SV2A Density Cannabis Use Disorder

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 usingcannabis.

7. Physically healthy i.e., no clinically unstable medical conditions.

8. For women of childbearing potential (WOCBP) and men, willingness to practice birthcontrol and to inform study staff immediately if either they (for women) or theirpartner (for men) becomes pregnant.

9. Additional criteria not disclosed here in order to minimize the risk of ineligiblesubjects enrolling in the study.

CUD Participants Exclusion Criteria:

1. Laboratory tests with clinically significant abnormalities or positive urinetoxicology 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 wouldpresent a risk during the MRI scanning procedure, or have worked with ferrous metalseither as a vocation or hobby (for example, as a sheet metal worker, welder, ormachinist) in such a way that might have led to unknown, indwelling metal fragmentsthat 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 tracerwould result in a cumulative exposure that exceeds recommended exposure limits.

5. History of a bleeding disorder or are currently taking anticoagulants (such asCoumadin, Heparin, Pradaxa, Xarelto) Subjects who have donated blood within 8 weeksof the present study

6. Medications that could alter synaptic density and, therefore, confound theinterpretation of study data.

7. Additional criteria not disclosed here in order to minimize the risk of ineligiblesubjects 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 birthcontrol, as determined by the principal investigator, for the duration of the studyand up to one month after completion of PET scans.

8. Able to read and write, able to communicate effectively with the investigator, andcomply with all study requirements, restrictions, and directions of the clinicstaff.

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 asCoumadin, Heparin, Pradaxa, Xarelto)

4. A condition that, in the opinion of the investigator, would prevent compliance withthe study protocol.

5. Medications that could alter synaptic density and, therefore, confound theinterpretation 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/orbody, or history working with ferrous metals either as a vocation or hobby in such away that might have led to unknown, indwelling metal fragments that could causeinjury during MRI etc.

7. Subjects who suffer from claustrophobia.

8. Participation in other research studies involving ionizing radiation within one yearof the PET scans that would cause the subject to exceed the yearly dose limits forhealthy volunteers

9. Additional criteria not disclosed here in order to minimize the risk of ineligiblesubjects enrolling in the study.