Our findings suggest that the serotonin brain imaging literature has focused on unusually heavy ecstasy use and therefore the conclusions from these studies are likely to overestimate the extent of serotonergic alterations experienced by the majority of people who use ecstays.

Both the average Usual Amount (pills/session) and Use Frequency (sessions/month) of neuroimaging study participants corresponded to the top 5–10% of the Global Drug Survey sample and imaging participants, on average, consumed 720% more pills over a year than the Global Drug Survey participants.

A systematic literature search revealed 10 imaging studies that compare serotonin transporter levels in recreational ecstasy users to matched controls. To characterize the ecstasy use patterns we relied on the Global Drug Survey, the world’s largest self-report database on drug use. The basis of the dose comparison were the Usual Amount (pills/session), Use Frequency (sessions/month) and Dose Intensity (pills/year) variables.

We examined the representativeness of ecstasy users enrolled in neuroimaging studies by comparing their ecstasy use habits with the use patterns of a large, international sample.

Neuroimaging studies imply that the regular use of ±3,4-methylenedioxymethamphetamine (MDMA), the major constituent of ecstasy pills, alters the brain’s serotonergic system in a dose-dependent manner. However, the relevance of these findings remains unclear due to limited knowledge about the ecstasy/MDMA use pattern of real-life users.

References

Barratt, MJ, Ferris, JA, Winstock, AR ( 2014 ) Use of silk road, the online drug marketplace, in the United Kingdom, Australia and the United States . Addiction 109: 774 – 783 .

Google Scholar Medline | ISI

Baumann, MH, Wang, X, Rothman, RB ( 2007 ) 3,4-methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: A reappraisal of past and present findings . Psychopharmacology 189: 407 – 424 .

Google Scholar

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 .

Google Scholar Medline | ISI

Bellis, MA, Quigg, Z, Hughes, K. ( 2015 ) Harms from other people’s drinking: An international survey of their occurrence, impacts on feeling safe and legislation relating to their control . BMJ Open 5: e010112 .

Google Scholar Medline

Brunt, TM, Niesink, RJ ( 2011 ) The drug information and monitoring system (DIMS) in the Netherlands: Implementation, results, and international comparison . Drug Test Anal 3: 621 – 634 .

Google Scholar

Brunt, TM, Nagy, C, Bücheli, A. ( 2016 ) Drug testing in Europe: Monitoring results of the Trans European Drug Information (TEDI) project . Drug Test Anal 9: 188 – 198 .

Google Scholar Medline

Buchert, R, Thomasius, R, Nebeling, B. ( 2003 ) Long-term effects of ecstasy use on serotonin transporters of the brain investigated by PET . J Nucl Med 44: 375 – 384 .

Google Scholar Medline | ISI

Buchert, R, Thomasius, R, Wilke, F. ( 2004 ) A voxel-based PET investigation of the long-term effects of “Ecstasy” consumption on brain serotonin transporters . Am J Psychiatry 161: 1181 – 1189 .

Google Scholar Medline | ISI

Colado, MI, O’Shea, E, Green, AR ( 2004 ) Acute and long-term effects of MDMA on cerebral dopamine biochemistry and function . Psychopharmacology 173: 249 – 263 .

Google Scholar Medline | ISI

Cowan, RL ( 2007 ) Neuroimaging research in human MDMA users: A review . Psychopharmacology 189: 539 – 556 .

Google Scholar Medline

de Win, MM, Jager, G, Booij, J. ( 2008 ) Sustained effects of ecstasy on the human brain: A prospective neuroimaging study in novel users . Brain 131(11): 2936 – 2945 .

Google Scholar Medline

Erritzoe, D, Frokjaer, VG, Holst, KK. ( 2011 ) In vivo imaging of cerebral serotonin transporter and serotonin 2a receptor binding in 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) and hallucinogen users . Arch Gen Psychiatry 68: 562 – 576 .

