human psychopharmacology Hum. Psychopharmacol Clin Exp 2012; 27: 352–363. Published online 14 June 2012 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/hup.2234 Simultaneous polysubstance use among Danish 3,4- methylenedioxymethamphetamine and hallucinogen users: combination patterns and proposed biological bases Cecilie L. Licht1*, Maria Christoffersen1, Mads Okholm1,LærkeDamgaard1, Anders Fink-Jensen2, Gitte M. Knudsen1 and David Erritzoe1 1Neurobiology Research Unit (NRU) and Center for Integrated Molecular Brain Imaging (Cimbi), University of Copenhagen and Rigshospitalet, Copenhagen, Denmark 2Psychiatric Centre Copenhagen and Laboratory of Neuropsychiatry, Department O, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark Objective To describe patterns of simultaneous polysubstance use (SPU) among Danish 3,4-methylenedioxymethamphetamine (MDMA) (“Ecstasy”) and hallucinogen users. Methods A cross-sectional survey of 98 active MDMA and/or hallucinogen users recruited through homepage advertisements, flyers, and word of mouth in Denmark. Lifetime and recent substance use and SPU at last recalled use was described by structured interviews. Hair samples from a subset of participants were analyzed for MDMA. Results The participants had used an average of 12.6 (95% confidence interval: 11.7–13.4) psychoactive substances during their lifetime. SPU was prevalent among MDMA, D-lysergic acid diethylamide (LSD), and psilocybin users, in particular with alcohol and cannabis. Among MDMA users, 69% had combined MDMA with amphetamines, 56% with hallucinogens, and 47% with cocaine. At last recalled use, MDMA was taken with 2.1 Æ 1.2 substances in 32 different combinations. The participants preferred specific drug combinations and named several, which in their experience enhanced or counteracted each other. Alcohol and cannabis were typically used before, during, and after MDMA, LSD, and psilocybin, whereas amphetamines were predominantly taken before these substances. When LSD was combined with MDMA, the majority took MDMA after LSD. Conclusions Simultaneous polysubstance use was common among Danish MDMA and hallucinogen users, and patterns of preferred substance combinations were evident. Copyright © 2012 John Wiley & Sons, Ltd. key words—substance-related disorders; 3,4-methylenedioxymethamphetamine; ecstasy; hallucinogens; designer drugs; street drugs INTRODUCTION particular, the simultaneous use of several drugs (simul- Substance-related disorders may have severe detrimental taneous polysubstance use, SPU) during the course of a effects on the health, social relationships, and employ- single drug use session is common among street drug ment of substance users, leading to substantial human users (Barrett et al., 2006; EMCDDA, 2009; Tossmann and financial loss to society. Many street drug users take et al., 2001) and may increase drug consumption (Barrett several different substances during their lifetime, a et al., 2006), morbidity and mortality from substance use (EMCDDA, 2009; Schifano et al., 2003), as well as phenomenon known as polysubstance use (EMCDDA, fl 2009; Tossmann et al., 2001; Wu et al., 2006). In in uence the development of drug tolerance in complex ways (Parrott, 2005). Often, particular substances are combined to enhance psychoactive effects or to relieve *Correspondence to: Dr. C. L. Licht, Neurobiology Research Unit (NRU) and unwanted after effects (Boys et al., 2001; Winstock Center for Integrated Molecular Brain Imaging (Cimbi), University of Copenha- et al., 2001). Whereas distinct characteristics of SPU gen and Rigshospitalet, Section 9201, Blegdamsvej 9, 2100 Copenhagen O, Denmark. Tel: +45 35456712; Fax: +45 35456713. E-mail: [email protected] have been described for different groups of street drug users and for users of particular substances including Dr. D. Erritzoe, Neuropsychopharmacology Unit, Imperial College London, 3,4-methylenedioxymethamphetamine (MDMA) (Barrett Burlington-Danes Building, Hammersmith Campus, 160 Du Cane Road, London W12 0NN, UK. Tel: +44 02075947047; Fax: +44 02075946548. et al., 2005; Tossmann et al., 2001), few studies have E-mail: [email protected] examined the order of substance administration and Received 15 February 2012 Copyright © 2012 John Wiley & Sons, Ltd. Accepted 3 May 2012 simultaneous polysubstance use among mdma users 353 the doses used during SPU. Given that substances can for LSD among 16–44-year olds (Ekholm et al., 2006). interact at many functional levels (pharmacokinetic However, in the dance club environment of European and pharmacodynamic) and that such interactions are metropolises, past month and lifetime prevalence rates affected by relative timing and dosage, this type of of hallucinogens of 8.1–21.6% and 21.1–66.8%, respec- information