Behavioral Pharmacology of Synthetic Cannabinoids

合成大麻素的行为药理学

基本信息

批准号：
8173411
负责人：
JENNY L. WILEY
金额：
$ 9.87万
依托单位：
RESEARCH TRIANGLE INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-01 至 2013-06-30
项目状态：
已结题

项目摘要

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.

描述（由申请人提供）：吸食大麻素增强型“香料”是一个新出现的药物滥用问题。尽管香料产品中发现的 JWH-018 和其他吲哚衍生大麻素会产生类似大麻的中毒效果，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，它们目前并不违法，并且可以通过互联网和总部轻松获得。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，特别是它们的行为影响知之甚少，因为 JWH 系列中 200 多种化合物中只有一小部分在临床前体内模型中进行了测试。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素，这些模型已用于研究大麻素的滥用特性。重点将放在确定此类大麻素的体内药理学特征与大麻植物的主要精神活性替代物α9-四氢大麻酚的体内药理学特征的不同程度。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人们对这些滥用大麻素对男女行为影响的了解，从而为评估与急性和重复使用这些化合物相关的潜在健康问题（包括其身体依赖性）提供科学依据。公共健康相关性：含有合成大麻素的草药混合物（“香料”）在互联网上以“熏香”的名义销售，被想要陶醉的吸毒者当作“合法大麻”吸食。尽管大多数用户报告这些化合物产生类似大麻的作用，但对此类大麻素完成的少数临床前体内研究的结果揭示了与主要精神活性成分 9-四氢大麻酚的差异和相似之处大麻。为了确定这些合成吲哚衍生大麻素的行为影响与 9-四氢大麻酚的行为影响有多大不同，拟议的研究将检查“香料”中已确定的选定合成大麻素在大麻素啮齿动物模型中的影响依赖性。