Efficacy of Psychoactive Drugs for the Treatment of Posttraumatic Stress Disorder: A Systematic Review of MDMA, Ketamine, LSD and Psilocybin

Abstract

The aim of this systematic review was to examine the efficacy of MDMA, ketamine, LSD, and psilocybin for the treatment of posttraumatic stress disorder (PTSD). A search of four databases for English language, peer-reviewed literature published from inception to 18th October 2019 yielded 2,959 records, 34 of which were screened on full-text. Observational studies and RCTs which tested the efficacy of MDMA, ketamine, LSD, or psilocybin for reducing PTSD symptoms in adults, and reported changes to PTSD diagnosis or symptomatology, were included. Nine trials (five ketamine and four MDMA) met inclusion criteria. Trials were rated on a quality and bias checklist and GRADE was used to rank the evidence. The evidence for ketamine as a stand-alone treatment for comorbid PTSD and depression was ranked "very low", and the evidence for ketamine in combination with psychotherapy as a PTSD treatment was ranked "low". The evidence for MDMA in combination with psychotherapy as a PTSD treatment was ranked "moderate".

In the evidence

This study is part of the evidence base for 2 syntheses in the library. Here is how each one recorded it.

• State of the evidence: Ketamine for PTSD ↕Mixed

  Ketamine as a stand-alone treatment for comorbid PTSD and depression was rated very low quality evidence, and ketamine plus psychotherapy low quality, versus moderate for MDMA plus psychotherapy.

  Synthesized October 22, 2026

• State of the evidence: Psilocybin for PTSD ?Unclear

  Nine trials met criteria (five ketamine, four MDMA); no psilocybin or LSD trials were identified, and MDMA plus psychotherapy had moderate-quality evidence while ketamine evidence was low to very low.

  Synthesized October 22, 2026

Comparable studies

Other systematic reviews and meta-analyses on psilocybin for PTSD, most cited first.