Examining brain changes in cannabis use disorder after abstinence

SV2A Density Cannabis Use Disorder

This study is testing if taking a break from cannabis for at least four weeks can help improve brain changes related to memory in people with cannabis use disorder.

Quick facts

• Phase: EARLY_PHASE1
• Study type: Interventional
• Enrollment: 51 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Yale University (other)
• Drugs / interventions: radiation
• Locations: 1 site (New Haven, Connecticut)
• Trial ID: NCT05472818 on ClinicalTrials.gov

What this trial studies

This study aims to assess whether the density of synaptic vesicles in the hippocampus improves in individuals with cannabis use disorder (CUD) after at least four weeks of confirmed abstinence from cannabis, compared to healthy controls. It will utilize imaging techniques with [11C]APP-311 and [11C]UCB-J to measure changes in synaptic vesicle density and correlate these changes with verbal memory performance. Additionally, the study will explore the relationship between hippocampal binding and cannabis exposure metrics, such as age of initiation and cumulative lifetime dose.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18-75 who have a diagnosis of moderate cannabis use disorder and are willing to abstain from cannabis.

Not a fit: Patients who are not daily cannabis users or who have clinically significant medical conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide insights into the neurobiological effects of cannabis use and inform treatment strategies for cannabis use disorder.

How similar studies have performed: While there have been studies examining brain changes in substance use disorders, this specific approach focusing on synaptic vesicle density in cannabis use disorder is relatively novel.

Eligibility criteria

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.

Where this trial is running

New Haven, Connecticut

• Yale University School of Medicine — New Haven, Connecticut, United States (RECRUITING)

Study contacts

• Principal investigator: Deepak C D'Souza — Yale University
• Study coordinator: Shannon Zeilman

Conditions: Cannabis Use Disorder, Healthy, Healthy subjects, synaptic vesicle density, [11C]APP311, UCB-J