This study will investigate whether psilocybin administered under supportive conditions can reduce illicit opioid use and improve quality of life in individuals with Opioid Use Disorder (OUD) in Methadone Maintenance Treatment (MMT) who are concurrently using other opioids illicitly.
Randomized, quadruple-blind, placebo-controlled trial (n=92) testing whether two dosing sessions of psilocybin (40 mg) reduce illicit opioid use and improve quality of life in people on methadone maintenance with ongoing opioid use.
Participants undergo two dosing sessions (baseline and at three months); initial randomisation assigns psilocybin or placebo at baseline, and the active group is re-randomised for the second dosing to evaluate single versus two-dose effects. Outcomes include urine toxicology, WHOQOL-BREF, mood, tobacco and other drug use, pain, and sleep.
Participants are adults (21-70) on MMT ≥3 months with positive urine for methadone and another opioid; medical and medication exclusions apply to reduce cardiovascular, seizure, and drug–drug interaction risks.
Oral psilocybin 40 mg capsule; dosing sessions at baseline and 3 months with blinding and re-randomisation for second dose in active group.
Participants undergo two dosing sessions (baseline and 3 months); active-first participants receive 40 mg at baseline; second dosing at 3 months varies per randomisation.
Oral placebo capsule; blinded dosing at baseline and 3 months per protocol.
Placebo matched capsule; all participants receive second blinded dosing at 3 months per study schema.