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High prevalence of quasi-legal psychoactive substance use among male patients in HIV care in Japan: a… Hayashi, Kanna; Wakabayashi, Chihiro; Ikushima, Yuzuru; Tarui, Masayoshi Feb 23, 2017

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RESEARCH Open AccessHigh prevalence of quasi-legalpsychoactive substance use among malepatients in HIV care in Japan: a cross-sectional studyKanna Hayashi1,2,6* , Chihiro Wakabayashi3, Yuzuru Ikushima4 and Masayoshi Tarui5AbstractBackground: Syndemics of illicit drug use and HIV remain as significant public health issues around the world.There has been increasing concern regarding the rapidly growing market of new psychoactive substances,particularly in Asia. In response, the Japanese government has increasingly banned such substances in recent years.We sought to identify the prevalence and correlates of use of quasi-legal psychoactive substances among peopleliving with HIV/AIDS (PLHIV) in Japan.Methods: Data were derived from a nationwide survey of PLHIV conducted at nine leading HIV/AIDS care hospitalsbetween July and December 2013. The prevalence and correlates of the use of quasi-legal psychoactive substances(e.g., synthetic cannabinoids, cathinone derivatives, etc. that had not been prohibited from using at the time ofsurvey) among male participants were examined using multivariate survey logistic regression.Results: Among 963 study participants, the majority (95.3%) were male. The most commonly used drug amongmen was quasi-legal psychoactive substances (55.3% ever and 12.8% in the previous year). In multivariate analysis,the lifetime use of tryptamine-type derivatives (i.e., 5-MeO-DIPT or N,N-diisopropyl-5-methoxytryptamine) (adjustedodds ratio [AOR]: 2.42; 95% confidence interval [CI]: 1.36–4.28) and methamphetamine/amphetamine (AOR: 3.59;95% CI: 2.13–6.04) were independently associated with recent quasi-legal psychoactive substance use.Conclusions: In our sample of male PLHIV in Japan, quasi-legal psychoactive substances were the most commonlyused drugs. Individuals who had ever used tryptamine-type derivatives or methamphetamine/amphetamine weremore likely to report recent quasi-legal psychoactive substance use, suggesting a potential shift in drug use patternsfrom regulated to unregulated substances among this population. These findings indicate a need for further researchto examine implications for HIV care.Keywords: New psychoactive substance, HIV/AIDS, Drug and narcotic control, Men who have sex with men,Epidemiology, Japan* Correspondence: uhri-kh@cfenet.ubc.ca1British Columbia Centre for Excellence in HIV/AIDS, St. Paul’s Hospital,608-1081 Burrard Street, Vancouver, BC V6Z 1Y6, Canada2Faculty of Health Sciences, Simon Fraser University, Blusson Hall, Room11300, 8888 University Drive, Burnaby, BC V5A 1S6, CanadaFull list of author information is available at the end of the article© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Hayashi et al. Substance Abuse Treatment, Prevention, and Policy  (2017) 12:11 DOI 10.1186/s13011-017-0097-2BackgroundMany countries in the world are contending with syn-demics of illicit drug use and HIV/AIDS [1, 2]. In Asia, un-safe injection use of opioids has traditionally been a keydriver of HIV epidemics [2]. However, a growing body ofresearch indicates that non-injection use of amphetamine-type stimulants is also common, and associated with anelevated HIV risk [2–4]. Specifically, methamphetamineuse has been shown to be highly prevalent, particularlyamong men who have sex with men (MSM), increase HIVseroconversion due to the associated risky sexual behav-iour, and compromise HIV treatment outcomes [5–7].However, little is known about the extent and patterns ofuse of other synthetic drugs in this context. This is con-cerning because the Asia-Pacific region has recently expe-rienced explosive increases in the availability of a variety ofquasi-legal, mostly synthetic psychoactive substances [8].These substances are designed to mimic the pharmaco-logical effects of regulated substances including metham-phetamine [8].In Japan, the prevalence of illicit drug use in the generalpopulation has historically been low at <3% (lifetime