• tobacco and alcohol craving [ Time Frame: during laboratory session ] [ Designated as safety issue: No ]
• tobacco and alcohol craving [ Time Frame: during the cue reactivity session ] [ Designated as safety issue: No ]

The purpose of this study is to examine the effect of smoking cessation medications on alcohol drinking.

Following 7 days of medication pre-treatment to achieve steady state levels, participants complete a laboratory session assessing alcohol self-administration behavior and a cue reactivity session assessing their reactivity to alcohol-related cues. Subjects are maintained on study medication for 4 weeks after the laboratory session.

The study is subdivided into three studies based on subject population.

Study 1A enrolls heavy drinking smokers (tested under nicotine deprivation). Study 1B enrolls heavy drinking smokers (not tested under nicotine deprivation), non-daily smokers, and nonsmokers. Study 1C enrolls smokers (not tested under nicotine deprivation) and nonsmokers who meet criteria for alcohol use disorders.

In Study 1A, volunteers are administered either varenicline (Chantix), bupropion (Zyban), or placebo. In Studies 1B and 1C, volunteers are administered either varenicline (Chantix) or placebo.

• Drug: varenicline
• Drug: bupropion
• Drug: placebo

• Experimental:

  Studies 1A and 1B: varenicline 2mg/day

  Study 1C: varenicline 1mg/day or 2mg/day

• Experimental: Study 1A only: Bupropion 300mg/day
• Placebo Comparator: Placebo Controlled

Inclusion Criteria:

• 21 years old or older
• Able to read and write in English
• Smokers, non-daily smokers, and non-smokers
• Heavy Drinkers and/or meet criteria for alcohol use disorders

Exclusion Criteria:

• Any significant current medical or psychiatric conditions that would contraindicate the consumption of alcohol
• Significant hepatocellular injury
• Positive test result at intake appointments on urine drug screens conducted for opiates, cocaine, or benzodiazepines
• Women who are pregnant or nursing
• Suicidal, homicidal, or evidence of severe mental illness
• Prescription of any psychotropic drug in the 30 days prior to study enrollment
• Blood donation within the past 8 weeks
• Individuals who are seeking treatment for drinking or smoking or who have attempted to quit drinking or smoking within the past 3 months
• Specific exclusions for administration of bupropion not specified above including: having taken monoamine inhibitors in the past six weeks; history of anorexia or bulimia; previous hypersensitivity to bupropion; history of alcohol or drug dependence in the past year; history of seizure disorder of any etiology
• Known allergy to varenicline or taking H2blockers
• Participation within the past 8 weeks in other studies that involve additive blood sampling and/or interventional measures that would be considered excessive in combination with the current study
• Subjects likely to exhibit clinically significant alcohol withdrawal during the study