Efficacy of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for posttraumatic stress disorder: A systematic review and meta-analysis of clinical and functional outcomes
Natalia E. Fares-Otero, Yuki Furukawa, Marit Sijbrandij, Stefan Leucht, Eduard Vieta, Pim Cuijpers, Mathias Harrer, Soraya Seedat
European Neuropsychopharmacology March 12, 2026 DOI: 10.1016/j.euroneuro.2026.112802 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review and meta-analysis Randomized Qualitative Peer reviewed |
|---|---|
| Sample size | 298 |
| Population | Adults with posttraumatic stress disorder (PTSD) |
| Interventions | 3 4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) |
| Topics | MDMA |
| Keywords | Dissociative Posttraumatic stress Clinical trial Cognition Grading engineering Randomized controlled trial Cognitive behavioral therapy Meta-analysis Placebo Clinical psychology Medline Cognitive therapy Physical therapy Psychological intervention Relative risk Certainty |
| Key findings | MDMA-assisted therapy was associated with reductions in PTSD symptom severity and dissociative symptoms, and may improve functioning, but the certainty of the evidence was very low. |
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]; I² = 68.8 %, τ2 = 1.02), dissociative symptoms (n = 148, k = 5, SMD = -0.37, 95 % CI [-0.70, -0.04]; I² = 0.0 %, τ2 = 0), and may improve functioning (n = 227, k = 4, SMD = -0.83, 95 % CI [-1.47, -0.19]; I² = 61.2 %, τ2 = 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.