Psychedelic-Assisted Psychotherapy for the Treatment of PTSD: A Systematic Review and Meta-Analysis
Fizza Mitter, Anton Sheptooha, Janni Leung, Sarangan Ketheesan, Wọlé Akóṣílè
Psychoactives June 8, 2026 DOI: 10.3390/psychoactives5020016 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review and meta-analysis Randomized Peer reviewed |
|---|---|
| Sample size | 358 |
| Population | Adults with post-traumatic stress disorder (PTSD) in randomized controlled trials |
| Interventions | MDMA-assisted psychotherapy Ketamine Cannabidiol |
| Topics | CBD MDMA Psychedelic-assisted therapy PTSD |
| Keywords | Systematic review Randomized controlled trial Clinical trial Meta-analysis Medline Psychotherapist Clinical psychology Hypnosis Placebo |
| Key findings | MDMA-assisted psychotherapy showed a significant moderate-to-large reduction in PTSD symptom severity, while ketamine and cannabidiol did not show significant or clear benefit. |
Abstract
Post-traumatic stress disorder (PTSD) remains inadequately treated by existing pharmacological and psychological interventions, prompting growing interest in psychedelic-assisted psychotherapy. Although randomised controlled trials have evaluated several psychedelic agents for PTSD, to our knowledge, no prior PTSD-specific synthesis has quantitatively examined multiple agent classes within a single review framework. This systematic review and meta-analysis searched PsycINFO, CINAHL, Embase, MEDLINE, and clinical trial registries to identify RCTs of psychedelic-assisted psychotherapy for PTSD. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool, and random-effects meta-analyses were conducted for efficacy outcomes; safety and therapeutic protocols were synthesised narratively. Eleven RCTs involving 358 participants met inclusion criteria, evaluating MDMA, ketamine, and cannabidiol, of which eight contributed to meta-analyses. MDMA-assisted psychotherapy demonstrated a significant moderate-to-large reduction in PTSD symptom severity with negligible heterogeneity, and participants were significantly more likely to achieve clinical response and loss of PTSD diagnosis. The pooled effect for ketamine was small and non-significant, and a single cannabidiol trial showed no clear benefit. All agents were generally well tolerated. MDMA-assisted psychotherapy showed a promising efficacy signal for PTSD symptom reduction, although safety data were heterogenous and remain insufficient for strong comparative conclusions. Evidence for ketamine and cannabidiol remains too limited to support clinical implementation and it is noted that the current evidence base is dominated by MDMA trials. Further adequately powered trials with standardised outcomes and direct comparative studies across agents are needed.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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MDMA-assisted psychotherapy showed a significant moderate-to-large reduction in PTSD symptom severity with negligible heterogeneity and higher rates of clinical response and loss of diagnosis; ketamine and cannabidiol did not show clear benefit.
Synthesized
Comparable studies
Other systematic reviews and meta-analyses on MDMA and psychedelic-assisted therapy, most cited first.
Citations in the library
Cites 16
- MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nature Medicine June 1, 2021
- The safety and efficacy of {+/-}3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. Journal of Psychopharmacology July 19, 2010
- 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial. The Lancet Psychiatry May 1, 2018
- A randomized, controlled pilot study of MDMA (±3,4-Methylenedioxymethamphetamine)-assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD) Journal of Psychopharmacology October 31, 2012
- MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial. Nature Medicine October 1, 2023
and 11 more in the library