Varenicline Treatment for Cannabis Use Disorder

General Inclusion Criteria

- Must meet DSM-5 criteria for cannabis use disorder and use cannabis at least 3 days
per week in the last 30 days.

- Must be between the ages of 18 and 65 years.

- If female and of childbearing potential, must agree to use acceptable methods of birth
control for the duration of the trial.

- Must consent to random assignment, and be willing to commit to medication ingestion.

- Must be able to read and provide informed consent.

- Must have body weight >110lbs (50kg) and have BMI between 18 and 32kg/m2

- Must function at an intellectual level and have knowledge of the English language to
sufficiently allow for accurate completion of assessments.

Additional Inclusion Criteria for fMRI Eligibility

- Must be right-handed. General Exclusion Criteria

- Women who are pregnant, nursing, or plan to become pregnant during the course of the
study.

- Individuals with severe renal impairment (creatinine clearance less than 30 mL per
minute).

- Lifetime history of DSM-5 Bipolar I or II Disorder, Schizophrenia or other psychotic
disorder. Stably treated MDD, Dysthymia, GAD, Social Phobia, and Specific Phobia
diagnoses are acceptable (i.e. same dose of medication has been prescribed for at
least 2 months prior to screening and no changes in current medication expected during
course of the trial).

- Suicidal ideation or behavior within the past 6 months. Subjects who are believed to
be at suicidal or homicidal risk (answers 'yes' on questions 4 or 5 of C-SSRS) will be
referred for assessment by a qualified mental health professional.

- Concomitant use of psychotropic medications, with the exception of stable doses
(defined as no dosing adjustments in the past two months) of non-MAO-I
antidepressants, non-benzodiazepine anxiolytics, and ADHD medications.

- Current use of medications prescribed for mania or psychosis.

- Current use of buproprion or nortryptiline.

- Moderate or severe non-cannabis substance use disorders within the past 60 days with
the exception of tobacco use disorder.

- Individuals taking an investigational agent within the last 30 days before baseline
visit.

- Individuals with clinically significant medical disorders or lab abnormalities.

- Any individual at screening with SGOT (AST) or SGPT (ALT) greater than 3 times the
upper limit of normal and/or total bilirubin greater than two times the upper limit of
normal.

- Individuals with clinically significant cardiovascular disease in the past 6 months
(e.g., myocardial infarction, CABG, PTCA, severe or unstable angina, serious
arrhythmia, or any clinically significant ECG conduction abnormality.

- Individuals with clinically significant cerebrovascular disease in the past 6 months
such as TIA, CVA, or stroke.

- Hypersensitivity to varenicline.

- Individuals who have participated in the clinical trial of any investigative compound
within the last 60 days.

Additional Exclusion Criteria for fMRI Eligibility

- Any psychiatric or medical issues, including claustrophobia, ferrous metal implants,
pacemakers, or other electronic devices that would interfere with ability to
participate in and successfully complete scanning procedures.

- Any person unable to lie still within the fMRI scanner for the required period of time
to obtaine useful images (use of anxiolytics will not be permitted for
anxiety/claustrophobia related to scanning procedures).