Opioid Use DisorderPhase 1NCT06160284
Exploration of Synaptotrophic Effects of Psilocybin in Opioid Use Disorder (OUD)
A Phase 1 study testing Psilocybin in people with Opioid Use Disorder, run by Yale University at 1 site in United States.
Trial summary
This study will examine the synaptotrophic effects of psilocybin among medically healthy, detoxified OUD subjects. Eligible OUD participants will undergo pre- and post- psilocybin administration PET scans with the [11C]-UCB-J radiotracer while inpatient. Read more about this study
- Who is it for?
- Ages 25 to 55 years
- Conditions the study is for
- Opioid Use Disorder
- What is being tested?
- Psilocybin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 28 May 2025to Jan 2027
- 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 25 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age between 25 and 55 years
- BMI between 19 and 35 kg/m2
- Voluntary, written, informed consent
- Physically healthy by medical history, physical, neurological, ECG, and laboratory examinations
- DSM-5 criteria for Opioid Use Disorder
- Documented evidence (by urine toxicology) of opioid use (upon screening)
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- Inpatient verified > 1 week of abstinence from illicit opioids
- For females, a negative serum pregnancy (beta-HCG) test
- Participants are required to commit to employing dual contraceptive methods throughout the study and to abstain from sperm or egg donation during the study period and for 28 days following the final drug dose for ova, and for 90 days following the final drug dose for sperm. Dual contraceptive methods encompass the use of a barrier contraceptive, such as condoms, coupled with another effective method capable of preventing pregnancy, such as oral or parenteral contraceptives, intrauterine devices, spermicide, and the like.
Who cannot join
- DSM-5 criteria for other substance use disorders (e.g., alcohol, cocaine, sedative hypnotics), except for nicotine (concurrent alcohol or drug use is allowed if it does not meet criteria for a substance use disorder and does not take place during inpatient stay)
- A primary DSM-5 Axis I diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder, or major depression, as determined by psychiatric history (Mini International Neuropsychiatric Interview, MINI) (Sheehan et al., 1998), or another disorder that may interfere with the study's primary outcomes in the view of PI
- Immediate (first-degree relative) family history of formally diagnosed schizophrenia or other psychotic disorders (e.g., delusional disorder, schizoaffective disorder), or bipolar I/II disorder
- Individuals with a history or evidence of psychosis, including substance and nonsubstance related, as evaluated in assessments (MINI and Brief Psychiatric Rating Scale [BPRS]) before psilocybin administration
- History of Hallucinogen Use Disorder or Hallucinogen Persisting Perceptive Disorder
- A history of significant and/or uncontrolled medical or neurological illness
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- Hypertension at screening defined as: systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg
- Heart rate outside the range of 60 to 100 beats per minute
- History of cardiovascular disease, including but not limited to clinically significant coronary artery disease, cardiac hypertrophy, cardiac ischemia, congestive heart failure, myocardial infarction, angina pectoris, coronary artery bypass graft or artificial heart valve, stroke, transient ischemic attack, or any clinically significant arrhythmia
- Any clinically significant abnormal electrocardiogram (ECG) finding, such as findings suggestive of ischemia or infarct, complete bundle branch block, atrial fibrillation or other symptomatic arrhythmia, or predominantly non-sinus rhythm, at screening
- Resting QT interval with Fridericia's correction (QTcF) ≥ 450 msec at Screening, or inability to determine QTcF interval
- Presence of risk factors for torsades de pointes, including: long QT syndrome, uncontrolled hypokalemia or hypomagnesemia, history of cardiac failure, history of clinically significant/symptomatic bradycardia, family history of idiopathic sudden death or congenital long QT syndrome, or concomitant use of a torsadogenic medication
- Current use of psychotropic and/or potentially psychoactive prescription medications considered to the investigators are likely to interfere clinically with human subject's safety (i.e., contraindicated drug-drug interactions with psilocybin) or scientifically (i.e., likely to influence or alter outcomes of the study)
- Current use of medications with serotonergic activity, as participants on these medications are at risk of serotonin syndrome or drug-drug interactions
- Medical contraindications to MRI procedures (e.g., ferromagnetic implants/foreign bodies, claustrophobia, etc.)