Google Scholar Medline

European Monitoring Centre for Drugs and Drug Addiction ( 2016 ) Recent changes in Europe’s MDMA/ecstasy market. European Monitoring Centre for Drugs and Drug Addiction Rapid Communication. Luxembourg : Publications Office of the European Union .

Google Scholar

Frokjaer, VG, Erritzoe, D, Holst, KK. ( 2014 ) In abstinent MDMA users the cortisol awakening response is off-set but associated with prefrontal serotonin transporter binding as in non-users . Int J Neuropsychopharmacol 17: 1119 – 1128 .

Google Scholar Medline

Gine, CV, Vilamala, MV, Espinosa, IF. ( 2016 ) Crystals and tablets in the Spanish ecstasy market 2000–2014: Are they the same or different in terms of purity and adulteration? Forensic Sci Int 263: 164 – 168 .

Google Scholar Medline

Gouwe, D, Brunt, TM, Laar, M. ( 2017 ) Purity, adulteration and price of drugs bought on-line versus off-line in the Netherlands . Addiction 112: 640 – 648 .

Google Scholar Medline

Green, AR, Sanchez, V, O’Shea, E. ( 2004 ) Effect of ambient temperature and a prior neurotoxic dose of 3,4-methylenedioxymethamphetamine (MDMA) on the hyperthermic response of rats to a single or repeated (binge ingestion) low dose of MDMA . Psychopharmacology 173: 264 – 269 .

Google Scholar Medline

Harrison, LD ( 1995 ) The validity of self-reported data on drug use . J Drug Issues 25: 91 – 111 .

Google Scholar SAGE Journals | ISI

Hysek, CM, Schmid, Y, Simmler, LD. ( 2013 ) MDMA enhances emotional empathy and prosocial behavior . Soc Cogn Affect Neurosci 9: 1645 – 1652 .

Google Scholar Medline

Kirkpatrick, MG, Baggott, MJ, Mendelson, JE. ( 2014 b) MDMA effects consistent across laboratories . Psychopharmacology 231: 3899 – 3905 .

Google Scholar Medline | ISI

Kirkpatrick, MG, Gunderson, EW, Perez, AY. ( 2012 ) A direct comparison of the behavioral and physiological effects of methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) in humans . Psychopharmacology 219: 109 – 122 .

Google Scholar Medline | ISI

Kirkpatrick, MG, Lee, R, Wardle, MC. ( 2014 a) Effects of MDMA and intranasal oxytocin on social and emotional processing . Neuropsychopharmacology 39: 1654 – 1663 .

Google Scholar Medline | ISI

Kish, SJ, Lerch, J, Furukawa, Y. ( 2010 ) Decreased cerebral cortical serotonin transporter binding in ecstasy users: A positron emission tomography/[11C]DASB and structural brain imaging study . Brain 133: 1779 – 1797 .

Google Scholar Medline | ISI

Klomp, A, den Hollander, B, de Bruin, K. ( 2012 ) The effects of ecstasy (MDMA) on brain serotonin transporters are dependent on age-of-first exposure in recreational users and animals . PLoS One 7: e47524 .

Google Scholar Medline

McCann, U, Szabo, Z, Scheffel, U. ( 1998 ) Positron emission tomographic evidence of toxic effect of MDMA (ecstasy) on brain serotonin neurons in human beings . Lancet 352: 1433 – 1437 .

Google Scholar Medline | ISI

McCann, UD, Szabo, Z, Seckin, E. ( 2005 ) Quantitative pet studies of the serotonin transporter in MDMA users and controls using [11C]McN5652 and [11C]DASB . Neuropsychopharmacology 30: 1741 – 1750 .

Google Scholar Medline | ISI

McCann, UD, Szabo, Z, Vranesic, M. ( 2008 ) Positron emission tomographic studies of brain dopamine and serotonin transporters in abstinent (±) 3,4-methylenedioxymethamphetamine (ecstasy) users: Relationship to cognitive performance . Psychopharmacology 200: 439 – 450 .

