A review of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy

Sessa, Ben; Higbed, Laurie; Nutt, David

doi:10.3389/fpsyt.2019.00138

Cited by 141Psychedelics and Drug StudiesPosttraumatic Stress Disorder ResearchTreatment of Major Depression

A review of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy

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Sessa, Ben, Higbed, Laurie, Nutt, David·2019·Frontiers in Psychiatry

DOI 10.3389/fpsyt.2019.00138PMC PMC6435835

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Abstract

This paper provides a brief review of the history, proposed pharmacological mechanisms, safety issues, and clinical applications of the medicine 3,4-methylenedioxymethamphetamine (MDMA). Most clinical MDMA research in patients to date has focused on MDMA-assisted psychotherapy to treat posttraumatic stress disorder (PTSD). In this review paper other potential therapeutic applications for MDMA therapy are described, including contemporary studies treating anxiety associated with autism and the authors' ongoing study exploring the potential role for MDMA-assisted psychotherapy to treat alcohol use disorder. MDMA therapy for PTSD is now entering the final Phase 3 stage of drug development, with a target set for licensing by the FDA and EMA in 2021. This means that if clinical efficacy criteria are achieved, MDMA would become a medicine.

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MDMA promotes openness and trust, helping individuals engage with difficult emotions in therapy.
“Moreover, it promotes openness and trust, helping individuals engage with difficult emotions in therapy (151).”
From Psychoanalytically informed MDMA-assisted therapy for pathological narcissism: a novel theoretical approach (2025) · cites this paper as [151]

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Bryant, R. A. (2019) · World Psychiatry · doi:10.1002/wps.20656 · Cited by 528 · see citing works
Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms
Inserra, A., De Gregorio, D., & Gobbi, G. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000056 · Cited by 232 · see citing works
Treatment of Posttraumatic Stress Disorder: A State-of-the-art Review
Burback, L., Brémault‐Phillips, S., Nijdam, M. J., McFARLANE, A. C., & Vermetten, E. H. G. J. M. (2023) · Current Neuropharmacology · doi:10.2174/1570159x21666230428091433 · Cited by 232 · see citing works
Learning to Let Go: A Cognitive-Behavioral Model of How Psychedelic Therapy Promotes Acceptance
Wolff, M., Evens, R., Mertens, L. J., Koslowski, M., Betzler, F., Gründer, G., & Jungaberle, H. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.00005 · Cited by 195 · see citing works
“This encompasses many of the most prevalent mental disorders, including some that are already in the focus of psychedelic research (e.g., depression and addiction) and others for which modern clinical trials have not yet been conducted, such as panic disorder, posttraumatic stress disorder (PTSD), or psychosomatic dis…”
BackgroundMethodInfluential
Pivotal mental states
Brouwer, A., & Carhart-Harris, R. L. (2020) · Journal of Psychopharmacology · doi:10.1177/0269881120959637 · Cited by 159 · see citing works
“Like the classic psychedelics, MDMA and ketamine have both been used as adjuncts to psychotherapy, with notable success (McGirr et al., 2017; Sessa et al., 2019; Wilkinson et al., 2017).”
Background
Psychedelic harm reduction and integration: A transtheoretical model for clinical practice
Gorman, I., Nielson, E. M., Molinar, A., Cassidy, K., & Sabbagh, J. (2021) · Frontiers in Psychology · doi:10.3389/fpsyg.2021.645246 · Cited by 147 · see citing works
“The Multidisciplinary Association for Psychedelic Studies (MAPS; Sessa et al., 2019) is at the forefront of psychedelic research, and is currently conducting Phase 3 clinical trials of 3,4-Methylenedioxymethamphetamine (MDMA)-assisted psychotherapy (“A Phase 3 Program of MDMA-Assisted Psychotherapy for the Treatment o…”
Background
First study of safety and tolerability of 3,4-methylenedioxymethamphetamine-assisted psychotherapy in patients with alcohol use disorder
Sessa, B., Higbed, L., O’Brien, S., Durant, C. F., Sakal, C., Titheradge, D., Williams, T. M., Rose‐Morris, A., Brew-Girard, E., Burrows, S., et al. (2021) · Journal of Psychopharmacology · doi:10.1177/0269881121991792 · Cited by 136 · see citing works
“Only 21% of participants who had undergone MDMA-assisted psychotherapy were drinking in excess of 14 units of alcohol a week in comparison with the 75% observed in the Outcomes Study.”
