43%, respectively (Chaput, Wong & Michaud, 2017), but were notably higher overall compared to the 2005 report. According to the PROMIS sleep disturbance scores from our findings, 34.7% of our medical 44 cannabis users were above the average t-score of 46.7, indicating a more severe sleep disturbance in the past seven days compared to other participants. Interestingly, there were more males within this higher disturbed sleep division, including a participant with the highest possible score (76.5), indicating substantial sleep issues. 4.4.1 Sleep Issues or Fatigue in Depression Moreover, patients with depression frequently report symptoms of extreme exhaustion that interrupts their daily functioning on a physical or mental level (Maurice-Tison et al., 1998), while the presence of regular fatigue or loss of energy is a secondary criterion for depression in the DSM-IV (American Psychiatric Association, 2000), fatigue is considered an essential feature for defining a depressive episode, according to the ICD-10 (Demyttenaere, De Fruyt & Stahl, 2005). While others suggest an occurrence of reduced energy may act as a contributing factor towards depressive disorders (Hell, 2015), and that fatigue is related to sleep issues as they may co-occur (Kennedy, 2008). From our study, we compared DSM-IV diagnoses with PROMIS scores, which supports the relation between depression and fatigue. Despite that only three participants were diagnosed with current depression, they had a significantly worse fatigue average score compared with the rest of this population. Similarly, individuals with a lifetime depressive disorder (n=33) also had significantly higher fatigue scores, although their average fatigue score was not as severe as those with current depression. Also, participants diagnosed with any anxiety disorder had a higher mean score for fatigue symptoms, indicating an association between an anxiety occurrence and a lack of energy. However, these findings were not discovered for sleep disturbance scores, which relates to past research, as sleep problems are not always present in patients with anxiety disorders, but there are strong associations between 45 specific anxiety disorders and sleep problems, such as insomnia and panic disorder (Uhde, Cortese & Vedeniapin, 2009). Overall, PROMIS fatigue scores from medical cannabis users showed similar results to their sleep disturbance scores, with 51.5 as the average score for fatigue. However, 56% of our participants showed above average scores for fatigue symptoms, presenting with more males than females, thirty-three and eighteen, respectively. 4.4.2 Self-Reported Sleep Issues In comparison with the perspective of participants, fifty-three participants listed insomnia/sleep issues as one of the conditions to treat with medical cannabis, while eighteen participants use medical cannabis to primarily treat sleep problems. Participants that had chosen the condition sleep issues had significantly higher PROMIS sleep disturbance scores, implying that these self-reports were relatively truthful and that some medical cannabis users have more severe sleep problems, however, there was not much difference between self-reported sleep problems and fatigue scores. Therefore, sleep disturbance is one of the more significant symptoms from a major depressive disorder, and other evidence points to disturbances in sleep could lead to the development of a major depressive episode (Riemann, Berger & Voderholzer, 2001). Thus, quality of sleep is important to consider when assessing an individual for certain psychiatric disorders. Meanwhile, anti-depressant drugs have been reported ineffective in treating sleep problems to eventually help with depression (Kennedy, 2008), therefore many patients have turned to medical cannabis with a significant preference for a higher CBD proportion according to studies (Belendiuk et al., 2015). Oher evidence suggest that cannabis may initially provide better sleep, but eventually could lead to tolerance and increasing doses of cannabis to provide the same beneficial effects, or even developing further sleep disturbances as 46 a withdrawal symptom from cannabis (Babson & Bonn-Miller, 2014). Consequently, cannabis doses must be controlled and observed by a medical doctor in order to provide a safe therapeutic option. 4.5 Cannabis for Pain An estimation of 22% Canadians, aged 18 or older, experienced chronic pain according to the Canadian Community Health Survey in 2008, affecting around six million people (Gilmour, 2015). While previous research indicates a link between chronic pain and mental health issues, reporting a higher prevalence of mood or anxiety disorders for people with chronic pain in comparison with mood/anxiety disorders in pain-free individuals (Ramage-Morin & Gilmour, 2010). Studies have suggested that pain and mental well-being are connected by the level of “activity restriction”, proposing that severe pain could limit normal activity, including personal care, employment, and family responsibilities, leading to poor psychological health (Williamson & Schulz, 1995). Moreover, as pain levels increased over time, the restriction of activity was higher, implying more depression amongst older age groups, however, results from past studies revealed that activity restriction caused by pain was more concerning for younger individuals, aged less than 65-years, as the expectation to function normally could cause more distress to individuals with chronic pain (Williamson & Schulz, 1995). Similarly, other studies found that the likelihood of chronic pain increased with age (Ramage-Morin & Gilmour, 2010), while results from our study support these reports as we found higher pain ratings in older age groups, particularly with pain interference, as significantly higher scores were shown for older age groups, 41-years and older, compared to younger ages. However, depression severity and 