Assessment of a cannabinoid antagonist in humans

-9-四氢大麻酚(THC)，主要 精神活性大麻素，发挥其中枢神经的大部分作用 与G蛋白相互作用的系统效应 大麻素CB1受体。第二个大麻素结合 七跨膜受体亚型，称为CB2，具有 被克隆并似乎参与了对 免疫功能。SR 141716是黄曲霉毒素的第一个拮抗剂 中枢大麻素受体CB1有待鉴定。它激起了敌意 大麻素受体激动剂对这两种受体的抑制作用 小鼠输精管收缩与腺苷环化酶活性的关系 脑膜。一种纯大麻素受体的可用性 拮抗剂可以在很大程度上帮助评估内源性 大麻素和阻止他们的行动。潜在的治疗方法 这种化合物在调节大量的 似乎表达大麻素CB1受体的大脑系统 特别有趣。大麻素对“奖赏”系统的影响 可能通过腹侧中等密度的受体介导 被盖区和伏隔核。确认并行度的步骤 关于对人类和动物的影响，SR 141716阻断的能力 THC对人类的急性影响正在进行首次评估 这一I期临床试验的时间。此外，SR的安全性 141716单独给轻量大麻吸毒者，或联合服用 吸入四氢呋喃和SR-141716的药代动力学 和THC正在确定中。健康的男性受试者有 服用安慰剂或服用有效的SR141716之前的大麻使用史 吸食安慰剂或活性大麻。生理、生化 并对行为测量进行监测以评估 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.