Single-dose (10 mg) psilocybin reduces symptoms in adults with obsessive-compulsive disorder: A pharmacological challenge study

Background Obsessive-compulsive disorder (OCD) is a common and disabling condition. A large proportion of patients fail to respond to first-line treatment with serotonin reuptake inhibitors either selective serotonin reuptake inhibitors (SSRIs) or clomipramine. Preliminary evidence suggests psilocybin, a serotonin receptor agonist, might be efficacious. We conducted a pharmacological challenge study to investigate the efficacy and mechanisms of effect of psilocybin in OCD. This analysis reports the clinical outcomes only. Methods Participants with a diagnosis of OCD of at least moderate severity, received two single doses of oral psilocybin, 1 mg followed by 10 mg, administered in fixed order separated by 4 weeks. On the day of dosing, they were treated in a day-care facility in the presence of clinicians experienced in the use of psychedelics for treating mental disorders. Psychological support was provided before, during and after dosing. Participants and raters were blinded to the order of treatment. They were assessed on the day before each dose (baseline 1, 2), on the day of dosing and at intervals over a 4-week period afterward using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) (primary clinical outcome) and secondary clinical outcomes including the Montgomery-Åsberg Depression Rating Scale (MADRS). Adverse effects were also recorded. Results Nineteen adult participants (aged 20–60) entered the study and 18 completed all assessments. Clinical outcomes following 1 mg and 10 mg psilocybin were compared using a linear mixed-effects model and ANOVA. A significant between-dosage effect favouring 10 mg psilocybin was found one-week after dosing on the Y-BOCS (Cohen's d = 0.82, p = 0.002). In particular, the effect one-week after dosing was statistically significant on the compulsion subscale of the Y-BOCS (Cohen's d: 0.74, p = 0.003), compared to obsession (Cohen's d: 0.50, p = 0.06). The effect diminished over the subsequent 3 weeks. No effect of psilocybin was detected on the MADRS. Psilocybin was well tolerated, with few adverse events reported at both dosages and no serious adverse events. Conclusions In this study, which was limited by a small sample size and the absence of randomisation, a 10 mg dose of oral psilocybin was found to be well-tolerated and potentially efficacious in patients with OCD. Psilocybin produced a rapid-onset, moderate to large effect on compulsive symptoms, which lasted up to one week after dosing. Future randomised placebo-controlled clinical trials investigating a longer course of multiple weekly doses of 10 mg psilocybin are indicated in OCD and in other obsessive-compulsive and related disorders characterised by compulsions.