use)[9]. The prevalence of HIV infection has also been low at<0.1% among the general population over the past threedecades [10]. However, as in other parts of Asia, the bur-den of HIV is disproportionately concentrated amongMSM [10]. It has been estimated that MSM accounted forover half of the recorded HIV diagnoses [11]. Previousstudies reported a very high prevalence (40%) of illicitdrug use among HIV-positive MSM in one hospital inTokyo [12]. Illicit drug use was identified as an independ-ent predictor of loss to follow-up for HIV care and hepa-titis C virus infection in this setting [13, 14]. However,these studies did not fully differentiate the use of trad-itional illicit drugs (e.g., methamphetamine, heroin) andother quasi-legal psychoactive substances.In response to the explosive spread of quasi-legal syn-thetic psychoactive substances [15], the Japanese govern-ment has made a series of important changes to thedrug control legislation over the past decade. Throughthe 2006 amendment of the Pharmaceutical Affairs Law,quasi-legal synthetic drugs that were deemed to have thepotential to cause health-related harms were newly clas-sified as “Designated Substances” [15]. The supply ofthese substances for non-medical purposes was prohib-ited [15]. By March 2013, 106 substances, includingsynthetic cannabinoids, tryptamine-type derivatives andphenethylamine derivatives, were listed as DesignatedSubstances [15, 16]. Since 2013, generic scheduling forcertain types of synthetic cannabinoids and cathinonederivatives has also been introduced [16].Despite the tighter control of supply, the possession andconsumption of Designated Substances have remainedlargely unregulated. By March 2013, only 13 of the 106Designated Substances, including mephedrone andtryptamine-type derivatives (e.g., 5-MeO-DIPT and Foxy[N,N-diisopropyl-5-methoxytryptamine]), have been cate-gorized as “Narcotics” under the Narcotics and Psychotro-pics Control Law and thereby have been prohibited frompossessing and consuming [16]. As such, many DesignatedSubstances have continued to be sold as herbal products,aroma products and bath salts, even in vending machineson the street.While drug use patterns could be affected by theselegislation changes, there is a paucity of epidemiologicdata regarding the use of quasi-legal psychoactive sub-stances (i.e., substances that have not been prohibitedfrom possessing or consuming under the Narcotics andPsychotropics Control Law) in Japan [9]. Given theprevious studies suggesting that illicit drug use couldcompromise HIV care and increase adverse health out-comes among HIV-positive MSM in this setting [13, 14],we sought to identify the prevalence and correlates ofquasi-legal psychoactive substance use among a large na-tionwide sample of people living with HIV/AIDS (PLHIV)in Japan.MethodsStudy designData for this study were derived from a nationwide cross-sectional survey of PLHIV conducted at nine leading HIV/AIDS referral hospitals in Japan between July and Decem-ber 2013. In brief, beginning in 2003, this is a quinquennialsurvey that aims to investigate the health and lifestylesamong PLHIV in Japan. The nine hospitals included in thesurvey represent tertiary care hospitals and collectivelycover the eight major geographical regions in Japan. In eachhospital, HIV/AIDS medical professionals were asked to re-cruit their patients living with HIV/AIDS in a serial manneras patients visit their hospitals. They explained the studyobjectives and procedures to potential participants, and ob-tained informed consent from them. The recruitment wascontinued until approximately 40% of their patients pro-vided informed consent. While we did not count the num-ber of patients who refused to participate in the survey,informal reports from hospitals indicated that such caseswere rare. Consented patients were asked to self-completean anonymous questionnaire and return it to an independ-ent researcher using a self-addressed, stamped envelopeprovided with the questionnaire. The questionnaire eliciteda range of information, including socio-demographic char-acteristics, HIV-related clinical histories, general health sta-tus, and substance use histories. All consented individualsreceived a 500 