The purpose of this study is to determine the efficacy of varenicline (Chantix™) for the
treatment of alcohol dependence.
By both providing a low level of reinforcement and down-grading any "high" associated with
concurrent administration of the abused drug, combined agonist/antagonist therapies promote
both initial and sustained abstinence. Based on varenicline's specific affinity for the
nicotinic acetylcholine receptors that are implicated in alcohol reward circuitry, it
appears to be a good candidate for treatment of alcohol dependence. Alcohol can exert its
reinforcing and dopamine-enhancing effects through activation of nicotinic receptors. In
addition to its partial agonist activity at heteromeric α4β2 nicotinic acetylcholine
receptors, varenicline has also been shown to be a full agonist at homomeric α7 nicotinic
acetylcholine receptors. That full agonism at α7 may be key in reducing alcohol withdrawal
and craving during early alcohol abstinence, and thus reducing relapse, as α7 receptors are
implicated in the neural reward circuitry activated by alcohol use.
- 1. Males and females, 18-70 years old.
- 2. Meets DSM-IV criteria for current diagnoses of alcohol dependence, determined by
the SCID-IV (First, 1996).
- 3. Meets the following drinking criteria as measured by the Timeline Followback
(TLFB) (Sobell, 1995)
- drank within 30 days of intake day,
- reports a minimum of 48 standard alcoholic drinks (avg. 12 drinks/wk) in a
consecutive 30-day period over the 90-day period prior to starting intake (i.e., a
minimum of 40% days drinking), and
- has 2 or more days of heavy drinking (defined as 5 or more drinks per day in males
and 4 or more drinks per day in females) in this same pre-treatment period.
- 4. Three consecutive days of abstinence from alcohol, determined by self-reports and
confirmed by a negative breathalyzer tests immediately before the day of
randomization, and a Clinical Institute Withdrawal Scale for Alcohol (CIWA-AR)
(Sullivan, 1989) score below eight on the day of randomization.
- 5. Lives a commutable distance from the TRC and agrees to attend all research visits
including follow-up visits.
- Speaks, understands, and prints in English.
- Has evidence of dependence on a substance other than alcohol (except nicotine or
marijuana); or tests positive on the urine drug screen and on a single allowed
retest, during the screening week, with the exception of a THC positive urine, and/or
a).positive result for benzodiazepines prescribed by a doctor for medically indicated
detox (prescription required).
- Has hepatocellular disease indicated by elevations of SGPT (ALT) and SGOT (AST) of at
least 4.5 times normal after the required 3 days of abstinence, or elevated bilirubin
(>1.3) (one retest allowed at the discretion of the Medical Director).
- Meets diagnostic criteria for a current unstable or serious psychiatric or medical
illness. For example, bipolar affective disorder, schizophrenia or any other
psychotic disorder, or organic mental disorder; has serious heart, lung, kidney,
immune system, GI tract (ulcerative colitis, regional enteritis, or gastrointestinal
- Has taken any psychotropic medications (including disulfiram, naltrexone or
acamprosate) regularly within the last 2 weeks or needs immediate treatment with a
psychotropic medication (with the exception of detoxification medications or benadryl
used sparingly for sleep).
- Tests positive on a pregnancy test, is contemplating pregnancy in the next 12 months,
is nursing, or is not using an effective contraceptive method if the subject is of
- Has participated in any investigational drug trial within 30 days prior to the study.
Subjects mandated to treatment based upon a legal decision or as a condition of
employment. This will be assessed by the subject's self-report.
- Known hypersensitivity to varenicline.
- Subjects with known AIDS or other serious illnesses that may require hospitalization
during the study.
- Clinical laboratory tests (CBC, blood chemistries, urinalysis) outside normal limits
that are clinically unacceptable to the Principal Investigator. (ECG 1st degree
heart block, sinus tachycardia, left axis deviation, and nonspecific ST or T wave
changes are allowed; liver function tests [LFTs] <5 x ULN are acceptable).