The main endocannabinoid receptor subtype, the CB1 receptor, is widely distributed in the brain. Endocannabinoids act presynaptically in the CNS to modulate the release of various neurotransmitters such as dopamine, GABA, and glutamate. In the limbic forebrain, they are involved with motivational aspects of feeding such as desire and reward. ? ? Early studies have shown that ethanol administration down-regulates the CB1 receptors present in mouse brain synaptic plasma membranes, while administration of a CB1 receptor agonist in rats increased their motivation to consume beer. This motivational effect could be blocked by administering the CB1 receptor antagonist, Rimonabant. Mice which lack the CB1 receptor drink significantly less alcohol than their wild-type littermates; administration of Rimonabant reduces ethanol drinking in the wild-type but not the CB1 receptor deficient mice. ? ? Based on an extensive animal literature implicating the endocannabinoid system in appetitive disorders such as alcoholism, we conducted a phase I/II clinical trial to assess if participants receiving Rimonabant would report less craving and exhibit decreased alcohol consumption compared to those receiving placebo. In this protocol, individuals between the ages of 21 and 45, consuming between 20 and 50 alcohol drinks per week, and who were not seeking alcohol treatment, were recruited from the community.? ? Participant enrollment and data analyses for this study have been completed. None of the measures addressed in this protocol were able to predict which of the particpants would be motivated to change their drinking behaviors. Currently, a manuscript is being preparared for publication.