- Arterial Line Exclusion: Blood donation within eight weeks of the start of the study
- Arterial Line Exclusion: History of a bleeding disorder or are currently taking anticoagulants (such as Coumadin, Heparin, Pradaxa, Xarelto)
- Participation in other research studies involving ionizing radiation within one year of the PET scans that would cause the subject to exceed the yearly dose limits followed by the Yale PET Center (21CFR361.1)
- Moderate to severe hepatic impairment (Child-Pugh B and C class)
- Use of enzyme inhibitors (UGT1A9, UGT1A10, MAO, and aldehyde or alcohol dehydrogenase).
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
Yale University
New Haven, Connecticut, 06520
About this study
This study will examine the synaptotrophic effects of psilocybin among medically healthy, detoxified OUD subjects. Eligible OUD participants will undergo pre- and post- psilocybin administration PET scans with the [11C]-UCB-J radiotracer while inpatient.
Read the detailed description
Participants will undergo screening as outpatients at the Clinical Neuroscience Research Unit (CNRU). Once deemed eligible, OUD subjects will be studied as inpatients. However, they will have the option of scheduling their second [11C]-UCB-J PET as an outpatient (pending these participants' agreement to undergo outpatient visits twice per week to provide urine toxicology to monitor abstinence before PET).
The only portion of the study that will be available as outpatient for OUD subjects will be the 1-2 weeks before the second [11C]-UCB-J PET scan. The subject will still be admitted for 1-2 weeks, which will include: inpatient detoxification, baseline [11C]-UCB-J PET scan, psilocybin administration, and overnight observation after psilocybin administration. However, they may be discharged the day following psilocybin administration and return 2x weekly for urine toxicology testing between discharge and the second [11C]-UCB-J PET to confirm abstinence.
Structural magnetic resonance imaging (MRI) scans will be obtained for anatomical registration/partial volume correction from all subjects. Functional MRI (fMRI) scans will be completed pre- and post-psilocybin administration to evaluate changes in resting state connectivity. All subjects will participate in a battery of behavioral assessments for exploratory correlations with [11C]-UCB-J. Inpatient subjects who smoke cigarettes will have the option of using nicotine gum and/or nicotine patch while on the unit in order to prevent or minimize nicotine withdrawal. The [11C]-UCB-J PET scans will be done at the Yale PET Center 1-2 weeks before (baseline) and after psilocybin administration.
This is a single-center study at Yale, that will have study activities completed at the following areas:
- Clinical Neuroscience Research Unit (CNRU) of the Connecticut Mental Health Center (CMHC)
- Yale Positron Emission Tomography (PET) Imaging Center
- Yale Magnetic Resonance Research Center (MRRC)
- Conditions
- Opioid Use Disorder
- Being tested
- Psilocybin
- 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.
PsilocybinDrug
Participants will receive a single dose of psilocybin administered in 20 mg or 25 mg doses depending on the participant's weight: 20 mg (among participants < 70 kg) or 25 mg (among participants >70 kg). Participants will be administered psilocybin at CNRU, within 1-2 weeks of the baseline [11C]-UCB-J PET.
| Study group | Role | What they receive |
|---|---|---|
| Current OUD diagnosis + psilocybin | Experimental | All participants will receive a [11C]-UCB-J PET scan and fMRI with in 1-2 weeks pre and post treatment with one dose of Psilocybin. Intravenous lines will be used for phlebotomy and administration of the [11C]-UCB-J radiotracer. On the PET scanning day, a radial arterial catheter may be inserted. Receives: Drug: Psilocybin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Synaptic Density
Change in synaptic density pre- and post- psilocybin administration will be measured using [11C]-UCB-J PET (volume of distribution [VT] and binding potential [BPND]) among OUD. The regions of interest (ROI) will be subregions of the prefrontal cortex identified by preclinical and preliminary clinical studies.
