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

Summary & key facts

Researchers gave 19 adults with moderate or worse obsessive-compulsive disorder two single oral doses of psilocybin, first a very low 1 mg dose and then a 10 mg dose four weeks later. The sessions took place in a day-care setting with clinicians and psychological support before, during and after each dose. One week after the 10 mg dose, people had a clear drop in compulsive symptoms that was moderate to large in size, but the benefit faded over the next three weeks. Psilocybin was generally well tolerated and did not change depression scores in this small, non-randomised study. The results suggest a single 10 mg dose might give short-term relief of compulsions, but larger controlled trials are needed to know if it really helps people in the longer term.

Key facts:

• Nineteen adults with moderate or worse OCD took part in the study, and 18 finished all the assessments.
• Each person received two oral psilocybin doses in the same order: a very low 1 mg dose first, then 10 mg four weeks later. Sessions included clinical supervision and psychological support.
• One week after the 10 mg dose there was a moderate to large reduction in overall OCD symptoms measured by a standard scale. The effect was stronger for compulsive behaviors than for obsessive thoughts.
• The beneficial effect on compulsions was largest at one week and got smaller over the next three weeks.
• There was no detectable change in depression scores after psilocybin when measured with a standard depression scale.
• Psilocybin at both doses was generally well tolerated. Few adverse events were reported and there were no serious adverse events.
• The study was small and not randomised. These limits mean the results are only preliminary and need confirmation in larger, controlled trials.

Abstract

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.

Topics

Forensic Toxicology and Drug Analysis Pain Management and Placebo Effect Psychedelics and Drug Studies

Categories

Clinical Psychology Psychology Social Sciences

Tags

Hallucinogen Medicine Obsessive compulsive Psilocybin Psychiatry Psychology

Substances

Psilocybin

Conditions & symptoms

Obsessive-Compulsive Disorder Sadness or low mood