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.
This study is exploring how psilocybin (a psychedelic drug) may improve mood and wellbeing. Many people report feeling better after taking psilocybin, but it is not clear why. The CoPEWell study will test whether these improvements come from the psychedelic experience itself (the "trip") or from direct effects on the brain. To study this, up to 120 participants will be enrolled to receive psilocybin either while awake or asleep and can expect to be on study for up to 4 months.
Participants in this group will receive psilocybin by intravenous (IV) infusion while awake and placebo (saline) by IV infusion while asleep during an overnight dosing visit. All participants will also receive oral clonidine prior to dosing to support sleep during the overnight visit.
Participants in this group will receive placebo (saline) by intravenous (IV) infusion while awake and psilocybin by IV infusion while asleep during an overnight dosing visit. All participants will also receive oral clonidine prior to dosing to support sleep during the overnight visit.
Participants in this group will receive placebo (saline) by intravenous (IV) infusion while awake and placebo by IV infusion while asleep during an overnight dosing visit. All participants will also receive oral clonidine prior to dosing to support sleep during the overnight visit.
Unmatched intervention: Clonidine