Evidence mapPaperPMID 37709999Full record

Trial reportNature medicine2023

MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial.

Jennifer M Mitchell, Marcela Ot'alora G, Bessel van der Kolk, Scott Shannon, Michael Bogenschutz, Yevgeniy Gelfand, Casey Paleos, Christopher R Nicholas, Sylvestre Quevedo, Brooke Balliett and 10 more

Erratum issued 3 registry-linked trialsOpen access · hybridAbstract readRandomized Controlled TrialClinical Trial, Phase III
In one paragraph

Trial report in Nature medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to 3 registered trials, which are not on this map. Cited by 189 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
189citing papers in PubMed, 9 pooled it
112.5field-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.

NCT04077437 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 Posttraumatic Stress Disorder of Moderate or Greater Severity

TypeinterventionalSponsorResilient PharmaceuticalsRan2020 to 2022Enrolled121ConditionsPosttraumatic Stress DisorderArmsTherapy, Midomafetamine, Placebo
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
NCT07737054 early_phase1recruitingnot on this mapstarted 2025, after this paper: background citation

Trauma-informed Psilocybin Assisted Psychotherapy (TiPAP) for Post-Traumatic Stress Disorder

TypeinterventionalSponsorTel-Aviv Sourasky Medical CenterRan2025 to 2026Enrolled13ConditionsPost-Traumatic Stress Disorder, PTSDArmsPsilocybin (drug), Trauma-Focused Psychotherapy
3 · Its place in the literature

Who cites it

189 citing papers in PubMed, 9 syntheses or guidelines pooled it, 360 citations in OpenAlex.

  1. 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. Autism, youth suicide, and psychedelics: A review of the 21st century evidence.Journal of the Chinese Medical Association : JCMA · 2024
    Pooled it
  9. 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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  15. Acute effects of MDMA, MDA, lysine-MDMA, and lysine-MDA in a randomized, double-blind, placebo-controlled, crossover trial in healthy participants.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
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  18. Acute effects of R-MDMA, S-MDMA, and racemic MDMA in a randomized double-blind cross-over trial in healthy participants.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024
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129 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 11 institutions in 2 countries.

Jennifer M MitchellNeuroscape, Department of Neurology, University of California, San Francisco, San Francisco, CA, USA. jennifer.mitchell@ucsf.edu.ORCID http://orcid.org/0000-0002-7567-8129
Marcela Ot'alora GAguazul-Bluewater, Inc, Boulder, CO, USA.ORCID http://orcid.org/0000-0001-6174-7317
Bessel van der KolkBoston University School of Medicine, Boston, MA, USA.
Scott ShannonWholeness Center, Fort Collins, CO, USA.
Michael BogenschutzDepartment of Psychiatry, New York University Grossman School of Medicine, New York, NY, USA.ORCID http://orcid.org/0000-0003-4530-3470
Yevgeniy GelfandZen Therapeutic Solutions, Mt. Pleasant, SC, USA.
Casey PaleosNautilus Sanctuary, New York, NY, USA.
Christopher R NicholasDepartment of Family Medicine and Community Health, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Sylvestre QuevedoDepartment of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, CA, USA.
Brooke BalliettNew School Research, LLC, Los Angeles, CA, USA.
Scott HamiltonMAPS Public Benefit Corporation, San Jose, CA, USA.
Michael MithoeferMedical University of South Carolina, Charleston, SC, USA.ORCID http://orcid.org/0000-0002-4267-6135
Sarah KleimanKleiman Consulting and Psychological Services, PC, Ivyland, PA, USA.
Kelly Parker-GuilbertKPG Psychological Services, LLC, Brunswick, ME, USA.
Keren TzarfatyUniversity of Haifa, Haifa, Israel.
Charlotte HarrisonMAPS Public Benefit Corporation, San Jose, CA, USA.
Alberdina de BoerTulip Medical Consulting, LLC, Port Townsend, WA, USA.
Rick DoblinMultidisciplinary Association for Psychedelic Studies (MAPS), San Jose, CA, USA.
Berra Yazar-KlosinskiMAPS Public Benefit Corporation, San Jose, CA, USA.
MAPP2 Study Collaborator Group
Public Service Electric and Gas (United States) · USBluewater International (United States) · USM.C. Townsend Associates (United States) · USMedical University of South Carolina · USMultidisciplinary Association for Psychedelic Studies · USNautilus (United States) · USNew School · USNew York University · USRoche (Israel) · ILSan Francisco VA Medical Center · USUniversity of California, San Francisco · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

This multi-site, randomized, double-blind, confirmatory phase 3 study evaluated the efficacy and safety of 3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) versus placebo with identical therapy in participants with moderate to severe post-traumatic stress disorder (PTSD). Changes in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total severity score (primary endpoint) and Sheehan Disability Scale (SDS) functional impairment score (key secondary endpoint) were assessed by blinded independent assessors. Participants were randomized to MDMA-AT (n = 53) or placebo with therapy (n = 51). Overall, 26.9% (28/104) of participants had moderate PTSD, and 73.1% (76/104) of participants had severe PTSD. Participants were ethnoracially diverse: 28 of 104 (26.9%) identified as Hispanic/Latino, and 35 of 104 (33.7%) identified as other than White. Least squares (LS) mean change in CAPS-5 score (95% confidence interval (CI)) was -23.7 (-26.94, -20.44) for MDMA-AT versus -14.8 (-18.28, -11.28) for placebo with therapy (P < 0.001, d = 0.7). LS mean change in SDS score (95% CI) was -3.3 (-4.03, -2.60) for MDMA-AT versus -2.1 (-2.89, -1.33) for placebo with therapy (P = 0.03, d = 0.4). Seven participants had a severe treatment emergent adverse event (TEAE) (MDMA-AT, n = 5 (9.4%); placebo with therapy, n = 2 (3.9%)). There were no deaths or serious TEAEs. These data suggest that MDMA-AT reduced PTSD symptoms and functional impairment in a diverse population with moderate to severe PTSD and was generally well tolerated. ClinicalTrials.gov identifier: NCT04077437 .

Indexed as

N-Methyl-3,4-methylenedioxyamphetamineStress Disorders, Post-TraumaticCombined Modality TherapyDouble-Blind MethodHumansTreatment OutcomeN-Methyl-3,4-methylenedioxyamphetamine

Identifiers

PMID37709999
PMCPMC10579091
OpenAlexW4386740988

What Socratic 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 Socratic graph.