Evaluating the efficacy and safety of MDMA for the treatment of Post Traumatic Stress Disorder: a systematic review

Megha Kodancha; Houssein Chahrour; Cassandra Carey; Hiva  Fazeli; Anahita Azadian; Sten Hiroshi Kajitani

doi:10.33178/SMJ.2025.1.4

Authors

Megha Kodancha https://orcid.org/0009-0002-4639-7499
Houssein Chahrour
Cassandra Carey
Hiva Fazeli
Anahita Azadian
Sten Hiroshi Kajitani

DOI:

https://doi.org/10.33178/SMJ.2025.1.4

Keywords:

MDMA, PTSD, post-traumatic stress disorder, psychotherapy, treatment-resistant, efficacy

Abstract

Background: Posttraumatic stress disorder (PTSD) affects approximately 5-7% of the population, with conventional treatments often proving inadequate for some patients. Recent studies suggest that methylenedioxymethamphetamine (MDMA) combined with psychotherapy may offer a novel therapeutic approach. This systematic review evaluates the efficacy and safety of MDMA-assisted psychotherapy for the treatment of PTSD in individuals with chronic, treatment-resistant forms of the disorder.

Methods: A comprehensive search was conducted in PubMed, OVID, Scopus, Cochrane databases, and select reference lists for randomized controlled trials (RCTs) evaluating MDMA as a treatment for PTSD. Eligibility criteria included RCTs with participants with confirmed PTSD diagnoses using standardized clinical assessments.

Results: In the RCT studies, there are significant reductions in PTSD symptoms (p<0.05) in those with MDMA-assisted psychotherapy compared to those with placebo and psychotherapy; dose-dependent improvements were observed in various measurements scales (specifically in CAPS-IV/CAPS-5 scores). Open-label trials further demonstrated improvements in PTSD symptoms when given MDMA-assisted therapy (p<0.05) and long-term analyses of studies demonstrated that effects of MDMA-assisted therapy were maintained for a minimum of 12 months post-intervention(p<0.05). Adverse effects were transient and mild to moderate, including anxiety, headache, fatigue, muscle tension, and insomnia.

Conclusion: Extant data suggests that MDMA-assisted psychotherapy for PTSD demonstrates significant symptom reduction, with sustained efficacy up to 12 months post-treatment. Functional unblinding is a major methodological challenge, which makes it difficult to interpret the magnitude of the effect MDMA has in the treatment of treatment-resistant PTSD. Future research should refine methodologies and explore long-term safety and efficacy in diverse populations.

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