This study is to determine if alcoholics who differ on genetic variations of serotonin activity respond differently to ondansetron (Zofran) treatment. Subjects will receive one week of single-blind placebo lead-in followed by randomization to 11 weeks of double-blind treatment with ondansetron or placebo. All subjects will receive weekly cognitive behavioral therapy and have brain imaging and genetic testing. Participants will be scheduled for followup assessments at 1, 2, 3, 6, and 9 months after treatment.

Ages Eligible for Study:  18 Years   -   65 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Current diagnosis of alcohol dependence and drinking greater than or equal to 14 alcohol drinks/week for women and greater than or equal to 21 alcohol drinks/week for men in the last 30 days.
• Provide a written, informed consent.
• Good physical health and must weigh within 30 percent of their ideal body weight and must weigh at least 88 pounds and no more than 341 pounds.
• Literate in English and able to read, understand, follow instructions, and complete questionnaires accurately.
• Willingness to participate in behavioral treatments for alcoholism.
• Provide evidence of stable residence in the last month prior to enrollment in the study and have no plans to move during the next nine months.

Exclusion Criteria:

• Current existing psychiatric disorder other than alcohol or nicotine dependence.
• Elevated liver enzymes greater than three times the normal range or elevated bilirubin. Serious medical co-morbidity requiring medical intervention or close supervision or any condition which can interfere with the receipt of ondansetron.
• Severe or life-threatening adverse reactions to medications or radiopharmaceuticals either in the past or during this clinical trial.
• Females who are pregnant, nursing, or not using an acceptable form of contraception at any time during the study.
• Received inpatient or outpatient treatment for alcohol dependence within the last 30 days.
• Members of the same household.
• History of severe hypersensitivity to any medication, radiopharmaceuticals, or environmental allergens.
• Active tuberculosis.
• Treated with antidepressants or any medications having a potential effect on alcohol consumption or mood.
• Urine must be free of opiates, cocaine, amphetamines, barbiturates, other prescription and non- prescription drugs.
• Ineligible to participate in the neuroimaging studies due to neurological or structural brain abnormalities.
• Have artificial devices of a magnetic nature (e.g. pacemakers).
• Receipt of ionizing radiation in the 6-month period prior to enrollment.
• Surgical procedure requiring general anesthesia in the last month.
• Severe alcohol withdrawal symptoms which require inpatient treatment.
• Mandatory participation in an alcohol treatment program.