Recruiting
Early Phase 1

Observational Study

Sponsor:

Yale University

Code:

NCT05472818

Conditions

Cannabis Use Disorder

Healthy

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Accepted

Interventions

[11C]APP311

Study Details

Brief summary:

The main purpose of this study is to determine whether hippocampal synaptic vesicle density estimated by hippocampal \[11C\]APP-311/\[11C\]UCB-J binding in individuals diagnosed with cannabis use disorder (CUDs) improves with at least 4 weeks of confirmed abstinence from cannabis, in comparison to healthy controls (HCs). Furthermore, any change in synaptic vesicle density will be placed in functional context by measuring verbal memory, which is sensitive to hippocampal function, before and after at least 4 weeks of confirmed abstinence. Finally, the relationship between hippocampal \[11C\]UCB-J binding in CUDs with measures of cannabis exposure (e.g., age of initiation, cumulative lifetime dose) will be explored.

Conditions

Cannabis Use Disorder

Healthy

Study ID

NCT05472818

Start date

Apr 12, 2022

Status verified date

Mar, 2026

Completion date

May, 2032

Anticipated

Primary completion date

May 30, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Accepted

CUD Participants Inclusion Criteria:

1. Able to provide informed consent
2. Male and female 18-75 years old
3. Daily cannabis use
4. Positive urine screen for cannabinoids and negative for all other drugs on
5. Diagnosis of DSM-5 cannabis use disorder (≥ moderate, i.e., ≥ 4 \[of 11\] symptoms).
6. Must express a willingness at screening to set a date to attempt to quit using cannabis.
7. Physically healthy i.e., no clinically unstable medical conditions.
8. For women of childbearing potential (WOCBP) and men, willingness to practice birth control and to inform study staff immediately if either they (for women) or their partner (for men) becomes pregnant.
9. Additional criteria not disclosed here in order to minimize the risk of ineligible subjects enrolling in the study.

CUD Participants Exclusion Criteria:

1. Laboratory tests with clinically significant abnormalities or positive urine toxicology screen with exception of cannabinoids.
2. Women with a positive pregnancy test or women who are lactating.
3. Have implanted or embedded metal objects or fragments in the head or body that would present a risk during the MRI scanning procedure, or have worked with ferrous metals either as a vocation or hobby (for example, as a sheet metal worker, welder, or machinist) in such a way that might have led to unknown, indwelling metal fragments that could cause injury if they moved in response to placement in the magnetic field
4. Have had exposure to ionizing radiation that in combination with the study tracer would result in a cumulative exposure that exceeds recommended exposure limits.
5. History of a bleeding disorder or are currently taking anticoagulants (such as Coumadin, Heparin, Pradaxa, Xarelto) Subjects who have donated blood within 8 weeks of the present study
6. Medications that could alter synaptic density and, therefore, confound the interpretation of study data.
7. Additional criteria not disclosed here in order to minimize the risk of ineligible subjects enrolling in the study.

Healthy Controls Inclusion Criteria:

1. Willing and able to give voluntary written informed consent
2. Male and Female subjects, age 18 to 75 years, inclusive
3. BMI within 19 to 35 kg/m2, inclusive
4. Must be in good health as determined by medical history, physical examination, ECG, serum/urine biochemistry, hematology, and serology tests.
5. Negative urine drug screen
6. If female, not pregnant or breastfeeding
7. If female of childbearing potential, must agree to use an acceptable method of birth control, as determined by the principal investigator, for the duration of the study and up to one month after completion of PET scans.
8. Able to read and write, able to communicate effectively with the investigator, and comply with all study requirements, restrictions, and directions of the clinic staff.
9. Have arterial access sufficient to allow blood sampling as per the protocol.

Healthy Controls Exclusion Criteria:

1. History or presence of clinically significant and unstable respiratory, GI, renal, hepatic, pancreatic, hematological, neurological (including history of seizure), cardiovascular, psychiatric (including known addictive disorders), musculoskeletal, genitourinary, immunological, or dermatological disorders, including all cancers.
2. Abnormal clinically significant laboratory or physical findings during screening
3. History of a bleeding disorder or are currently taking anticoagulants (such as Coumadin, Heparin, Pradaxa, Xarelto)
4. A condition that, in the opinion of the investigator, would prevent compliance with the study protocol.
5. Medications that could alter synaptic density and, therefore, confound the interpretation of study data.
6. MRI incompatible implants and other contraindications for MRI, such as pace-maker, artificial joints, non-removable body piercings, metal fragments in head and/or body, or history working with ferrous metals either as a vocation or hobby in such a way that might have led to unknown, indwelling metal fragments that could cause injury during MRI etc.
7. Subjects who suffer from claustrophobia.
8. 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 for healthy volunteers
9. Additional criteria not disclosed here in order to minimize the risk of ineligible subjects enrolling in the study.

Study Design

Enrollment

51 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

active comparator: CUD Group

Participants will be scanned using anatomical magnetic resonance imaging (MRI) and PET. All participants will receive two PET scans, 4 weeks apart. CUD participants will be asked to abstain from cannabis for the 4 week period.

active comparator: Healthy Controls

Participants will be scanned using anatomical magnetic resonance imaging (MRI) and PET. All participants will receive two PET scans, 4 weeks apart.

Interventions

[11C]APP311

For each \[11C\]APP311 (UCB-J) PET scan, up to 20 mCi of \[11C\]APP311 (UCB-J) will be administered by infusion pump. All participants will receive at least two \[11C\]APP311 (UCB-J) PET scans approx. 4 weeks days apart. Approximately 8 CUD participants will be asked to return for a third \[11C\]APP311 (UCB-J) PET scan after an additional 4 weeks following their second scan.

Primary outcome measure

  • Hippocampal SV2A synaptic density [ Time Frame: All participants will receive at least two [11C]APP311 (UCB-J) PET scans approx. 4 weeks days apart. ]

Central Contacts and Locations

Central contacts

Locations

Yale University School of Medicine

Recruiting

New Haven, Connecticut, United States, 06511

More Information

Sponsor

Yale University

Last update posted

Mar 12, 2026

Last verified

Mar, 2026

Keywords

  • Cannabis Use Disorder (CUD)
  • Healthy subjects
  • synaptic vesicle density
  • [11C]APP311
  • UCB-J

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Yale University on 2026-03-12.