The psychotherapeutic potential of MDMA (3,4-methylenedioxymethamphetamine): An evidence-based review
Abstract
Unlabelled AIMS AND RATIONALE: The purpose of this study was to review whether methylenedioxymethamphetamine (MDMA) has the appropriate pharmacodynamic profile to be a therapeutic agent.Materials and methods Empirical descriptions of MDMA's subjective effects in humans will be reviewed to evaluate the proposal that MDMA has psychotherapeutic properties. The focus will be published evidence on its functional effects in therapeutic, medical, and other situations.Results MDMA is a powerful central nervous system (CNS) stimulant which affects several neurotransmitter systems and intensifies a range of psychobiological functions. Its acute mood effects can be very positive and life enhancing, and the affirmative cognitions engendered during MDMA therapy may well endure afterwards. However, MDMA also has a number of potential anti-therapeutic characteristics. Acutely, it can also intensify negative cognitions, and these may similarly endure over time. Psychotherapists have found that setting, intention, and expectancy are crucial for a positive outcome, but these factors cannot be guaranteed. Post-MDMA, there is a period of neurotransmitter recovery when low moods predominate, and these may exacerbate psychiatric distress. The explanations proposed for MDMA-assisted therapy are all psychodynamic, and a neurochemical model needs to be outlined. It has been suggested that enduring therapeutic gains can follow a single session, but again, this lacks a clear psychopharmacological rationale. Finally, diathesis-stress models suggest that psychiatric individuals are more prone to acute and chronic abreactions to CNS stimulants such as MDMA.Conclusions There are a number of issues which need to be addressed before it can be argued that MDMA might be clinically useful for psychotherapy.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The drug's supposed empathogenic properties are a key reason it has been proposed as an adjunct in psychotherapy.
“MDMA’s apparent empathogenic effects are also central to the rationale for the use of the drug as a psychotherapeutic adjunct [1, 5–6].”
From Is Ecstasy an “Empathogen”? Effects of +/- 3,4-Methylenedioxymethamphetamine on Prosocial Feelings and Identification of Emotional States in Others (2010) · cites this paper as [1]
MDMA is reported to cause atypical mental effects, such as heightened empathy and prosocial sentiment.
“MDMA (±3,4-methylenedioxymethamphetamine, ‘ecstasy’) is reported to have unusual, so-called ‘empathogenic’ effects, such as increased empathy and prosocial feelings [e.g. see 1].”
From Is Ecstasy an “Empathogen”? Effects of +/- 3,4-Methylenedioxymethamphetamine on Prosocial Feelings and Identification of Emotional States in Others (2010) · cites this paper as [1]
Cites
The Pharmacology and Clinical Pharmacology of 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”)
Green, A. R., Mechan, A. O., Elliott, J. M., O’Shea, E., & Colado, M. I. (2003) · Pharmacological Reviews · doi:10.1124/pr.55.3.3 · Cited by 1,272 · see citing works
Nichols, D. E. (1986) · Journal of Psychoactive Drugs · doi:10.1080/02791072.1986.10472362 · Cited by 564 · see citing works
Vollenweider, F. X., Gamma, A., Liechti, M., & Huber, T. (1998) · Neuropsychopharmacology · doi:10.1016/s0893-133x(98)00013-x · Cited by 448 · see citing works
Subjective Reports of the Effects of MDMA in a Clinical Setting
Greer, G., & Tolbert, R. (1986) · Journal of Psychoactive Drugs · doi:10.1080/02791072.1986.10472364 · Cited by 413 · see citing works
Gender differences in the subjective effects of MDMA
Liechti, M. E., Gamma, A., & Vollenweider, F. X. (2001) · Psychopharmacology · doi:10.1007/s002130000648 · Cited by 360 · see citing works
Human psychopharmacology of Ecstasy (MDMA): a review of 15 years of empirical research
Parrott, A. C. (2001) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.351 · Cited by 344 · see citing works
Self-citationEcstasy (MDMA) effects upon mood and cognition: before, during and after a Saturday night dance
Parrott, A. C., & Lasky, J. (1998) · Psychopharmacology · doi:10.1007/s002130050714 · Cited by 342 · see citing works
Self-citationRecreational Ecstasy/MDMA, the serotonin syndrome, and serotonergic neurotoxicity
Parrott, A. C. (2002) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(01)00711-0 · Cited by 325 · see citing works