Japanese Yen (approximately US$5.00) giftcertificate. The study was approved by the research ethicsboards at the Saitama Prefectural University as well as eachparticipating hospital.Hayashi et al. Substance Abuse Treatment, Prevention, and Policy  (2017) 12:11 Page 2 of 8Participants and measuresIn total, 1,100 (61.6%) of 1,786 consented individualscompleted and returned the questionnaire, including 51(4.7%) females. For a gender-based descriptive analysisof drug use patterns, the sample was restricted to 963(87.5%) individuals (918 males and 45 females) who hadcomplete data. For an analysis examining correlates ofpast year quasi-legal psychoactive substance use amongmen, the sample was further restricted to 895 male par-ticipants with complete data.For the present analysis, the primary outcome of inter-est was reporting quasi-legal psychoactive substance usein the previous year, defined as answering “Yes” to aquestion: “In the past year, have you used quasi-legaldrugs in the form of herbal products, aroma liquid, pow-der, oil, bath salts, or amyl nitrites including ‘rush’ and‘poppers’?” As such, quasi-legal psychoactive substancesencompassed a range of substances that had been largelyregulated as Designated Substances but had not beenprohibited from possessing or consuming under theNarcotics and Psychotropics Control Law by December2013. Specifically, these substances would include syn-thetic cannabinoids, synthetic cathinones, phenethyla-mine and thiophene derivatives, and amyl nitrites (e.g.,rush, poppers). The term “quasi-legal drugs” was usedbecause it commonly referred to the aforementioned setof quasi-legal psychoactive substances of our interest inJapan, and also because people usually do not know theexact substance contained in the product.Then, we selected a range of explanatory variables thatwe hypothesized were potentially associated with the out-come. Socio-demographic characteristics included: age;education (< secondary education vs. ≥ secondary educa-tion); currently living alone (yes vs. no) and annual income(<1 million, 1–2.99 million, 3–4.99 million vs. ≥ 5 millionYen). HIV-related measures included: antiretroviral therapy(ART) use (currently on ART vs. never on ART); ever hadAIDS (yes vs. no); perceived route of HIV exposure (male-to-male sexual behaviour vs. other; as a proxy measure forMSM); and engagement in HIV-related peer supportgroups in the previous year (yes vs. no). Psychological dis-tress was measured using the Kessler psychological distressscale (K6) [17]. This variable was dichotomized into a scoreof ≥ 13 vs. a score of < 13, using the recommended cut-offscore to screen serious mental illness [17]. Histories of Illicitdrug use included: ever used tryptamine-type derivatives(i.e., 5-MeO-DIPT or Foxy [N,N-diisopropyl-5-methoxy-tryptamine]), ever used cannabis, ever used methampheta-mine/amphetamine, ever used MDMA, and ever usedheroin/cocaine (all yes vs. no).Statistical analysesFirst, socio-demographic and HV-related clinical charac-teristics were compared between males and females,using the Wilcoxon Rank Sum Test (for continuousvariables) and the Pearson’s Chi-squared test (for cat-egorical variables). Since the prevalence of drug usewas extremely low among women (11.1% ever and 0%in the previous year), descriptive statistics were usedto compare drug use patterns between males andfemales.For bivariate and multivariate analyses of factors pre-dicting past year quasi-legal psychoactive substance useamong male participants, we used the survey logistic re-gression in the SAS software to account for possible clus-tering effects at the hospital level. A multivariate modelwas fit using an a priori-defined statistical protocolwhereby all variables that were significantly associatedwith past year quasi-legal psychoactive substance use atthe p < 0.05 level in the bivariate logistic regression ana-lyses. In a sub-analysis, we examined the proportion ofthose who had never used any illicit drugs (i.e.,tryptamine-type derivatives, cannabis, methamphetamine/amphetamine, MDMA, heroin or cocaine) among maleparticipants who used quasi-legal psychoactive substancein the previous year. We also examined the propor-tion of those who used drugs for sexual