Method
Effects of chronic stress on cognitive function – From neurobiology to intervention
Girotti, M., Bulin, S. E., & Carreno, F. R. (2024) · Neurobiology of Stress · doi:10.1016/j.ynstr.2024.100670 · Cited by 141 · see citing works
“…(MDMA) with psychotherapy has shown improvement in PTSD symptoms Such studies suggest novel drugs that may be useful in combination with behavioral interventions to shorten treatment duration and potentially enhance efficacy (Bahji et al., 2020; Mitchell et al., 2023; Sessa et al., 2019).”
Psychedelic therapy in the treatment of addiction: the past, present and future
Zafar, R. R., Siegel, M., Harding, R., Barba, T., Agnorelli, C., Suseelan, S., Roseman, L., Wall, M. B., Nutt, D., & Erritzøe, D. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1183740 · Cited by 108 · see citing works
“It has been investigated clinically for its ability to enhance psychotherapy [for review see (71)], specifically in couples counseling (72), as a treatment for PTSD (73, 74), and for AUD (58).”
Background
Registered clinical studies investigating psychedelic drugs for psychiatric disorders
Siegel, A. N., Meshkat, S., Benitah, K., Lipsitz, O., Gill, H., Lui, L. M. W., Teopiz, K. M., McIntyre, R. S., & Rosenblat, J. D. (2021) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2021.05.019 · Cited by 97 · see citing works
MDMA-assisted therapy significantly reduces eating disorder symptoms in a randomized placebo-controlled trial of adults with severe PTSD
Brewerton, T. D., Wang, J. B., Lafrance, A., Pamplin, C., Mithoefer, M., Yazar-Klosinki, B., Emerson, A., & Doblin, R. (2022) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2022.03.008 · Cited by 86 · see citing works
The Psychedelic Future of Post-Traumatic Stress Disorder Treatment
Zaretsky, T. G., Jagodnik, K. M., Barsic, R., Antonio, J. H., Bonanno, P. A., MacLeod, C., Pierce, C., Carney, H., Morrison, M. T., Saylor, C. F., et al. (2024) · Current Neuropharmacology · doi:10.2174/1570159x22666231027111147 · Cited by 85 · see citing works
Acute subjective effects in LSD- and MDMA-assisted psychotherapy
Schmid, Y., Gasser, P., Oehen, P., & Liechti, M. E. (2021) · Journal of Psychopharmacology · doi:10.1177/0269881120959604 · Cited by 85 · see citing works
“Several patients were sequentially administered MDMA and LSD, particularly patients suffering from complex PTSD and comorbid personality disorders, as this may have prepared them to the more confrontational and transformative effects of LSD.”
BackgroundMethodInfluential
Exploring the case for research on incorporating psychedelics within interventions for borderline personality disorder
Zeifman, R. J., & Wagner, A. C. (2020) · Journal of Contextual Behavioral Science · doi:10.1016/j.jcbs.2019.11.001 · Cited by 67 · see citing works
The emerging role of psilocybin and MDMA in the treatment of mental illness
Gill, H., Gill, B., Chen-Li, D. C. J., El‐Halabi, S., Rodrigues, N. B., Cha, D. S., Lipsitz, O., Lee, Y. L., Rosenblat, J. D., Majeed, A., et al. (2020) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2020.1826931 · Cited by 62 · see citing works
MDMA/ecstasy use and psilocybin use are associated with lowered odds of psychological distress and suicidal thoughts in a sample of US adults
Jones, G. M., & Nock, M. K. (2022) · Journal of Psychopharmacology · doi:10.1177/02698811211058923 · Cited by 62 · see citing works
Medicinal psychedelics for mental health and addiction: Advancing research of an emerging paradigm
Perkins, D., Sarris, J. J., Rossell, S. L., Bonomo, Y. A., Forbes, D., Davey, C. G., Hoyer, D., Loo, C. K. A., Murray, G., Hood, S. D., et al. (2021) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867421998785 · Cited by 55 · see citing works
“Elevated levels of oxytocin attenuate stress response and support prosocial feelings, and it appears likely from animal models that increased BDNF in the amygdala may facilitate the safe recall of usually avoided traumatic memories (Sessa et al., 2019).”
