Psilocybin's effects on obsessive-compulsive behaviors: A systematic review of preclinical and clinical evidence
Psychedelics. October 28, 2025 James J Gattuso, Bilgenur Bezcioglu, Carey Wilson et al. 1 citation
Psilocybin, a serotonergic psychedelic, shows growing evidence for reducing obsessive-compulsive symptoms. A systematic review of 13 studies (4 clinical trials, 9 preclinical) found that single doses rapidly reduced symptoms in patients with OCD and body dysmorphic disorder. In wild-type mice, psilocybin briefly decreased marble-burying behavior only on the first day. In SAPAP3 knockout mice, a genetic model of compulsive behavior, a single dose produced robust, lasting reductions in excessive grooming, replicated across labs and doses. Chronic hallucinogenic doses did not improve anxiety or compulsive behavior in these mice, but chronic sub-hallucinogenic doses in rats reduced self-grooming and increased synaptic markers in the paraventricular thalamus. The evidence suggests transient clinical effects and lasting anti-compulsive effects in animal models, warranting larger placebo-controlled trials with neuroimaging.