, Volume 231, Issue 19, pp 3899–3905 | Cite as

MDMA effects consistent across laboratories

  • Matthew G. Kirkpatrick
  • Matthew J. Baggott
  • John E. Mendelson
  • Gantt P. Galloway
  • Matthias E. Liechti
  • Cédric M. Hysek
  • Harriet de WitEmail author
Original Investigation



Several laboratories have conducted placebo-controlled drug challenge studies with 3,4-methylenedioxymethamphetamine (MDMA), providing a unique source of data to examine the reliability of the acute effects of the drug across subject samples and settings. We examined the subjective and physiological responses to the drug across three different laboratories and investigated the influence of prior MDMA use.


Overall, 220 healthy volunteers with varying levels of previous MDMA experience participated in laboratory-based studies in which they received placebo or MDMA orally (1.5 mg/kg or 125-mg fixed dose) under double-blind conditions. Cardiovascular and subjective effects were assessed before and repeatedly after drug administration. The studies were conducted independently by investigators in Basel, San Francisco, and Chicago.


Despite methodological differences between the studies and differences in the subjects’ drug use histories, MDMA produced very similar cardiovascular and subjective effects across the sites. The participants’ prior use of MDMA was inversely related to feeling “Any Drug Effect” only at sites testing more experienced users.


These data indicate that the pharmacological effects of MDMA are robust and highly reproducible across settings. There was also modest evidence for tolerance to the effects of MDMA in regular users.


MDMA Tolerance Mood Humans 



This research was supported by DA02812 and DA026570 (Chicago: Harriet de Wit PI), DA017716 and DA016776 (SF: John E. Mendelson PI), and SNSF320030_138481 and SNFF32323B_144996 (Basel: Matthias E. Liechti PI).

Conflict of interest

The authors declare no conflicts of interest.