Measured: baseline and 1-2 weeks post treatment
Association between VT and BPND
Association between VT and BPND assessed to determine whether changes in VT are associated with changes in BPND.
Measured: up to 12 weeks
Time to relapse
Mean number of days to relapse assessed by self- report
Measured: up to 12 weeks
Urine toxicology post treatment
The mean number of positive urine tests post treatment will be assessed. Urine samples will be tested for the presence of opioids. A positive test indicates opioid usage in the last 2 weeks.
Measured: up to 12 weeks
Secondary outcomes (11)
Change in vital signs- heart rate (HR)
Mean change in heart rate measured in beats per minute during Psilocybin session
Measured: immediately prior to psilocybin treatment with and up to 5 hours+ post treatment
Change in vital signs- respiratory rate (RR)
Mean change in respiratory rate measured in breaths per minute during Psilocybin session
Measured: immediately prior to psilocybin treatment with and up to 5 hours+ post treatment
Change in vital signs- oxygen saturation
Mean change in percent oxygen saturation assessed using a pulse oximeter during Psilocybin session
Measured: immediately prior to psilocybin treatment with and up to 5 hours+ post treatment
Change in vital signs- systolic blood pressure
Mean change in systolic blood pressure in mmHg during Psilocybin session
Measured: immediately prior to psilocybin treatment with and up to 5 hours+ post treatment
Change in vital signs- diastolic blood pressure
Mean change in diastolic blood pressure in mmHg during Psilocybin session
Measured: immediately prior to psilocybin treatment with and up to 5 hours+ post treatment
Change in vital signs- body temperature
Mean change in body temperature in degrees Fahrenheit during Psilocybin session
Measured: immediately prior to psilocybin treatment with and up to 5 hours+ post treatment
Total number of participants with treatment emergent adverse events
Total number of participants with any treatment emergent adverse events while on study assessed using the Systematic Assessment for Treatment Emergent Events (SAFTEE).
Measured: up to 12 weeks
Change in Profile of Mood States (POMS) Score
POMS is a validated 30 item questionnaire used to assess an individual's mood states. Total scores range from 0 to 120 with lower scores indicating a better mood state.
Measured: approximately 30 and 150 minutes post Psilocybin treatment
Change in Clinical Opioid Withdrawal Scale (COWS) Score
COWS is an 11-item scale to rate common signs and symptoms of opiate withdrawal and monitor these symptoms over time. The summed score determines the stage/severity of opiate withdrawal and assess the level of physical dependence on opioids. Score: 5- 12 = mild; 13-24 = moderate; 25-36 = moderately severe; more than 36 = severe withdrawal
Measured: approximately 30 and 150 minutes post Psilocybin treatment
Change in Subjective Opioid Withdrawal Scale (SOWS) Score
SOWS is a self-administered scale for opioid withdrawal symptoms. It has16 symptoms whose intensity is rated on a scale of 0 (not at all) to 4 (extremely). Mild Withdrawal = score of 1-10, Moderate withdrawal = 11-20, Severe withdrawal = 21-30
Measured: approximately 30 and 150 minutes post Psilocybin treatment
Change in Opioid Symptom Checklist (OSC)
The OSC is a 13-item opioid symptom checklist consisting of true/false questions designed to measure opioid effects (e.g., "My skin is itchy"). True scores are totaled up to acute opiate positive and negative symptoms and low true scores will mean not feeling any of the negative and positive symptoms.
Measured: approximately 30 and 150 minutes post Psilocybin treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2023
- Study start28 May 2025
- Primary completionJan 2027 (estimated)
- Study completionJan 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 Yale UniversityThe 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
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Participants will be medically healthy females and males with OUD.
