Clinical TrialOpioid Use Disorder (OUD)PsilocybinPlaceboWithdrawn

Psilocybin for Opioid Use Disorder in Patients on Methadone Maintenance With Ongoing Opioid Use

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.

Target Enrollment
92 participants
Study Type
Phase II interventional
Design
Randomized, quadruple Blind

Detailed Description

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.

Study Protocol

Preparation

sessions

Dosing

2 sessions

Integration

sessions

Therapeutic Protocol

support

Study Arms & Interventions

Psilocybin

experimental

Oral psilocybin 40 mg capsule; dosing sessions at baseline and 3 months with blinding and re-randomisation for second dose in active group.

Interventions

  • Psilocybin40 mg
    via Oral• single dose

    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.

Placebo

inactive

Oral placebo capsule; blinded dosing at baseline and 3 months per protocol.

Interventions

  • Placebo
    via Oral• single dose

    Placebo matched capsule; all participants receive second blinded dosing at 3 months per study schema.

Participants

Ages
21 – 70
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • Age 21-70 years
  • Have OUD
  • Enrolled in a methadone maintenance program for at least 3 months
  • Urine toxicology positive for methadone
  • Urine toxicology positive for an additional opioid
  • Access to stable housing
  • Read, write, and speak English
  • Be judged by study team clinicians to be at low risk for suicidality
  • Have limited lifetime use of classic psychedelics (no use in the past 5 years; total classic psychedelic use less than 20 times)
  • Are local to the Baltimore area

Exclusion Criteria

  • Exclusion Criteria:
  • Women who are pregnant, nursing, or not practicing an effective means of birth control
  • Cardiovascular conditions: hypertension with resting blood pressure systolic >140 or diastolic >90, angina, a clinically significant ECG abnormality (e.g., atrial fibrillation, corrected QT interval > 450), transient ischemic attack in the last 6 months stroke, peripheral or pulmonary vascular disease
  • Epilepsy
  • Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia
  • Currently taking a prescribed psychoactive medication on a daily basis (except methadone)
  • Currently taking on a daily basis any medications (including herbal substances and supplements) with a central nervous system effect on serotonin, including serotonin-reuptake inhibitors and monoamine oxidase inhibitors.
  • o For individuals who have intermittent or as needed use of such medications, psilocybin sessions will not be conducted until at least 5 half-lives of the agent have elapsed after the last dose.
  • Currently taking efavirenz, Acetaldehyde dehydrogenase inhibitors such as disulfiram (Antabuse), Alcohol dehydrogenase inhibitors, or Uridine 5'-diphospho-glucuronosyltransferase Family 1 Member A9 (UGT1A9) inhibitors or UGT1A10 inhibitors such as phenytoin, regorafenib, eltrombopag.
  • Have a seizure disorder, multiple sclerosis, history of significant head trauma, central nervous system tumor, movement disorders or any neurodegenerative condition.
  • Morbidly obese (>100 lbs above idea body weight, or BMI >=40, or BMI >=35 with high blood pressure or diabetes)
  • Body weight < 45kg
  • Recent (within past 12 months) or extensive history of classic psychedelic use (>19 lifetime uses).
  • Physiological dependence on benzodiazepines or alcohol
  • Abnormal screening labs: values for hemoglobin, white blood count, creatinine, potassium, and bilirubin outside of the normal lab reference rage. Transaminases greater than x2 the upper limit of normal lab reference range.

Study Details

Locations

United States

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