  1. Baggott M, Heifets B, Jones RT, Mendelson J, Sferios E, Zehnder J (2000) Chemical analysis of ecstasy pills. JAMA 284:2190PubMedCrossRefGoogle Scholar
  2. Baumann MH, Clark RD, Rothman RB (2008) Locomotor stimulation produced by 3,4-methylenedioxymethamphetamine (MDMA) is correlated with dialysate levels of serotonin and dopamine in rat brain. Pharmacol Biochem Behav 90:208–217PubMedCrossRefPubMedCentralGoogle Scholar
  3. Bedi G, Hyman D, de Wit H (2010) Is ecstasy an “empathogen”? Effects of ±3,4-methylenedioxymethamphetamine on prosocial feelings and identification of emotional states in others. Biol Psychiatry 68:1134–1140PubMedCrossRefPubMedCentralGoogle Scholar
  4. Carlin AS, Bakker CB, Halpern L, Post RD (1972) Social facilitation of marijuana intoxication: impact of social set and pharmacological activity. J Abnorm Psychol 80:132–140PubMedCrossRefGoogle Scholar
  5. de la Torre R, Farre M, Ortuno J, Mas M, Brenneisen R, Roset PN, Segura J, Cami J (2000) Non-linear pharmacokinetics of MDMA (‘ecstasy’) in humans. Br J Clin Pharmacol 49:104–109PubMedCrossRefPubMedCentralGoogle Scholar
  6. de Wit H, Clark M, Brauer LH (1997) Effects of d-amphetamine in grouped versus isolated humans. Pharmacol Biochem Behav 57:333–340PubMedCrossRefGoogle Scholar
  7. Degenhardt L, Barker B, Topp L (2004) Patterns of ecstasy use in Australia: findings from a national household survey. Addiction 99:187–195PubMedCrossRefGoogle Scholar
  8. Doty P, de Wit H (1995) Effect of setting on the reinforcing and subjective effects of ethanol in social drinkers. Psychopharmacology (Berlin) 118:19–27CrossRefGoogle Scholar
  9. Dumont GJH, Wezenberg E, Valkenberg MMGJ, De Jong CAJ, Buitelaar JK, Van Gerven JMA, Verkes RJ (2008) Acute neuropsychological effects of MDMA and ethanol (co-) administration in healthy volunteers. Psychopharmacol 197:465–474Google Scholar
  10. Dumont GJ, Sweep FC, van der Steen R, Hermsen R, Donders AR, Touw DJ, van Gerven JM, Buitelaar JK, Verkes RJ (2009) Increased oxytocin concentrations and prosocial feelings in humans after ecstasy (3,4-methylenedioxymethamphetamine) administration. Soc Neurosci 4:359–366PubMedCrossRefGoogle Scholar
  11. Fantegrossi WE, Woolverton WL, Kilbourn M, Sherman P, Yuan J, Hatzidimitriou G et al (2004) Behavioral and neurochemical consequences of long-term intravenous self-administration of MDMA and its enantiomers by rhesus monkeys. Neuropsychopharmacology 29:1270–1281PubMedCrossRefGoogle Scholar
  12. Frederick DL, Ali SF, Gillam MP, Gossett J, Slikker W, Paule MG (1998) Acute effects of dexfenfluramine (d-FEN) and methylenedioxymethamphetamine (MDMA) before and after short-course, high-dose treatment. Ann N Y Acad Sci 844:183–190PubMedCrossRefGoogle Scholar
  13. Harris DS, Baggott M, Mendelson JH, Mendelson JE, Jones RT (2002) Subjective and hormonal effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans. Psychopharmacology (Berlin) 162:396–405CrossRefGoogle Scholar
  14. Hart AB, de Wit H, Palmer AA (2013) Candidate gene studies of a promising intermediate phenotype: failure to replicate. Neuropsychopharmacology 38:802–816PubMedCrossRefPubMedCentralGoogle Scholar
  15. Hysek CM, Liechti ME (2012) Effects of MDMA alone and after pretreatment with reboxetine, duloxetine, clonidine, carvedilol, and doxazosin on pupillary light reflex. Psychopharmacology (Berlin) 224:363–376CrossRefGoogle Scholar
  16. Kirkpatrick MG, de Wit H (2013) In the company of others: social factors alter acute alcohol effects. Psychopharmacology (Berlin) 230:215–226CrossRefGoogle Scholar
  17. Kirkpatrick MG, Gunderson EW, Perez AY, Haney M, Foltin RW, Hart CL (2012) A direct comparison of the behavioral and physiological effects of methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) in humans. Psychopharmacology (Berlin) 219:109–122CrossRefGoogle Scholar
  18. Liechti ME, Geyer MA, Hell D, Vollenweider FX (2001) Effects of MDMA (ecstasy) on prepulse inhibition and habituation of startle in humans after pretreatment with citalopram, haloperidol, or ketanserin. Neuropsychopharmacology 24:240–252PubMedCrossRefGoogle Scholar
  19. 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 106:1293–1300PubMedCrossRefGoogle Scholar
  20. 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 (Berlin) 173:234–241CrossRefGoogle Scholar
  21. Parrott AC (2005) Chronic tolerance to recreational MDMA (3,4-methylenedioxymethamphetamine) or ecstasy. J Psychopharmacol 19:71–83PubMedCrossRefGoogle Scholar
  22. Pashler H, Coburn N, Harris CR (2012) Priming of social distance? Failure to replicate effects on social and food judgments. PLoS One 7:e42510PubMedCrossRefPubMedCentralGoogle Scholar
  23. Pliner P, Cappell H (1974) Modification of affective consequences of alcohol: a comparison of social and solitary drinking. J Abnorm Psychol 83:418–425PubMedCrossRefGoogle Scholar
  24. Sherlock K, Wolff K, Hay AW, Conner M (1999) Analysis of illicit ecstasy tablets: implications for clinical management in the accident and emergency department. J Accid Emerg Med 16:194–197PubMedCrossRefPubMedCentralGoogle Scholar
  25. Smith JL, Barry RJ, Steiner GZ (2013) CNV resolution does not cause NoGo anteriorisation of the P3: a failure to replicate Simson et al. Int J Psychophysiol 89:349–357PubMedCrossRefGoogle Scholar
  26. Solowij N, Hall W, Lee N (1992) Recreational MDMA use in Sydney: a profile of ‘ecstacy’ users and their experiences with the drug. Br J Addict 87:1161–1172PubMedCrossRefGoogle Scholar
  27. Spruit IP (2001) Monitoring synthetic drug markets, trends, and public health. Subst Use Misuse 36:23–47PubMedCrossRefGoogle Scholar
  28. Studerus E, Gamma A, Kometer M, Vollenweider FX (2012) Prediction of psilocybin response in healthy volunteers. PLoS One 7:e30800. doi: 10.1371/journal.pone.0030800 PubMedCrossRefPubMedCentralGoogle Scholar
  29. Sumnall HR, Cole JC, Jerome L (2006) The varieties of ecstatic experience: an exploration of the subjective experiences of ecstasy. J Psychopharmacol 20:670–682PubMedCrossRefGoogle Scholar
  30. Tancer M, Johanson CE (2003) Reinforcing, subjective, and physiological effects of MDMA in humans: a comparison with d-amphetamine and mCPP. Drug Alcohol Depend 72:33–44PubMedCrossRefGoogle Scholar
  31. Verheyden SL, Hadfield J, Calin T, Curran VH (2002) Sub-acute effects of MDMA (±3, 4-methylenedioxymethamphetamine, “ecstasy”) on mood: evidence of gender differences. Psychopharmacol 161:23–31Google Scholar
  32. Verheyden SL, Henry JA, Curran HV (2003) Acute, sub-acute and long-term subjective consequences of ‘ecstasy’ (MDMA) consumption in 430 regular users. Hum Psychopharmacol 18:507–517PubMedCrossRefGoogle Scholar
  33. White TL, Justice AJ, de Wit H (2002) Differential subjective effects of d-amphetamine by gender, hormone levels and menstrual cycle phase. Pharmacol Biochem Behav 73(4):729–741PubMedCrossRefGoogle Scholar
  34. Winstock AR, Griffiths P, Stewart D (2001) Drugs and the dance music scene: a survey of current drug use patterns among a sample of dance music enthusiasts in the UK. Drug Alcohol Depend 64:9–17PubMedCrossRefGoogle Scholar
  35. Yong E (2012) Replication studies: bad copy. Nature 485:298–300PubMedCrossRefGoogle Scholar
  36. Zacny JP, Virus RM, Woolverton WL (1990) Tolerance and cross-tolerance to 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine and methylenedioxyamphetamine. Pharmacol Biochem Behav 35:637–642PubMedCrossRefGoogle Scholar
  37. Zacny JP, Bodker BK, de Wit H (1992) Effects of setting on the subjective and behavioral effects of d-amphetamine in humans. Addict Behav 17:27–33PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Matthew G. Kirkpatrick
    • 1
  • Matthew J. Baggott
    • 1
    • 2
  • John E. Mendelson
    • 2
  • Gantt P. Galloway
    • 2
  • Matthias E. Liechti
    • 3
  • Cédric M. Hysek
    • 3
  • Harriet de Wit
    • 1
    Email author
  1. 1.Department of Psychiatry and Behavioral NeuroscienceUniversity of ChicagoChicagoUSA
  2. 2.Addiction & Pharmacology Research LaboratoryCalifornia Pacific Medical CenterSan FranciscoUSA
  3. 3.Division of Clinical Pharmacology and ToxicologyUniversity Hospital and University of BaselBaselSwitzerland

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