A Randomized, Double-blind, Placebo Controlled Trial (RCT) of Varenicline to Reduce Alcohol Consumption in Heavy Drinkers

This study will determine whether varenicline, a drug that acts on the brain's nicotine receptors and is used to help smokers stop smoking, will have an impact on alcohol self-administration.

People between 24 and 60 years of age who regularly consume alcoholic drinks (more than 15 drinks per week for women, and more than 20 drinks per week for men) may be eligible for this study. The study requires five outpatient visits and one overnight hospital admission at the NIH Clinical Center.

Participants undergo the following procedures:

Visit 1 (outpatient: 4-5 hours)

• Standard assessments, including vital signs measurements, breathalyzer test, blood and urine tests (including pregnancy test for females), questionnaires about mood, symptoms, alcohol use and smoking, if applicable
• Questionnaires about medical and psychological status
• Health assessment and assessment of alcohol drinking behavior

Visit 2 (outpatient: 8 hours)

• Standard assessments (see above)
• Computer-Assisted Self-infusion of Ethanol (CASE) session: Subjects will receive a priming intravenous infusion of alcohol. After 25 min, they will be allowed to give themselves additional exposures of alcohol over a period of 2 hours by pressing a button on a computer that controls the infusion pump.

Visit 3 (outpatient: 2 hours)

-Standard assessments

Visit 4 (outpatient: 8 hours)

• Standard assessments
• Brain functional magnetic resonance imaging scan (MRI). This test uses a magnetic field and radio waves to produce images of the brain. The patient lies on a table that can slide in and out of the scanner, wearing earplugs to muffle loud sounds that occur during the scanning process. Initial pictures are taken of the brain's structure and additional scans measure brain activity while the subject performs simple tasks.
• Alcohol Infusion. Subjects receive an intravenous infusion of alcohol while in the MRI scanner to measure the brain s response to alcohol.

Visit 5 (overnight)

• Standard assessments
• Repeat CASE session
• Interview about the subject's experiences participating in the protocol, including any symptoms and urges to drink

Visit 6 (outpatient)

• Standard assessments (without blood tests)
• Interview about participation in the study

Telephone follow-up

After 3 weeks, subjects are called to check on their symptoms and gather information on their drinking and, if applicable, smoking.