Skip to main content
SpringerLink
Log in

Linking the pharmacological content of ecstasy tablets to the subjective experiences of drug users

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Most studies on the subjective effects of ecstasy are based on the assumption that the substance that was taken is 3,4-methylenedioxymethamphetamine (MDMA). However, many tablets sold as ecstasy contain other substances and MDMA in varying doses. So far, few attempts have been made to take this into account while assessing subjective effects.

Objectives

This study aims to link the pharmacological content of tablets sold as ecstasy to the subjective experiences reported by ecstasy users.

Methods

Self-reported effects on ecstasy tablets were available from 5,786 drug users who handed in their tablets for chemical analysis at the Drug Information and Monitoring System (DIMS) in the Netherlands. Logistic regression was employed to link the pharmacological content of ecstasy tablets to the self-reported subjective effects and compare effects with MDMA to other substances present.

Results

MDMA showed a strong association with desirable subjective effects, unparalleled by any other psychoactive substance. However, the association of MDMA was dose-dependent, with higher doses (>120 mg/tablet) likely to evoke more adverse effects. The novel psychostimulants mephedrone and p-fluoroamphetamine were considered relatively desirable, whereas meta-chlorophenylpiperazine (mCPP) and p-methoxymethamphetamine (PMMA) were strongly associated with adverse subjective effects. Also, 3,4-methylene-dioxyamphetamine (MDA) and benzylpiperazine (BZP) were not appreciated as replacement for MDMA.

Conclusion

Linking the pharmacological content of ecstasy sold on the street to subjective experiences contributes to a better understanding of the wide range of subjective effects ascribed to ecstasy and provides a strong rationale for the prolonged endurance of MDMA as the key ingredient of the ecstasy market.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Aerts LA, Mallaret M, Rigter H (2000) N-Methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (MBDB): its properties and possible risks. Addict Biol 5:269–282

    Article  PubMed  CAS  Google Scholar 

  • Antia U, Lee HS, Kydd RR, Tingle MD, Russell BR (2009) Pharmacokinetics of ‘party pill’ drug N-benzylpiperazine (BZP) in healthy human participants. Forensic Sci Int 186:63–67

    Article  PubMed  CAS  Google Scholar 

  • Baylen CA, Rosenberg H (2006) A review of the acute subjective effects of MDMA/ecstasy. Addiction 101:933–947

    Google Scholar 

  • Becker J, Neis P, Röhrich J, Zörntlein S (2003) A fatal paramethoxymethamphetamine intoxication. Leg Med (Tokyo) 5:S138–S141

    Article  Google Scholar 

  • Bossong MG, Van Dijk JP, Niesink RJ (2005) Methylone and mCPP, two new drugs of abuse? Addict Biol 10:321–323

    Article  PubMed  CAS  Google Scholar 

  • Bossong M, Brunt TM, Van Dijk JP, Rigter S, Hoek J, Goldschmidt H, Niesink RJ (2010) mCPP: an undesired addition to the ecstasy market. J Psychopharmacol 24:1395–1401

    Article  PubMed  CAS  Google Scholar 

  • Boyer EW, Quang L, Woolf A, Shannon M, Magnani B (2001) Dextromethorphan and ecstasy pills. JAMA 285:409–410

    Article  PubMed  CAS  Google Scholar 

  • Brunt TM, Poortman A, Niesink RJ, van den Brink W (2010) Instability of the ecstasy market and a new kid on the block: mephedrone. J Psychopharmacol. doi:10.1177/0269881110378370

  • Butler RA, Sheridan JL (2007) Highs and lows: patterns of use, positive and negative effects of benzylpiperazine-containing party pills (BZP-party pills) amongst young people in New Zealand. Harm Reduct J 4:18

    Article  PubMed  Google Scholar 

  • Bytzer P, Hallas J (2000) Drug-induced symptoms of functional dyspepsia and nausea. A symmetry analysis of one million prescriptions. Aliment Pharmacol Ther 14:1479–1484

    Article  PubMed  CAS  Google Scholar 

  • Caldicott DG, Edwards NA, Kruys A, Kirkbride KP, Sims DN, Byard RW, Prior M, Irvine RJ (2003) Dancing with “death”: p-methoxyamphetamine overdose and its acute management. J Toxicol Clin Toxicol 41:143–154

    Article  PubMed  CAS  Google Scholar 

  • Callaghan PD, Irvine RJ, Daws LC (2005) Differences in the in vivo dynamics of neurotransmitter release and serotonin uptake after acute para-methoxyamphetamine and 3,4-methylenedioxymethamphetamine revealed by chronoamperometry. Neurochem Int 47:350–361

