Efficacy of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for posttraumatic stress disorder: A systematic review and meta-analysis of clinical and functional outcomes.

Meta-AnalysisPubMedMarch 13, 2026PMID: 41825162 DOI

Abstract

Posttraumatic stress disorder (PTSD) is a chronic and disabling condition and identifying beneficial therapies is timely and important. We aimed to estimate the efficacy of 3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) compared with control on clinical and functional outcomes in PTSD. A PRISMA-compliant search (PROSPEROCRD42022353261) up to August 14, 2025, covered nine databases and manual searches to identify randomised controlled trials (RCTs). Methodological quality was assessed using the Cochrane Risk of Bias tool (RoB2), and the certainty of the evidence for each outcome was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Of 1035 records identified, 14 studies met inclusion criteria for qualitative synthesis; eight trials provided sufficient data for quantitative synthesis (k = 24). Random-effects meta-analyses indicated that MDMA-AT was associated with reductions in PTSD symptom severity (n = 298, k = 9, SMD = -1.19, 95 % CI [-1.95, -0.42]; I = 68.8 %, 2 = 1.02), dissociative symptoms (n = 148, k = 5, SMD = -0.37, 95 % CI [-0.70, -0.04]; I = 0.0 %, 2 = 0), and may improve functioning (n = 227, k = 4, SMD = -0.83, 95 % CI [-1.47, -0.19]; I = 61.2 %, 2 = 0.27). No clear evidence of benefit was observed for depressive symptoms. Most studies showed a high risk of bias in the measurement of the outcome, and some concerns due to deviations from the intended intervention; the overall certainty of the evidence was very low. The number of trials remains limited, with considerable heterogeneity in certain outcomes, small sample sizes, and the absence of active controls in most studies, which likely compromised blinding integrity. Current findings suggest that MDMA-AT may warrant further investigation as a potential treatment for PTSD; however, larger, higher-quality RCTs with active controls and long-term follow-up are needed to determine its efficacy.

Authors (8)

Natalia E Fares-OteroLeadInstitute of Neurosciences, University of Barcelona (UBNeuro), Department of Psychiatry and Psychology, Bipolar and Depressive Disorders Unit, Hospital Clínic, Fundació Clínic per a la Recerca Biomèdica, Institut d'Investigacions Biomèdiques August Pi i Sunyer (FCRB-IDIBAPS), Barcelona, Catalonia, Spain; Section for Evidence-Based Medicine in Psychiatry and Psychotherapy, School of Medicine and Health, Technical University of Munich (TUM), Munich, Germany. Electronic address: nefares@recerca.clinic.cat.

Yuki FurukawaSection for Evidence-Based Medicine in Psychiatry and Psychotherapy, School of Medicine and Health, Technical University of Munich (TUM), Munich, Germany.

Marit SijbrandijDepartment of Clinical, Neuro, and Developmental Psychology, WHO Collaborating Centre for Research and Dissemination of Psychological Interventions, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.

Stefan LeuchtSection for Evidence-Based Medicine in Psychiatry and Psychotherapy, School of Medicine and Health, Technical University of Munich (TUM), Munich, Germany; German Center for Mental Health (DZPG), Munich, Germany.

Eduard VietaInstitute of Neurosciences, University of Barcelona (UBNeuro), Department of Psychiatry and Psychology, Bipolar and Depressive Disorders Unit, Hospital Clínic, Fundació Clínic per a la Recerca Biomèdica, Institut d'Investigacions Biomèdiques August Pi i Sunyer (FCRB-IDIBAPS), Barcelona, Catalonia, Spain; Faculty of Medicine and Health Sciences, University of Barcelona (UB), Barcelona, Catalonia, Spain; Network Centre for Biomedical Research in Mental Health (CIBERSAM), Health Institute Carlos III (ISCIII), Madrid, Spain.

Pim CuijpersDepartment of Clinical, Neuro, and Developmental Psychology, WHO Collaborating Centre for Research and Dissemination of Psychological Interventions, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.

Mathias HarrerSection for Evidence-Based Medicine in Psychiatry and Psychotherapy, School of Medicine and Health, Technical University of Munich (TUM), Munich, Germany; Department of Clinical, Neuro, and Developmental Psychology, WHO Collaborating Centre for Research and Dissemination of Psychological Interventions, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.

South African PTSD Research Programme of Excellence, Department of Psychiatry, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa; South African Medical Research Council Genomics of Brain Disorders Research Unit, Department of Psychiatry, Stellenbosch University, Cape Town, South Africa.

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Efficacy of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for posttraumatic stress disorder: A systematic review and meta-analysis of clinical and functional outcomes.

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