This study aims to investigate the effects of oral psilocybin on OCD symptomatology and provide the first evidence of the neural mechanism that may mediate psilocybin's purported therapeutic effects on OCD.
Randomised, double-blind, active-placebo-controlled, single-dose study (psilocybin 0.25 mg/kg vs niacin 250 mg) in participants with moderate–severe OCD; participants are admitted inpatient for the dosing week.
Primary clinical assessments at 24 and 48 hours and at 1 week, 2 weeks, 1 month and 3 months; resting-state fMRI at baseline and 48 hours to examine fronto-striatal connectivity changes and their relation to symptom improvement.
Psilocybin 0.25 mg/kg oral
Inpatient dosing with baseline and 48-hour fMRI follow-up
Niacin 250 mg (active placebo)
Active-placebo comparator; participants offered open-label psilocybin after 48 hours
Qualitative interviews with 12 participants from a randomized, placebo‑controlled single‑dose psilocybin trial for treatment‑refractory OCD showed that set and setting strongly shaped acute (often partial) perceptual, emotional and metacognitive experiences, which were followed by post‑dosing changes in OCD symptoms, perceptions and behavioural/metacognitive processes. These changes mapped onto putative mechanisms of ERP and ACT, suggesting hypotheses for further study and potential value in integrating psilocybin with structured psychotherapy for OCD.