    Article  PubMed  CAS  Google Scholar 

  • Camilleri AM, Caldicott D (2005) Underground pill testing, down under. Forensic Sci Int 151:53–58

    Article  PubMed  Google Scholar 

  • Carhart-Harris RL, King LA, Nutt DJ (2011) A web-based survey on mephedrone. Drug Alcohol Depend. doi:10.1016/j.drugalcdep.2011.02.011

  • Cohen BM, Butler R (2010) BZP-party pills: a review of research on benzylpiperazine as a recreational drug. Int J Drug Policy 22:95–101

    Article  Google Scholar 

  • Cole JC, Bailey M, Sumnall HR, Wagstaff GF, King LA (2002) The content of ecstasy tablets: implications for the study of their long-term effects. Addiction 97:1531–1536

    Article  PubMed  Google Scholar 

  • Cunningham RS (1997) 5-HT3-receptor antagonists: a review of pharmacology and clinical efficacy. Oncol Nurs Forum 24:33–40

    PubMed  CAS  Google Scholar 

  • de Boer D, Bosman IJ, Hidvégi E, Manzoni C, Benkö AA, dos Reys LJ, Maes RA (2001) Piperazine-like compounds: a new group of designer drugs-of-abuse on the European market. Forensic Sci Int 121:47–56

    Article  PubMed  Google Scholar 

  • Dumont GJ, Verkes RJ (2006) A review of acute effects of 3,4-methylenedioxymethamphetamine in healthy volunteers. J Psychopharmacol 20:176–187

    Article  PubMed  CAS  Google Scholar 

  • EMCDDA (2003–2011) European information system and database on new drugs, EWS final reports 2003–2011, http://ednd.emcdda.europa.eu/

  • EMCDDA (2010) European Monitoring Centre for Drugs and Drug Addiction, Annual Report 2010, http://www.emcdda.europa.eu/attachements.cfm/att_120104_EN_EMCDDA_AR2010_EN.pdf

  • Erowid (2006) Erowid 4-Fluoroamphetamine (para-Fluoroamphetamine) Vault, http://www.erowid.org/chemicals/4_fluoroamphetamine/

  • Erowid (2010) Erowid Experience Vaults: 4-Methylmethcathinone Reports, http://www.erowid.org/experiences/subs/exp_4Methylmethcathinone.shtml

  • Europol-EMCDDA (2010) Annual Report on the implementation of Council Decision 2005/387/JHA,http://www.emcdda.europa.eu/attachements.cfm/att_132857_EN_EMCDDA-Europol%20Annual%20Report%202010A.pdf

  • Feuchtl A, Bagli M, Stephan R, Frahnert C, Kölsch H, Kühn KU, Rao ML (2004) Pharmacokinetics of m-chlorophenylpiperazine after intravenous and oral administration in healthy male volunteers: implication for the pharmacodynamic profile. Pharmacopsychiatry 37:180–188

    Article  PubMed  CAS  Google Scholar 

  • Gijsman HJ, Cohen AF, van Gerven JM (2004) The application of the principles of clinical drug development to pharmacological challenge tests of the serotonergic system. J Psychopharmacol 18:7–13

    Article  PubMed  CAS  Google Scholar 

  • Giraudon I, Bello PY (2007) Monitoring ecstasy content in France: results from the National Surveillance System 1999–2004. Subst Use Misuse 42:1567–1578

    Article  PubMed  Google Scholar 

  • Glennon RA, Ismaiel AE, McCarthy BG, Peroutka SJ (1989) Binding of arylpiperazines to 5-HT3 serotonin receptors: results of a structure-affinity study. Eur J Pharmacol 168:387–392

    Article  PubMed  CAS  Google Scholar 

  • Gouzoulis-Mayfrank E, Thelen B, Habermeyer E, Kunert HJ, Kovar KA, Lindenblatt H, Hermle L, Spitzer M, Sass H (1999) Psychopathological, neuroendocrine and autonomic effects of 3,4-methylenedioxyethylamphetamine (MDE), psilocybin and d-methamphetamine in healthy volunteers. Results of an experimental double-blind placebo-controlled study. Psychopharmacology Berl 142:41–50

    Article  PubMed  CAS  Google Scholar 

  • Hegadoren KM, Baker GB, Bourin M (1999) 3,4-Methylenedioxy analogues of amphetamine: defining the risks to humans. Neurosci Biobehav Rev 23:539–553

