Behavioral Pharmacology of Synthetic Cannabinoids

描述(申请人提供)：吸食含有大麻素的“香料”是一种新出现的药物滥用问题。虽然JWH-018和香料产品中已查明的其他吲哚衍生大麻素会产生类似大麻的醉意，但它们在结构上不同于大麻植物中所含的大麻素类；因此，在许多州，它们目前并不非法，而且很容易在互联网和购物中心买到。吲哚类大麻素最初是作为研究工具开发的，用于研究大麻素受体的性质；然而，人们对它们的药理学，特别是它们的行为影响知之甚少，因为JWH系列中的200多种化合物中只有一小部分在临床前的体内模型中进行了测试。这项拟议的研究将在啮齿动物模型中合成和评估JWH-018和相关的吲哚衍生大麻类化合物，这些模型已被用于研究大麻类化合物的滥用特性。重点将放在确定这类大麻素的体内药理特征与大麻植物的主要精神活性取代物？9-四氢大麻酚的不同程度上。此外，使用雄性和雌性啮齿动物将允许检查这些大麻类化合物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对两性行为影响的了解，从而为评估与急性和重复使用这些化合物有关的潜在健康问题，包括他们的身体依赖倾向提供科学基础。 与公共健康相关：含有合成大麻素的草药混合物(“香料”)在互联网上被称为“香”，被想要沉醉的吸毒者作为“合法大麻”来吸食。尽管大多数使用者报告说，这些化合物产生类似大麻的作用，但对这类大麻进行的少数临床前体内研究的结果显示，与大麻的主要精神活性成分？9-四氢大麻酚既有区别，也有相似之处。为了确定这些合成吲哚类大麻素的行为效应与9-四氢大麻酚的行为效应有多大的不同，拟议的研究将检查选定的合成大麻素在大麻素依赖啮齿动物模型中的影响。

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. PUBLIC HEALTH RELEVANCE: Herbal blends ("Spice") containing synthetic cannabinoids, marketed over the internet as "incense," are being smoked as "legal marijuana" by drug abusers wanting to become intoxicated. Although most users report that these compounds produce marijuana-like effects, results of the handful of preclinical in vivo studies that have been completed with this class of cannabinoids have revealed differences, as well as similarities, with ?9-tetrahydrocannabinol, the primary psychoactive ingredient of marijuana. To determine the extent to which the behavioral effects of these synthetic indole-derived cannabinoids are distinct from those of ?9-tetrahydrocannabinol, the proposed research will examine the effects of selected synthetic cannabinoids that have been identified in "Spice" in rodent models of cannabinoid dependence.