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New treatments for OCD? Evidence for cannabinoids and psychedelics.

Michael Van Ameringen, Vidhi Patel, Beth Patterson, Paige Hopkinson, Maryam Rahat

J Psychiatr Res November 26, 2025 DOI: 10.1016/j.jpsychires.2025.11.021 via PubMed

Summary

AI-generated from the abstract

Obsessive-compulsive disorder (OCD) involves imbalances in serotonin, dopamine, and glutamate. About 40-60% of patients do not respond to first-line treatments and are considered treatment resistant. There is no gold-standard treatment for these patients. This scoping review examined evidence for cannabinoids and psychedelics (psilocybin, LSD, DMT, MDMA) in OCD. Most evidence comes from surveys and case reports, with few controlled trials. The review found a lack of evidence supporting cannabinoids for OCD, but a stronger signal for psilocybin in treatment-resistant OCD. Well-controlled randomized trials are needed.

Study at a glance

Characteristics Scoping review Cross-sectional Peer reviewed
Key finding The current evidence indicates a lack of support for cannabinoids in treating OCD, but a stronger signal for psilocybin in treatment-resistant OCD.

Abstract

The etiology of OCD is complex and appears to involve multiple biological pathways. Imbalances in central serotonin, dopamine, and glutamate activities are widely thought to play a causative role. Despite strong evidence supporting first-line OCD pharmacotherapies, approximately 40-60 % of OCD patients remain unresponsive and are considered treatment resistant (TR). Although a range of agents have been examined in TR-OCD, there is no gold-standard, indicating a need to broaden our clinical armamentarium. Cannabis has been used for centuries in many cultures for both medicinal and recreational purposes. Clinical interest in these agents has recently re-emerged. The current evidence for the use of cannabinoids in OCD is very small and includes survey-based, self-report studies with very few controlled trials. Additionally, after a long hiatus from psychiatric research, psychedelics have re-emerged as agents of interest within the past decade. A comprehensive scoping review of the OCD literature including published and grey literature was conducted and detailed in this paper. The current evidence associated with Cannabinoids, Psilocybin, Lysergic acid diethylamide (LSD), N,N-Dimethyltryptamine (N,N-DMT), and Methylenedioxyphenethylamine (MDMA) in the treatment of OCD is detailed. Much of the current evidence examining cannabinoids and psychedelics in OCD is from cross-sectional surveys and case reports, as well as some small clinical trials. There is a shortage of well-controlled, methodologically rigorous RCTs to properly test the efficacy of cannabinoids or psychedelics in OCD and related disorders. However, the current evidence appears to indicate a lack of evidence supporting the use of either synthetic or natural cannabinoids to treat OCD, but a stronger signal for the use of psilocybin in TR-OCD.

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