Self-citationKrystal, J. H., Perry, E. B., Gueorguieva, R., Belger, A., Madonick, S. H., Abi-Dargham, A., Cooper, T. B., MacDougall, L., Abi-Saab, W., & D’Souza, D. C. (2005) · Archives of General Psychiatry · doi:10.1001/archpsyc.62.9.985 · Cited by 317 · see citing works
(±)3,4-Methylenedioxymethamphetamine (‘Ecstasy’)-Induced Serotonin Neurotoxicity: Studies in Animals
Ricaurte, G. A., Yuan, J., & McCann, U. D. (2000) · Neuropsychobiology · doi:10.1159/000026664 · Cited by 292 · see citing works
Curran, H. V., & Travill, R. A. (1997) · Addiction · doi:10.1111/j.1360-0443.1997.tb02951.x · Cited by 284 · see citing works
Psychobiological problems in heavy 'ecstasy' (MDMA) polydrug users
Parrott, A. C., Sisk, E., & Turner, J. J. (2000) · Drug and Alcohol Dependence · doi:10.1016/s0376-8716(99)00146-5 · Cited by 279 · see citing works
Self-citationJulien, R. M. (1975) · Cited by 262 · see citing works
Vollenweider, F. X., Gamma, A., Liechti, M. E., et al. (1998) · Neuropsychopharmacology · doi:10.1038/sj.npp.1395197 · Cited by 245 · see citing works
The Background and Chemistry of MDMA
Shulgin, A. T. (1986) · Journal of Psychoactive Drugs · doi:10.1080/02791072.1986.10472361 · Cited by 233 · see citing works
Parrott, A. C. (2004) · Psychopharmacology · doi:10.1007/s00213-003-1712-7 · Cited by 232 · see citing works
Self-citationThe Psychological and Physiological Effects of MDMA on Normal Volunteers
Downing, J. (1986) · Journal of Psychoactive Drugs · doi:10.1080/02791072.1986.10472366 · Cited by 226 · see citing works
Parrott, A. C., Milani, R. M., Parmar, R., & Turner, J. J. (2001) · Psychopharmacology · doi:10.1007/s002130100897 · Cited by 210 · see citing works
Self-citationA review of the acute subjective effects of MDMA/ecstasy
Baylen, C. A., & Rosenberg, H. (2006) · Addiction · doi:10.1111/j.1360-0443.2006.01423.x · Cited by 209 · see citing works
Neurotoxicity of MDMA (ecstasy): the limitations of scaling from animals to humans
de la Torre, R., & Farré, M. (2004) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2004.08.001 · Cited by 192 · see citing works
(±)3,4-Methylenedioxymethamphetamine (‘Ecstasy’)-Induced Serotonin Neurotoxicity: Clinical Studies
McCann, U. D., Eligulashvili, V., & Ricaurte, G. A. (2000) · Neuropsychobiology · doi:10.1159/000026665 · Cited by 190 · see citing works
Causes and consequences of methamphetamine and MDMA toxicity
Quinton, M. S., & Yamamoto, B. K. (2006) · The AAPS Journal · doi:10.1007/bf02854904 · Cited by 188 · see citing works
Can Drugs Be Used to Enhance the Psychotherapeutic Process?
Grinspoon, L., & Bakalar, J. B. (1986) · American Journal of Psychotherapy · doi:10.1176/appi.psychotherapy.1986.40.3.393 · Cited by 187 · see citing works
A Method of Conducting Therapeutic Sessions with MDMA
Greer, G. R., & Tolbert, R. (1998) · Journal of Psychoactive Drugs · doi:10.1080/02791072.1998.10399713 · Cited by 182 · see citing works
3,4-Methylenedioxy analogues of amphetamine: Defining the risks to humans
Hegadoren, K., Baker, G. B., & Bourin, M. (1999) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(98)00046-3 · Cited by 178 · see citing works
Grob, C. S., Poland, R. E., Chang, L., & Ernst, T. (1995) · Behavioural Brain Research · doi:10.1016/0166-4328(96)00078-2 · Cited by 175 · see citing works
Scholey, A. B., Parrott, A. C., Buchanan, T., Heffernan, T., Ling, J., & Rodgers, J. (2004) · Addictive Behaviors · doi:10.1016/j.addbeh.2004.02.022 · Cited by 166 · see citing works
Self-citationCHARACTERIZATION OF THREE NEW PSYCHOTOMIMETICS
Alexander, T., & Nichols, D. E. (1978) · Elsevier eBooks · doi:10.1016/b978-0-08-021938-7.50010-2 · Cited by 163 · see citing works
Gamma, A. (2000) · Neuropsychopharmacology · doi:10.1016/s0893-133x(00)00130-5 · Cited by 162 · see citing works
Ecstasy/MDMA attributed problems reported by novice, moderate and heavy recreational users
Parrott, A. C., Buchanan, T., Scholey, A. B., Heffernan, T., Ling, J., & Rodgers, J. (2002) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.415 · Cited by 161 · see citing works
Self-citationThomasius, R., Zapletalova, P., Petersen, K. U., Buchert, R., Andresen, B., Wartberg, L., Nebeling, B., & Schmoldt, A. (2006) · Journal of Psychopharmacology · doi:10.1177/0269881106059486 · Cited by 158 · see citing works
Impulsivity, risk taking and recreational 'ecstasy' (MDMA) use.
