MECHANISM OF ACTION OF CANNABIS

该提案的总体目标是提供进一步的证据， 一种大麻素的作用机制， 是重要的调解人。 以前的研究表明，THC和 其他大麻素引起花生四烯酸的主要变化 在体外和体内的各种系统中的代谢。 这些反过来又导致前列腺素水平的变化， 影响c-AMP产生和/或引起神经递质介导的 方面的影响. 实验提出，这将试图显示一个偶然的 THC诱导的前列腺素变化与 小鼠中的僵住症和/或运动毒性。 脂质的作用 在发育和恢复过程中的代谢变化 从容忍到THC将提供第二种方法， 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主动免疫与花生四烯酸的研究 在对THC有不同反应的小鼠品系中进行代谢。 最后，研究了主要代谢物delta 1-THC- 7-酸，在THC的药效学将继续 特别是其对前列腺素的抑制作用 合成. 更好地了解THC的作用机制是 需要（1）设计旨在促进我们的实验 关于使用大麻的健康后果的知识（2）提供 探索大麻素治疗用途的合理基础 （3）增进我们对一类独特药物的了解。

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.