    Article  PubMed  CAS  Google Scholar 

  • Hermle L, Spitzer M, Borchardt D, Kovar KA, Gouzoulis E (1993) Psychological effects of MDE in normal subjects. Are entactogens a new class of psychoactive agents? Neuropsychopharmacology 8:171–176

    PubMed  CAS  Google Scholar 

  • Higgins GA, Kilpatrick GJ (1999) 5-HT(3) receptor antagonists. Expert Opin Investig Drugs 8:2183–2188

    Article  PubMed  CAS  Google Scholar 

  • Hiyama T, Yoshihara M, Tanaka S, Haruma K, Chayama K (2009) Effectiveness of prokinetic agents against diseases external to the gastrointestinal tract. J Gastroenterol Hepatol 24:537–546

    Article  PubMed  CAS  Google Scholar 

  • Hosmer DW, Lemeshow S (2000) Applied logistic regression, 2nd edn. Wiley, University of Massachusetts, Massachusetts

    Book  Google Scholar 

  • Huxster JK, Pirona A, Morgan MJ (2006) The sub-acute effects of recreational ecstasy (MDMA) use: a controlled study in humans. J Psychopharmacol 20:281–290

    Article  PubMed  Google Scholar 

  • Jan RK, Lin JC, Lee H, Sheridan JL, Kydd RR, Kirk IJ, Russell BR (2010) Determining the subjective effects of TFMPP in human males. Psychopharmacology Berl 211:347–353

    Article  PubMed  CAS  Google Scholar 

  • Johnstone AC, Lea RA, Brennan KA, Schenk S, Kennedy MA, Fitzmaurice PS (2007) Benzylpiperazine: a drug of abuse? J Psychopharmacol 21:888–894

    Article  PubMed  CAS  Google Scholar 

  • Johansen SS, Hansen AC, Müller IB, Lundemose JB, Franzmann MB (2003) Three fatal cases of PMA and PMMA poisoning in Denmark. J Anal Toxicol 27:253–256

    PubMed  CAS  Google Scholar 

  • Kalasinsky KS, Hugel J, Kish SJ (2004) Use of MDA (the “love drug”) and methamphetamine in Toronto by unsuspecting users of ecstasy (MDMA). J Forensic Sci 49:1106–1112

    Article  PubMed  Google Scholar 

  • Kenyon SL, Ramsey JD, Lee T, Johnston A, Holt DW (2005) Analysis for identification in amnesty bin samples from dance venues. Ther Drug Monit 27:793–798

    Article  PubMed  Google Scholar 

  • Kolbrich EA, Goodwin RS, Gorelick DA, Hayes RJ, Stein EA, Huestis MA (2008) Physiological and subjective responses to controlled oral 3,4-methylenedioxymethamphetamine administration. J Clin Psychopharmacol 28:432–440

    Article  PubMed  CAS  Google Scholar 

  • Liechti ME, Gamma A, Vollenweider FX (2001) Gender differences in the subjective effects of MDMA. Psychopharmacology Berl 154:161–168

    Article  PubMed  CAS  Google Scholar 

  • Lin DL, Liu HC, Yin HL (2007) Recent paramethoxymethamphetamine (PMMA) deaths in Taiwan. J Anal Toxicol 31:109–113

    PubMed  CAS  Google Scholar 

  • Lin JC, Bangs N, Lee H, Kydd RR, Russell BR (2009) Determining the subjective and physiological effects of BZP on human females. Psychopharmacology Berl 207:439–446

    Article  PubMed  CAS  Google Scholar 

  • Lin JC, Jan RK, Lee H, Jensen MA, Kydd RR, Russell BR (2011) Determining the subjective and physiological effects of BZP combined with TFMPP in human males. Psychopharmacology Berl 214:761–768

    Article  PubMed  CAS  Google Scholar 

  • Lora-Tamayo C, Tena T, Rodríguez A, Moreno D, Sancho JR, Enseñat P, Muela F (2004) The designer drug situation in Ibiza. Forensic Sci Int 140:195–206

    Article  PubMed  CAS  Google Scholar 

  • Marona-Lewicka D, Rhee GS, Sprague JE, Nichols DE (1995) Psychostimulant-like effects of p-fluoroamphetamine in the rat. Eur J Pharmacol 287:105–113

    Article  PubMed  CAS  Google Scholar 

  • Matok I, Gorodischer R, Koren G, Sheiner E, Wiznitzer A, Levy A (2009) The safety of metoclopramide use in the first trimester of pregnancy. N Engl J Med 360:2528–2535

