Investigation of Synthetic Cannabinoid Exposures and Pharmacological Consequences

合成大麻素暴露和药理学后果的调查

基本信息

批准号：
9132440
负责人：
Brian F Thomas
金额：
$ 45.81万
依托单位：
RESEARCH TRIANGLE INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2021-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9132440
关键词：
Affinity Animal Model Behavioral Beryllium Binding Biological Assay Breathing CNR1 gene CNR2 gene Cannabinoids Cannabis Chemical Exposure Chemical Structure Chemicals Designer Drugs Detection Drug Formulations Drug Kinetics Electronic cigarette Evaluation Exposure to Formulation Goals Health Heating Hepatocyte Human In Vitro Individual Indoles Intoxication Investigation Knowledge Ligands Liquid substance Literature Manufacturer Name Marijuana Mass Fragmentography Metabolic Metabolism Mus Outcome Parents Pathway interactions Pattern Pharmaceutical Preparations Pharmacology Pharmacology and Toxicology Plants Preparation Property Receptor Signaling Reporting Research Rodent Route Safety Signal Transduction Smoke Smoking Structure Structure-Activity Relationship Substance abuse problem System Techniques Training analog animal data base cannabinoid receptor chemical stability cigarette smoking drug abuser functional group in vivo in vivo Model mouse model non-cannabinoid novel public health relevance receptor research study scaffold synthetic cannabinoid vapor vaporization

项目摘要

DESCRIPTION (provided by applicant): Vaporization or smoking of synthetic cannabinoid-containing e-liquids or herbal formulations is a significant substance abuse problem. Although JWH-018 and other indole-derived cannabinoids that have been identified in these illicit products produce marijuana-like intoxication, they are structurally distinct from cannabinoids contained in the cannabis plant; hence, very little is known about the actual chemical exposures that occur during their use, or their pharmacology, particularly with regards to their actions at non-cannabinoid receptors and their behavioral and toxicological effects. Furthermore, the variety of structural scaffolds and analogs of synthetic cannabinoids that are being reported in these designer drug formulations continues to increase as individuals seek to become intoxicated and avoid detection, and the manufacturers and distributors of these chemicals and formulations appear to have little regard for the chemical reliability or safety of their products. Indeed, chemicals are frequently appearing in designer drug formulations that have not been previously described as cannabinoids in the scientific literature. Moreover, some of these compounds possess thermally unstable substituents of known carcinogenic activity that may be liberated during use. The proposed research will characterize synthetic cannabinoid formulations and the chemical exposures that occur during storage and use, and evaluate their pharmacological fate in in vitro and in vivo models. Emphasis will be placed on the identification of the compounds that are inhaled or produced during actual use scenarios, and the extent to which they can interact with cannabinoid CB1 and CB2 receptors, as well as with non-cannabinoid receptors, and the degree to which they produce in vivo pharmacological and toxicological effects in mouse models. The proposed studies will thereby increase knowledge of the structure-activity relationships at cannabinoid receptors and the behavioral and toxicological effects of these abused synthetic cannabinoid substances, and provide a scientific basis for evaluation of potential health concerns associated with use of these compounds.

描述（应用程序提供）：含有合成大麻素的电子液体或草药配方的蒸发或吸烟是一个重大的药物滥用问题。尽管在这些非法产品中已经鉴定出的JWH-018和其他吲哚衍生的大麻素会产生类似大麻的肠毒性，但它们在结构上与大麻植物中包含的大麻素不同。因此，对于它们在使用过程中发生的实际化学暴露或药理学的实际化学暴露，特别是在非大麻素受体及其行为和毒理学作用方面，知之甚少。此外，随着个人寻求陶醉并避免检测，在这些设计师药物配方中所报告的合成大麻素的结构支架和类似物的种类持续增加，这些化学品和配方的制造商和分销商似乎对其产品的化学可靠性或安全性几乎没有考虑。实际上，化学物质经常出现在设计师药物配方中，这些公式以前尚未被描述为科学文献中的大麻素。此外，其中一些化合物具有在使用过程中可以释放的已知致癌活性的热不稳定取代基。拟议的研究将表征合成大麻素配方式以及在储存和使用过程中发生的化学暴露，并评估其在体外和体内模型中的药物命运。将重点放在鉴定实际使用情况下所涉及或产生的化合物，以及它们可以与大麻素CB1和CB2受体以及非核素受体以及非核素受体以及它们在小鼠模型中产生的体内药理和毒性效应的程度。拟议的研究将增加对大麻素受体的结构活性关系以及这些滥用合成大麻素物质的行为和毒理学作用的了解，并为评估与使用这些化合物相关的潜在健康问题的科学基础。