Novel mGluR5 Modulator Effects on Alcohol Drinking and MRI Outcomes

Eligibility Criteria

• 1. Age 21-40 (to focus on an age group still on a trajectory of increasing alcohol consumption, consistent with our pilot data and past iterations of the ARC).
• 2. Meets Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria for current Alcohol Use Disorder, with at least Moderate severity.
• 3. Reports drinking, on average, at least 20 standard alcoholic drinks per week for at least the past 3 months.
• 4. Currently not engaged in, and does not want treatment for, alcohol-related problems.
• 5. Able to read and understand questionnaires and informed consent.
• 6. Lives within 50 miles of the study site.
• 7. Able to maintain abstinence from alcohol the evening prior to appointments (without the aid of detoxification medications), as determined by self-report and breathalyzer measurements.
• 8. Amenable to drinking liquor in fruit juice.
• 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 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. Using CYP2C19 and/or CYP3A4 inhibitors or inducers in the 14 days before dosing or during the study.
• 6. Need for maintenance or acute treatment with any psychoactive medication, including antiepileptic medications.
• 7. Currently taking medication known to affect alcohol intake (e.g., disulfiram, naltrexone, acamprosate, topiramate).
• 8. History of severe alcohol withdrawal (e.g., tremor, sweating, anxiety, seizure, delirium tremens), as evidenced by self-report and assessment with Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-Ar).
• 9. Clinically significant medical problems such as cardiovascular, renal, gastrointestinal, or endocrine problems that would impair participation or limit medication ingestion.
• 10. Past alcohol-related medical illness, such as gastrointestinal bleeding, pancreatitis, or peptic ulcer.
• 11. Has hepatocellular disease indicated by elevations of SGPT (ALT) or SGOT (AST) greater than 2.5 times normal at screening.
• 12. Females of childbearing potential who are pregnant (by urine HCG), nursing, or who are not using a reliable form of birth control.
• 13. Current charges pending for a violent crime (not including DUI-related offenses).
• 14. Lack of a stable living situation.
• 15. Presence of ferrous metal in the body, as evidenced by metal screening and self-report.
• 16. Severe claustrophobia or extreme obesity that preclude placement in the MRI scanner.
• 17. Neurological disease or history of head injury with \> 2 minutes of unconsciousness.