Background
Targeting the 5-HT system: Potential side effects
Hoyer, D. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108233 · Cited by 42 · see citing works
Beyond ecstasy: Alternative entactogens to 3,4-methylenedioxymethamphetamine with potential applications in psychotherapy
Oeri, H. E. (2020) · Journal of Psychopharmacology · doi:10.1177/0269881120920420 · Cited by 41 · see citing works
“Considerable research concerning its pharmacological effects and efficacy as a tool in psychotherapy, including several clinical studies in human volunteers, has been conducted recently (Danforth et al., 2018; de la Torre et al., 2004; Jerome et al., 2013; Parrott, 2007; Patel and Titheradge, 2015; Sessa et al., 2019).”
BackgroundMethod
Current Perspective on the Therapeutic Preset for Substance-Assisted Psychotherapy
Thal, S. B., Bright, S. J., Sharbanee, J. M., Wenge, T., & Skeffington, P. (2021) · Frontiers in Psychology · doi:10.3389/fpsyg.2021.617224 · Cited by 38 · see citing works
“Recent research has used the psychedelic approach (Bogenschutz et al., 2018; Nielson and Guss, 2018) as treatment for conditions such as addiction disorders and depression (Johnson et al., 2014; Bogenschutz et al., 2015; Carhart-Harris et al., 2016; Griffiths et al., 2016).”
BackgroundInfluential
A proposed mechanism for the MDMA-mediated extinction of traumatic memories in PTSD patients treated with MDMA-assisted therapy
Sottile, R., & Vida, T. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.991753 · Cited by 35 · see citing works
Psychedelic‐assisted treatment for substance use disorder: A narrative systematic review
Piper, T., Small, F., Brown, S., Kelleher, M., Mitcheson, L., Rucker, J., Young, A. H., & Marsden, J. (2025) · Addiction · doi:10.1111/add.16762 · Cited by 35 · see citing works
Psychedelic drug abuse potential assessment research for new drug applications and Controlled Substances Act scheduling
Henningfield, J. E., Coe, M. A., Griffiths, R. R., Belouin, S. J., Berger, A. M., Coker, A. R., Comer, S. D., Heal, D. J., Hendricks, P. S., Nichols, C. D., et al. (2022) · Neuropharmacology · doi:10.1016/j.neuropharm.2022.109220 · Cited by 35 · see citing works
From Mental Health Industry to Humane Care. Suggestions for an Alternative Systemic Approach to Distress
Stupak, R., & Dobroczyński, B. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18126625 · Cited by 34 · see citing works
“Examples of such an approach would be the current studies on the use of 3,4-methylenedioxymethamphetamine (MDMA) for the treatment of Posttraumatic Stress Disorder, where the psychoactive effects of MDMA are thought to allow for a specific therapeutic relationship to be established [75,76].”
Background
Presence, Trust, and Empathy: Preferred Characteristics of Psychedelic Carers
Thal, S. B., Engel, L. B., & Bright, S. J. (2022) · Journal of Humanistic Psychology · doi:10.1177/00221678221081380 · Cited by 33 · see citing works
The potential use of N-methyl-3,4-methylenedioxyamphetamine (MDMA) assisted psychotherapy in the treatment of eating disorders comorbid with PTSD
Brewerton, T. D., Lafrance, A., & Mithoefer, M. C. (2020) · Medical Hypotheses · doi:10.1016/j.mehy.2020.110367 · Cited by 30 · see citing works
Psychedelics as a Training Experience for Psychedelic Therapists: Drawing on History to Inform Current Practice
Nielson, E. M. (2021) · Journal of Humanistic Psychology · doi:10.1177/00221678211021204 · Cited by 27 · see citing works
“…for Psychedelic Studies (A Phase 3 Program of MDMA-Assisted Psychotherapy for the Treatment of Severe Posttraumatic Stress Disorder, n.d.; Sessa et al., 2019) is conducting the second of two Phase 3 clinical trials of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy…”
Background
MDMA-assisted psychotherapy for people diagnosed with treatment-resistant PTSD: what it is and what it isn’t
Morgan, L. (2020) · Annals of General Psychiatry · doi:10.1186/s12991-020-00283-6 · Cited by 26 · see citing works
Compassionate use of psychedelics
Greif, A., & Šurkala, M. (2020) · Medicine Health Care and Philosophy · doi:10.1007/s11019-020-09958-z · Cited by 25 · see citing works
“The authors of this study furthermore state that therapy did not only ameliorate the participants’ PTSD symptoms, but it also improved their sleep quality, emotional control, and coping mechanism.”