activities inthe previous year among the same aforementionedsub-sample. All p-values were two-sided. All statisticalanalyses were performed using SAS software version9.3 (SAS, Cary, NC).ResultsIn total, 963 participants were eligible for the presentstudy, including 45 (4.7%) females. Table 1 shows samplecharacteristics and drug use patterns, stratified by gen-der. As shown, the median age of the entire sample was42 (interquartile range: 37–50) years. There was no sig-nificant gender-based difference in age. While femaleparticipants were more likely than males to be diagnosedwith HIV before 2005, the majority of both males and fe-males reported currently receiving ART. Annual incomewas significantly lower among women, compared to men.Among men, more than half reported a history of illicitdrug use (including quasi-legal psychoactive substances),while only a handful of women did so. Among men, themost commonly used drug was quasi-legal psychoactivesubstances, followed by 5-MeO-DPT/Foxy and metham-phetamine/amphetamine. Of note, the use of 5-MeO-DPT/Foxy in the previous year substantially dropped to0.4%. Among women, the most commonly used drug wascannabis, followed by quasi-legal psychoactive substancesand methamphetamine/amphetamine.Table 2 shows the results of bivariate analyses of fac-tors predicting past year quasi-legal psychoactive sub-stance use among male participants. As shown, factorssignificantly associated with the outcome included: age;Hayashi et al. Substance Abuse Treatment, Prevention, and Policy  (2017) 12:11 Page 3 of 8currently living alone; male-to-male sexual behaviour asa perceived route of HIV exposure; and all illicit druguse histories considered.Table 3 presents the results of the multivariate logisticregression analysis. As presented, age remained independ-ently and negatively associated with past year quasi-legalTable 1 Drug use patterns among HIV-positive male and female patients accessing HIV care in Japan (n = 963)Characteristic Total n (%) Male Female p – value918 (95.3%) 45 (4.7%)Age (median, IQR) 42 (37–50) 42 (37–50) 41 (35–48) 0.4491Calendar year of HIV diagnosis <0.00121984–2005 337 (35.0%) 309 (33.7%) 28 (62.2%)2006–2009 302 (31.4%) 293 (31.9%) 9 (20.0%)2010–2013 324 (33.6%) 316 (34.4%) 8 (17.8%)Currently receiving ART 911 (94.6%) 870 (94.8%) 41 (91.1%) 0.2893Annual income 0.0444< 1 million Yena 272 (28.3%) 253 (27.5%) 19 (42.2%)1–2.99 million Yena 242 (25.1%) 231 (25.2%) 11 (24.4%)3–4.99 million Yena 243 (25.2%) 231 (25.2%) 12 (26.7%)≥ 5 million Yena 206 (21.4%) 203 (22.1%) 3 (6.7%)Quasi-legal psychoactive substance usebEver 510 (53.0%) 508 (55.3%) 2 (4.4%)In the previous year 117 (12.2%) 117 (12.8%) 0 (0.0%)Tryptamine-type derivatives (i.e., 5-MeO-DPT or Foxy) useEver 255 (26.5%) 255 (27.8%) 0 (0.0%)In the previous year 4 (0.4%) 4 (0.4%) 0 (0.0%)Cannabis useEver 91 (9.5%) 88 (9.6%) 3 (6.7%)In the previous year 4 (0.4%) 4 (0.4%) 0 (0.0%)Methamphetamine/amphetamine useEver 110 (11.4%) 109 (11.9%) 1 (2.2%)In the previous year 23 (2.4%) 23 (2.5%) 0 (0.0%)MDMA useEver 58 (6.0%) 58 (6.3%) 0 (0.0%)In the previous year 4 (0.4%) 4 (0.4%) 0 (0.0%)Heroin useEver 5 (0.5%) 5 (0.5%) 0 (0.0%)In the previous year 0 (0.0%) 0 (0.0%) 0 (0.0%)Cocaine useEver 22 (2.3%) 22 (2.4%) 0 (0.0%)In the previous year 1 (0.1%) 1 (0.1%) 0 (0.0%)Use of any drugs listed aboveEver 522 (54.2%) 517 (56.3%) 5 (11.1%)In the previous year 127 (13.2%) 127 (13.8%) 0 (0.0%)IQR interquartile range1P-value was derived from the Wilcoxon Rank Sum Test2Chi-square value = 15.475, df = 23Chi-square value = 1.125, df = 14Chi-square value = 8.098, df = 3aUS$1.00 ≈ 100 Yen. “<1 million Yen” includes those without any incomebIncludes variations of synthetic cannabinoids, synthetic cathinones, phenethylamine and thiophene derivatives, and amyl nitrites (e.g., rush, poppers). At the timeof surveying, the possession or consumption of these substances was not prohibitedHayashi et al. Substance Abuse Treatment, Prevention, and Policy  (2017) 12:11 Page 4 of 8Table 2 Bivariate analyses of factors predicting past year quasi-legal psychoactive substance use among HIV-positive males accessingHIV care in Japan (n = 895)Characteristic Quasi-legal psychoactive substance use in the previous