Opioid Use DisorderPhase 1NCT04161066
Adjunctive Effects of Psilocybin and a Formulation of Buprenorphine
A Phase 1 study testing Psilocybin with facilitated counseling in people with Opioid Use Disorder, run by University of Wisconsin, Madison at 1 site in United States.
Trial summary
Primary Aim: In participants with OUD, to characterize adverse events associated with adding two psilocybin doses to a stable buprenorphine-naloxone formulation. Secondary Aim: To evaluate the effect of psilocybin treatment on the effectiveness of a buprenorphine-naloxone maintenance therapy. Read more about this study
- Who is it for?
- Ages 21 to 65 years
- Conditions the study is for
- Opioid Use Disorder
- What is being tested?
- Psilocybin with facilitated counseling
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Jan 2021to Dec 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- 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
- Use of a prescription opioid for a purpose (e.g. intoxication, anxiety relief) other than that for which it was prescribed.
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- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Wisconsin
Madison, Wisconsin, 53705
Randall Brown, MD PhD
About this study
Official title: Phase I Study of the Safety and Adjunctive Effects of Psilocybin in Adults With Opioid Use Disorder Maintained on a Buprenorphine/Naloxone Formulation
Primary Aim: In participants with OUD, to characterize adverse events associated with adding two psilocybin doses to a stable buprenorphine-naloxone formulation.
Secondary Aim: To evaluate the effect of psilocybin treatment on the effectiveness of a buprenorphine-naloxone maintenance therapy.
Secondary Aim: To evaluate the effect of concurrent buprenorphine-naloxone use on the effects of psilocybin therapy.
Descriptive Aim: To describe any changes in self-efficacy, quality of life, pain.
Read the detailed description
The primary objective of this clinical trial is to determine the safety of psilocybin in adult patients with opioid use disorder concurrently taking buprenorphine-naloxone.
Eligible participants will be adults with active opioid use disorder (OUD) who are willing to begin and maintain a daily dose of buprenorphine-naloxone throughout study participation. Initiation, stabilization, and maintenance of buprenorphine-naloxone will be overseen by a qualified study medical provider. After psychological screening and at least 6 hours of preparatory counseling and preparation for the psilocybin dosing, set, and setting, each participant will ingest 1 oral dose of psilocybin. All dosing sessions will be attended by 2 specially trained facilitators, in a dedicated Clinical Research Facility. After eight hours of observation in the dosing room, the participant will be kept overnight in the hospital Clinical Research Unit, and complete an integration session with a psychologist before discharge to home. Approximately 4 weeks after the first dose, the participant will receive a second oral dose of psilocybin, with the same length of observation.
Participants who have been administered the first dose but decline to receive the second dose will remain evaluable. At study termination, their active study participation will end, but completion of the 28 day post-dose follow up will be requested.
The primary endpoint is the assessment of the safety of concurrent administration of a buprenorphine-naloxone formulation and psilocybin as determined by physiological measures (ECG, respiratory rate, blood pressure, body temperature, and blood oxygen saturation) and validated clinical and self-report measures (Clinical Opiate Withdrawal Scale (COWS), Opioid Craving Scale (OCS), Timeline Follow-Back (TLFB)).
If you are interested in participating in this study, please fill out a brief 1-minute survey at the link in the "More Information" section at the bottom of this record.
- Conditions
- Opioid Use Disorder
- Being tested
- Psilocybin with facilitated counseling
- Keywords
- Psilocybin, Buprenorphine, Naloxone, Buprenorphine-Naloxone, Psilocybin-Assisted Therapy, Opioid, Substance Use Disorder, Psychedelic
- Medical subject headings
- Opioid-Related Disorders, Substance-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Psilocybin with facilitated counselingDrug
open-label pilot study
| Study group | Role | What they receive |
|---|---|---|
| Open-label | Experimental | Psilocybin with facilitated counseling: Psilocybin will be administered in the form of capsules, taken orally with water. Each participant will receive 2 doses, approximately 4 weeks apart. Receives: Drug: Psilocybin with facilitated counseling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety Measured by Incidence and Severity of Adverse Events 24 hrs post-dose
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.
Measured: approximately Week 1
Safety Measured by Incidence and Severity of Adverse Events 24 hrs post-dose
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.
Measured: approximately Week 5
Mean Change in Symptoms of Opioid Withdrawal Measured by COWS Instrument
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.
Measured: up to 5 weeks
Mean Change in Peripheral Capillary Oxygen
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.
Measured: up to 5 weeks
Mean Change in ECG
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.
Measured: up to 5 weeks
Secondary outcomes (2)
Change in Opioid Craving Scale (OCS) from baseline through end of study
To evaluate the effect of psilocybin treatment on the effectiveness of buprenorphine-naloxone maintenance therapy. The hypothesis is that co-administration of oral psilocybin with a buprenorphine-naloxone formulation will not cause an increase in opioid craving, as measured by the OCS at baseline, week 1, week 5, and week 9. The OCS is a 3-item visual analog scale to measure the frequency and intensity of opioid craving. Total score ranges from 0-30 where the higher the number, the higher the craving.
