Effects of Cortical Dopamine Regulation on Drinking, Craving, and Cognitive Control
Condition: Alcohol Use Disorder
MeSH terms: Alcoholism
Intervention: Tolcapone; Placebo
Intervention MeSH terms: Tolcapone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 90.0
Sex: All
Minimum age: 21 Years
Maximum age: 40 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine whether the catechol-O-methyltransferase (COMT)
      inhibitor tolcapone, relative to placebo, reduces alcohol drinking and alcohol cue-elicited
      brain activation and increases brain activation associated with cognitive control as a
      function of a participant's genotype at a polymorphism in the COMT gene.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age 21-40 (to focus on an age group still on a trajectory of increasing alcohol
             consumption).

          2. Meets Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5)
             criteria for current Alcohol Use Disorder.

          3. Currently not engaged in, and does not want treatment for, alcohol-related problems.

          4. Able to read and understand questionnaires and informed consent.

          5. Lives within 50 miles of the study site.

          6. Able to maintain abstinence from alcohol for two days (without the aid of
             detoxification medications), as determined by self report and breathalyzer
             measurements.

        Exclusion Criteria:

          1. Current DSM-5 diagnosis of any other substance use disorder except Nicotine Use
             Disorder.

          2. Any psychoactive substance use (except marijuana and nicotine) within the last 30
             days, as indicated by self-report and urine drug screen. For marijuana, no use within
             the last seven days by verbal report and negative (or decreasing) urine
             tetrahydrocannibinol (THC) levels.

          3. Current DSM-5 Axis I diagnosis, including major depression, panic disorder,
             obsessive-compulsive disorder, post-traumatic stress disorder, bipolar affective
             disorder, schizophrenia, dissociative disorders, eating disorders, or any other
             psychotic or organic mental disorder.

          4. Current suicidal ideation or homicidal ideation.

          5. Need for maintenance or acute treatment with any psychoactive medication, including
             antiepileptic medications.

          6. Currently taking medication known to affect alcohol intake (e.g., disulfiram,
             naltrexone, acamprosate, topiramate).

          7. History of severe alcohol withdrawal (e.g., seizure, delirium tremens), as evidenced
             by self-report and assessment with Clinical Institute Withdrawal Assessment for
             Alcohol-Revised (CIWA-Ar).

          8. Clinically significant medical problems such as cardiovascular, renal,
             gastrointestinal, or endocrine problems that would impair participation or limit
             medication ingestion.

          9. Past alcohol-related medical illness, such as gastrointestinal bleeding, pancreatitis,
             or peptic ulcer.

         10. Current or past hepatocellular disease, as indicated by verbal report or elevations of
             alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than the
             upper limit of the normal range at screening.

         11. Females of childbearing potential who are pregnant (by urine human chorionic
             gonadotropin), nursing, or who are not using a reliable form of birth control.

         12. Current charges pending for a violent crime (not including drinking while
             intoxicated).

         13. Lack of a stable living situation.

         14. Presence of ferrous metal in the body, as evidenced by metal screening and
             self-report.

         15. Severe claustrophobia or morbid obesity that preclude placement in the MRI scanner.

         16. History of head injury with > 2 minutes of unconsciousness.