Purpose <p>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.</p> Recent Findings <p>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.</p> Summary <p>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.</p>