BackgroundInfluential
Therapeutic (Sub)stance: Current practice and therapeutic conduct in preparatory sessions in substance-assisted psychotherapy—A systematized review
Thal, S. B., Wieberneit, M., Sharbanee, J. M., Skeffington, P., Baker, P., Bruno, R., Wenge, T., & Bright, S. J. (2022) · Journal of Psychopharmacology · doi:10.1177/02698811221127954 · Cited by 24 · see citing works
“Likewise, there are no reports of long-term adverse effects of MDMA in clinical trials (Mithoefer et al., 2019) and several studies offer evidence that doses used in clinical trials are safe and tolerable (e.g., Mithoefer et al., 2011, 2018; Sessa et al., 2019b).”
BackgroundInfluential
Comparative psychopharmacology of autism and psychotic-affective disorders suggests new targets for treatment
Crespi, B. J. (2019) · Evolution Medicine and Public Health · doi:10.1093/emph/eoz022 · Cited by 23 · see citing works
“Current clinical use focuses on MDMAassisted psychotherapy for post-traumatic stress disorder, for which it is in phase 3 trials as of early 2019 [227].”
Background
Therapeutic Potential of Dopamine and Related Drugs as Anti-Inflammatories and Antioxidants in Neuronal and Non-Neuronal Pathologies
Bandala, C., Cárdenas‐Rodríguez, N., Mendoza‐Torreblanca, J. G., Contreras‐García, I. J., Martínez-López, V., Cruz-Hernández, T. R., Carro-Rodríguez, J., Vargas-Hernández, M. A., Ignacio‐Mejía, I., Alfaro-Rodríguez, A., et al. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15020693 · Cited by 22 · see citing works
Bedside to bench: the outlook for psychedelic research
Acero, V. P., Cribas, E. S., Browne, K. D., Rivellini, O. M., Burrell, J. C., O’Donnell, J. C., Das, S., & Cullen, D. K. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1240295 · Cited by 22 · see citing works
“Patients with remission have been reported to maintain remission for up to 6 years (Sessa et al., 2019).”
MDMA-assisted psychotherapy for posttraumatic stress disorder: A promising novel approach to treatment
Vermetten, E. H. G. J. M., & Yehuda, R. (2019) · Neuropsychopharmacology · doi:10.1038/s41386-019-0482-9 · Cited by 21 · see citing works
“The European sites—in the Netherlands, United Kingdom, Germany, Finland, Portugal and the Czech Republic—are in the process of seeking approvals and are projected to start later in 2019, putting MDMA on course to becoming a licensed treatment in 2021 [6].”
Asymmetry in Psychoactive Research: A Bibliometric Study on 15 Psychoactive Drugs
Lebrero-Tatay, J., Sebag, A., & Ezquerra-Romano, I. (2022) · Journal of Drug Issues · doi:10.1177/00220426211068439 · Cited by 18 · see citing works
Molecular basis of mood and cognitive adverse events elucidated via a combination of pharmacovigilance data mining and functional enrichment analysis
Andronis, C., Silva, J. P., Lekka, E., Virvilis, V., Carmo, H., Bampali, K., Ernst, M. C., Hu, Y., Loryan, I., Richard, J., et al. (2020) · Archives of Toxicology · doi:10.1007/s00204-020-02788-1 · Cited by 18 · see citing works
Set and setting of psychedelics for therapeutic use in psychiatry: A systematic review
Estric, C., Duron, T., Kabani, S., & López‐Castromán, J. (2025) · Journal of Psychopharmacology · doi:10.1177/02698811251338214 · Cited by 17 · see citing works
“The medical applications of MDMA are mostly for post-traumatic stress disorder (Sessa et al., 2019).”
Coping motives mediate the relationship between PTSD and MDMA use in adolescents with substance use disorders
Basedow, L. A., Wiedmann, M. F., Roessner, V., Golub, Y., & Kuitunen‐Paul, S. (2022) · Addiction Science & Clinical Practice · doi:10.1186/s13722-022-00329-y · Cited by 17 · see citing works
Evenings with Molly: Adult Couples’ Use of MDMA for Relationship Enhancement
Colbert, R., & Hughes, S. (2022) · Culture Medicine and Psychiatry · doi:10.1007/s11013-021-09764-z · Cited by 16 · see citing works
“For the past two decades, researchers have attempted to counter and dispel prohibition era myths about the inherent harms of MDMA and examine the therapeutic potential for MDMAassisted psychotherapy for mental health conditions (Cole, 2014; Sessa, Higbed, and Nutt, 2019).”