Butler, G., & Montgomery, A. M. J. (2004) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2004.04.003 · Cited by 156 · see citing works
Parrott, A. C. (2004) · Neuropsychobiology · doi:10.1159/000080961 · Cited by 152 · see citing works
Self-citationThe content of ecstasy tablets: implications for the study of their long‐term effects
Cole, J. C., Bailey, M., Sumnall, H. R., Wagstaff, G. F., & King, L. (2002) · Addiction · doi:10.1046/j.1360-0443.2002.00222.x · Cited by 150 · see citing works
A review of acute effects of 3,4-methylenedioxymethamphetamine in healthy volunteers
Dumont, G. J. H., & Verkes, R. J. (2006) · Journal of Psychopharmacology · doi:10.1177/0269881106063271 · Cited by 149 · see citing works
Liechti, M. E., & Vollenweider, F. X. (2000) · Journal of Psychopharmacology · doi:10.1177/026988110001400313 · Cited by 144 · see citing works
Hallucinogenic Drugs and Plants in Psychotherapy and Shamanism
Metzner, R. (1998) · Journal of Psychoactive Drugs · doi:10.1080/02791072.1998.10399709 · Cited by 142 · see citing works
Parrott, A. C. (2006) · Journal of Psychopharmacology · doi:10.1177/0269881106063268 · Cited by 139 · see citing works
Self-citationClub drugs: MDMA, gamma-hydroxybutyrate (GHB), Rohypnol, and ketamine.
Gahlinger, P. M. (2004) · PubMed · Cited by 137 · see citing works
Huether, G., Zhou, D., & R�ther, E. (1997) · Journal of Neural Transmission · doi:10.1007/bf01285547 · Cited by 136 · see citing works
Phenomenology and Sequelae of 3,4-Methylenedioxymethamphetamine Use
Liester, M. B., Grob, C. S., BRAVO, G. L., & WALSH, R. N. (1992) · The Journal of Nervous and Mental Disease · doi:10.1097/00005053-199206000-00001 · Cited by 128 · see citing works
The Psychopharmacology of Hallucinogens
(1978) · Elsevier eBooks · doi:10.1016/c2013-0-02910-6 · Cited by 123 · see citing works
Former chronic methylenedioxymethamphetamine (MDMA or ecstasy) users report mild depressive symptoms
MacInnes, N., Handley, S. L., & Harding, G. F. A. (2001) · Journal of Psychopharmacology · doi:10.1177/026988110101500310 · Cited by 120 · see citing works
Wolff, K., Tsapakis, E. M., Winstock, A. R., Hartley, D., Holt, D., Forsling, M. L., & Aitchison, K. J. (2006) · Journal of Psychopharmacology · doi:10.1177/0269881106061514 · Cited by 108 · see citing works
Doblin, R. (2002) · Journal of Psychoactive Drugs · doi:10.1080/02791072.2002.10399952 · Cited by 99 · see citing works
Neuroimaging findings with MDMA/ecstasy: technical aspects, conceptual issues and future prospects
Reneman, L., de Win, M. M. L., van den Brink, W., Booij, J., & den Heeten, G. J. (2006) · Journal of Psychopharmacology · doi:10.1177/0269881106061515 · Cited by 85 · see citing works
Curran, H. V., Rees, H., Hoare, T., Hoshi, R., & Bond, A. J. (2004) · Psychopharmacology · doi:10.1007/s00213-003-1713-6 · Cited by 83 · see citing works
Schifano, F. (2000) · Neuropsychobiology · doi:10.1159/000026667 · Cited by 83 · see citing works
Soar, K., Turner, J. J., & Parrott, A. C. (2001) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.350 · Cited by 80 · see citing works
Self-citationSymptoms of anxiety and depression in childhood and use of MDMA: prospective, population based study
Huizink, A. C., Ferdinand, R. F., van der Ende, J., & Verhulst, F. C. (2006) · BMJ · doi:10.1136/bmj.38743.539398.3a · Cited by 77 · see citing works
