Overview

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.

Eligibility

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.