MECHANISM OF ACTION OF CANNABIS

该提案的总体目标是为 前列腺素类药物对大麻素的作用机制 都是重要的调解人。先前的研究表明，THC和 其他大麻素可引起花生四烯酸的重大变化 在体外和体内的各种系统中的代谢。 这些反过来又会导致前列腺素水平的变化，这可能 影响c-AMP的产生和/或导致神经递质介导 效果。 有人提出了一些实验，试图展示一种随意的 四氢呋喃诱导的前列腺素变化与前列腺素水平的关系 小鼠的过敏症和/或运动毒性。脂类的作用 发育、恢复过程中的代谢变化 从容忍到THC将提供另一种途径 机制问题。 其他方法将涉及对小鼠THC反应的研究 前列腺素E_2主动免疫及花生四烯酸的研究 对THC有不同反应的小鼠品系的代谢。 最后，对主要代谢物Delta1-THC的作用进行了研究。 THC药效学中的7-OIC酸将继续存在 特别是其对前列腺素的抑制作用 综合。 更好地理解THC的作用机制是 需要(1)设计旨在进一步提高我们的 关于使用大麻的健康后果的知识(2)提供 探索大麻类药物治疗用途的合理依据 以及(3)提高我们对一类独特药物的认识。

The overall goal of the proposal is to provide further evidence for a mechanism of action for cannabinoids in which prostaglandins are important mediators. Previous work has shown that THC and other cannabinoids cause major changes in arachidonic acid metabolism in a variety of systems both in vitro and in vivo. These, in turn, lead to changes in prostaglandin levels which may affect c-AMP production and/or cause neurotransmitter mediated effects. Experiments are proposed which will attempt to show a casual relationship between THC-induced prostaglandin changes and catalepsy and/or motor toxicity in the mouse. The role of lipid metabolism changes during the development of, and recovery from tolerance to THC will provide a second approach to the question of mechanism. Other approaches will involve the study of THC responses in mice actively immunized against PGE2 and the study of arachidonate metabolism in mouse strains with different responses to THC. Finally, studies on the role of the major metabolite, delta1-THC- 7-oic acid, in the pharmacodynamics of THC will be continued with special regard to its inhibitory effects on prostaglandin synthesis. A better understanding of the mechanism of action of THC is needed to (1) design experiments aimed at furthering our knowledge of the health consequences of cannabis use (2) provide a rational basis for exploring the therapeutic uses of cannabinoids and (3) improve our understanding of a unique class of drugs.