Novel mGluR5 Modulator Effects on Alcohol Drinking and MRI Outcomes

Inclusion criteria

• 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).
• Meets Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria for current Alcohol Use Disorder, with at least Moderate severity.
• Reports drinking, on average, at least 20 standard alcoholic drinks per week for at least the past 3 months.
• Currently not engaged in, and does not want treatment for, alcohol-related problems.
• Able to read and understand questionnaires and informed consent.
• Lives within 50 miles of the study site.
• 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.
• Amenable to drinking liquor in fruit juice.

Exclusion criteria

• Current DSM-5 diagnosis of any other substance use disorder except Nicotine Use Disorder.
• 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.
• 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.
• Current suicidal ideation or homicidal ideation.
• Using CYP2C19 and/or CYP3A4 inhibitors or inducers in the 14 days before dosing or during the study.
• Need for maintenance or acute treatment with any psychoactive medication, including antiepileptic medications.
• Currently taking medication known to affect alcohol intake (e.g., disulfiram, naltrexone, acamprosate, topiramate).
• 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).
• Clinically significant medical problems such as cardiovascular, renal, gastrointestinal, or endocrine problems that would impair participation or limit medication ingestion.
• Past alcohol-related medical illness, such as gastrointestinal bleeding, pancreatitis, or peptic ulcer.
• Has hepatocellular disease indicated by elevations of SGPT (ALT) or SGOT (AST) greater than 2.5 times normal at screening.
• Females of childbearing potential who are pregnant (by urine HCG), nursing, or who are not using a reliable form of birth control.
• Current charges pending for a violent crime (not including DUI-related offenses).
• Lack of a stable living situation.
• Presence of ferrous metal in the body, as evidenced by metal screening and self-report.
• Severe claustrophobia or extreme obesity that preclude placement in the MRI scanner.
• Neurological disease or history of head injury with > 2 minutes of unconsciousness.