SV2A Density Cannabis Use Disorder

NCT05472818 | Recruiting Early Phase 1 FDA Drug

• 2 other identifiers: 20000321811R01DA054314
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

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

Healthy; Cannabis Use Disorder

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Hippocampal SV2A synaptic density

  Hippocampal SV2A synaptic density will be measured using \[11C\]APP311 (UCB-J).

  All participants will receive at least two [11C]APP311 (UCB-J) PET scans approx. 4 weeks days apart.

Secondary Outcomes (2)

• Hippocampal binding and Hippocampal Verbal Memory Task

  The Auditory Verbal Learning Task (AVLT) will be administered before and after the 4 week abstinence period.

• Hippocampal binding and Groton Maze Learning in CUDs

  The Groton Maze Learning Task will be administered before and after the 4 week abstinence period.

Other Outcomes (3)

• Hippocampal synaptic density and first age of cannabis exposure

  Before and after the 4 week abstinence period.

• Hippocampal synaptic density and cumulative lifetime cannabis exposure.

  Before and after the 4 week abstinence period.

• Hippocampal SV2A synaptic density after 8 weeks

  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. (8 weeks in total).

Study Arms (2)

CUD Group

ACTIVE COMPARATOR

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.

Drug: [11C]APP311

Healthy Controls

ACTIVE COMPARATOR

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

Drug: [11C]APP311

Interventions

[11C]APP311 DRUG

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.

CUD Group; Healthy Controls

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide informed consent
• Male and female 18-75 years old
• Daily cannabis use
• Positive urine screen for cannabinoids and negative for all other drugs on
• Diagnosis of DSM-5 cannabis use disorder (≥ moderate, i.e., ≥ 4 \[of 11\] symptoms).
• Must express a willingness at screening to set a date to attempt to quit using cannabis.
• Physically healthy i.e., no clinically unstable medical conditions.
• 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.
• Additional criteria not disclosed here in order to minimize the risk of ineligible subjects enrolling in the study.

You may not qualify if:

• Laboratory tests with clinically significant abnormalities or positive urine toxicology screen with exception of cannabinoids.
• Women with a positive pregnancy test or women who are lactating.
• 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
• Have had exposure to ionizing radiation that in combination with the study tracer would result in a cumulative exposure that exceeds recommended exposure limits.
• 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
• Medications that could alter synaptic density and, therefore, confound the interpretation of study data.
• Additional criteria not disclosed here in order to minimize the risk of ineligible subjects enrolling in the study.
• Willing and able to give voluntary written informed consent
• Male and Female subjects, age 18 to 75 years, inclusive
• BMI within 19 to 35 kg/m2, inclusive
• Must be in good health as determined by medical history, physical examination, ECG, serum/urine biochemistry, hematology, and serology tests.
• Negative urine drug screen
• If female, not pregnant or breastfeeding
• 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.
• 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.

Sponsors & Collaborators

• Yale University: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Yale University School of Medicine

New Haven, Connecticut, 06511, United States

RECRUITING

Study Officials

• Deepak C D'Souza

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shannon Zeilman

CONTACT

203-974-7822; shannon.zeilman@yale.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry

Model Details: In this study, patients with cannabis use disorder (CUD) and matched healthy controls 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. A small subset of CUD participants will be asked to continue abstaining for an additional approx. 4 weeks to complete one additional scan. Participants may also complete a neurocognitive battery, various psychiatric evaluations, a physical examination, an ECG, blood tests, and questionnaires. CUD participants will complete bi-weekly study visits to confirm abstinence.

Study Record Dates

• First Submitted: July 14, 2022
• First Posted: July 25, 2022
• Study Start: April 12, 2022
• Primary Completion (Estimated): May 30, 2027
• Study Completion (Estimated): May 1, 2032
• Last Updated: March 12, 2026

Record last verified: 2026-03

Locations

US (1)