Rimonabant to Reduce Alcohol Consumption
Condition: Healthy; Alcohol Drinking
MeSH terms: Alcohol Drinking
Study type: Interventional
Phase: Phase 2

Summary: 
      This study will examine whether Rimonabant, a drug that blocks cannabinoid-1 (CB1) receptors
      in the brain, affects alcohol consumption. Substances called endocannabinoids, which have
      many of the same effects of marijuana, bind to CB1 receptors. Animal studies show that when
      CB1 receptors are blocked, the animals consume less alcohol.

      Healthy normal volunteers between 21 and 40 years of age who consume between 20 and 40
      alcoholic drinks per week, drink at least 4 days a week, and are not seeking treatment for
      alcoholism may be eligible for this study. Candidates are screened with a medical history,
      including questions about alcohol and drug use, physical examination, blood and urine tests,
      breath alcohol test, and electrocardiogram.

      Participants are asked about their mental health history and use of alcohol, cigarettes and
      illicit drugs, and fill out questionnaires evaluating their emotional state and personality.
      Then, they begin a baseline evaluation in which they call a number at the NIH Clinical Center
      for 21 days to report how much alcohol they drank that day. One week after starting the
      baseline evaluation, they are randomly assigned to take either Rimonabant or placebo (a pill
      with no active ingredient) for 2 weeks. Before starting the drug, they have a urine drug
      screen and measurement of blood alcohol level. After 1 week on the test medication, they
      return to the Clinical Center to monitor drug or placebo side effects, if any, and to have a
      blood alcohol level test, urine drug screen, and blood tests for routine blood chemistries.
      After 2 weeks on the test medication, they come to the Clinical Center at noon for an alcohol
      self-administration test. Before the test, they are given a breath alcohol test and a urine
      drug test. The results of both tests must be negative to continue in the study.

      The alcohol self-administration test is videotaped. A heparin lock is placed in a vein in the
      participant's arm. This small needle remains in the arm for the duration of the study to
      avoid multiple needle sticks for blood draws. Blood is drawn periodically during the test to
      determine routine laboratory values, cotinine level (assessment of smoking status), the
      amount of Rimonabant or placebo in the body, and levels of various hormones. Thirty minutes
      before the test begins and every 30 minutes during the test, participants complete
      questionnaires and rating scales regarding their mood and desire to drink. Five minutes
      before the test be...
    

Detailed description: 
      Recent studies show that endogenous cannabinoids modulate appetitive behaviors. For example,
      an antagonist of the CB1 cannabinoid receptor, SR141716, decreases food intake in animals as
      well as in humans and decreases alcohol consumption in rodent models of voluntary ethanol
      consumption. In this protocol, individuals consuming between 20 and 40 alcohol drinks per
      week, and who are not seeking alcohol treatment, will be recruited from the community.
      Following a one week baseline evaluation, participants will be randomized according to a
      double-blind design to receive either placebo or SR141716 for two additional weeks prior to
      being admitted to the hospital to participate in an alcohol self-administration experiment.
      The design of this experiment has been previously shown by O'Malley et al. (1) to be an
      effective paradigm to study the effects of medication on alcohol consumption. Following
      baseline psychological and endocrine measures, participants will receive a priming dose of
      ethanol designed to raise the breath alcohol levels (BAL) to 0.03 g/dl and then have the
      opportunity to consume up to eight drinks or to receive $3 dollars for each drink not
      consumed over a two hour period. It is hypothesized that participants receiving SR141716,
      compared to those receiving placebo, will have decreased alcohol consumption. Following the
      study, each participant will be carefully counseled about their alcohol consumption and
      provided referrals for alcohol treatment.
    

Intervention name(s): SR141716 (Rimonabant)
Intervention type(s): Drug
Intervention MeSH terms: Rimonabant
Primary purpose: Treatment
Keywords: Alcohol Consumption; Alcohol Treatment; Medication Trial; Craving; Cannabinoids; CB 1 Receptor Antagonist; SR141716; Alcoholism