Efficacy and risks of psychedelics in treatment of posttraumatic stress disorder: A systematic review

This systematic review aimed to identify which psychedelics have the best efficacy evidence for PTSD, assess safety data, and examine whether demographic factors influence outcomes. Searches were conducted across PubMed, Web of Science, and Scopus, with 13 RCTs ultimately meeting inclusion criteria - 6 evaluating MDMA-assisted psychotherapy and 7 evaluating intravenous ketamine.

Purpose

The purpose of this review is to evaluate which psychedelics have the most efficacy data to support their use in the treatment of posttraumatic stress disorder (PTSD). This review also aims to assess safety data and concerns related to psychedelic therapies and identify demographic characteristics that may influence clinical outcomes.

Summary

A systematic review of the literature was conducted on PubMed, Web of Science, and Scopus to identify randomized controlled studies evaluating the use of psychedelic therapy in treatment of PTSD. Thirteen studies met our inclusion criteria and were included in the review. Six studies evaluated 3,4-methylenedioxymethamphetamine (MDMA)–assisted psychotherapy, while 7 studies evaluated ketamine. Study findings regarding efficacy were mixed. Four of the 6 studies evaluating MDMA-assisted psychotherapy demonstrated statistically significant improvement in PTSD symptoms, while 3 of the 7 studies evaluating intravenous ketamine (ketamine IV) demonstrated statistically significant efficacy (eg, reduced PTSD symptoms, durable effect) in relation to comparators. Both therapies were generally well tolerated. The majority of studies were conducted in primarily civilian populations, with one MDMA study and 2 ketamine IV studies focused on veterans.

Conclusion

MDMA and ketamine IV currently have the greatest support in the literature for efficacy in PTSD. Studies suggest treatment with these agents under supervision may lead to improvements in PTSD symptoms, with the medications being generally well tolerated. However, caution should be used when interpreting study results due to limitations such as treatment expectancy effect and the potential for inadequate blinding. Randomized controlled studies of other psychedelics (eg, psilocybin, lysergic acid diethylamide) are needed to assess their utility in PTSD.

Jennifer E Thomas, Anna Dellarole, Joshua Caballero, Efficacy and risks of psychedelics in treatment of posttraumatic stress disorder: A systematic review, American Journal of Health-System Pharmacy, 2026;, zxag062, Read Paper

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