Behavioral Pharmacology of Synthetic Cannabinoids

描述（由申请人提供）：吸食大麻素增强的“香料”是一种新兴的药物滥用问题。虽然在香料产品中发现的JWH-018和其他吲哚衍生的大麻素会产生类似大麻的中毒，但它们在结构上与大麻植物中含有的大麻素不同；因此，在许多州，它们目前并不是非法的，而且很容易在互联网上和商店里买到。吲哚衍生的大麻素最初是作为研究大麻素受体性质的研究工具而开发的；然而，人们对它们的药理学知之甚少，尤其是它们的行为效应，因为在JWH系列的200多种化合物中，只有一小部分样本在临床前体内模型中进行了测试。本研究拟在啮齿类动物模型中合成和评价JWH-018及相关吲哚衍生大麻素，这些大麻素已被用于研究大麻素的滥用特性。重点将放在确定这类大麻素的体内药理学特征与？9-四氢大麻酚，大麻植物的主要精神活性取代物。此外，使用雄性和雌性啮齿动物将允许检查这些大麻素的影响可能存在的性别差异。这里提出的研究结果将增加对这些滥用大麻素在两性中的行为影响的认识，从而为评估与急性和重复使用这些化合物相关的潜在健康问题提供科学依据，包括它们的身体依赖性。

DESCRIPTION (provided by applicant): Smoking of cannabinoid-enhanced "spices" is an emerging substance abuse problem. Although JWH-018 and other indole-derived cannabinoids that have been identified in Spice products produce marijuana-like intoxication, they are structurally distinct from cannabinoids contained in the cannabis plant; hence, in many states, they are not currently illegal and are readily available over the internet and in headshops. Indole-derived cannabinoids were originally developed as research tools to investigate the nature of cannabinoid receptors; however, very little is known about their pharmacology, particularly their behavioral effects, as only a small sample of the over 200 compounds in the JWH series have been tested in preclinical in vivo models. The proposed research will synthesize and evaluate JWH-018 and related indole-derived cannabinoids in rodent models that have been used to investigate the abuse properties of cannabinoids. Emphasis will be placed on determination of the extent to which the in vivo pharmacological profile of this class of cannabinoids differs from that of ?9-tetrahydrocannabinol, the primary psychoactive substituent of the marijuana plant. Further, use of male and female rodents will allow examination of possible sex differences in the effects of these cannabinoids. Results of the studies proposed here will increase knowledge of the behavioral effects of these abused cannabinoids in both sexes, thereby providing a scientific basis for evaluation of potential health concerns associated with acute and repeated use of the compounds, including their physical dependence liability.