47 anxiety disorders did not show any significant association with pain ratings within our population, possibly explained by the low average scores from the BPI. 4.5.1 Gender Differences in Pain Moreover, gender differences show that more females report incidences of chronic pain (Gilmour, 2015), which was similar to the Canadian Community Health Survey in 2008, also reporting higher percentage of females with chronic pain than males, 12% and 9%, respectively (Ramage-Morin & Gilmour, 2010). These studies suggest that gender plays a role in preventative actions for pain and gender differences may occur in the way people cope with pain, and thus, the severity of mental health problems (Geerlings et al., 2002). However, although pain severity and pain interference scores were higher in females within our study, these results were not statistically significant. Yet, a significant difference was found between females and males for PHQ-15 mean scores, showing that females report greater physical symptoms compared to males. Despite this, general physical symptoms among medical cannabis users were still considered “low” according to the patient health questionnaire rankings. A similar study analyzing the profiles of medical cannabis users in Rhode Island revealed moderate pain ratings and pain interference from the BPI, with average scores of five out of ten for pain severity and 5.1 out of ten for pain interference with their daily functioning (Zaller et al., 2015). These results were slightly higher compared to our BPI results, indicating lower levels of pain within our study of medical cannabis users in Vancouver. 48 4.5.2 Cannabis for Pain Treatment Past literature has provided evidence that cannabis has potential to treat pain symptoms with anti-inflammatory effects and pain reduction (Boehnke et al., 2019). A systematic review of cannabinoids and analgesic properties displayed more evidence that cannabinoids produce similar levels of pain relief compared with placebos or an active placebo drug (Stevens & Higgins, 2017). More specifically, studies have examined whether cannabis could offer an alternative to current pain medications, as these drugs have a high potential for addiction and tolerance, thus medical cannabis could help reduce the risks of opioid dependence or overdose (Reiman, Welty & Soloman, 2017). A study reported 63% of their medical cannabis users had substituted prescription medication with cannabis (Lucas & Walsh, 2017), while other medical cannabis users have claimed that cannabis produces similar effects of pain reduction compared to opioid-based medications (Reiman, Welty & Soloman, 2017). With less usage of opioids, patients would be able to lower their opioid dose gradually and manage their pain symptoms without the addition of withdrawal effects and other problems caused by substance dependence (Boehnke et al., 2019). Additionally, the cannabinoid composition within varieties of cannabis may affect the analgesic potency, as high THC concentrations within cannabis strains are implemented for people with pain and other specific conditions (Sinclair, 2016), but cannabis with both THC and CBD had more analgesic efficacy in comparison with THC only cannabis strains (Johnson et al., 2010). However, it is important to note that higher THC and low CBD levels are associated with risks for adverse reactions, including cognitive and memory impairment, or developing psychosis within vulnerable and high-risk groups (Englund et al., 2013). 49 4.6 Cannabis Use Characteristics Information collected in 2015 showed that around 12% of the Canadian population (3.6 million) had used cannabis in the past year, and among these users, 17% were British Columbia residents and 24% had reported using cannabis for medical reasons (Health Canada, 2015). These data also report a higher prevalence of cannabis use among males compared to females, 15% and 10% respectively (Health Canada, 2015). Likewise, our results within the medical cannabis population showed more males (68%) compared to females (32%). Data collected within the general Canadian population indicated the median age of their first cannabis use was around 17-years old (Health Canada, 2015), while for our medical cannabis users, the median age was 16-years old. More specifically, the majority of our population showed that high numbers of participants first used cannabis at around 15-years to 20-years old or younger. Furthermore, Health Canada (2015) reports the most frequent age range for cannabis use was ages 20 to 24-years old (30%), with a similar percentage (35%) to our medical cannabis population. Therefore, suggesting that the profiles of medical cannabis users show some similarity to the general population within Canada. 4.6.1 Amount of Cannabis Use Most past-year cannabis users in 2015 reported cannabis use within the past three months (72%), while 33% reported using cannabis on a daily or almost daily basis (Health Canada, 2015). Results from our study showed higher percentages of daily consumption (74%), similar to other studies examining medical cannabis patients, reporting with 67% of patients using cannabis daily (Reinarman et al., 2011). However, daily cannabis use was substantially higher (90.5%) in patients from Rhode Island mostly using medical cannabis to treat chronic pain (Zaller et al., 50 2015). Meanwhile, the average cannabis amount used per week within our study appeared consist with a study from California, where 40.1% used 3 grams per week and 23.3% used 7 grams (Reinarman et al., 2011). In contrast, the Rhode Island study reported larger amounts of dried cannabis use per week, with 34.5% using more than 8 grams per week (Zaller et al., 2015). Together with previous studies, our data shows that the medical cannabis population has a much higher cannabis dose and frequency of use compared to the general population. 