Assessment of a cannabinoid antagonist in humans

Delta-9- tetrahydrocannabinol（THC），主要的 精神活性大麻素，发挥其大部分中枢神经 通过与G-蛋白连接的相互作用产生系统效应 大麻素CB 1受体第二种大麻素结合 七跨膜受体亚型，称为CB 2， 被克隆，似乎与调节 免疫功能。SR 141716是第一个拮抗剂， 中枢大麻素受体CB 1有待鉴定。它会对抗 大麻素受体激动剂对这两种细胞的抑制作用 小鼠输精管收缩与大鼠腺苷酸环化酶活性 脑细胞膜纯大麻素受体的可用性 拮抗剂可以大大有助于评估内源性 cannabinoids大麻素and blocking块their其actions行动.潜在的治疗 这种化合物在调节大量的 表达大麻素CB 1受体的大脑系统 特别有趣大麻素对“奖励”系统的影响 可以通过腹侧的中等受体密度介导 被盖区和延髓核。确认并行性 在人类和动物中的作用，SR 141716阻断 四氢大麻酚对人体的急性影响正在进行评估， 在这个I期临床试验中。此外，SR的安全性 141716当单独给予轻度大麻使用者时，或联合使用时 通过吸入THC和SR 141716的药代动力学 和THC正在测定中。健康男性受试者， 大麻使用史接受安慰剂或活性SR 141716之前 吸食安慰剂或活性大麻生理生化 和行为指标进行监测， 药效学效应

Delta-9- tetrahydrocannabinol (THC), the primary psychoactive cannabinoid, exerts the majority of its central nervous system effects through interaction with the G-protein linked cannabinoid CB1 receptor. A second cannabinoid-binding seven-transmembrane spanning receptor subtype, termed CB2, has been cloned and appears to be involved with regulation of immunological functions. SR 141716 is the first antagonist of the central cannabinoid receptor CB1 to be identified. It antagonizes the inhibitory effects of cannabinoid receptor agonists on both mouse vas deferens contractions and adenylcyclase activity in rat brain membranes. Availability of a pure cannabinoid receptor antagonist could help substantially in assessing roles of endogenous cannabinoids and blocking their actions. The potential therapeutic utilities of such a compound in modulating the large number of brain systems that appear to express cannabinoid CB1 receptors are especially interesting. Cannabinoid effects on "reward" systems could be mediated through moderate receptor densities in ventral tegmental area and the nucleus accumbens. To confirm parallelism of effects in humans and animals, the ability of SR 141716 to block the acute effects of THC in humans is being assessed for the first time in this phase I clinical trial. In addition, the safety of SR 141716 when given alone to light cannabis users, or in combination with THC via inhalation and the pharmacokinetics of SR 141716 and THC are being determined. Healthy male subjects with a history of cannabis use receive placebo or active SR141716 prior to smoking placebo or active marijuana. Physiological, biochemical and behavioral measures are being monitored to evaluate pharmacodynamic effects.