Effectiveness of Psychedelic-Assisted Interventions for Trauma Treatment: A Systematic Review

Background and Purpose: Psychedelic-assisted interventions have emerged as promising alternatives for trauma-related disorders, with growing evidence supporting their potential to reduce trauma symptoms. However, existing studies vary widely in terms of psychedelic substances, trauma types and sources, intervention settings, and methodological approaches. Thus, it remains unclear which treatments are most effective, under what conditions, and for what types of trauma. This systematic review aims to synthesize current evidence and clarify the scope, efficacy, and practical implications of psychedelic-assisted interventions in trauma treatment.

Methods: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist and was managed using Covidence software. A comprehensive keyword search was conducted across seven electronic databases. Studies were included if they were published between 1994 and 2024, written in English, peer-reviewed, involved an adult study sample, focused on psychedelic substances in relation to trauma-related outcomes, examined intervention effectiveness/outcomes, and employed robust empirical methodologies. The initial search identified 1,646 articles. After removing duplicates (n=367), 1,279 articles were independently screened by two reviewers at the title and abstract level. Discrepancies were resolved through weekly team discussions. Sixty-three articles advanced to full-text review, and 47 were included in the final analysis.

Results: Sample sizes ranged from 6 to 452 participants. Most studies focused on chronic or complex trauma, often resulting from military combat, sexual and physical abuse, and developmental trauma. Secondary trauma (e.g., witnessing violence) and racial trauma (e.g., racial discrimination) were also reported. Post-Traumatic Stress Disorder (PTSD) was the primary focus in 38 studies. Other trauma-related conditions included probable PTSD (without formal diagnosis), Acute Stress Disorder, and Adjustment Disorder. The most frequently studied substances were ketamine, MDMA, and psilocybin. Other examined substances included ibogaine, 5-MeO-DMT, LSD, ayahuasca, mescaline, and combined use. Randomized controlled trials (RCTs) were the most common study design, especially for ketamine and MDMA, followed by open-label pilot studies, cross-sectional observational studies, and qualitative investigations. Most interventions were conducted in structured, protocolized clinical environments (e.g., hospitals), while a smaller number of studies examined non-clinical settings, including self-directed experiences and ayahuasca retreats. Regarding intervention effectiveness, ketamine showed rapid relief of suicidality and depressive symptoms. MDMA demonstrated enduring benefits for chronic and complex PTSD. Psilocybin facilitated emotional breakthroughs and trauma processing. Ceremonial ayahuasca use showed significant subjective reports of emotional and spiritual healing. Combined ibogaine and 5-MeO-DMT programs indicated therapeutic potential for trauma treatment among veterans.

Conclusion and implications: Psychedelic-assisted interventions demonstrated meaningful reductions in trauma-related symptoms across psychedelics, with both acute and sustained benefits. Among them, ketamine and MDMA showed the most robust and lasting outcomes, supported by rigorous study designs. Other substances, such as psilocybin, ayahuasca, ibogaine, and 5-MeO-DMT, also demonstrated therapeutic potential for emotional healing and trauma processing. Intervention setting emerged as a critical factor influencing treatment outcomes, with structured clinical trials yielded more consistent outcomes and ceremonial contexts offered unique experiences. Future research should prioritize methodological consistency and more inclusive sampling. In practice, careful consideration of patient characteristics, trauma histories, and treatment context is essential to ensure safe and effective implementation.