Understanding drugs and behaviour
Parrott, A. C., Morinan, A., Moss, M. C., & Scholey, A. B. (2005) · Swinburne figshare (Swinburne University of Technology) · Cited by 69 · see citing works
Self-citationBuchert, R., Thomasius, R., Petersen, K. U., Wilke, F., Obrocki, J., Nebeling, B., Wartberg, L., Zapletalova, P., & Clausen, M. (2005) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-005-1850-8 · Cited by 63 · see citing works
Rodgers, J., Buchanan, T., Pearson, C., Parrott, A. C., Ling, J., Heffernan, T., & Scholey, A. B. (2006) · Journal of Psychopharmacology · doi:10.1177/0269881105058777 · Cited by 63 · see citing works
Self-citationThe Love Drug: Marching to the Beat of Ecstasy
Stimmel, B., & Cohen, R. S. (1998) · Medical Entomology and Zoology · Cited by 61 · see citing works
Greer, G. R., & Tolbert, R. (1990) · Topics in the Neurosciences · doi:10.1007/978-1-4613-1485-1_2 · Cited by 57 · see citing works
Gerra, G., Zaimovic, A., Ampollini, R., Giusti, F., Delsignore, R., Raggi, M. A., Giovanni Laviola, A., Macchia, T., & Brambilla, F. (2001) · Journal of Substance Abuse · doi:10.1016/s0899-3289(01)00094-3 · Cited by 57 · see citing works
Check, E. (2004) · Nature · doi:10.1038/429126a · Cited by 53 · see citing works
Greer, E. (1985) · Advances · Cited by 53 · see citing works
Tucker, P. M., MD, Potter-Kimball, R., RN, MS, Wyatt, D. B., Masters, B., Parker, D. E., PhD, Burgin, C. E., et al. (2025) · Psychopharmacology Bulletin · doi:10.64719/pb.4179 · Cited by 49 · see citing works
The love drug: marching to the beat of ecstasy
(1999) · Choice Reviews Online · doi:10.5860/choice.36-3357 · Cited by 49 · see citing works
Evidence for a role of energy dysregulation in the MDMA-induced depletion of brain 5-HT
Darvesh, A. S., & Gudelsky, G. A. (2005) · Brain Research · doi:10.1016/j.brainres.2005.07.009 · Cited by 44 · see citing works
Halpern, J. H. (2003) · Current Psychiatry Reports · doi:10.1007/s11920-003-0067-4 · Cited by 42 · see citing works
Psychedelic and Entactogenic Drugs in the Treatment of Depression
Riedlinger, T. J., & Riedlinger, J. E. (1994) · Journal of Psychoactive Drugs · doi:10.1080/02791072.1994.10472600 · Cited by 39 · see citing works
Davidson, J. R. T. (2004) · International Clinical Psychopharmacology · doi:10.1097/00004850-200403000-00005 · Cited by 39 · see citing works
Caton, C. L. M., Samet, S., & Hasin, D. S. (2000) · Journal of Psychiatric Practice · doi:10.1097/00131746-200009000-00006 · Cited by 36 · see citing works
Speed, Ecstasy, Ritalin: The Science of Amphetamines
Rawson, R. A. (2007) · Addiction · doi:10.1111/j.1360-0443.2007.01866.x · Cited by 35 · see citing works
Understanding Drugs and Behaviour
Harding-Price, D. (2005) · Mental Health Practice · doi:10.7748/mhp.8.5.33.s22 · Cited by 26 · see citing works
Nutt, D. (2006) · Journal of Psychopharmacology · doi:10.1177/0269881106064592 · Cited by 23 · see citing works
Effects of Smoking and Smoking Deprivation on the Articulatory Loop of Working Memory
Blake, J. J., & Smith, A. P. (1997) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/(sici)1099-1077(199705/06)12:3 · Cited by 23 · see citing works
Decreased pain tolerance and mood in recreational users of MDMA
O'Regan, M. C., & Clow, A. (2004) · Psychopharmacology · doi:10.1007/s00213-003-1748-8 · Cited by 18 · see citing works
Drug-related schizophrenic syndromes.