4.6.2 Smoking Different methods of cannabis consumption lead to different rates of absorption and may produce distinctive effects (Huestis, 2007). For example, smoking delivers drugs quickly and effectively to the brain, which contributes to the potential for substance abuse and dependence (Huestis, 2007). The prevalence of cigarette smoking in Canada was 13% in 2015, with 9% reporting daily smoking and a higher number of male smokers reporting current smoking (Health Canada, 2015). Whereas, 21% of medical cannabis users within our study currently smoked cigarettes, which is considerably higher than the general population, however, Fagerström scores mostly showed low to average levels of nicotine dependence. Scientific literature indicates an association between cannabis use and persistent cigarette smoking (Weinberger et al., 2018), and that weekly use of cannabis during adolescence is related with the risk of tobacco use initiation, which could progress to nicotine dependence (Patton et al., 2005). Moreover, smoking cigarettes is generally known to be strongly associated with medical diseases and health problems (National Center for Chronic Disease Prevention and Health Promotion, 2014; Centers for Disease Control and Prevention, 2010), thus vaporizers have become popular for cannabis users 51 and may be a safer alternative as vaporizing results with fewer respiratory symptoms and lung problems compared to smoking cannabis (Earleywine and Barnwell, 2007). 4.6.3 Other Methods of Cannabis Consumption Oral ingestion results with a lower bioavailability of THC as the liver degrades it and converts THC to 11-hydroxy-THC, which is another psychoactive component that contributes to psychological effects (Sharma, Murthy, & Bharath, 2012). This could be enough reason to choose vaporizing over oral intake, as vaporizing can deliver a higher number of cannabinoids into the bloodstream, and thus, may be more effective (Huestis, 2007). Within the general population of Canada in 2015, 28% of past-year cannabis users reported administrating cannabis with a vaporizer device (Health Canada, 2015), while in 2018, vaporizer use increased to 39.8%, with more females compared to males, 23.6% and 16.2% respectively (Statistics Canada, 2018). Similarly, forty-two people from our medical cannabis population reported using a vaporizer for cannabis use, however only 18% of vaporizer users exclusively used their vaporizers and did not smoke cannabis as well, which was consistent in other medical cannabis profile studies (Reinarman et al., 2011; Grella et al., 2014; Zaller et al., 2015). 4.6.4 Risks for Cannabis Dependence or Abuse Medical cannabis are usually frequent users of cannabis, so have higher chances of developing cannabis dependence (Coffey et al., 2003), which has evidence to support the increased risk of developing other mental health issues in relation to drug abuse (Budney & Moore, 2002). However, not all frequent cannabis users develop dependence, with studies reporting that around 20% to 50% of daily users meet criteria for cannabis dependence (Coffey 52 et al., 2002). Moreover, previous research found no major differences between cannabis-dependent and non-dependent cannabis users after using potential predictors from general population studies, such as amount of cannabis exposure and early first cannabis use (van der Pol et al., 2013). Other potential factors that could predict the potential for cannabis abuse includes surroundings during cannabis use, and time of use, as these were shown to be different between cannabis dependent users and non-dependence cannabis users (Noack, Hofler & Lueken, 2011). Although most medical cannabis users did not use cannabis during the middle of the night (12am-6am), 70% of those that did were also diagnosed with cannabis abuse. Despite this, most participants used cannabis in the evenings, late at night, or on an as-needed basis, similar to previous studies (Reinarman et al., 2011). In contrast, although cannabis may help substance abusers with their symptoms and gradually reduce high substance doses, cannabis may not be implicated for all cases as some people have more vulnerability factors, such as a family history of developing drug addictions, that increase their risks of cannabis dependence or other psychiatric disorders (van der Pol et al., 2013). Thus, establishing high-risk groups for cannabis use is just as important as finding conditions that considerably improve with medical cannabis. However, over the past few decades, THC content has increased by around 20% more (Mehmedic et al., 2010), but different cannabis strains can still vary considerably in THC or CBD levels (Mehmedic et al., 2010). Therefore, it is important to know the cannabinoid content before consuming cannabis. 4.6.5 The “Entourage Effect” While pharmaceuticals have created synthetic THC for therapeutic use, clinical trials have resulted with small but insignificant effects (Tsang & Giudice, 2016), as many scientists 53 indicate that the resulting effect of cannabis is due to the distinctive chemical composition within the plant itself working in unison, namely the “entourage” effect, especially with CBD and terpenes (Russo et al., 2011). Therefore, including only one cannabinoid for a medical treatment may not give patients the best possible therapeutic form of cannabis. Furthermore, many different factors can disrupt an effective dose of cannabis, as individuals differ and depends on their tolerance, form of consumption, frequency of use and any negative effects experienced (Borgelt et al., 2013), thus, the same dose of cannabis may bring different effects or consequences for different people. 