    Article  PubMed  CAS  Google Scholar 

  • Maurer HH, Kraemer T, Springer D, Staack RF (2004) Chemistry, pharmacology, toxicology, and hepatic metabolism of designer drugs of the amphetamine (ecstasy), piperazine, and pyrrolidinophenone types: a synopsis. Ther Drug Monit 26:127–131

    Article  PubMed  CAS  Google Scholar 

  • McElrath K, O’Neill C (2011) Experiences with mephedrone pre- and post-legislative controls: perceptions of safety and sources of supply. Int J Drug Policy 22:120–127

    Article  PubMed  Google Scholar 

  • Morefield KM, Keane M, Felgate P, White JM, Irvine RJ (2011) Pill content, dose and resulting plasma concentrations of 3,4-methylendioxymethamphetamine (MDMA) in recreational ‘ecstasy’ users. Addiction 106:1293–1300

    Article  PubMed  Google Scholar 

  • Murphy PN, Wareing M, Fisk J (2006) Users’ perceptions of the risks and effects of taking ecstasy (MDMA): a questionnaire study. J Psychopharmacol 20:447–455

    Article  PubMed  Google Scholar 

  • Nagai F, Nonaka R, Satoh Hisashi Kamimura K (2007) The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain. Eur J Pharmacol 559:132–137

    Article  PubMed  CAS  Google Scholar 

  • Páleníček T, Balíková M, Rohanová M, Novák T, Horáček J, Fujáková M, Höschl C (2011) Behavioral, hyperthermic and pharmacokinetic profile of para-methoxymethamphetamine (PMMA) in rats. Pharmacol Biochem Behav 98:130–139

    Article  PubMed  Google Scholar 

  • Parrott AC, Buchanan T, Scholey AB, Heffernan T, Ling J, Rodgers J (2002) Ecstasy/MDMA attributed problems reported by novice, moderate and heavy recreational users. Hum Psychopharmacol 17:309–312

    Article  PubMed  CAS  Google Scholar 

  • Parrott AC (2004) Is ecstasy MDMA? A review of the proportion of ecstasy tablets containing MDMA, their dosage levels, and the changing perceptions of purity. Psychopharmacology Berl 173:234–241

    Article  PubMed  CAS  Google Scholar 

  • Parrott AC (2006) MDMA in humans: factors which affect the neuropsychobiological profiles of recreational ecstasy users, the integrative role of bioenergetic stress. J Psychopharmacol 20:147–163

    Article  PubMed  CAS  Google Scholar 

  • Parrott AC, Rodgers J, Buchanan T, Ling J, Heffernan T, Scholey AB (2006) Dancing hot on Ecstasy: physical activity and thermal comfort ratings are associated with the memory and other psychobiological problems reported by recreational MDMA users. Hum Psychopharmacol 21:285–298

    Article  PubMed  CAS  Google Scholar 

  • Peroutka SJ, Newman H, Harris H (1988) Subjective effects of 3,4-methylenedioxymethamphetamine in recreational users. Neuropsychopharmacology 1:273–277

    PubMed  CAS  Google Scholar 

  • Rohanova M, Balikova M (2009) Studies on distribution and metabolism of para-methoxymethamphetamine (PMMA) in rats after subcutaneous administration. Toxicology 259:61–68

    Article  PubMed  CAS  Google Scholar 

  • Schifano F, Corkery J, Deluca P, Oyefeso A, Ghodse AH (2006) Ecstasy (MDMA, MDA, MDEA, MBDB) consumption, seizures, related offences, prices, dosage levels and deaths in the UK (1994–2003). J Psychopharmacol 20:456–463

    Article  PubMed  Google Scholar 

  • Schifano F, Albanese A, Fergus S, Stair JL, Deluca P, Corazza O, Davey Z, Corkery J, Siemann H, Scherbaum N, Farré M, Torrens M, Demetrovics Z, Ghodse AH, Psychonaut Web Mapping; ReDNet Research Groups (2011) Mephedrone (4-methylmethcathinone; ‘meow meow’): chemical, pharmacological and clinical issues. Psychopharmacology Berl 214:593–602

    Article  PubMed  CAS  Google Scholar 

  • Simonsen KW, Kaa E, Nielsen E, Rollmann D (2003) Narcotics at street level in Denmark. A prospective investigation from 1995 to 2000. Forensic Sci Int 131:162–170

