Clinical Trial of the Cannabinoid CB1 Receptor Antagonist, SR141716 (Rimonabant), to Reduce Voluntary Ethanol Drinking in Healthy, Non-Treatment Seeking Individuals Who Consume Between 20 and 50 Drinks Per Week

Study start date: December 31, 2003

* INCLUSION CRITERIA Male and female healthy participants, between 21 and 45 years of age. Weight and Body Mass Index: Males: between 60 kg and 90 kg; Body Mass Index between 18 and 28. Females: between 45 kg and 80 kg; Body Mass Index between 18 and 28. Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination). Normal vital signs after 10 minutes in supine position: systolic blood pressure between 95 mmHg and 140 mmHg, diastolic blood pressure between 50 mmHg and 90 mmHg, heart rate between 45 bpm and 90 bpm. Normal 12-lead EKG, PR less than 210 ms, QRS less than 120 ms, QTcB(1) less than or equal to 430 ms for male and less than or equal to 450 ms for female (incomplete right bundle branch block can be accepted). Laboratory results should be within the normal range. Laboratory results which are found to be marginally outside the normal range (i.e., minor variances in the complete blood count (CBC) or electrolytes) will be clinically evaluated for relevance to this protocol. Liver functions must be less than two times normal. Written informed consent prior to study participation. Female participants of childbearing capability must use a double contraceptive method (such as oral contraceptives, condom with spermicide or intra-uterine device with spermicide) from the start of the study until two months post medication trial. Normal dietary habits and willingness to abstain from grapefruit juice consumption during the study. (Grapefruit juice inhibits hepatic enzymes which could potentially interfere with the metabolism of SR141716.) Must agree to abstain from the use of illicit drugs for the duration of the study. EXCLUSION CRITERIA: Any history or presence of significant cardiovascular, pulmonary, gastro-intestinal, hepatic, renal, metabolic, hematological, neurologic (including any history of convulsions), systemic, infectious diseases, or psychiatric disorders (i.e., a current diagnosis of major depression, panic disorder, eating disorders, or history of schizophrenia, bipolar disorder, or obsessive compulsive disorder). Individuals who report suicidal ideation or who have a past history of suicide attempts. Frequent headaches and/or migraine, recurrent nausea and/or vomiting. Symptomatic hypotension whenever the decrease of blood pressure or asymptomatic postural hypotension defined by a decrease in systolic blood pressure (SBP) equal to or greater than 20 mmHg within two minutes when changing from the supine to the standing position. Blood donation within three months before administration. Presence or history of any allergy or unusual reactions to drugs or anesthetics that would suggest the participant could have a problem tolerating SR141716 or placebo. A participant who, in the judgment of the Investigator, is likely to be non-compliant, is violent when drinking, or is unable to cooperate because of a language problem or poor mental development. Participant who cannot be contacted in case of emergency. Currently taking any prescription medications or over-the-counter medications on a regular basis. Participants will be allowed to take an occasional pain medication or an antibiotic, if they get sick during their participation in the protocol. Excessive consumption of beverages with xanthine bases (greater than 6 cups or glasses/day). Female participants who have a positive Beta-HCG test (urine and/or plasma) or who are lactating. Positive reaction to any of the following tests: HBs antigen, anti-HCVantibody, anti-HIV1 antibodies, anti-HIV2 antibodies. (Hepatitis could interfere with the metabolism of SR141716 in the liver. HIV could alter brain function.) Positive results of screening for drugs of abuse (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, or opiates). A DSM-IV diagnosis of illicit drug dependence in the last 6 months. Participants who come to the NIAAA Clinic and evidence withdrawal symptoms that result in a score of 8 or above on the CIWA Instrument.