54 Chapter 5: Conclusions 5.1 Summary The present study provides a further understanding about the medical cannabis community, both in terms of patterns of cannabis use and mental health. We administered a standardized clinical interview along with disorder-specific severity tests to obtain a detailed evaluation of psychiatric conditions within this particular cohort. In addition to this, we combined this information with their cannabis use characteristics to produce a well-rounded profile of medical cannabis users. Generally, most participants from this study were diagnosed with a lifetime mental illness, with a large proportion meeting criterion for multiple diagnoses. However, the prevalence of current mental disorders was low for mood disorders, but higher for anxiety disorders and substance dependence or abuse. This was generally reflected in the mental health perception of individuals, as they mostly self-reported with anxiety, but also reported sleep issues and depression for medical cannabis use. These results were comparable to similar previous studies examining the profiles of medical cannabis users (Reinarman et al., 2011; Zaller et al., 2015). Previous work has also indicated that dispensaries are able to provide medical cannabis users with further assistance, with reports of better quality, safety, convenience and positive experiences compared to other sources of cannabis (Capler et al., 2017). Mental health symptom severity was relatively higher for participants diagnosed with certain psychiatric disorders, such as a diagnosis of generalized anxiety disorder would usually be related with higher perceived stress. Earlier onset of regular cannabis use was revealed for substance dependence/abuse, together with a higher frequency of cannabis use. While alcohol or non-cannabis substance dependence were associated with panic disorder or social phobia 55 diagnoses and higher perceived stress. Overall, medical cannabis users from our study showed low to moderate severity in psychiatric disorders, with few severe cases. However, this specific research area requires further study in order to better define the role that cannabis plays in mental health. Especially since the huge variation between cannabis strains may elicit uncertain effects, due to the complex nature of the components within cannabis, as much is still unknown about the mechanisms of interaction within our bodies. Nevertheless, this study has expanded on current research and may help further studies better understand the role of cannabis in medical conditions as it becomes more available and welcome as an alternative to conventional treatments. 5.2 Limitations Although the present study provides a detailed analysis of the health characteristics of medical cannabis users, it is not without limitation. Firstly, the present study was only able to recruit participants from one dispensary in Vancouver, which is not representative of the general population of Canada, nevertheless, since participants were selected at random, our study population may illustrate the profiles of individuals who use cannabis dispensaries. Secondly, there are numerous types of psychiatric disorders, however, not all were frequently diagnosed within the modest size of our study sample. Therefore, some psychiatric disorders, such as Bipolar Disorder or OCD, did not have sufficient numbers to reliably compare with characteristics of cannabis use or symptom severity. Thirdly, many participants reported medical cannabis use to treat focus and attention disorders, such as attention deficit hyperactivity disorder (ADHD), but a diagnostic test was not included in the sixth version of the MINI neuropsychiatric test. Therefore, we were unable to indicate the number of medical cannabis users with specific 56 attention disorders. However, the sixth version of the MINI has been well-validated with studies supporting its reliability, while previous research in cannabis have also used this version of the MINI (Skalisky et al., 2017), and thus provides better comparisons with our data. Finally, the exact composition of the cannabis used within our medical cannabis population is unknown, thus future studies looking into medical cannabis users should identify their cannabis type and source of medical cannabis. 5.3 Future Work Cannabis presents as a therapeutic option for some conditions with many reports of its benefits in managing symptoms, however, as different medical conditions require the unique balance of certain cannabinoids, cannabis should be regulated, analyzed, and given with specific medical instructions, and thus, cannabis should be regarded as a medicine for some people. Our study can be used to help people suffering from mental health better regulate their medical cannabis use and also educate the public population about the benefits for certain mental conditions. Future studies should focus on using similar and detailed assessments of mental health from our study, but within a larger study sample and also incorporate multiple dispensaries throughout other provinces of Canada in order to achieve a more thorough understanding of Canadian medical cannabis users. Moreover, the legalization of recreational cannabis will help those seeking medical cannabis to describe their issues to a certified doctor with confidence, and to receive high quality cannabis that is more specific to their medical requirements. Ultimately, medical cannabis represents both an exciting therapeutic opportunity and enormous commercial opportunity that Canada is ideally suited to benefit from. 57 Bibliography Albucher, R. C. & Liberzon, I. (2002). Psychopharmacological treatment in PTSD: a critical review. J Psychiatr Res, 36(6), 355-367. American Psychiatric Association. (2000). Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Text Revision. 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Thesis/Dissertation
eng
Pharmacology and Therapeutics
Vancouver : University of British Columbia Library
Attribution-ShareAlike 4.0 International
Graduate
Characterization of mental health in cannabis dispensary users, using structured clinical interviews and standardized assessment instruments
Text