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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：
9250112
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/9250112
关键词：
Affinity Animal Model Behavioral Binding Biological Assay Breathing CNR1 gene CNR2 gene Cannabinoids Cannabis Chemical Exposure Chemical Structure Chemicals Designer Drugs Detection Drug Formulations Drug Kinetics Electronic cigarette Elements 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 Toxicology Training analog animal data cannabinoid receptor carcinogenicity chemical stability cigarette smoking drug abuser experimental study functional group in vivo in vivo Model mouse model non-cannabinoid novel predictive modeling public health relevance receptor 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.