Cannabis Use DisorderEarly Phase 1NCT05472818
SV2A Density Cannabis Use Disorder
A Early Phase 1 study testing [11C]APP311 in people with Cannabis Use Disorder and Healthy, run by Yale University at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Cannabis Use Disorder, Healthy
- What is being tested?
- [11C]APP311
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 51 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Apr 2022to May 2032
- Phase
- Early 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 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
CUD Participants Inclusion Criteria:
- 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.
CUD Participants Exclusion Criteria:
- 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.
Healthy Controls Inclusion Criteria:
- 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.
- Have arterial access sufficient to allow blood sampling as per the protocol.
Healthy Controls Exclusion Criteria:
- 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.
- Abnormal clinically significant laboratory or physical findings during screening
- History of a bleeding disorder or are currently taking anticoagulants (such as Coumadin, Heparin, Pradaxa, Xarelto)
- A condition that, in the opinion of the investigator, would prevent compliance with the study protocol.
- Medications that could alter synaptic density and, therefore, confound the interpretation of study data.
- 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.
- Subjects who suffer from claustrophobia.
- 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
- Additional criteria not disclosed here in order to minimize the risk of ineligible subjects enrolling in the study.
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 School of Medicine
New Haven, Connecticut, 06511
About this study
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
- Being tested
- [11C]APP311
- Keywords
- Cannabis Use Disorder (CUD), Healthy subjects, synaptic vesicle density, [11C]APP311, UCB-J
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[11C]APP311Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: [11C]APP311 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hippocampal SV2A synaptic density
Hippocampal SV2A synaptic density will be measured using [11C]APP311 (UCB-J).
Measured: 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
To determine the relationship between hippocampal [11C]APP311 (UCB-J) binding and performance on the hippocampal verbal memory task (Auditory Verbal Learning Task [AVLT]), a cognitive task that measures total immediate recall, before and after 4 weeks of confirmed cannabis abstinence.
Measured: 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
To determine the relationship between hippocampal [11C]APP311 (UCB-J) binding and performance on the Groton Maze Learning task, a cognitive task that measures total number of errors, in CUDs before and after 4 weeks of confirmed cannabis abstinence.
Measured: The Groton Maze Learning Task will be administered before and after the 4 week abstinence period.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2022
- Study start12 Apr 2022
- Primary completion30 May 2027 (estimated)
- Study completionMay 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cannabis 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
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 51 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Principal investigator, Deepak C. D'Souza, Yale University
- Investigators
- Deepak C D'Souza, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05472818
- Sponsor's protocol ID
- 2000032181
- Other IDs
- 1R01DA054314
- Status last verified
- Mar 2026
- First submitted
- 14 Jul 2022
- Last updated
- 12 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SV2A Density Cannabis Use Disorder
- ClinicalTrials.gov ID
- NCT05472818
- Acronym / sponsor ID
- 2000032181
- Conditions
- Cannabis Use Disorder, Healthy
- Keywords
- Cannabis Use Disorder (CUD), Healthy subjects, synaptic vesicle density, [11C]APP311, UCB-J
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 51 participants (estimated)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 12 Apr 2022 (actual)
- Primary completion
- 30 May 2027 (estimated)
- Study completion
- May 2032 (estimated)
- First posted
- 25 Jul 2022 (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 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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| CUD Group | Active comparator | Drug: [11C]APP311Participants 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. |
| Healthy Controls | Active comparator | Drug: [11C]APP311Participants will be scanned using anatomical magnetic resonance imaging (MRI) and PET. All participants will receive two PET scans, 4 weeks apart. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| [11C]APP311For 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. | Drug | CUD Group, Healthy Controls |
Primary outcome
Hippocampal SV2A synaptic density
Time frame: All participants will receive at least two [11C]APP311 (UCB-J) PET scans approx. 4 weeks days apart.
Hippocampal SV2A synaptic density will be measured using [11C]APP311 (UCB-J).
2 secondary outcomes
Hippocampal binding and Hippocampal Verbal Memory Task
Time frame: 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
Time frame: The Groton Maze Learning Task will be administered before and after the 4 week abstinence period.
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 12 Mar 2026.
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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.
Deepak C D'Souza 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 Early Phase 1 study testing [11C]APP311 in people with Cannabis Use Disorder and Healthy, 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?
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 12 Mar 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 Shannon Zeilman (203-974-7822, shannon.zeilman@yale.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the 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.). 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 12 Mar 2026.