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA), Yale Biomedical Imaging Institute
- Responsible party
- Principal investigator, Gustavo Angarita, Yale University
- Investigators
- Gustavo Angarita, MD, MHS, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06160284
- Sponsor's protocol ID
- 2000036178
- Other IDs
- R21DA046030
- Status last verified
- Jul 2026
- First submitted
- 28 Nov 2023
- Last updated
- 7 Jul 2026
- Results posted
- No
- 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 7 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exploration of Synaptotrophic Effects of Psilocybin in Opioid Use Disorder (OUD)
- ClinicalTrials.gov ID
- NCT06160284
- Acronym / sponsor ID
- 2000036178
- Conditions
- Opioid Use Disorder
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA), Yale Biomedical Imaging Institute
- Study start
- 28 May 2025 (actual)
- Primary completion
- Jan 2027 (estimated)
- Study completion
- Jan 2027 (estimated)
- First posted
- 7 Dec 2023 (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.
This study will examine the synaptotrophic effects of psilocybin among medically healthy, detoxified OUD subjects. Eligible OUD participants will undergo pre- and post- psilocybin administration PET scans with the [11C]-UCB-J radiotracer while inpatient.
Detailed description
Participants will undergo screening as outpatients at the Clinical Neuroscience Research Unit (CNRU). Once deemed eligible, OUD subjects will be studied as inpatients. However, they will have the option of scheduling their second [11C]-UCB-J PET as an outpatient (pending these participants' agreement to undergo outpatient visits twice per week to provide urine toxicology to monitor abstinence before PET).
The only portion of the study that will be available as outpatient for OUD subjects will be the 1-2 weeks before the second [11C]-UCB-J PET scan. The subject will still be admitted for 1-2 weeks, which will include: inpatient detoxification, baseline [11C]-UCB-J PET scan, psilocybin administration, and overnight observation after psilocybin administration. However, they may be discharged the day following psilocybin administration and return 2x weekly for urine toxicology testing between discharge and the second [11C]-UCB-J PET to confirm abstinence.
Structural magnetic resonance imaging (MRI) scans will be obtained for anatomical registration/partial volume correction from all subjects. Functional MRI (fMRI) scans will be completed pre- and post-psilocybin administration to evaluate changes in resting state connectivity. All subjects will participate in a battery of behavioral assessments for exploratory correlations with [11C]-UCB-J. Inpatient subjects who smoke cigarettes will have the option of using nicotine gum and/or nicotine patch while on the unit in order to prevent or minimize nicotine withdrawal. The [11C]-UCB-J PET scans will be done at the Yale PET Center 1-2 weeks before (baseline) and after psilocybin administration.
This is a single-center study at Yale, that will have study activities completed at the following areas:
- Clinical Neuroscience Research Unit (CNRU) of the Connecticut Mental Health Center (CMHC)
- Yale Positron Emission Tomography (PET) Imaging Center
- Yale Magnetic Resonance Research Center (MRRC)
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Participants will be medically healthy females and males with OUD.
