Opioid Use DisorderPhase 2NCT06810310
Psilocybin on Brain Mechanisms of Motivation in OUD
A Phase 2 study testing Psilocybin (high dose) and psilocybin (low dose) in people with Opioid Use Disorder, run by University of Pennsylvania at 1 site in United States.
Trial summary
The goal of this study is to test addiction-related brain circuitry (motivation/reward and inhibition) as well as neurocognitive circuitry prior to and following low or high dose psilocybin (PEX010 from Filament). Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Opioid Use Disorder
- What is being tested?
- Psilocybin (high dose) and psilocybin (low dose)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Dec 2025to 1 May 2027
- Phase
- Phase 2
- 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 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- An informed consent document voluntarily signed and dated by the subject.
- Either 1) have a confirmed prescription for BUP-NX in a drug monitoring program database, have been on a stable dose of BUP-NX for at least one week, and plan to continue taking BUP-NX for at least 12 weeks or 2) have received an injection of Sublocade® within the past month, or 3) are currently on methadone maintenance therapy and on a consistent dose for at least a week. Subject must provide a urine that is buprenorphine-positive (for subjects taking buprenorphine) or methadone-positive (for subjects taking methadone), during screening.
- Physically healthy males and females, aged 18-60 years old, who meet criteria for opioid use disorder (based on DSM-5 criteria) as their primary diagnosis and are voluntarily seeking treatment.
- Females must be non-pregnant and non-lactating. Additionally, for females with childbearing potential (i.e., have not undergone sterilization via hysterectomy, bilateral tubal ligation, or bilateral oophorectomy, or at least 1 year post-menopausal) participants must agree to use an acceptable form of contraception (e.g. abstinence, intrauterine device, hormonal injection, hormonal implant, hormonal patch/ring/pill, condoms (male or female), etc.) during study participation and to continue its use for the duration of the study
- Subject must read at or above eighth grade level and speak, understand, and write in English.
- IQ score of greater than or equal to 80.
Who cannot join
- Participation in clinical trial and receipt of investigational drug(s) during 30 days prior to the research study, except as explicitly approved by the Principal Investigator.
- Currently meets DSM-5 criteria for moderate to severe substance use disorder for any substance other than cocaine, alcohol, marijuana or nicotine as determined by the semi-structured interview. Any prior use of psilocybin is exclusionary. Patients with comorbid Alcohol Use Disorder will be accepted if their alcohol use disorder is not severe enough to require a medicated alcohol detoxification.
- Meets current or lifetime DSM-5 criteria for schizophrenia or any psychotic disorder, or organic mental disorder or has a first-degree family history of these disorders, this includes a history of hallucinogen-persistent perception disorder (HPPD)
- Meets current DSM-5 criteria for bipolar disorder
- --Meets current DSM-5 criteria for severe Major Depressive Disorder (mild and moderate MDD as well as in stable remission are allowed if no suicidal risk and no ongoing antidepressant therapy).
- Current or past significant trauma exposure with elevated Post-Traumatic Stress symptoms at the discretion of the PI.
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- Presence of any another psychiatric disorder that in the opinion of the PI will interfere with completion of the study or place the patient at heightened risk through participation in the study.
- Current or past month active suicidal ideations or lifetime history of serious suicidal attempt.
- Has evidence of significant hepatocellular injury as evidenced by elevated bilirubin levels (greater than 1.3), or, pulmonary (e.g., COPD), endocrine, cardiovascular, renal (creatinine clearance less than or equal to 60ml/min) or gastrointestinal disease (e.g., Crohn's disease), or current HIV infection, and/or clinically significant levels (over 3.5x upper limit of normal) of aspartate aminotransferase (AST), and serumalanine aminotransferase (ALT). Patients with documented Gilbert's syndrome will be included regardless of bilirubin levels.
- History of serious head trauma or injury causing loss of consciousness that lasted more than 3 minutes and/or associated with skull fracture or intracranial bleeding or abnormal MRI.
- Seizure disorder or history of seizures not related to drug or alcohol withdrawal (excluding childhood febrile seizure).
- Presence of magnetically active prosthetics, plates, pins, broken needles, permanent retainer, bullets, etc. in patient's body (unless a radiologist confirms that its presence is unproblematic). An x-ray may be obtained to determine eligibility.
- Claustrophobia or other medical condition that disables the participant from lying in the MRI for approximately 60 minutes.
- Non-removable skin patches, at discretion of PI.
- Has received medication that could interact adversely with psilocybin within the time of administration of study agent based on the Medical Director's guidance.
