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

A systematic review of nine trials found that the evidence for MDMA combined with psychotherapy as a treatment for PTSD is of moderate quality, while the evidence for ketamine—whether used alone for comorbid PTSD and depression or combined with psychotherapy—is very low to low. The review searched four databases for peer-reviewed literature up to October 2019 and included five ketamine and four MDMA trials. No trials of LSD or psilocybin met the inclusion criteria. The authors used a quality checklist and GRADE to rank the evidence, concluding that MDMA-assisted psychotherapy shows the strongest support among the psychedelics examined for reducing PTSD symptoms.

Study at a glance

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".