Aripiprazole Effects on Alcohol Drinking and Craving

The purpose of this study is to determine whether aripiprazole (marketed dopamine stabilizer) is effective in reducing of alcohol craving and drinking compared to placebo depending on participant's baseline level of impulsivity.

Non-treatment seeking individuals meeting criteria for alcohol dependence (N=120) will be recruited through advertisement and paid for their participation. Subjects will have blood drawn for DNA analysis of various brain dopamine system genes. Alcoholics, after baseline evaluation, will be assigned through urn randomization to one of two experimental groups, depending on their baseline level of impulsivity, in which they will receive either aripiprazole (up to 15 mg/day) or an identical placebo. Subjects will take the study drug or placebo for 8 days (day 1-6 being the natural observation period). After a minimum of 24 hours of abstinence from alcohol (day 7-8) they will undergo an alcohol administration (priming dose) and motivated free choice drinking procedure (on day 8). Alcoholic subjects will receive a brief counseling session at the end of the study to enhance their awareness of problem drinking and to motivate them to seek treatment. Referral for treatment will be offered.

Each subject will undergo a functional MRI (functional magnetic resonance imaging) brain scan with cue stimulation on day 7, on the evening before the alcohol administration paradigm. fMRI (functional magnetic resonance) imaging brain imaging technology will be used to determine if alcoholics treated with aripiprazole differ in alcohol cue-induced activity in the nucleus accumbens. It is hypothesized that aripiprazole will reduce nucleus accumbens activation to alcohol cues compared to placebo.

Whether dopamine system genetic differences will be predict drinking, nucleus accumbens activity, and aripiprazole response will be explored.

Eligibility Criteria:
Inclusion Criteria:

1. Age 21 - 40 (to focus on an age group still on a trajectory of increasing alcohol consumption).
2. Meets the DSM IV criteria for current alcohol dependence including criterion 3 and/or 4 "loss of control over drinking" or "the inability to cut-down or stop drinking".
3. Currently not engaged in, and does not want treatment for, alcohol related problems.
4. Able to read and understand questionnaires and informed consent.
5. Lives within 50 miles of the study site.
6. Able to maintain abstinence for two days (without the aid of detoxification medications) as determined by self report and breathalyzer measurements.

Inclusion for fMRI (functional magnetic resonance imaging) Imaging:

1. Does not have metal objects in the head/neck.
2. Does not have a history of claustrophobia leading to significant clinical anxiety symptoms.

Exclusion Criteria:

1. Currently meets DSM IV criteria for any other psychoactive substance dependence disorder.
2. Any psychoactive substance use (except marijuana and nicotine) within the last 30 days 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 (tetrahydrocannabinol) levels.
3. Meets DSM IV criteria for current axis I disorders of major depression, panic disorder, obsessive compulsive disorder, post traumatic stress syndrome, bipolar affective disorder, schizophrenia, dissociate disorders and eating disorders, any other psychotic disorder or organic mental disorder.
4. Has current suicidal ideation or homicidal ideation.
5. Need for maintenance or acute treatment with any psychoactive medication including anti-seizure medications and medications for ADHD (attention deficit hyperactivity disorder .
6. Currently taking medication known to affect alcohol intake (e.g., disulfiram, naltrexone, acamprosate, topiramate).
7. Clinically significant medical problems such as cardiovascular, renal, GI, or endocrine problems that would impair participation or limit medication ingestion.
8. Past history of alcohol related medical illness such as gastrointestinal bleeding, pancreatitis, peptic ulcer, hepatic cirrhosis or alcoholic hepatitis.
9. Hepatocellular disease indicated by elevations of SGPT (ALT) or SGOT (AST) greater than 2.5 times normal at screening.
10. Females of childbearing potential who are pregnant (by urine HCG), nursing, or who are not using a reliable form of birth control.
11. Has current charges pending for a violent crime (not including DUI (Driving Under Intoxication) related offenses).
12. Does not have a stable living situation.