- Needs treatment with any psychoactive (e.g., anti-depressants) medications (with the exception of Benadryl used sparingly, if necessary, for sleep).
- *Have the following cardiovascular conditions:
- coronary artery disease, congenital long QT syndrome (prior diagnosis), cardiac hypertrophy, cardiac ischemia, congestive heart failure, myocardial infarction (prior diagnosis);
- tachycardia (defined as heart rate greater than 100 beats per minute);
- a clinically significant Screening ECG abnormality (e.g., atrial fibrillation); Note: A QTcF interval greater than 450 milliseconds is considered a clinically significant ECG abnormality
- artificial heart valve;
- any other significant current or history of cardiovascular condition, based on the clinical judgment of Medical Director, that would make a participant unsuitable for the study.
- *At Screening or Baseline have elevated blood pressure as defined as:
- Screening blood pressure SBP greater than135 mmHg or DBP greater than 85 mmHg on three separate readings; or
- Baseline blood pressure SBP greater than140 mmHg or DBP greater than 90 mmHg on three separate readings
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 Pennsylvania
Philadelphia, Pennsylvania, 19104
Megan Ivey, MS, 215-746-7712, megan.ivey@pennmedicine.upenn.edu
Anna Rose Childress, PhD
About this study
Official title: Psilocybin: Capturing Brain Mechanisms of Motivation and Neurocognition in Individuals With Opioid Use Disorder
The goal of this study is to test addiction-related brain circuitry (motivation/reward and inhibition) as well as neurocognitive circuitry prior to and following low or high dose psilocybin (PEX010 from Filament). Using fMRI, brain circuits will be examined that are relevant to drug relapse as well as neurocognitive flexibility circuits in individuals with opioid use disorder.
Investigators will randomize 24 males and females, aged 18 - 60, in the greater Philadelphia area, to either 1mg or 25 mg of psilocybin. Participants will come to our offices for screening visits - these are assessments, interviews, and some medical tests (such as a history and physical, as well as a fasting blood draw) to help determine eligibility for our study. If eligible, participants will be brought to research offices at 3535 Market Street in Philadelphia for about 7 visits. These visits include pre-dose psilocybin preparation therapy, baseline assessments and neuropsychological testing, psilocybin dosing, post dose therapy visits, and post dose assessments.
- Conditions
- Opioid Use Disorder
- Being tested
- Psilocybin (high dose), psilocybin (low dose)
- Medical subject headings
- Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Psilocybin (high dose)Drug
PEX010 is the psilocybin produced by Filament
psilocybin (low dose)Drug
1mg psilocybin, produced by Filament
| Study group | Role | What they receive |
|---|---|---|
| Low dose psilobyin | Active comparator | 1 mg PEX010 capsule, single dose Receives: Drug: psilocybin (low dose) |
| High dose psilocybin | Experimental | 25 mg PEX010 capsule, single dose Receives: Drug: Psilocybin (high dose) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Brain measure of GO domain
Using fMRI, Investigators will measure the brain response to 500ms evocative cues and 6 second drug-related videos that trigger drug desire
Measured: One week pre dose and one week post dose
Behavioral measure of GO domain
Using a the Affect Bias behavioral task, Investigators will measure the affective bias to opioid and other evocative visual cues.
Measured: One week pre dose and one week post dose
Secondary outcomes (2)
Brain measure of STOP domain
Using fMRI, Investigators will measure the brain response during an Affect-congruent Go-NoGo task, and during 6 second videos with instruction to "Reduce participant's response to the video by considering the negative consequences of acting on participant's craving."
Measured: weeks 1 through 8 (outcomes phase)
Behavioral measure of STOP domain
Using a standard behavioral Go0NoGo task, Investigators will measure errors of commission.
Measured: One week pre dose and one week post dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2025
- Study start22 Dec 2025
- Primary completion1 May 2027 (estimated)
- Study completion1 May 2027 (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 PennsylvaniaThe 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 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Anna Rose Childress, Ph.D., University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06810310
- Sponsor's protocol ID
- 857697
- Status last verified
- Jul 2026
- First submitted
- 30 Jan 2025
- Last updated
- 9 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Psilocybin: Capturing Brain Mechanisms of Motivation and Neurocognition in Individuals With Opioid Use Disorder
- ClinicalTrials.gov ID
- NCT06810310
- Acronym / sponsor ID
- 857697
- Conditions
- Opioid Use Disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 22 Dec 2025 (actual)
- Primary completion
- 1 May 2027 (estimated)
- Study completion
- 1 May 2027 (estimated)
- First posted
- 5 Feb 2025 (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.