year Odds Ratio (95% CI) p - valueYes 115 (12.9%) No 780 (87.1%)AgeMedian (IQR) 39 (33–44) 43 (37–52)Per year older 0.95 (0.93–0.97) <0.001Education< Secondary education 1 (0.9%) 21 (2.7%) 0.32 (0.07–1.53) 0.153≥ Secondary education 114 (99.1%) 759 (97.3%) refCurrently living aloneYes 61 (53.0%) 344 (44.1%) 1.43 (1.04–1.97) 0.028No 54 (47.0%) 436 (55.9%) refAnnual income< 1 million Yena 28 (24.4%) 210 (26.9%) 0.76 (0.54–1.09) 0.4441–2.99 million Yena 29 (25.2%) 196 (25.1%) 0.85 (0.52–1.39) 0.9953–4.99 million Yena 28 (24.3%) 202 (25.9%) 0.80 (0.63–1.01) 0.518≥ 5 million Yena 30 (26.1%) 171 (22.1%) refART useCurrently on ART 106 (92.2%) 741 (95.0%) 0.62 (0.29–1.31) 0.210Never on ART 9 (7.8%) 39 (5.0%) refEver had AIDSYes 32 (27.8%) 236 (30.3%) 0.89 (0.55–1.43) 0.625No 83 (72.2%) 544 (69.7%) refPerceived route of HIV exposureMale-to-male sexual behaviour 111 (96.5%) 647 (82.9%) 5.70 (3.29–9.88) <0.001Other 4 (3.5%) 133 (17.1%) refEngagement in HIV-related peer support groups in the previous yearYes 9 (7.8%) 46 (5.9%) 1.36 (0.67–2.72) 0.394No 106 (92.2%) 734 (94.1%) refKessler psychological distress scale (K6)Score of≥ 13 13 (11.3%) 99 (12.7%) 0.88 (0.48–1.61) 0.672Score of < 13 102 (88.7%) 681 (87.3%) refEver used tryptamine-type derivatives (5-MeO-DPT or Foxy)Yes 65 (56.5%) 187 (24.0%) 4.12 (2.90–5.86) <0.001No 50 (43.5%) 593 (76.0%) refEver used cannabisYes 25 (21.7%) 62 (8.0%) 3.22 (1.79–5.78) <0.001No 90 (78.3%) 718 (92.0%) refEver used methamphetamine/amphetamineYes 41 (35.7%) 68 (8.7%) 5.80 (3.79–8.88) <0.001No 74 (64.3%) 712 (91.3%) refEver used MDMAYes 19 (16.5%) 39 (5.0%) 3.76 (2.41–5.87) <0.001No 96 (83.5%) 741 (95.0%) refHayashi et al. Substance Abuse Treatment, Prevention, and Policy  (2017) 12:11 Page 5 of 8psychoactive substance use. Factors that remained inde-pendently and positively associated with past year quasi-legal psychoactive substance use included: currently livingalone; male-to-male sexual behaviour as a perceived routeof HIV exposure; ever used 5-MeO-DPT/Foxy; and everused methamphetamine/amphetamine.In the sub-analysis, among the 115 male participantswho used quasi-legal psychoactive substances in the pre-vious year, 38 (33.0%) reported having never used otherillicit drugs. Sixty-nine (60.0%) individuals reported hav-ing used drugs for sexual activities in the previous year.DiscussionIn our sample of PLHIV in Japan, illicit drug use wasmuch more common among males than females. Themost commonly used drugs among men were quasi-legal psychoactive substances. Over half of male partici-pants reported having ever used quasi-legal psychoactivesubstances, and approximately 12% reported having usedthese substances in the previous year. The majority(97%) of those who used quasi-legal psychoactive sub-stances in the previous year were presumably MSM. Ap-proximately one-third of them had no history of usingother illicit drugs. In the multivariate analysis, the life-time use of 5-MeO-DPT/Foxy or methamphetamine/amphetamine, younger age, living alone, and male-to-male sexual behaviour as a perceived route of HIVexposure were independently and positively associatedwith recent quasi-legal psychoactive substance useamong male PLHIV.We found that male PLHIV who had ever used 5-MeO-DPT/Foxy were more likely to have used quasi-legal psy-choactive substances in the previous year. While thecross-sectional nature of the study limits the assessmentof temporal relationships, available data and literature sug-gest possible shifts in the patterns of drug use in thissetting, from the use of fully banned to yet-to-be-fully-prohibited substances. As presented in Table 1, in oursample, 5-MeO-DPT/Foxy were second-ranked amongthe drugs that have ever been used in the lifetime (28%).However, past year use substantially dropped to <0.5%.Given that these tryptamine-type derivatives became fullyprohibited under the Narcotics and Psychotropics ControlLaw in 2005, our findings suggest that “substance dis-placement” might have occurred in this setting [18]whereby those who had used these illegal stimulants mayTable 2 Bivariate analyses of factors predicting past year quasi-legal psychoactive substance use among HIV-positive males accessingHIV care in Japan (n = 895) (Continued)Ever