Lichtman Aron H, Martin Billy R
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond 23298-0613, USA.
J Clin Pharmacol. 2002 Nov;42(S1):20S-27S. doi: 10.1002/j.1552-4604.2002.tb05999.x.
Although the proposition that repeated marijuana use can lead to marijuana dependence has long been accepted, only recently has evidence emerged suggesting that abstinence leads to clinically significant withdrawal symptoms. Converging evidence from human and animal studies has increased our understanding of cannabinoid dependence. One of the most powerful tools to advance this area of research is the CB1 cannabinoid receptor antagonist SR 141716A, which reliably precipitates withdrawal syndromes in mice, rats, and dogs that have been treated repeatedly with cannabinoids. In addition, the use of CB1 receptor knockout mice has revealed that not only cannabinoid dependence is mediated through a CB1 receptor mechanism of action, but CB1 receptors also modulate opioid dependence. Moreover, the results of other genetically altered mouse models suggest the existence of a reciprocal relationship between cannabinoid and opioid systems in drug dependence. Undoubtedly, these animal models will play pivotal roles in further characterizing cannabinoid dependence and elucidating the mechanisms of action, as well as developing potential pharmacotherapies for cannabinoid dependence.
尽管长期以来人们一直认为反复使用大麻会导致大麻依赖，但直到最近才有证据表明戒断会导致临床上显著的戒断症状。来自人类和动物研究的越来越多的证据增进了我们对大麻素依赖的理解。推进这一研究领域的最有力工具之一是CB1大麻素受体拮抗剂SR 141716A，它能可靠地诱发经反复给予大麻素治疗的小鼠、大鼠和犬出现戒断综合征。此外，使用CB1受体基因敲除小鼠已表明，不仅大麻素依赖是通过CB1受体作用机制介导的，而且CB1受体还调节阿片类药物依赖。此外，其他基因改造小鼠模型的结果表明，大麻素和阿片类药物系统在药物依赖方面存在相互关系。毫无疑问，这些动物模型将在进一步明确大麻素依赖特征、阐明作用机制以及开发大麻素依赖的潜在药物治疗方法方面发挥关键作用。
