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, Suzie Bratuskins, Musa Samir Sultani, Brooke Blakeley, Christopher G. Davey, J Simon Bell
Australian & New Zealand Journal of Psychiatry April 1, 2025 DOI: 10.1177/00048674251315642 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Umbrella review Peer reviewed |
|---|---|
| Sample size | 353 |
| Population | Adults with post-traumatic stress disorder |
| Intervention | MDMA-assisted psychotherapy |
| Dose | 50-125 mg |
| Topics | Psychedelic-assisted therapy PTSD MDMA |
| Keywords | MDMA-Assisted Therapy Psychedelics Umbrella review MDMA Treatment Trauma therapy PTSD Care Psychedelic medicine psychedel |
| Citations | 16 |
| Key findings | Meta-analyses show substantial benefits of MDMA-assisted psychotherapy for PTSD symptoms, response, and remission, but the evidence is rated low to very low certainty due to methodological limitations, while safety evidence is moderate to very low certainty with concerns about adverse event reporting and long-term data. |
Abstract
To critically evaluate published and unpublished systematic reviews and meta-analyses on the safety and efficacy of methylenedioxymethamphetamine-assisted psychotherapy for post-traumatic stress disorder. 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. 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. 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.
Comparable studies
Other systematic reviews and meta-analyses on MDMA and psychedelic-assisted therapy, most cited first.
Citations in the library
Cited by 15
- Current perspectives on psychedelic treatments in Europe. The Lancet Regional Health - Europe November 20, 2025
- Novel psychedelic interventions for post-traumatic stress disorder and their promise for precision medicine. Therapeutic Advances in Psychopharmacology December 4, 2025
- LSD: Mechanisms and relevance to the treatment of depression Neuroscience & Biobehavioral Reviews October 10, 2025
- Development of an Australian Clinical Practice Guideline on methylenedioxymethamphetamine (MDMA)-assisted Psychotherapy for Post-traumatic Stress Disorder. Journal of Affective Disorders July 17, 2025
- Subjective and neurocognitive profiling of clinical doses of 3,4-methylenedioxymethamphetamine (MDMA) in healthy volunteers: implications for therapeutic use Molecular Psychiatry April 8, 2026
and 10 more in the library
Cites 19
- MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nature Medicine June 1, 2021
- MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial. Nature Medicine October 1, 2023
- Blinding and expectancy confounds in psychedelic randomized controlled trials Expert Review of Clinical Pharmacology May 26, 2021
- A Meta-Analysis of Placebo-Controlled Trials of Psychedelic-Assisted Therapy Journal of Psychoactive Drugs June 12, 2020
- Adverse events in clinical treatments with serotonergic psychedelics and MDMA: A mixed-methods systematic review Journal of Psychopharmacology August 26, 2022
and 14 more in the library