Google Scholar

Mithoefer, MC, Wagner, MT, Mithoefer, AT. ( 2011 ) The safety and efficacy of ±3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: The first randomized controlled pilot study . J Psychopharmacol 25: 439 – 452 .

Google Scholar SAGE Journals | ISI

Mithoefer, MC, Wagner, MT, Mithoefer, AT. ( 2013 ) Durability of improvement in post-traumatic stress disorder symptoms and absence of harmful effects or drug dependency after ±3,4-methylenedioxymethamphetamine-assisted psychotherapy: A prospective long-term follow-up study . J Psychopharmacol 27: 28 – 39 .

Google Scholar SAGE Journals | ISI

Oehen, P, Traber, R, Widmer, V. ( 2013 ) A randomized, controlled pilot study of MDMA (±3,4-methylenedioxymethamphetamine) assisted psychotherapy for treatment of resistant, chronic post-traumatic stress disorder (PTSD) . J Psychopharmacol 27: 40 – 52 .

Google Scholar SAGE Journals | ISI

Parrott, AC, Lasky, J ( 1998 ) Ecstasy (MDMA) effects upon mood and cognition: before, during and after a Saturday night dance . Psychopharmacology 139: 261 – 268 .

Google Scholar Medline | ISI

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

Google Scholar SAGE Journals | ISI

Parrott, AC ( 2010 ) Conscious awareness versus optimistic beliefs in recreational Ecstasy/MDMA users . In: Perry, E, Collerton, D, LeBeau, F. (eds) New Horizons in the Neuroscience of Consciousness. Amsterdam : John Benjamins Publishers , pp. 148 – 158 .

Google Scholar

Parrott, AC ( 2013 ) MDMA, serotonergic neurotoxicity, and the diverse functional deficits of recreational ‘Ecstasy’ users . Neurosci Biobehav Rev 37: 1466 – 1484 .

Google Scholar Medline | ISI

Parrott, AC ( 2014 ) The potential dangers of using MDMA for psychotherapy . J Psychoactive Drugs 46: 37 – 43 .

Google Scholar Medline | ISI

Parrott, AC, Lock, J, Conner, AC. ( 2008 ) Dance clubbing on MDMA and during abstinence from Ecstasy/MDMA: Prospective neuroendocrine and psychobiological changes . Neuropsychobiology 57: 165 – 180 .

Google Scholar Medline | ISI

Quelch, D, Parker, C, Nutt, D. ( 2012 ) Influence of different cellular environments on [3H]DASB radioligand binding . Synapse 66: 1035 – 1039 .

Google Scholar Medline | ISI

Reneman, L, Booij, J, de Bruin, K. ( 2001 a) Effects of dose, sex, and long-term abstention from use on toxic effects of MDMA (ecstasy) on brain serotonin neurons . Lancet 358: 1864 – 1869 .

Google Scholar Medline | ISI

Reneman, L, de Win, MM, van den Brink, W. ( 2006 ) Neuroimaging findings with MDMA/ecstasy: Technical aspects, conceptual issues and future prospects . J Psychopharmacol 20: 164 – 175 .

Google Scholar SAGE Journals | ISI

Reneman, L, Lavalaye, J, Schmand, B. ( 2001 b) Cortical serotonin transporter density and verbal memory in individuals who stopped using ±3,4-methylenedioxymethamphetamine (MDMA or ecstasy): Preliminary findings . Arch Gen Psychiatry 58: 901 – 906 .

Google Scholar Medline

Roberts, CA, Jones, A, Montgomery, C ( 2016 ) Meta-analysis of molecular imaging of serotonin transporters in ecstasy/polydrug users . Neurosci Biobehav Rev 63: 158 – 167 .

