Clinical trial of SR141716, Rimonabant, to reduce voluntary ethanol consumption

内源性大麻素受体的主要亚型是CB1受体，广泛分布于大脑。内源性大麻素在中枢神经系统中起突触前作用，调节多巴胺、GABA和谷氨酸等多种神经递质的释放。在边缘前脑中，它们与进食的激励方面有关，如欲望和奖励。 早期的研究表明，乙醇能下调小鼠脑突触质膜上存在的CB1受体，而大鼠服用CB1受体激动剂则增加了他们喝啤酒的动机。给予CB1受体拮抗剂利莫那班可以阻断这种兴奋作用。缺乏CB1受体的小鼠饮酒量明显低于野生型小鼠；服用利莫那班减少了野生型小鼠的酒精饮用量，但CB1受体缺陷小鼠的饮酒量却没有减少。 在大量动物文献的基础上，我们进行了一项I/II期临床试验，以评估与服用安慰剂的参与者相比，服用利莫那班的参与者是否会报告较少的渴望和酒精消耗量。在这项方案中，从社区招募了年龄在21岁到45岁之间、每周消费20到50杯酒精饮料并且没有寻求酒精治疗的人。 这项研究的参与者登记和数据分析已经完成。该协议中涉及的措施都不能预测哪些参与者会被激励改变他们的饮酒行为。目前，正在准备出版手稿。

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.