Measured: Baseline, Week 1, Week 5, and Week 9
Mean Number of Days of Participant Opioid Use via Time Line Follow Back (TLFB)
It is hypothesized that co-administration of oral psilocybin with a buprenorphine-naloxone formulation will not be associated with an increase in self-reported illicit opioid use. This will be measured by Time Line Follow-Back calendar method for up to the 28 days following the last dosing session. Participants will be asked to recall the previous 28 days of substance use at the first in-person visit.
Measured: up to 9 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2019
- Study start13 Jan 2021
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Opioid Use DisorderStudies of the same condition, open and under way.
- More trials run by University of Wisconsin, MadisonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Health services research
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- open-label pilot study
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- Heffter Research Institute, Etheridge Foundation
- Responsible party
- Sponsor
- Investigators
- Randall Brown, MD PhD, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04161066
- Sponsor's protocol ID
- 2019-0187
- Other IDs
- A532007, SMPH/FAMILY MEDICINE, Protocol Version 02/17/2025
- Status last verified
- Jul 2026
- First submitted
- 22 Aug 2019
- Last updated
- 7 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: No individual participant data sharing is planned
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of the Safety and Adjunctive Effects of Psilocybin in Adults With Opioid Use Disorder Maintained on a Buprenorphine/Naloxone Formulation
- ClinicalTrials.gov ID
- NCT04161066
- Acronym / sponsor ID
- 2019-0187
- Conditions
- Opioid Use Disorder
- Keywords
- Psilocybin, Buprenorphine, Naloxone, Buprenorphine-Naloxone, Psilocybin-Assisted Therapy, Opioid, Substance Use Disorder, Psychedelic
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- Heffter Research Institute, Etheridge Foundation
- Study start
- 13 Jan 2021 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 13 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary Aim: In participants with OUD, to characterize adverse events associated with adding two psilocybin doses to a stable buprenorphine-naloxone formulation.
Secondary Aim: To evaluate the effect of psilocybin treatment on the effectiveness of a buprenorphine-naloxone maintenance therapy.
Secondary Aim: To evaluate the effect of concurrent buprenorphine-naloxone use on the effects of psilocybin therapy.
Descriptive Aim: To describe any changes in self-efficacy, quality of life, pain.
Detailed description
The primary objective of this clinical trial is to determine the safety of psilocybin in adult patients with opioid use disorder concurrently taking buprenorphine-naloxone.
Eligible participants will be adults with active opioid use disorder (OUD) who are willing to begin and maintain a daily dose of buprenorphine-naloxone throughout study participation. Initiation, stabilization, and maintenance of buprenorphine-naloxone will be overseen by a qualified study medical provider. After psychological screening and at least 6 hours of preparatory counseling and preparation for the psilocybin dosing, set, and setting, each participant will ingest 1 oral dose of psilocybin. All dosing sessions will be attended by 2 specially trained facilitators, in a dedicated Clinical Research Facility. After eight hours of observation in the dosing room, the participant will be kept overnight in the hospital Clinical Research Unit, and complete an integration session with a psychologist before discharge to home. Approximately 4 weeks after the first dose, the participant will receive a second oral dose of psilocybin, with the same length of observation.
Participants who have been administered the first dose but decline to receive the second dose will remain evaluable. At study termination, their active study participation will end, but completion of the 28 day post-dose follow up will be requested.
The primary endpoint is the assessment of the safety of concurrent administration of a buprenorphine-naloxone formulation and psilocybin as determined by physiological measures (ECG, respiratory rate, blood pressure, body temperature, and blood oxygen saturation) and validated clinical and self-report measures (Clinical Opiate Withdrawal Scale (COWS), Opioid Craving Scale (OCS), Timeline Follow-Back (TLFB)).
If you are interested in participating in this study, please fill out a brief 1-minute survey at the link in the "More Information" section at the bottom of this record.
Study design
- Primary purpose
- Health services research
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- open-label pilot study
| Arm | Type | Receives |
|---|---|---|
| Open-label | Experimental | Drug: Psilocybin with facilitated counselingPsilocybin with facilitated counseling: Psilocybin will be administered in the form of capsules, taken orally with water. Each participant will receive 2 doses, approximately 4 weeks apart. |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Psilocybin with facilitated counselingopen-label pilot study | Drug | Open-label |
Primary outcome
Safety Measured by Incidence and Severity of Adverse Events 24 hrs post-dose
Time frame: approximately 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-dose
Time frame: approximately 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 Instrument
Time frame: up 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 Oxygen
Time frame: up 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 ECG
Time frame: up 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.
2 secondary outcomes
Change in Opioid Craving Scale (OCS) from baseline through end of study
Time frame: Baseline, Week 1, Week 5, and Week 9
Mean Number of Days of Participant Opioid Use via Time Line Follow Back (TLFB)
Time frame: up to 9 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2026.
- Click this link to contact us to see if you qualifyLink provided by the sponsor.
- Individual participant dataSharing planned: No. No individual participant data sharing is planned
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Randall Brown, MD PhD principal investigator
University of Wisconsin, Madison
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Psilocybin with facilitated counseling in people with Opioid Use Disorder, run by University of Wisconsin, Madison at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 7 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact PROTEA Research (608-444-2397, protea.research@mailplus.wisc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety Measured by Incidence and Severity of Adverse Events 24 hrs post-dose (time frame: approximately Week 1). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2026.