A Systematic Review of the efficacy, safety, and Tolerability of Psychedelics in the Treatment of post-traumatic Stress Disorder
Manasicha P. Wongpaiboon, Jackson L. Shelton, Eric Delgado Rendon, Maddison Vail
Current Treatment Options in Psychiatry December 26, 2025 DOI: 10.1007/s40501-025-00373-w (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Interventions | Ketamine MDMA ayahuasca DMT LSD ibogaine psilocybin |
| Topics | Ketamine Psilocybin PTSD |
| Keywords | Hallucinogens 3,4-methylenedioxymethamphetamine Psychotherapy adjunctive |
| Key findings | Ketamine and MDMA have the most developed evidence supporting their potential therapeutic roles in PTSD, though findings should be interpreted cautiously due to heterogeneity across study designs. |
Abstract
Purpose A systematic review was conducted to synthesize the efficacy, safety, and tolerability of psychedelics including ketamine, MDMA, ayahuasca, LSD, DMT, ibogaine, and psilocybin in the treatment of PTSD. Recent Findings Among 5,155 studies identified, 42 studies met criteria and were included in our systematic review. Ketamine consistently produced rapid symptom improvement that attenuated in single-dose trials; but, persisted when repeated or in conjunction with psychotherapy. Studies using MDMA was associated with substantial and durable PTSD symptom improvement in controlled settings. Data for ayahuasca, DMT, LSD, ibogaine, and psilocybin were preliminary but suggested potential benefits. Safety was assessed in most studies and were overall well tolerated with transient autonomic changes being the most common adverse effects. Summary While MDMA and ketamine currently have the most developed evidence that supports their potential therapeutic roles in PTSD, findings should be interpreted cautiously given heterogeneity across study designs including sample size, sample make-up, protocols, and reporting. Other compounds show early promise but remain investigational. Large sample sizes and methodological rigorous studies with standardized objective endpoints and long-term safety follow-up are needed before these psychedelic-assisted interventions can be widely implemented or recommended in clinical practice.
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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Found ketamine and MDMA have the most developed evidence for PTSD, while data for ayahuasca, DMT, LSD, ibogaine, and psilocybin were preliminary but suggested potential benefits; safety was overall well tolerated.
Synthesized
Comparable studies
Other systematic reviews and meta-analyses on psilocybin for PTSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Efficacy of Psychoactive Drugs for the Treatment of Posttraumatic Stress Disorder: A Systematic Review of MDMA, Ketamine, LSD and Psilocybin Adults with PTSD | 2020 | Systematic review | n = 9 |
| A Systematic Review of the Neurocognitive Effects of Psychedelics in Healthy Populations: Implications for Depressive Disorders and Post-Traumatic Stress Disorder Healthy individuals and patients with PTSD or MDD | 2024 | Systematic review | n = 43 |
| Psychedelic-Assisted Psychotherapy for Post-Traumatic Stress Disorder, Anxiety Disorders, Mood Disorders, or Substance Use Disorders Patients with various mental health conditions | 2021 | Systematic review |