is important in understanding the biologi- tively, have been found (Tossmann et al., 2001). cal bases and effects of specific SPU patterns. Aims of the study MDMA is a widely used substance of abuse among teenagers and young adults with a past year and life- The aim of the present study was to examine patterns time prevalence of 1.7% and 5.8%, respectively, of lifetime and recent SPU, including drug order, among 15–34-year olds in the EU (EMCDDA, dosing, and adverse effects of MDMA use, among 2010). In Denmark (a member of the EU), the past year Danish MDMA and hallucinogen users. A detailed prevalence in 2010 was 0.8% among 16—34-year and qualitative description of SPU patterns may in olds (Sundhedsstyrelsen, 2010). MDMA exerts its the light of known psychopharmacological effects of main effects on serotonin (5-hydroxytryptamine, 5-HT), combining specific drugs further understanding of dopamine, and norepinephrine transporters, releasing SPU involving MDMA and hallucinogens. monoamines into the extracellular space, and has psychostimulant, empathogenic, and mild hallucinogenic METHODS properties (Capela et al., 2009; Gudelsky and Yamamoto, 2008). When used repeatedly and in high Participants doses, MDMA may have neurotoxic effects on seroto- Young Danish adults between the age of 18 and nergic neurons, although this contention is a subject of 35 years, who reported a lifetime history of at least 15 ongoing debate (Baumann et al., 2007; Capela et al., illicit drug experiences (excluding cannabis) and use 2009; Kish et al., 2010; Thomasius et al., 2003). The of MDMA or hallucinogens (at least once) within the use of MDMA may cause acute hyperthermia, which past 12 months, were included in the study. Participants exacerbates longer term adverse effects on memory were recruited between November 2005 and April 2008 and mood (Parrott, 2006). Polysubstance use is reported through advertisements posted on homepages used by by nearly all MDMA users and includes alcohol, nicotine, Danish hallucinogen and MDMA users and on flyers cannabis, amphetamines, cocaine, and hallucinogens distributed at music events, as well as by word of (Carlson et al., 2005; Parrott et al., 2001; Topp et al., mouth. A total of 284 subjects expressed interest in 1999). In particular, psychostimulant and hallucinogen the study, and 166 met the inclusion criteria. Interviews use has been significantly related to extent of MDMA were completed with 98 (87% male, 13% female) parti- use (Hammersley et al., 1999). Simultaneous use of cipants. It was not possible to schedule the remaining MDMA and other psychoactive substances was prevalent 68 for interview because of practical limitations. Each among participants in the European and Canadian techno subject provided informed consent and received a finan- dance scene and included several kinds of compounds cial compensation of DKK 110/h (EUR 15/h) for the 2- (Barrett et al., 2005; Tossmann et al., 2001). Importantly, hour duration of the interviews. A subset of participants simultaneous use of alcohol and MDMA prolonged was also included in a positron emission tomography feelings of euphoria in a controlled clinical experiment (PET) study (Erritzoe et al., 2011). The Research Ethics (Hernandez-Lopez et al., 2002) and may increase abuse Committee for the Capital Region of Denmark (H-KF-01- liability of MDMA (Jones et al., 2010). 124/04) approved the study. Hallucinogens are a group of perception-altering substances including psilocybin (“magic”) mushrooms, Structured interviews mescaline (peyote cacti), and ayahuasca, as well as A modified Danish version of the Customary Drinking semi-synthetic compounds such as D-lysergic acid and Drug Use Record (CDDR) domain “use frequency diethylamide (LSD), which exert their main effects as and quantity” was used to describe the participants’ agonists at the 5-HT2A receptor (Halpern, 2003; alcohol and substance use in details (Brown et al., Nichols, 2004). The use of hallucinogenic compounds 1998). The CDDR substance use domain collects in the general population is less prevalent than MDMA information on recent (past 3 months) and lifetime with past year and lifetime prevalence of 0.2–5.9% and alcohol and substance use (quantity and frequency of 0.3–14.1% for psilocybin mushrooms, and “very low” 13 specified substance types and any additional drugs and 0–6.1% for LSD among 15–34-year olds in the EU named by the participant), age of initiation, and doses (EMCDDA, 2010). In Denmark, the past year prevalence typically administered. The CDDR substance use in 2005 was 0.4% for psilocybin mushrooms and 0.1% domain had 1-week test–retest reliability coefficients Copyright © 2012 John Wiley & Sons, Ltd. Hum. Psychopharmacol Clin Exp 2012; 27: 352–363. DOI: