Evidence map›Paper›PMID 33972795›Full record

Trial reportNature medicine2021

MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study.

Jennifer M Mitchell, Michael Bogenschutz, Alia Lilienstein, Charlotte Harrison, Sarah Kleiman, Kelly Parker-Guilbert, Marcela Ot'alora G, Wael Garas, Casey Paleos, Ingmar Gorman and 28 more

5 registry-linked trialsOpen access · hybridAbstract readClinical Trial, Phase IIIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Nature medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 5 registered trials, which are not on this map. Cited by 408 papers, 13 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
408citing papers in PubMed, 13 pooled it
99.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03537014 phase3completednot on this map

A Randomized, Double-Blind, Placebo-Controlled, Multi-Site Phase 3 Study of the Efficacy and Safety of Manualized MDMA-Assisted Psychotherapy for the Treatment of Severe Posttraumatic Stress Disorder

TypeinterventionalSponsorResilient PharmaceuticalsRan2018 to 2020Enrolled100ConditionsPosttraumatic Stress DisorderArmsTherapy, midomafetamine HCl, Placebo
NCT05219175 phase2recruitingnot on this mapstarted 2024, after this paper: background citation

MDMA-Assisted Therapy 6 to 12 Months After Childbirth for People With Co-occurring Opioid Use and Post Traumatic Stress Disorders

TypeinterventionalSponsorUniversity of New MexicoRan2024 to 2027Enrolled15ConditionsStress Disorders, Post-Traumatic, Opioid Use DisorderArmsMDMA Assisted Therapy
NCT05783817 phase2recruitingnot on this mapstarted 2025, after this paper: background citation

MDMA-Assisted Cognitive Behavioral Therapy (CBT) Compared With Methamphetamine-Assisted CBT in Obsessive-Compulsive Disorder (OCD): A Phase II Study

TypeinterventionalSponsorCarolyn RodriguezRan2025 to 2026Enrolled40ConditionsObsessive-Compulsive DisorderArms3,4-Methyl enedioxy methamphetamine, Methamphetamine, Cognitive Behavioral Therapy (CBT)
NCT05790239 phase2recruitingnot on this mapstarted 2025, after this paper: background citation

A Randomized, Double-Blind, Single-Site Phase II 2-Arm Study to Compare the Safety and Preliminary Efficacy of Manualized MDMA-Assisted Therapy to Low Dose D-Amphetamine Assisted Therapy in Veterans For The Treatment of Moderate to Severe PTSD

TypeinterventionalSponsorStephen Robert MarderRan2025 to 2028Enrolled40ConditionsPost Traumatic Stress DisorderArms3,4-methylenedioxymethamphetamine, d-amphetamine, Therapy
NCT06954025 phase2enrolling by invitationnot on this mapstarted 2025, after this paper: background citation

High-Intensity Inpatient MDMA-Assisted Psychotherapy for Treatment-Refractory Posttraumatic Stress Disorder: An Open-Label Pilot Study

TypeinterventionalSponsorARQ National Psychotrauma CentreRan2025 to 2027Enrolled20ConditionsPosttraumatic Stress Disorder (PTSD)ArmsHigh-intensity inpatient MDMA-assisted psychotherapy
3 · Its place in the literature

Who cites it

408 citing papers in PubMed, 13 syntheses or guidelines pooled it, 914 citations in OpenAlex.

  1. Pooled it
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  3. Magnitude of response in treatment and control groups within psychedelic trials for psychiatric disorders: A meta-analysis.European psychiatry : the journal of the Association of European Psychiatrists · 2026
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  8. Effect of amphetamines on blood pressure.The Cochrane database of systematic reviews · 2025
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  12. Side-effects of mdma-assisted psychotherapy: a systematic review and meta-analysis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024
    Pooled it
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  19. Rapid and sustained antidepressant effects of vaporized N,N-dimethyltryptamine: a phase 2a clinical trial in treatment-resistant depression.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025
    Trial
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348 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

38 authors at 11 institutions in 3 countries.

