Consciousness and Psilocybin Effects on Well-Being: The CoPEWell Study

This Phase I, randomised, double‑blind, parallel trial (n=120) will evaluate whether intravenous psilocybin improves wellbeing when administered while awake versus while asleep, and whether psilocybin given during sleep differs from saline placebo, in healthy adults aged 18–45 with sub‑optimal self‑reported wellbeing. The primary outcome is change in Warwick–Edinburgh Mental Wellbeing Scale (WEMWBS) score from baseline (Day 0) to post‑dosing Day 29. Participants are randomised to one of three overnight dosing arms: psilocybin while awake with saline while asleep; saline while awake with psilocybin while asleep; or saline while awake with saline while asleep. Psilocybin is given intravenously as an infusion of 3.2 mg over 10 minutes followed by 0.8 mg over the next 20 minutes; placebo is 20 mL saline drawn into a 30 mL syringe. All participants receive 0.2 mg oral clonidine 60 minutes prior to the initial infusion to support sleep. Key secondary outcomes include psychological flexibility, social connectedness and measures of wellbeing, life satisfaction, purpose and meaning ascribed to the intervention, and participants can expect to be on study for up to 4 months.