Background
MDMA-assisted psychotherapy for borderline personality disorder
Traynor, J. M., Roberts, D. E., Ross, S., Zeifman, R., & Choi-Kain, L. (2022) · Focus · doi:10.1176/appi.focus.20220056 · Cited by 15 · see citing works
Facing death, returning to life: A qualitative analysis of MDMA-assisted therapy for anxiety associated with life-threatening illness
Barone, W. P., Mitsunaga-Whitten, M., Blaustein, L. O., Perl, P., Swank, M., & Swift, T. C. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.944849 · Cited by 15 · see citing works
Design of smart nanoparticles for the electrochemical detection of 3,4‐methylenedioxymethamphetamine to allow in field screening by law enforcement officers
Truta, F. M., García‐Cruz, Á., Drăgan, A.-M., Tertiş, M., Cowen, T., Stefan, M., Topală, T. L., Slosse, A., Piletska, E. V., Durme, F. V., et al. (2023) · Drug Testing and Analysis · doi:10.1002/dta.3605 · Cited by 15 · see citing works
Fully Validated, Multi-Kilogram cGMP Synthesis of MDMA
Nair, J. B., Hakes, L. B., Yazar‐Klosinski, B., & Paisner, K. (2021) · ACS Omega · doi:10.1021/acsomega.1c05520 · Cited by 14 · see citing works
Invisible wounds: Suturing the gap between the neurobiology, conventional and emerging therapies for posttraumatic stress disorder
Gonda, X., Döme, P., Erdelyi-Hamza, B., Krause, S., Elek, L. P., Sharma, S., & Tarazi, F. I. (2022) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2022.05.010 · Cited by 14 · see citing works
Psychedelic medicines for mood disorders: current evidence and clinical considerations.
Sarris, J. J., Rubiano, D. P., Day, K., Coelho, N. L. G., & Perkins, D. (2022) · PubMed · doi:10.1097/yco.0000000000000759 · Cited by 12 · see citing works
“Other contemporary clinical studies with MDMA involving careful screening, preparation, monitoring, and follow-up have taken place with no serious adverse events reported [55,56].”
Background
Psychedelics as Reemerging Treatments for Anxiety Disorders: Possibilities and Challenges in a Nascent Field
King, F., & Hammond, R. (2021) · FOCUS The Journal of Lifelong Learning in Psychiatry · doi:10.1176/appi.focus.20200047 · Cited by 12 · see citing works
Premise, promise and challenges of MDMA assisted therapy for PTSD
Madero, S., & Bobo, Ó. Á. (2023) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2023.02.002 · Cited by 12 · see citing works
Emerging Psychedelic-Assisted Therapies: Implications for Nursing Practice
Denis-Lalonde, D., & Estefan, A. (2020) · Journal of Mental Health and Addiction Nursing · doi:10.22374/jmhan.v4i1.40 · Cited by 11 · see citing works
“It has also been discussed that MDMAassisted therapy may be helpful for the treatment of trauma-induced alcohol dependence and substance use disorders.(47) An open-label proof-of-concept study demonstrated the safety and tolerability of an 8-week course of MDMA-assisted psychotherapy for alcohol use disorder, with lon…”
Background
Balancing Therapeutic Efficacy and Safety of MDMA and Novel MDXX Analogues as Novel Treatments for Autism Spectrum Disorder
Kaur, H., Karabulut, S., Gauld, J. W., Fagot, S. A., Holloway, K. N., Shaw, H. E., & Fantegrossi, W. E. (2023) · Psychedelic Medicine · doi:10.1089/psymed.2023.0023 · Cited by 10 · see citing works
Will MDMA-assisted psychotherapy become a breakthrough in treatment-resistant post-traumatic stress disorder? A critical narrative review.
Szafoni, S., Więckiewicz, G., Pudło, R., Gorczyca, P. W., & Piegza, M. J. (2021) · Psychiatria Polska · doi:10.12740/pp/onlinefirst/133919 · Cited by 9 · see citing works
“It is worth mentioning that the risk of MDMA abuse is moderate, lower than in the case of drugs such as cocaine or amphetamine [27].”
