Combining Psilocybin with Buprenorphine for Opioid Use Disorder

Phase I Study of the Safety and Adjunctive Effects of Psilocybin in Adults With Opioid Use Disorder Maintained on a Buprenorphine/Naloxone Formulation

Phase 1 Interventional University of Wisconsin, Madison · NCT04161066

This study is testing if adding psilocybin to buprenorphine treatment can help adults with opioid use disorder feel better and improve their quality of life.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment10 (estimated)
Ages21 Years to 65 Years
SexAll
SponsorUniversity of Wisconsin, Madison Academic / other
Locations1 site (Madison, Wisconsin)
Trial IDNCT04161066 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the safety and effects of adding psilocybin to a stable buprenorphine-naloxone regimen in adults with opioid use disorder. Participants will receive two doses of psilocybin, each followed by a period of observation and psychological support. The study will assess adverse events, the effectiveness of the combined treatment, and any changes in self-efficacy and quality of life. The trial is conducted in a controlled environment with trained facilitators to ensure participant safety and support.

Who should consider this trial

Good fit: Ideal candidates are adults aged 21 to 65 with moderate to severe opioid use disorder who are currently misusing opioids.

Not a fit: Patients who are not currently misusing opioids or those with mild opioid use disorder may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could enhance treatment outcomes for patients struggling with opioid use disorder.

How similar studies have performed: While the combination of psilocybin and buprenorphine is a novel approach, previous studies on psilocybin-assisted therapy have shown promising results in other mental health conditions.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* 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:

  1. Use of illicit opioids, such as heroin or street fentanyl; or use of a prescription opioid (such as oxycodone, morphine, or hydrocodone) through a route (e.g. nasal, injected) other than FDA approved , and/or
  2. Use of a prescription opioid for a purpose (e.g. intoxication, anxiety relief) other than that for which it was prescribed.
* 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 Criteria:

* 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

Where this trial is running

Madison, Wisconsin

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Opioid Use DisorderPsilocybinBuprenorphineNaloxoneBuprenorphine-NaloxonePsilocybin-Assisted TherapyOpioidSubstance Use Disorder
Last reviewed 2026-06-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.