Efficacy of Psychoactive Drugs for the Treatment of Posttraumatic Stress Disorder: A Systematic Review of MDMA, Ketamine, LSD and Psilocybin
This review (2020, s=9) investigated the therapeutic potential of MDMA, ketamine, LSD, and psilocybin as therapeutic agents for PTSD. However, only studies concerning ketamine and MDMA were found and included in the review, and it is suggested that MDMA-assisted psychotherapy holds moderate promise.
Authors
- Varker, T.
- Watson, L.
- Gibson, K.
Published
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”.
Research Summary of 'Efficacy of Psychoactive Drugs for the Treatment of Posttraumatic Stress Disorder: A Systematic Review of MDMA, Ketamine, LSD and Psilocybin'
Introduction
Varker and colleagues frame the review by noting that standard first-line treatments for posttraumatic stress disorder (PTSD), such as trauma-focused cognitive behavioural therapy and EMDR, have substantial non‑response rates and barriers to access. They describe renewed clinical interest in drugs with psychedelic or hallucinogenic properties—specifically ketamine, MDMA, LSD and psilocybin—as potential adjuncts or alternatives for people who do not benefit from or cannot access conventional interventions. The introduction summarises putative mechanisms relevant to PTSD for each agent: ketamine’s glutamatergic actions and possible reversal of stress‑related synaptic deficits; MDMA’s serotonergic, oxytocinergic and cortisol effects that may reduce amygdala activity and enhance prosocial emotion and therapeutic alliance; and LSD and psilocybin’s serotonergic (5‑HT2A) activity with effects on affect, cognition and fear extinction observed in preclinical and clinical work. This review was commissioned by the Department of Veterans’ Affairs to assess the clinical evidence for MDMA, ketamine, LSD and psilocybin as stand‑alone treatments or in combination with psychotherapy for adults with PTSD. The authors sought to fill a gap in the literature by systematically identifying and appraising controlled trials and observational studies, and by grading the overall quality of the evidence to inform research and practice priorities.
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Study Details
- Study Typemeta
- Journal
- Compounds
- Topics
- APA Citation
Varker, T., Watson, L., Gibson, K., Forbes, D., & O’Donnell, M. L. (2021). Efficacy of Psychoactive Drugs for the Treatment of Posttraumatic Stress Disorder: A Systematic Review of MDMA, Ketamine, LSD and Psilocybin. Journal of Psychoactive Drugs, 53(1), 85-95. https://doi.org/10.1080/02791072.2020.1817639
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