used heroin or cocaineYes 8 (7.0%) 15 (1.9%) 3.81 (1.62–9.01) 0.002No 107 (93.0%) 765 (98.1%) refIQR: interquartile range. ART: antiretroviral therapyaUS$1.00 ≈ 100 Yen. “<1 million Yen” includes those without any incomeTable 3 Multivariate logistic regression analysis of factors predicting past year quasi-legal psychoactive substance use amongHIV-positive males accessing HIV care in Japan (n = 895)Variable Adjusted Odds Ratio 95% Confidence Interval p - valueAge(per year older) 0.96 (0.93–0.99) 0.004Living alone(yes vs. no) 1.66 (1.10–2.49) 0.015Perceived route of HIV exposure(male-to-male sexual behaviour vs. other) 2.56 (1.48–4.43) <0.001Ever used tryptamine-type derivatives (5-MeO-DPT or Foxy)(yes vs. no) 2.42 (1.36–4.28) 0.003Ever used cannabis(yes vs. no) 1.04 (0.51–2.12) 0.912Ever used methamphetamine/amphetamine(yes vs. no) 3.59 (2.13–6.04) <0.001Ever used MDMA(yes vs. no) 0.90 (0.54–1.48) 0.667Ever used heroin or cocaine(yes vs. no) 1.04 (0.56–1.96) 0.895Hayashi et al. Substance Abuse Treatment, Prevention, and Policy  (2017) 12:11 Page 6 of 8have shifted to other quasi-legal psychoactive substanceswith similar psychoactive effects as these psychoactivesubstances became easily available. This is also congruentwith previous forensic laboratory reports suggesting thatstricter controls of certain substances have met with theemergence of new analogues of controlled substances inJapan [16].Likewise, the independent association between lifetimeuse of methamphetamine/amphetamine and recent use ofquasi-legal psychoactive substances could also be inter-preted as switching from the former to the latter. How-ever, a recent qualitative study reported that quasi-legalpsychoactive substance use might subsequently lead to theuse of methamphetamine/amphetamine among somePLHIV in Japan [19]. In light of this previous study find-ing, the observed association may also suggest that someof those who used quasi-legal psychoactive substances inthe previous year subsequently used methamphetamine/amphetamine. Future research should determine thepotential role of quasi-legal psychoactive substance use inthe initiation of methamphetamine/amphetamine use inthis setting.We also found that those who were younger and thosewho were likely MSM were more likely to report recentuse of quasi-legal psychoactive substances. This is con-sistent with a previous study conducted in Tokyo [12].According to a recent qualitative investigation of pat-terns of illicit drug use among HIV-positive MSM inJapan, illicit drugs (including quasi-legal psychoactivesubstances) were used for several purposes in this popu-lation, including as a strategy to cope with depressionand sexual minority stress, and as a sexual stimulant[20]. Regardless of the purposes, illicit drug use oftenresulted in increasing sexual HIV risk behaviour [20].Consistent with these qualitative research findings, inour study, two-thirds of the past year quasi-legal psycho-active substance users reported having used drugs forsexual purposes. Previous literature also indicated highrates of sexual stimulant use among HIV-positive MSMin other countries [21]. Ongoing quasi-legal psychoactivesubstance use and the potentially associated risky sexualbehaviour among HIV-positive MSM are concerning.They warrant greater efforts to address factors that leadto illicit drug use and to reduce drug-related harms inthis setting.Internationally, identifying effective regulations ofnew psychoactive substances is a major topic of de-bate [22, 23]. In April 2014, the Japanese governmentpenalized the personal possession and consumption ofall Designated Substances [24]. This legislation changein Japan, which outright banned more than 1,300Designated Substances [24], could be viewed as a boldattempt to contain the illicit psychoactive substancemarket through law enforcement. Some commentatorsraised a concern regarding the overreliance on suchlaw enforcement-based approaches [25]. They claimedthat as new psychoactive substances are moving tar-gets, such approaches may potentially increase thedrug-related harm among those who continue to usethose controlled substances [25]. Our findings sug-gesting the possible shift from the use of banned tounregulated