    Article  PubMed  CAS  Google Scholar 

  • Staack RF (2007) Piperazine designer drugs of abuse. Lancet 369:1411–1413

    Article  PubMed  Google Scholar 

  • Staack RF, Maurer HH (2003) Piperazine-derived designer drug 1-(3-chlorophenyl)piperazine (mCPP): GC-MS studies on its metabolism and its toxicological detection in rat urine including analytical differentiation from its precursor drugs trazodone and nefazodone. J Anal Toxicol 27:560–568

    PubMed  CAS  Google Scholar 

  • Sumnall HR, Cole JC, Jerome L (2006) The varieties of ecstatic experience: an exploration of the subjective experiences of ecstasy. J Psychopharmacol 20:670–682

    Article  PubMed  Google Scholar 

  • Tancer ME, Johanson CE (2001) The subjective effects of MDMA and mCPP in moderate MDMA users. Drug Alcohol Depend 65:97–101

    Article  PubMed  CAS  Google Scholar 

  • Tancer M, Johanson CE (2003) Reinforcing, subjective, and physiological effects of MDMA in humans: a comparison with d-amphetamine and mCPP. Drug Alcohol Depend 72:33–44

    Article  PubMed  CAS  Google Scholar 

  • Tanner-Smith EE (2006) Pharmacological content of tablets sold as “ecstasy”: results from an online testing service. Drug Alcohol Depend 83:247–254

    Article  PubMed  CAS  Google Scholar 

  • Thomasius R, Petersen K, Buchert R, Andresen B, Zapletalova P, Wartberg L, Nebeling B, Schmoldt A (2003) Mood, cognition and serotonin transporter availability in current and former ecstasy (MDMA) users. Psychopharmacology Berl 167:85–96

    PubMed  CAS  Google Scholar 

  • Thompson I, Williams G, Caldwell B, Aldington S, Dickson S, Lucas N, McDowall J, Weatherall M, Robinson G, Beasley R (2010) Randomised double-blind, placebo-controlled trial of the effects of the ‘party pills’ BZP/TFMPP alone and in combination with alcohol. J Psychopharmacol 24:1299–1308

    Article  PubMed  CAS  Google Scholar 

  • UNODC (2010) United Nations Office on Drugs and Crime, World Drug Report 2010, http://www.unodc.org/documents/wdr/WDR_2010/World_Drug_Report_2010_lo-res.pdf

  • Verheyden SL, Hadfield J, Calin T, Curran HV (2002) Sub-acute effects of MDMA (+/−3,4-methylenedioxymethamphetamine, “ecstasy”) on mood: evidence of gender differences. Psychopharmacology Berl 161:23–31

    Article  PubMed  CAS  Google Scholar 

  • Vogels N, Brunt TM, Rigter S, van Dijk P, Vervaeke H, Niesink RJ (2009) Content of ecstasy in the Netherlands: 1993–2008. Addiction 104:2057–2066

    Article  PubMed  Google Scholar 

  • Wee S, Anderson KG, Baumann MH, Rothman RB, Blough BE, Woolverton WL (2005) Relationship between the serotonergic activity and reinforcing effects of a series of amphetamine analogs. J Pharmacol Exp Ther 313:848–854

    Article  PubMed  CAS  Google Scholar 

  • Winstock AR, Mitcheson LR, Deluca P, Davey Z, Corazza O, Schifano F (2011) Mephedrone, new kid for the chop? Addiction 106:154–161

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This research was financially supported by the Dutch Ministry of Health, Welfare and Sports. The authors would like to acknowledge Dr. Cristina Mayo for her statistical advice, and Sander Rigter, Mariëtte Pouw and Peter van Dijk for their assistance with data collection. The authors would also like to thank all participants of the DIMS network.

Conflict of interest

The authors have no conflict of interest to declare.

Author information

Authors and Affiliations

  1. Drug Information and Monitoring System, Netherlands Institute of Mental Health and Addiction, Utrecht, The Netherlands

    Tibor M. Brunt & Raymond J. M. Niesink

  2. Amsterdam Institute for Addiction Research, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands

    Maarten W. Koeter & Wim van den Brink

  3. Trimbos Institute, Netherlands Institute of Mental Health and Addiction, PO Box 725, 3500, VJ, Utrecht, The Netherlands

    Tibor M. Brunt

Authors
  1. Tibor M. Brunt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maarten W. Koeter
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Raymond J. M. Niesink
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wim van den Brink
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tibor M. Brunt.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brunt, T.M., Koeter, M.W., Niesink, R.J.M. et al. Linking the pharmacological content of ecstasy tablets to the subjective experiences of drug users. Psychopharmacology 220, 751–762 (2012). https://doi.org/10.1007/s00213-011-2529-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-011-2529-4

Keywords

Search

Navigation