Jennifer M MitchellDepartment of Neurology, University of California San Francisco, San Francisco, CA, USA. jennifer.mitchell@ucsf.edu.ORCID http://orcid.org/0000-0002-7567-8129
Michael BogenschutzDepartment of Psychiatry, New York University Grossman School of Medicine, New York, NY, USA.
Alia LiliensteinMultidisciplinary Association for Psychedelic Studies (MAPS), San Jose, CA, USA.
Charlotte HarrisonMAPS Public Benefit Corporation (MAPS PBC), San Jose, CA, USA.
Sarah KleimanKleiman Consulting and Psychological Services, Sayreville, NJ, USA.
Kelly Parker-GuilbertKPG Psychological Services LLC, Brunswick, ME, USA.
Marcela Ot'alora GAguazul-Bluewater Inc., Boulder, CO, USA.ORCID http://orcid.org/0000-0001-6174-7317
Wael GarasAguazul-Bluewater Inc., Boulder, CO, USA.
Casey PaleosNautilus Sanctuary, New York, NY, USA.
Ingmar GormanFluence, Woodstock, NY, USA.ORCID http://orcid.org/0000-0003-4674-2969
Christopher NicholasDepartment of Family Medicine and Community Health, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Michael MithoeferMAPS Public Benefit Corporation (MAPS PBC), San Jose, CA, USA.
Shannon CarlinMAPS Public Benefit Corporation (MAPS PBC), San Jose, CA, USA.
Bruce PoulterAguazul-Bluewater Inc., Boulder, CO, USA.ORCID http://orcid.org/0000-0002-0489-2806
Ann MithoeferMDMA Therapy Training Program, MAPS Public Benefit Corporation, San Jose, CA, USA.
Sylvestre QuevedoDepartment of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, CA, USA.
Gregory WellsSan Francisco Insight and Integration Center, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-0902-5282
Sukhpreet S KlaireBritish Columbia Centre on Substance Use, Vancouver, British Columbia, Canada.
Bessel van der KolkBoston University School of Medicine, Boston, MA, USA.
Keren TzarfatyMDMA Therapy Training Program, MAPS Public Benefit Corporation, San Jose, CA, USA.
Revital AmiazChaim Sheba Medical Center, Tel HaShomer, Israel.
Ray WorthyRay Worthy Psychiatry LLC, New Orleans, LA, USA.
Scott ShannonWholeness Center, Fort Collins, CO, USA.
Joshua D WoolleyDepartment of Psychiatry and Behavioral Sciences, University of California San Francisco, San Francisco, CA, USA.
Cole MartaNew School Research LLC, North Hollywood, CA, USA.
Yevgeniy GelfandZen Therapeutic Solutions, Mt Pleasant, SC, USA.
Emma HapkeUniversity of Toronto, Toronto, Ontario, Canada.
Simon AmarDr Simon Amar Inc., Montreal, Quebec, Canada.
Yair WallachBe'er Ya'akov Ness Ziona Mental Health Center, Be'er Ya'akov, Israel.
Randall BrownFluence, Woodstock, NY, USA.
Scott HamiltonStanford School of Medicine, Stanford, CA, USA.
Julie B WangMAPS Public Benefit Corporation (MAPS PBC), San Jose, CA, USA.
Allison CokerDepartment of Neurology, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-5353-4653
Rebecca MatthewsMAPS Public Benefit Corporation (MAPS PBC), San Jose, CA, USA.
Alberdina de BoerMAPS Public Benefit Corporation (MAPS PBC), San Jose, CA, USA.
Berra Yazar-KlosinskiMultidisciplinary Association for Psychedelic Studies (MAPS), San Jose, CA, USA.
Amy EmersonMAPS Public Benefit Corporation (MAPS PBC), San Jose, CA, USA.
Rick DoblinMultidisciplinary Association for Psychedelic Studies (MAPS), San Jose, CA, USA.
Public Service Electric and Gas (United States) · USUniversity of California, San Francisco · USMultidisciplinary Association for Psychedelic Studies · USBritish Columbia Centre on Substance Use · CAMedical University of South Carolina · USNautilus (United States) · USNew School · USNew York University · USSheba Medical Center · ILStanford Medicine · USUniversity of Toronto · CA

Funding

Mentoring the next generation of addiction clinician scientists while responding to the opioid epidemicR25DA037756 · NIDA · UNIVERSITY OF BRITISH COLUMBIA · PI FAIRBAIRN, NADIA · 2014 to 2023
$3.6M
NIDA NIH HHS R25 DA037756
6 · The paper itself

Abstract

Post-traumatic stress disorder (PTSD) presents a major public health problem for which currently available treatments are modestly effective. We report the findings of a randomized, double-blind, placebo-controlled, multi-site phase 3 clinical trial (NCT03537014) to test the efficacy and safety of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of patients with severe PTSD, including those with common comorbidities such as dissociation, depression, a history of alcohol and substance use disorders, and childhood trauma. After psychiatric medication washout, participants (n = 90) were randomized 1:1 to receive manualized therapy with MDMA or with placebo, combined with three preparatory and nine integrative therapy sessions. PTSD symptoms, measured with the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5, the primary endpoint), and functional impairment, measured with the Sheehan Disability Scale (SDS, the secondary endpoint) were assessed at baseline and at 2 months after the last experimental session. Adverse events and suicidality were tracked throughout the study. MDMA was found to induce significant and robust attenuation in CAPS-5 score compared with placebo (P < 0.0001, d = 0.91) and to significantly decrease the SDS total score (P = 0.0116, d = 0.43). The mean change in CAPS-5 scores in participants completing treatment was -24.4 (s.d. 11.6) in the MDMA group and -13.9 (s.d. 11.5) in the placebo group. MDMA did not induce adverse events of abuse potential, suicidality or QT prolongation. These data indicate that, compared with manualized therapy with inactive placebo, MDMA-assisted therapy is highly efficacious in individuals with severe PTSD, and treatment is safe and well-tolerated, even in those with comorbidities. We conclude that MDMA-assisted therapy represents a potential breakthrough treatment that merits expedited clinical evaluation.

Indexed as

AdultCombined Modality TherapyDouble-Blind MethodDrug-Related Side Effects and Adverse ReactionsFemaleHumansMaleMiddle AgedN-Methyl-3,4-methylenedioxyamphetamineStress Disorders, Post-TraumaticTreatment OutcomeN-Methyl-3,4-methylenedioxyamphetamine

Identifiers

PMID33972795
PMCPMC8205851
OpenAlexW3160990818

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.