Background
Drug use among medical students in São Paulo, Brazil: a cross-sectional study during the coronavirus disease 2019 pandemic
Lemos-Santos, P., Blumrich, L., Debia, J. B., Castaldelli-Maia, J. M., Suen, P. J. C., & Malbergier, A. (2023) · Sao Paulo Medical Journal · doi:10.1590/1516-3180.2022.0493.r1.150623 · Cited by 9 · see citing works
Cannabis and Other Substance Misuse: Implications and Regulations
Khairinisa, M. A., Alfaqeeh, M., Rafif, S. N., Muljono, F. O., & Colin, M. N. (2023) · Toxics · doi:10.3390/toxics11090756 · Cited by 9 · see citing works
Effect of MDMA-assisted therapy on mood and anxiety symptoms in advanced-stage cancer (EMMAC): study protocol for a double-blind, randomised controlled trial
Bhagavan, C., Glue, P., Evans, W., Reynolds, L., Turner, T., King, C., Russell, B. R., Morunga, E., Mills, J. L., Layton, G., et al. (2024) · Trials · doi:10.1186/s13063-024-08174-x · Cited by 8 · see citing works
“…with the current paradigm of psychedelic-assisted therapy which has so far been based on a model whereby a psychedelic substance is used as a catalyst or adjuvant of psychotherapeutic work, in the case of PTSD enabling access to and processing of repressed memories and past traumas [117, 118].”
Background
Increased kynurenine concentration attenuates serotonergic neurotoxicity induced by 3,4-methylenedioxymethamphetamine (MDMA) in rats through activation of aryl hydrocarbon receptor
Abuin-Martínez, C., Vidal, R., Gutiérrez‐López, M. D., Pérez‐Hernández, M., Giménez‐Gómez, P., Morales‐Puerto, N., O’Shea, E., & Colado, M. I. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108490 · Cited by 8 · see citing works
A Systematic Review of the MDMA Model to Address Social Impairment in Autism
Chaliha, D. R., Mamo, J. C. L., Albrecht, M. A., Lam, V., Takechi, R., & Vaccarezza, M. (2021) · Current Neuropharmacology · doi:10.2174/1570159x19666210101130258 · Cited by 7 · see citing works
“We direct the reader to an excellent review on the molecular effects of MDMA [68], as going more into detail is beyond the scope of this RCT-focused review.”
Background
Repeated intermittent administration of 3,4-methylenedioxymethamphetamine mitigates demyelination in the brain from cuprizone-treated mice
Zhao, M., Eguchi, A., Murayama, R., Xu, D., Zhu, T., Xu, B., Liu, G., Mori, C., Yang, J., & Hashimoto, K. (2025) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2025.177345 · Cited by 7 · see citing works
Trauma and Remembering: From Neuronal Circuits to Molecules
Kéri, S. (2022) · Life · doi:10.3390/life12111707 · Cited by 7 · see citing works
“In the postsynaptic membrane, MDMA activates type 1A and 2A serotonin receptors (5-HT1A, 5-HT2A) [53,72,73].”
Background
A roadmap for psychedelic pharmacy in Canada: A proposed policy and operations approach for controlled access to select psychedelics for treatment of mental illness
Brandt, J. (2023) · Drug Science Policy and Law · doi:10.1177/20503245231170340 · Cited by 7 · see citing works
“It has been clinically re-purposed for various psychiatric conditions with promising, early results in recent years (Sessa et al., 2019).”
Background
Psychoanalytically informed MDMA-assisted therapy for pathological narcissism: a novel theoretical approach
Albert, A. E., & Back, A. L. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1529427 · Cited by 6 · see citing works
“…stimuli could mitigate avoidance and defensiveness in therapeutic settings, both reinforcing its relevance as an intervention targeting emotional tolerance and regulation and suggesting that MDMA-AT could help narcissistic individuals to engage with dif ﬁ cult emotions in therapy (151, 153).”