Mh, S. (1973) · PubMed · Cited by 17 · see citing works
Ecstasy versus alcohol: Tolstoy and the variations of unhappiness
Parrott, A. C. (2007) · Journal of Psychopharmacology · doi:10.1177/0269881106073123 · Cited by 12 · see citing works
Self-citationThe effects of consciousness-expanding drugs on prisoner rehabilitation.
Leary, T. (1969) · Cited by 12 · see citing works
Psychopharmacological Agents for the Terminally Ill and Bereaved
Craytor, J. K., Goldberg, I. K., Malitz, S., & Kutscher, A. H. (1974) · AJN American Journal of Nursing · doi:10.2307/3469702 · Cited by 8 · see citing works
PSYCHOPHARMACOLOGICAL AGENTS FOR THE TERMINALLY ILL AND BEREAVED
&NA; (1974) · AJN American Journal of Nursing · doi:10.1097/00000446-197406000-00057 · Cited by 8 · see citing works
A Clinical Crossroads for MDMA
Guillot, C. R. (2005) · Journal of Psychoactive Drugs · doi:10.1080/02791072.2005.10399818 · Cited by 2 · see citing works
Alcohol, ecstasy, Aldous Huxley’s ‘soma’
Parrott, A. C. (2007) · Journal of Psychopharmacology · doi:10.1177/0269881106075426 · Cited by 1 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
The Peptide That Binds: A Systematic Review of Oxytocin and its Prosocial Effects in Humans
MacDonald, K., & MacDonald, T. M. (2010) · Harvard Review of Psychiatry · doi:10.3109/10673220903523615 · Cited by 585 · see citing works
Bedi, G., Hyman, D., & de Wit, H. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.08.003 · Cited by 247 · see citing works
Dumont, G. J. H., Sweep, F. C. G. J., van der Steen, R., Hermsen, R., Donders, A. R. T., Touw, D. J., van Gerven, J. M. A., Buitelaar, J. K., & Verkes, R. J. (2009) · Social Neuroscience · doi:10.1080/17470910802649470 · Cited by 238 · see citing works
Effects of MDMA on sociability and neural response to social threat and social reward
Bedi, G., Phan, K. L., Angstadt, M., & de Wit, H. (2009) · Psychopharmacology · doi:10.1007/s00213-009-1635-z · Cited by 206 · see citing works
MacDonald, K., & Feifel, D. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00035 · Cited by 181 · see citing works
Bahji, A., Forsyth, A., Groll, D., & Hawken, E. R. (2020) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2019.109735 · Cited by 88 · see citing works
MDMA decreases the effects of simulated social rejection
Frye, C. G., Wardle, M. C., Norman, G. J., & de Wit, H. (2014) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2013.11.030 · Cited by 85 · see citing works
Anxiolytic drug discovery: What are the novel approaches and how can we improve them?
Stewart, A. M., & Kalueff, A. V. (2014) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2014.857309 · Cited by 22 · see citing works
- Authors
- Parrott, A. C.
- Affiliations
- Swansea University (GB)
- Corresponding author
- Parrott, A. C.
- Venue
- Psychopharmacology
- Published
- 2007-02-13
- Volume
- 191
- Issue
- 2
- Pages
- 181-193
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W2147606470
- Cited by
- 87
- References
- 77
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 1 · 2021: 3 · 2020: 3 · 2019: 8 · 2018: 4 · 2017: 3 · 2016: 3 · 2015: 3 · 2014: 9 · 2013: 13 · 2012: 6
- FWCI
- 1.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- MDMA, ecstasy, MDMA-assisted psychotherapy, psychostimulants, neurotransmitter systems, mood improvement, negative thinking, diathesis-stress model, psychodynamic theory
- MeSH terms
- Central Nervous System Stimulants, Mental Disorders, Hallucinogens, Humans, Models, Biological, Neural Pathways, Psychotherapy, Serotonin Agents, Patient Selection, N-Methyl-3,4-methylenedioxyamphetamine
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