Google Scholar Medline

Schmidt, CJ, Taylor, VL ( 1987 ) Depression of rat brain tryptophan hydroxylase activity following the acute administration of methylenedioxymethamphetamine . Biochem Pharmacol 36: 4095 – 4102 .

Google Scholar Medline | ISI

Schmidt, CJ, Wu, L, Lovenberg, W ( 1986 ) Methylenedioxymethamphetamine: A potentially neurotoxic amphetamine analogue . Eur J Pharmacol 124: 175 – 178 .

Google Scholar Medline | ISI

Schouw, M, Gevers, S, Caan, M. ( 2012 ) Mapping serotonergic dysfunction in MDMA(ecstasy) users using pharmacological MRI . Eur Neuropsychopharmacol 22: 537 – 545 .

Google Scholar Medline

Selvaraj, S, Hoshi, R, Bhagwagar, Z. ( 2009 ) Brain serotonin transporter binding in former users of MDMA (ecstasy) . Br J Psychiatry 194: 355 – 359 .

Google Scholar Medline | ISI

Semple, DM, Ebmeier, KP, Glabus, MF. ( 1999 ) Reduced in vivo binding to the serotonin transporter in the cerebral cortex of MDMA (’ecstasy’) users . Br J Psychiatry 175: 63 – 69 .

Google Scholar Medline | ISI

Simmler, L, Buser, T, Donzelli, M. ( 2013 ) Pharmacological characterization of designer cathinones in vitro . Br J Pharmacol 168: 458 – 470 .

Google Scholar Medline | ISI

Thomasius, R, Petersen, K, Buchert, R. ( 2003 ) Mood, cognition and serotonin transporter availability in current and former ecstasy (MDMA) users . Psychopharmacology 167: 85 – 96 .

Google Scholar Medline | ISI

Thomasius, R, Zapletalova, P, Petersen, K. ( 2006 ) Mood, cognition and serotonin transporter availability in current and former ecstasy (MDMA) users: The longitudinal perspective . J Psychopharmacol 20: 211 – 225 .

Google Scholar SAGE Journals

Thompson, M, Callaghan, P, Hunt, G. ( 2007 ) A role for oxytocin and 5-HT 1a receptors in the prosocial effects of 3,4- methylenedioxymethamphetamine (ecstasy) . Neuroscience 146: 509 – 514 .

Google Scholar Medline | ISI

Urban, NB, Girgis, RR, Talbot, PS. ( 2012 ) Sustained recreational use of ecstasy is associated with altered pre- and postsynaptic markers of serotonin transmission in neocortical areas . Neuropsychopharmacology 37: 1465 – 1473 .

Google Scholar Medline | ISI

Van de Mortel, TF ( 2008 ) Faking it: Social desirability response bias in self-report research . Aust J Adv Nurs 25: 40 .

Google Scholar ISI

Verheyden, SL, Henry, JA, Curran, HV ( 2003 ) Acute, subacute and long-term subjective consequences of ecstasy (MDMA) consumption in 430 regular users . Hum Psychopharmacol 18: 507 – 517 .

Google Scholar Medline | ISI

Winstock, AR, Mitcheson, L ( 2012 ) New recreational drugs and the primary care approach to patients who use them . BMJ 344: 35 – 40 .

Google Scholar

Winstock, AR, Marsden, J, Mitcheson, L ( 2010 ) What should be done about mephedrone? BMJ 340: c1605 .

Google Scholar Medline

Winstock, A, Lynskey, M, Borschmann, R. ( 2015 ) Risk of emergency medical treatment following consumption of cannabis or synthetic cannabinoids in a large global sample . J Psychopharmacol 29: 698 – 703 .

Google Scholar SAGE Journals | ISI

Wolff, K, Tsapakis, EM, Pariante, CM. ( 2012 ) Pharmacogenetic studies of change in cortisol on ecstasy (MDMA) consumption . J Psychopharmacol 26: 419 – 428 .

Google Scholar SAGE Journals | ISI