The endocannabinoid system in obsessive-compulsive disorder: A scoping review
Hanan Idd1, Gil Angela Dela Cruz2, Jenelle Athansius2
1Institute of Medical Science, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada; General Adult Psychiatry and Health Systems, Centre for Addiction and Mental Health, 100 Stokes Street, Toronto, Ontario M6J 1H4, Canada.
Neuroscience and Biobehavioral Reviews
|March 23, 2026
Summary
The endocannabinoid system (ECS) may be downregulated in obsessive-compulsive disorder (OCD). Enhancing ECS activity reduced compulsive behaviors in preclinical studies, suggesting a potential therapeutic target for OCD.
Area of Science:
- Neuroscience
- Psychiatry
- Pharmacology
Background:
- Obsessive-compulsive disorder (OCD) affects 40% of individuals unresponsive to current treatments.
- The endocannabinoid system (ECS) regulates physiological and cognitive processes, potentially implicated in OCD.
- The brain's ECS role in OCD pathophysiology is largely unexplored.
Purpose of the Study:
- To evaluate current literature on the endocannabinoid system (ECS) in obsessive-compulsive disorder (OCD).
- To explore the potential role of the brain ECS in OCD.
- To identify future research directions for ECS in OCD.
Main Methods:
- A comprehensive literature search was conducted on OVID (Embase, MedLine, PsychINFO).
- Included preclinical and human studies investigating the ECS in OCD.
- 13 eligible studies were identified from 489 publications.
Main Results:
- Preclinical findings consistently show enhancing ECS activity attenuates compulsive behaviors.
- Inhibiting ECS activity exacerbates compulsive and habitual behaviors.
- One study reported reduced expression of ECS genes and receptors in OCD patients and animal models.
Conclusions:
- Findings suggest a possible downregulation of endocannabinoid signaling in OCD.
- The ECS may play a role in modulating fronto-striatal circuitry relevant to OCD.
- Further research, particularly clinical studies, is warranted to investigate brain ECS activity in OCD.
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