A living systematic review, meta-analysis, and open data resource of trials of MDMA-assisted therapy for PTSD
Brooke L. Sevchik, S. Parker Singleton, Analiese Lahey, Pim Cuijpers, Mathias Harrer, Megan T. Jones, Sandeep M. Nayak, Eric C. Strain, Simon N. Vandekar, David B. Yaden, Robert H. Dworkin, J. Cobb Scott, Theodore D. Satterthwaite
medRxiv Preprint Server March 27, 2026 preprint DOI: 10.64898/2026.03.27.26349536 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review and meta-analysis Randomized |
|---|---|
| Sample size | 286 |
| Population | Participants from randomized controlled trials of MDMA for PTSD |
| Intervention | MDMA-assisted therapy |
| Topics | MDMA PTSD |
| Key findings | MDMA-assisted therapy reduces PTSD symptoms more than control conditions, with a standardized mean difference of -0.71, and higher dosing sessions and cumulative dose are associated with larger effects. |
Abstract
3,4-methylenedioxymethamphetamine (MDMA) has emerged as a potential treatment for post-traumatic stress disorder (PTSD), generating considerable enthusiasm in the field. However, rapidly changing evidence in a fast-moving field can be challenging to integrate. Here, we present a living systematic review and open-data meta-analytic resource on MDMA treatment for PTSD. In this initial release, six randomized controlled trials comprising 286 participants are included in the database. Our primary model uses inverse-variance random-effects meta-analysis of standardized mean differences on primary outcomes of PTSD. Compared to control conditions, MDMA showed a greater reduction in PTSD symptoms (Hedges’ g = -0.71). Meta-regression on both the number of dosing sessions and cumulative dose showed that a higher number of dosing sessions and a higher cumulative dose was related to larger effects of MDMA. Treatment with MDMA as compared to placebo also resulted in higher response (risk ratio (RR) = 1.35) and remission (RR = 2.25) rates. Most studies included in the database had a low risk of bias according to Cochrane guidelines, though these fail to capture pertinent challenges in the field such as expectancy, functional unblinding, potential issues with study conduct, and safety. The current findings were assigned an overall low certainty rating using the GRADE approach. Together, this systematic review and meta-analysis suggests that MDMA-assisted therapy results in short-term decreases in PTSD symptoms across studies to date, though more trials are needed. This living systematic review, meta-analysis, database, and online dashboard (sypres.io) will continue to be updated as evidence emerges, providing a valuable, open, and transparent resource for researchers in a rapidly evolving field.