| Arm | Type | Receives |
|---|---|---|
| Current OUD diagnosis + psilocybin | Experimental | Drug: PsilocybinAll participants will receive a [11C]-UCB-J PET scan and fMRI with in 1-2 weeks pre and post treatment with one dose of Psilocybin. Intravenous lines will be used for phlebotomy and administration of the [11C]-UCB-J radiotracer. On the PET scanning day, a radial arterial catheter may be inserted. |
Who may qualify
- Ages
- 25 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Age between 25 and 55 years
- BMI between 19 and 35 kg/m2
- Voluntary, written, informed consent
- Physically healthy by medical history, physical, neurological, ECG, and laboratory examinations
- DSM-5 criteria for Opioid Use Disorder
Key exclusion criteria (20 listed)
- DSM-5 criteria for other substance use disorders (e.g., alcohol, cocaine, sedative hypnotics), except for nicotine (concurrent alcohol or drug use is allowed if it does not meet criteria for a substance use disorder and does not take place during inpatient stay)
- A primary DSM-5 Axis I diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder, or major depression, as determined by psychiatric history (Mini International Neuropsychiatric Interview, MINI) (Sheehan et al., 1998), or another disorder that may interfere with the study's primary outcomes in the view of PI
- Immediate (first-degree relative) family history of formally diagnosed schizophrenia or other psychotic disorders (e.g., delusional disorder, schizoaffective disorder), or bipolar I/II disorder
- Individuals with a history or evidence of psychosis, including substance and nonsubstance related, as evaluated in assessments (MINI and Brief Psychiatric Rating Scale [BPRS]) before psilocybin administration
- History of Hallucinogen Use Disorder or Hallucinogen Persisting Perceptive Disorder
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 |
|---|---|---|
| PsilocybinParticipants will receive a single dose of psilocybin administered in 20 mg or 25 mg doses depending on the participant's weight: 20 mg (among participants < 70 kg) or 25 mg (among participants >70 kg). Participants will be administered psilocybin at CNRU, within 1-2 weeks of the baseline [11C]-UCB-J PET. | Drug | Current OUD diagnosis + psilocybin |
Primary outcome
Change in Synaptic Density
Time frame: baseline and 1-2 weeks post treatment
Change in synaptic density pre- and post- psilocybin administration will be measured using [11C]-UCB-J PET (volume of distribution [VT] and binding potential [BPND]) among OUD. The regions of interest (ROI) will be subregions of the prefrontal cortex identified by preclinical and preliminary clinical studies.
Association between VT and BPND
Time frame: up to 12 weeks
Association between VT and BPND assessed to determine whether changes in VT are associated with changes in BPND.
Time to relapse
Time frame: up to 12 weeks
Mean number of days to relapse assessed by self- report
Urine toxicology post treatment
Time frame: up to 12 weeks
The mean number of positive urine tests post treatment will be assessed. Urine samples will be tested for the presence of opioids. A positive test indicates opioid usage in the last 2 weeks.
11 secondary outcomes
Change in vital signs- heart rate (HR)
Time frame: immediately prior to psilocybin treatment with and up to 5 hours+ post treatment
Change in vital signs- respiratory rate (RR)
Time frame: immediately prior to psilocybin treatment with and up to 5 hours+ post treatment
Change in vital signs- oxygen saturation
Time frame: immediately prior to psilocybin treatment with and up to 5 hours+ post treatment
Change in vital signs- systolic blood pressure
Time frame: immediately prior to psilocybin treatment with and up to 5 hours+ post treatment
Change in vital signs- diastolic blood pressure
Time frame: immediately prior to psilocybin treatment with and up to 5 hours+ post treatment
Change in vital signs- body temperature
Time frame: immediately prior to psilocybin treatment with and up to 5 hours+ post treatment
Total number of participants with treatment emergent adverse events
Time frame: up to 12 weeks
Change in Profile of Mood States (POMS) Score
Time frame: approximately 30 and 150 minutes post Psilocybin treatment
Change in Clinical Opioid Withdrawal Scale (COWS) Score
Time frame: approximately 30 and 150 minutes post Psilocybin treatment
Change in Subjective Opioid Withdrawal Scale (SOWS) Score
Time frame: approximately 30 and 150 minutes post Psilocybin treatment
Change in Opioid Symptom Checklist (OSC)
Time frame: approximately 30 and 150 minutes post Psilocybin treatment
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.
- 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.
Gustavo Angarita, MD, MHS principal investigator
Yale University
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 in people with Opioid Use Disorder, run by Yale University 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 9 inclusion and 20 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 Gustavo Angarita, MD, MHS ((203) 974-7536, gustavo.angarita@yale.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Synaptic Density (time frame: baseline and 1-2 weeks post treatment). The study lists 4 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.