The endocannabinoid system in obsessive-compulsive disorder: A scoping review

About 40% of individuals suffering from obsessive-compulsive disorder (OCD) do not respond to current interventions such as pharmacotherapy and psychotherapy. The endocannabinoid system (ECS), which regulates several physiological, behavioural, and cognitive processes, has been suggested to contribute to the pathophysiology of OCD. However, the role of brain ECS in OCD remains largely unexplored. This scoping review evaluates the current literature on the ECS in OCD. A comprehensive literature search for preclinical and human studies of the ECS in OCD was conducted on OVID including Embase, MedLine, and PsychINFO databases. The search identified 489 publications. Of these, 13 were eligible studies and included in this review; 12 were preclinical and one study, incorporated both animal and human samples. Overall, preclinical findings consistently demonstrated that enhancing ECS activity attenuates compulsive and habitual behaviours, whereas inhibiting ECS activity exacerbates these behaviours. The study that utilized both animal and human samples reported reduced expression of genes encoding ECS enzymes and receptors in OCD. Overall, the findings reported in this review suggest the possibility of downregulation of endocannabinoid signaling in OCD and OCD-like behaviours, preliminarily raising the possibility that the ECS may have a role in modulating fronto-striatal circuitry. Further research is warranted investigating brain ECS activity and in particular clinical studies investigating the brain ECS in OCD.