Psilocybin and Buprenorphine for Opioid Use Disorder

This study is looking at whether adding psilocybin (a psychedelic compound) to a standard treatment for opioid use disorder (OUD) called buprenorphine-naloxone is safe. Researchers want to see if psilocybin can be given safely to adults with OUD who are also taking buprenorphine-naloxone. They will also explore if psilocybin helps with the effectiveness of buprenorphine-naloxone and how buprenorphine-naloxone might affect psilocybin's effects. You might be able to join if you are 21-65 years old, have a moderate or severe OUD diagnosis, and are currently misusing opioids. The study plans to enroll 10 participants, but its current status is unclear.

Study design
This is an open-label pilot study, meaning both you and the researchers will know what treatment you are receiving. It is an interventional study, but the phase is not specified, and it plans to enroll 10 participants.
What's involved
You would take a daily dose of buprenorphine-naloxone, attend at least 6 hours of preparatory counseling, and receive two oral doses of psilocybin about 4 weeks apart. Each psilocybin dosing session involves 8 hours of observation, an overnight stay, and an integration session with a psychologist.
Compensation
Not stated in the trial record.
Follow-up
Your safety will be measured 24 hours after each psilocybin dose (around Week 1 and Week 5). Opioid withdrawal symptoms will be tracked for up to 5 weeks.

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NCT04161066

Adjunctive Effects of Psilocybin and a Formulation of Buprenorphine

Recruiting
PHASE1Ages 21–65InterventionalHealth services
University of Wisconsin, Madison
~10 participants
Updated 2026-07-07 on ClinicalTrials.gov
What's tested:Psilocybin with facilitated counseling

At a glance

Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Safety Measured by Incidence and Severity of Adverse Events 24 hrs post-dose
Measured over approximately Week 1
+4 more outcomes measured
Opioid Use Disorder
1 sites across 1 states
Wisconsin1
  • Randall Brown, MD PhD · PRINCIPAL_INVESTIGATOR · University of Wisconsin, Madison

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Eligibility criteria

Inclusion

Aged 21 to 65 years
Able to read, speak, and understand spoken and written English
Diagnosis of moderate or severe opioid use disorder (OUD)
Current opioid misuse, with misuse occurring on at least 10 of the last 30 days (at least 5 of last 30 days if already on buprenorphine/naloxene. See exclusion #1). Misuse will be defined as either:
Able to achieve stable daily dose of a buprenorphine-naloxone formulation that controls opioid withdrawal symptoms
Persons of childbearing potential must agree to practice an effective means of contraception throughout their participation in the study, beginning at screening and throughout follow-up
Ability and willingness to adhere to study requirements, including attending all study visits, preparatory and follow-up sessions, and evaluations
Healthy kidney function
Able to provide contact information for a local support person. This person must be available during both 24-hour treatment and observation periods, and willing to provide the participant social/emotional support the day after each treatment and as needed during the dosing day and/or overnight observation period.

Exclusion

Currently prescribed and has taken buprenorphine or buprenorphine formulation (e.g., Suboxone®) for over four months immediately prior to initial study contact
Currently receiving pharmacotherapy of any duration with methadone
Current participation in a drug treatment court program or other legal supervision. Individuals who are under legal supervision will be advised that participating in this study could potentially violate terms of probation, parole, or extended supervision. Contact information for the individual's community supervision officer must be collected to confirm whether study participation may impact the potential participant's status on probation or parole
Inadequately treated hypertension
Current acute coronary syndrome or angina
Evidence of ischemic disease, cardiac conduction defects, and/or ventricular arrhythmias on screening ECG
History of heart transplant
Current insulin dependence, due to Type I or Type II diabetes
Urine drug test containing non-prescribed drugs of abuse
Any finding(s), based on the screening process, that the PI feels makes the study unsuitable for the participant
  • Safety Measured by Incidence and Severity of Adverse Events 24 hrs post-doseapproximately Week 1

    In participants with OUD, the safety of this intervention will be assessed by characterize adverse events associated with adding two psilocybin doses to a stable buprenorphine regimen.

  • Safety Measured by Incidence and Severity of Adverse Events 24 hrs post-doseapproximately Week 5

    In participants with OUD, the safety of this intervention will be assessed by characterizing adverse events associated with adding two psilocybin doses to a stable buprenorphine-naloxone regimen.

  • Mean Change in Symptoms of Opioid Withdrawal Measured by COWS Instrumentup to 5 weeks

    It is hypothesized that co-administration of oral psilocybin with a buprenorphine-naloxone formulation will not cause signs and symptoms of opioid withdrawal. This will be measured by the Clinical Opiate Withdrawal Scale (COWS) instrument, an 11-item scale administered by the clinician where total score of: 5- 12 = mild withdrawal; 13-24 = moderate withdrawal; 25-36 = moderately severe withdrawal; and more than 36 = severe withdrawal. Administered before the dose and again 8 hours after the dose.

  • Mean Change in Peripheral Capillary Oxygenup to 5 weeks

    It is hypothesized that co-administration of oral psilocybin with a buprenorphine-naloxone formulation will not cause opioid intoxication. Opioid intoxication will be determined by drops peripheral capillary oxygen saturation (SpO2) before and after dosing.

  • Mean Change in ECGup to 5 weeks

    It is hypothesized that co-administration of oral psilocybin with a buprenorphine-naloxone formulation will not cause a clinically significant increase in the QTc interval. The QTc interval will be measured by electrocardiogram (ECG) before and after dosing. If a QTc(F), calculated by the CardioCard system exceeds 470msec, a study physician will be contacted immediately for further monitoring and treatment recommendations.