The goal of this study is to test addiction-related brain circuitry (motivation/reward and inhibition) as well as neurocognitive circuitry prior to and following low or high dose psilocybin (PEX010 from Filament). Using fMRI, brain circuits will be examined that are relevant to drug relapse as well as neurocognitive flexibility circuits in individuals with opioid use disorder.
Investigators will randomize 24 males and females, aged 18 - 60, in the greater Philadelphia area, to either 1mg or 25 mg of psilocybin. Participants will come to our offices for screening visits - these are assessments, interviews, and some medical tests (such as a history and physical, as well as a fasting blood draw) to help determine eligibility for our study. If eligible, participants will be brought to research offices at 3535 Market Street in Philadelphia for about 7 visits. These visits include pre-dose psilocybin preparation therapy, baseline assessments and neuropsychological testing, psilocybin dosing, post dose therapy visits, and post dose assessments.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low dose psilobyin | Active comparator | Drug: psilocybin (low dose)1 mg PEX010 capsule, single dose |
| High dose psilocybin | Experimental | Drug: Psilocybin (high dose)25 mg PEX010 capsule, single dose |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- An informed consent document voluntarily signed and dated by the subject.
- Either 1) have a confirmed prescription for BUP-NX in a drug monitoring program database, have been on a stable dose of BUP-NX for at least one week, and plan to continue taking BUP-NX for at least 12 weeks or 2) have received an injection of Sublocade® within the past month, or 3) are currently on methadone maintenance therapy and on a consistent dose for at least a week. Subject must provide a urine that is buprenorphine-positive (for subjects taking buprenorphine) or methadone-positive (for subjects taking methadone), during screening.
- Physically healthy males and females, aged 18-60 years old, who meet criteria for opioid use disorder (based on DSM-5 criteria) as their primary diagnosis and are voluntarily seeking treatment.
- Females must be non-pregnant and non-lactating. Additionally, for females with childbearing potential (i.e., have not undergone sterilization via hysterectomy, bilateral tubal ligation, or bilateral oophorectomy, or at least 1 year post-menopausal) participants must agree to use an acceptable form of contraception (e.g. abstinence, intrauterine device, hormonal injection, hormonal implant, hormonal patch/ring/pill, condoms (male or female), etc.) during study participation and to continue its use for the duration of the study
- Subject must read at or above eighth grade level and speak, understand, and write in English.
Key exclusion criteria (25 listed)
- Participation in clinical trial and receipt of investigational drug(s) during 30 days prior to the research study, except as explicitly approved by the Principal Investigator.
- Currently meets DSM-5 criteria for moderate to severe substance use disorder for any substance other than cocaine, alcohol, marijuana or nicotine as determined by the semi-structured interview. Any prior use of psilocybin is exclusionary. Patients with comorbid Alcohol Use Disorder will be accepted if their alcohol use disorder is not severe enough to require a medicated alcohol detoxification.
- Meets current or lifetime DSM-5 criteria for schizophrenia or any psychotic disorder, or organic mental disorder or has a first-degree family history of these disorders, this includes a history of hallucinogen-persistent perception disorder (HPPD)
- Meets current DSM-5 criteria for bipolar disorder
- --Meets current DSM-5 criteria for severe Major Depressive Disorder (mild and moderate MDD as well as in stable remission are allowed if no suicidal risk and no ongoing antidepressant therapy).
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 (high dose)PEX010 is the psilocybin produced by Filament | Drug | High dose psilocybin |
| psilocybin (low dose)1mg psilocybin, produced by Filament | Drug | Low dose psilobyin |
Primary outcome
Brain measure of GO domain
Time frame: One week pre dose and one week post dose
Using fMRI, Investigators will measure the brain response to 500ms evocative cues and 6 second drug-related videos that trigger drug desire
Behavioral measure of GO domain
Time frame: One week pre dose and one week post dose
Using a the Affect Bias behavioral task, Investigators will measure the affective bias to opioid and other evocative visual cues.
2 secondary outcomes
Brain measure of STOP domain
Time frame: weeks 1 through 8 (outcomes phase)
Behavioral measure of STOP domain
Time frame: One week pre dose and one week post dose
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 9 Jul 2026.
- Individual participant dataSharing planned: No
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Psilocybin (high dose) and psilocybin (low dose) in people with Opioid Use Disorder, run by University of Pennsylvania 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 6 inclusion and 25 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 9 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Anna Rose Childress, PhD (215-746-1803, childress@pennmedicine.upenn.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Brain measure of GO domain (time frame: One week pre dose and one week post dose). The study lists 2 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 9 Jul 2026.