Behavioral Pharmacology of Synthetic Cannabinoids

合成大麻素的行为药理学

• 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
• 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
• 来源: https://reporter.nih.gov/project-details/8173411
• 关键词: Acute; Advertising; Affinity; Appearance; Behavioral; Behavioral Assay; CNR1 gene; Cannabinoids; Cannabis; Dependence; Drug Tolerance; Drug abuse; Evaluation; Female; Future; Goals; Gold; Grant; Health; Housing; Indoles; Internet; Intoxication; Knowledge; Legal; Marijuana; Marketing; Motor; Mus; Nature; Pharmacology; Physical Dependence; Plants; Procedures; Process; Property; Reporting; Research; Research Personnel; Rodent; Rodent Model; Sampling; Series; Sex Characteristics; Smoke; Smoking; Source; Spices; Structure; Structure-Activity Relationship; Substance abuse problem; Testing; Tetrahydrocannabinol; Time; Universities; base; behavioral pharmacology; cannabinoid receptor; drug abuser; drug discrimination; fluoromethyl 2,2-difluoro-1-(trifluoromethyl)vinyl ether; follow-up; in vivo; in vivo Model; male; pre-clinical; research study; sex; tool

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）：大麻素增强的“香料”吸烟是一种新兴的药物滥用问题。尽管在香料产品中鉴定出的JWH-018和其他吲哚衍生的大麻素会产生大麻样中毒，但它们在结构上与大麻植物中包含的大麻素不同。因此，在许多州，它们目前不是非法的，并且可以通过互联网和校园容易获得。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开发的。然而，关于它们的药理学，尤其是其行为效应，知之甚少，因为在临床前体内模型中，仅测试了JWH系列中200多种化合物中的一小部分。拟议的研究将在啮齿动物模型中综合和评估JWH-018和相关吲哚衍生的大麻素，这些大麻素用于研究大麻素的滥用性能。重点将放在确定这类大麻素的体内药理学特征的程度上，这与大麻植物的主要精神活性取代基的9-二氢糖醇不同。此外，使用雄性和雌性啮齿动物将允许检查这些大麻素的作用中可能的性别差异。这里提出的研究的结果将增加对两性滥用大麻素的行为影响的了解，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提供了科学依据，包括其身体依赖责任。 公共卫生相关性：含有合成大麻素的草药混合物（“香料”），在互联网上以“熏香”销售，被希望被陶醉的毒品被吸毒。尽管大多数用户报告说这些化合物会产生类似大麻的作用，但与此类大麻素一起完成的少数临床前体内研究的结果揭示了差异以及相似性，以及？9-四氢可纳比尼醇（Marijuana的主要精神活性成分）。为了确定这些合成吲哚衍生的大麻素的行为效应在多大程度上与9-四氢大麻酚的行为效应不同，拟议的研究将研究在大麻素依赖性啮齿动物模型中“香料”中所选合成大麻素的作用。