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Meta-Analysis
. 2025 Apr;59(4):339-360.
doi: 10.1177/00048674251315642. Epub 2025 Feb 20.

Safety and efficacy of methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in post-traumatic stress disorder: An overview of systematic reviews and meta-analyses

Alene Sze Jing Yong  1 , Suzie Bratuskins  2 , Musa Samir Sultani  1   3 , Brooke Blakeley  1 , Christopher G Davey  4 , J Simon Bell  1
Affiliations
Meta-Analysis

Safety and efficacy of methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in post-traumatic stress disorder: An overview of systematic reviews and meta-analyses

Alene Sze Jing Yong et al. Aust N Z J Psychiatry. 2025 Apr.

Abstract

Objective: To critically evaluate published and unpublished systematic reviews and meta-analyses on the safety and efficacy of methylenedioxymethamphetamine-assisted psychotherapy for post-traumatic stress disorder.

Methods: Six bibliometric databases and grey literature were searched from inception to 9 May 2024 for systematic reviews on the safety and efficacy of methylenedioxymethamphetamine (MDMA)-assisted psychotherapy compared to psychotherapy alone among adults with post-traumatic stress disorder. Quality assessment using the AMSTAR-2 tool was conducted independently by two investigators.

Results: Fourteen systematic reviews comprising 20 primary studies involving up to 353 participants were included. All reviews included studies of one-to-three sessions of 50-125 mg MDMA-assisted psychotherapy (some with supplemental dosage) compared to either 25-40 mg of MDMA or inactive placebo with psychotherapy. Four were deemed high quality. Meta-analyses reported substantial benefits of MDMA-assisted psychotherapy in improving post-traumatic stress disorder symptoms (standardised mean difference, 0.8-1.3), response rate (relative risk, 1.3-3.5) and remission rate (relative risk, 2.3-2.9) compared to psychotherapy alone. However, for reviews that assessed the certainty of evidence, the evidence was rated as low to very low certainty due to high risk of bias, indirectness and imprecision. There was moderate-quality evidence that MDMA-assisted psychotherapy was associated with an increased odd of transient adverse events. However, reviews noted reliance on spontaneous rather than systematic adverse event reporting, discrepancies between adverse events reported in published studies and clinical trial registries, and a lack of long-term safety data.

Conclusion: Four high-quality systematic reviews suggest low to very low certainty evidence for efficacy outcomes and moderate to very low quality evidence for safety outcomes.

Keywords: MDMA-assisted therapy; Psychedelics; post-traumatic stress disorder; umbrella review.

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Conflict of interest statement

Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: J.S.B. has received grant funding or consulting funds from the National Health and Medical Research Council, Victorian Government Department of Health and Human Services, Dementia Australia Research Foundation, Yulgilbar Foundation, Aged Care Quality and Safety Commission, Dementia Centre for Research Collaboration, Pharmaceutical Society of Australia, Society of Hospital Pharmacists of Australia, GlaxoSmithKline Supported Studies Programme, Amgen and several aged care provider organisations unrelated to this work. All grants and consulting funds were paid to the employing institution. M.S.S. was supported by the Turing Mobility Funding for overseas UK students. All the other authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Figures

Figure 1.
Figure 1.
Reporting guideline for overviews of reviews of healthcare interventions: the Preferred Reporting Items for Overviews of Reviews (PRIOR) statement. Source: Gates et al. (2022).
See this image and copyright information in PMC

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