Varenicline Treatment of Alcohol Dependence in Smokers

Building upon knowledge about the role of nicotinic acetylcholine receptors in alcohol
drinking and smoking, varenicline, a smoking cessation treatment that targets these
receptors, will be tested as a potential treatment for alcohol dependent smokers seeking
alcohol treatment.

Inclusion Criteria:

- are 18 - 70 years of age and seeking treatment of alcohol drinking;

- meet DSM-IV TR Criteria for Alcohol Dependence

- report smoking 100 cigarettes or more in their lifetime and currently smoke at least
twice weekly on average in the past 90 days and have a urinary cotinine level of >
30ng/mL by semi-quantitative urinalysis or equivalent plasma cotinine level (> 6
ng/mL);

- report heavy drinking on at least 2 days on average per week (i.e., ≥ 4 drinks on an
occasion for women and ≥ 5 drinks for men) for the past 90 days and no more than 7
consecutive days of abstinence at intake.

Exclusion Criteria:

- exhibit current, clinically significant physical disease or abnormality based on
medical history, physical examination, or routine laboratory evaluation including:

- any unexplained elevations in liver enzymes (i.e., transaminases, bilirubin)

- clinically significant, unstable cardiovascular disease/uncontrolled hypertension

- hepatic or renal impairment

- severe obstructive pulmonary disease

- diabetes mellitus requiring insulin or certain oral medications (i.e.,
sulfonylureas) and an A1C hemoglobin test score of > 7 for participants not
prescribed these medications

- baseline systolic blood pressure higher than 150 mm Hg or diastolic blood
pressure higher than 95 mm Hg

- have a history of cancer (except treated basal cell or squamous cell carcinoma of the
skin)

- have a history of serious hypersensitivity reactions or skin reactions to varenicline;

- exhibit serious psychiatric illness (i.e., schizophrenia, bipolar disorder, severe
major depression, panic disorder, borderline personality disorder, organic mood or
mental disorders by history or psychological examination

- report current suicidal ideation (past 6 months) or lifetime hx of suicidal behavior
assessed with the Columbia Suicide Severity Rating Scale 60; or risk for aggression
using a cut-off of 15 or more on the Overt Aggression Scale - Modified Aggression
Scale or 6 or more on the OAS-M Irritability Subscale 61.

- have used any psychotropic drug in the past month, except individuals who are on a
stable dose of a Selective Serotonin Reuptake Inhibitor for at least two months or who
report occasional use of prescription sleep aids that they are willing to discontinue;

- have a current DSM-IV diagnosis of drug dependence other than nicotine or alcohol

- are at risk for an alcohol withdrawal syndrome as evidenced by:

- a history of seizures, delirium, or hallucinations during alcohol withdrawal

- a Clinical Institute Withdrawal Assessment scale 62 score of > 8,

- report drinking to avoid withdrawal symptoms

- have required medical treatment of alcohol withdrawal within the past 6 months

- have used another investigational drug within 30 days or have used medications to
treat alcohol (e.g., naltrexone, topiramate, acamprosate, disulfiram) or nicotine use
(e.g., clonidine, varenicline, bupropion, nicotine replacement) in the past 3 months
or intend to use these medications;prior use of nicotine replacement in situations
where smoking is not permitted (e.g., planes) without the intention to quit smoking is
not exclusionary;

- intend to donate blood or blood products during the treatment phase of the study

- have a Body Mass Index (calculated as weight in kilograms divided by the square of
height in meters) less than 15 or greater than 39.99 or weight less than 45 kg;

- are a female of childbearing potential who is pregnant, nursing, or not practicing
effective contraception (oral, injectable, or implantable contraceptives, intrauterine
device, or barrier method with spermicide).