substances reinforce the concern. Giventhat new unregulated substances may pose increasedor different kinds of harm, the findings indicate aneed to address various social and structural factorsthat predispose vulnerable populations to illicit druguse and the associated harm.Our study has several limitations. First, as the studysample was not randomly selected, our findings may notbe generalizable to PLHIV in Japan or elsewhere. Second,the self-reported data may be affected by reporting biases,including recall bias and socially desirable responding.However, we note that the anonymous nature of the ques-tionnaire may have helped reduce some of the biases.Third, as with all observational studies, the associationsbetween the explanatory variables and outcome assessedmay be under the influence of unmeasured confound-ing factors. However, we sought to address this biaswith multivariate adjustment of the key demographicand behavioural predictors of quasi-legal psychoactivesubstance use.ConclusionIn sum, illicit drug use was much more common amongmale patients in HIV care in Japan, compared to their fe-male counterparts. Among male participants, quasi-legalpsychoactive substances were the most commonly useddrugs. We also found a substantial decline in recent use of5-MeO-DPT/Foxy. Individuals who had ever used thesetryptamine derivatives or methamphetamine/amphetaminewere more likely to report recent quasi-legal psychoactivesubstance use. These findings suggest a potential shift indrug use patterns from regulated to unregulated substancesamong this population. Given that a new regulation insti-tuted in April 2014 fully banned presumably most of thequasi-legal psychoactive substances considered in thisstudy, further research is warranted to examine changingdrug patterns and implications for HIV care in this setting.AbbreviationsAIDS: Acquired immune deficiency syndrome; HIV: Humanimmunodeficiency virus; MSM: Men who have sex with men; PLHIV: Peopleliving with HIV/AIDSAcknowledgementsThe authors thank the study participants for their contribution to theresearch, as well as current and past researchers and staff.FundingThe study was supported by the Japanese Ministry of Health, Labour andWelfare’s Sciences Research Grant (H24-AIDS-013). Kanna Hayashi isHayashi et al. Substance Abuse Treatment, Prevention, and Policy  (2017) 12:11 Page 7 of 8supported by the Canadian Institutes of Health Research New InvestigatorAward (MSH-141971).Availability of data and materialsThe data used for this study is not publicly available. For further information onthe data and materials used in this study, please contact the correspondingauthor.Authors’ contributionsCW, YI and MT designed and implemented the survey. KH designed thepresent analysis plan, conducted the statistical analyses, drafted the manuscript,and incorporated suggestions from all co-authors. All authors made significantcontributions to the conception of the analyses, interpretation of the data, anddrafting of the manuscript.Competing interestsThe authors report no conflicts of interest. The authors alone are responsiblefor the content and writing of this paper.Consent for publicationNot applicable.Ethics approval and consent to participateAll participants provided written informed consent for study participation.The study was approved by the research ethics boards at the SaitamaPrefectural University as well as each participating hospital.Author details1British Columbia Centre for Excellence in HIV/AIDS, St. Paul’s Hospital,608-1081 Burrard Street, Vancouver, BC V6Z 1Y6, Canada. 2Faculty of HealthSciences, Simon Fraser University, Blusson Hall, Room 11300, 8888 UniversityDrive, Burnaby, BC V5A 1S6, Canada. 3Department of Health Sciences,Saitama Prefectural University, 820 Sannomiya, Koshigaya-shi, Saitama343-8540, Japan. 4Positive Living and Community Empowerment Tokyo(Place Tokyo), 4-11-5-403 Takadanobaba, Shinjuku-ku, Tokyo 169-0075, Japan.5Faculty of Letters, Keio University, 2-15-45 Mita, Minato-ku, Tokyo 108-8345,Japan. 6BC Centre for Excellence in HIV/AIDS, 1026 Nelson Street, Vancouver,BC V6E 4S7, Canada.Received: 24 December 2016 Accepted: 22 February 2017References1. 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