The entactogen 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) as a treatment aid in psychotherapy and its safety concerns
Baldo, B. A. (2024) · Archives of Toxicology · doi:10.1007/s00204-024-03765-8 · Cited by 6 · see citing works
“With the background of what some described as “demoni-zation” of ecstasy (Sessa et al. 2019), by the early 2000s, claims were increasingly made for the safety of clinical usage of MDMA based on the tiny numbers of recorded deaths in the very large numbers of recreational ecstasy users and the…”
MDMA-assisted brief cognitive behavioral conjoint therapy for PTSD: Study protocol for a pilot study
Morland, L. A., Perivoliotis, D., Wachsman, T. R., Alam, M. A., Knopp, K. C., Khalifian, C. E., Ramanathan, D., Chargin, B. E., Bismark, A. W., Glynn, S. M., et al. (2024) · Contemporary Clinical Trials Communications · doi:10.1016/j.conctc.2024.101314 · Cited by 6 · see citing works
“…(5-HT) system, elevates hormones and neurotransmitters that increase feelings of connection, safety, and love (e.g., oxytocin, vasopressin, dopamine, and serotonin), decreases the fear response via the amygdala, and decreases attachment to and rigidity of memories via the hippocampus [18,19].”
Background
Exploring the structural and electronic characteristics of phenethylamine derivatives: a density functional theory approach
Bhaskarapillai, A., Parayil, S., Santhamma, J., Mangalam, D., & Anandakumar, V. M. (2024) · Journal of Engineering and Applied Science · doi:10.1186/s44147-024-00461-3 · Cited by 6 · see citing works
“Additionally, MDMA’s influence on the hypothalamic-pituitary-adrenal axis leads to increased cortisol and prolactin levels, along with elevated levels of hormones such as oxytocin and vasopressin [7].”
Background
MDMA-Assisted Therapy: Challenges, Clinical Trials, and the Future of MDMA in Treating Behavioral Disorders
O’Brien, S., & Nutt, D. (2025) · Cambridge University Press eBooks · doi:10.1017/9781009585330.008 · Cited by 6 · see citing works
Differential sensitivity to detect prosocial effects of 3,4‐methylenedioxymethamphetamine (MDMA) in different social approach paradigms in mice
Mukai, S., Nakada, S., Kamada, H., Yaguchi, R., Deyama, S., & Kaneda, K. (2020) · Neuropsychopharmacology Reports · doi:10.1002/npr2.12124 · Cited by 6 · see citing works
The Overview Effect and Well-Being
Nezami, A., Persaud, L., & White, F. (2021) · Expanding Worldviews: Astrobiology, Big History and Cosmic Perspectives · doi:10.1007/978-3-030-70482-7_10 · Cited by 4 · see citing works
Voltammetric MDMA Analysis of Seized Ecstasy Samples
Tadini, M. C., Ipólito, A. J., & de Oliveira, M. F. (2023) · Psychoactives · doi:10.3390/psychoactives2040023 · Cited by 6 · see citing works
“MDMA is an entactogen psychotropic drug that acts on the central nervous system (CNS), releasing the neurotransmitters serotonin (5-HT), noradrenaline, and dopamine [6,7].”
Pharmacogenomics of 3,4-Methylenedioxymethamphetamine (MDMA): A Narrative Review of the Literature
Drevin, G., Peña-Martín, M. C., Bauduin, A., Baudriller, A., Briet, M. B., & Abbara, C. (2024) · Pharmaceutics · doi:10.3390/pharmaceutics16081091 · Cited by 5 · see citing works
Effects of 3,4-methylenedioxymethamphetamine on the gut microbiota and metabolites in the small intestine, cecum, and colon of male rats
Xu, D., Eguchi, A., Murayama, R., Liu, G., Zhao, M., Zhu, T., Cai, Y., Yue, Y. G., Wan, X., Fujita, Y., et al. (2024) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2024.111223 · Cited by 6 · see citing works
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Authors: Sessa, B., Higbed, L., & Nutt, D.
Affiliations: Imperial College London (GB)
Corresponding author: Sessa, Ben
ORCID: Sessa, Ben
Nutt, David
Venue: Frontiers in Psychiatry
Publisher: Frontiers Media SA
Published: 2019-03-20
Volume: 10
Pages: 138-138
ISSN: 1664-0640 (ISSN-L)
DOI: 10.3389/fpsyt.2019.00138
PMC: PMC6435835
OpenAlex: W2923355729
Cited by: 141
References: 72
Citations by year: 2026: 9 · 2025: 22 · 2024: 17 · 2023: 26 · 2022: 22 · 2021: 23 · 2020: 18 · 2019: 4
FWCI: 2.65
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Frontiers in Psychiatry (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: Imperial College London
University of Bristol
Topics: Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords: MDMA-assisted psychotherapy, MDMA, 3,4-methylenedioxymethamphetamine, post-traumatic stress disorder, pharmacological mechanisms, drug safety, alcoholism, psychedelic therapy, drug development

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A review of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy

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