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MDMA effects consistent across laboratories

Abstract

Rationale

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.

Methods

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.

Results

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.

Conclusions

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.

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References

  1. Baggott M, Heifets B, Jones RT, Mendelson J, Sferios E, Zehnder J (2000) Chemical analysis of ecstasy pills. JAMA 284:2190

    PubMed  Article  CAS  Google 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 90:208–217

    PubMed  Article  CAS  PubMed Central  Google 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 68:1134–1140

    PubMed  Article  CAS  PubMed Central  Google 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 80:132–140

    PubMed  Article  CAS  Google 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 49:104–109

    PubMed  Article  PubMed Central  Google Scholar 

  6. de Wit H, Clark M, Brauer LH (1997) Effects of d-amphetamine in grouped versus isolated humans. Pharmacol Biochem Behav 57:333–340

    PubMed  Article  Google Scholar 

  7. Degenhardt L, Barker B, Topp L (2004) Patterns of ecstasy use in Australia: findings from a national household survey. Addiction 99:187–195

    PubMed  Article  Google Scholar 

  8. Doty P, de Wit H (1995) Effect of setting on the reinforcing and subjective effects of ethanol in social drinkers. Psychopharmacology (Berlin) 118:19–27

    Article  CAS  Google 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 197:465–474

    Google 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 4:359–366

    PubMed  Article  CAS  Google 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 29:1270–1281

    PubMed  Article  CAS  Google 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 844:183–190

    PubMed  Article  CAS  Google 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) 162:396–405

    Article  CAS  Google Scholar 

  14. Hart AB, de Wit H, Palmer AA (2013) Candidate gene studies of a promising intermediate phenotype: failure to replicate. Neuropsychopharmacology 38:802–816

    PubMed  Article  CAS  PubMed Central  Google 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) 224:363–376

    Article  CAS  Google Scholar 

  16. Kirkpatrick MG, de Wit H (2013) In the company of others: social factors alter acute alcohol effects. Psychopharmacology (Berlin) 230:215–226

    Article  CAS  Google 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) 219:109–122

    Article  CAS  Google 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 24:240–252

    PubMed  Article  CAS  Google 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 106:1293–1300

    PubMed  Article  Google 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) 173:234–241

    Article  CAS  Google Scholar 

  21. Parrott AC (2005) Chronic tolerance to recreational MDMA (3,4-methylenedioxymethamphetamine) or ecstasy. J Psychopharmacol 19:71–83

    PubMed  Article  CAS  Google 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:e42510

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  23. Pliner P, Cappell H (1974) Modification of affective consequences of alcohol: a comparison of social and solitary drinking. J Abnorm Psychol 83:418–425

    PubMed  Article  CAS  Google 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 16:194–197

    PubMed  Article  CAS  PubMed Central  Google 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 89:349–357

    PubMed  Article  Google 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 87:1161–1172

    PubMed  Article  CAS  Google Scholar 

  27. Spruit IP (2001) Monitoring synthetic drug markets, trends, and public health. Subst Use Misuse 36:23–47

    PubMed  Article  CAS  Google 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

    PubMed  Article  CAS  PubMed Central  Google Scholar 

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

    PubMed  Article  Google 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 72:33–44

    PubMed  Article  CAS  Google 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 161:23–31

    Google 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 18:507–517

    PubMed  Article  CAS  Google 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):729–741

    PubMed  Article  CAS  Google 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 64:9–17

    PubMed  Article  CAS  Google Scholar 

  35. Yong E (2012) Replication studies: bad copy. Nature 485:298–300

    PubMed  Article  Google Scholar 

  36. Zacny JP, Virus RM, Woolverton WL (1990) Tolerance and cross-tolerance to 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine and methylenedioxyamphetamine. Pharmacol Biochem Behav 35:637–642

    PubMed  Article  CAS  Google 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 17:27–33

    PubMed  Article  CAS  Google Scholar 

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Acknowledgments

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.

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Correspondence to Harriet de Wit.

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Kirkpatrick, M.G., Baggott, M.J., Mendelson, J.E. et al. MDMA effects consistent across laboratories. Psychopharmacology 231, 3899–3905 (2014). https://doi.org/10.1007/s00213-014-3528-z

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Keywords

  • MDMA
  • Tolerance
  • Mood
  • Humans