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：
10521643
负责人：
RANGAN MAITRA
金额：
$ 56.72万
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 2027-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10521643
关键词：
Accounting Acute Address Adverse reactions Aerosols Affect Agonist Animal Model Behavioral Behavioral Mechanisms Biological Biological Assay Biological Markers CNR1 gene CNR2 gene Cannabinoids Cessation of life Chemicals Collaborations Country Designer Drugs Detection Dose Drug Kinetics Endocannabinoids European Union Evaluation Exposure to Female Forensic Medicine Foundations Goals Government Agencies Health Heart Rate Heating Human In Vitro Inhalation Injections International Investigation Knowledge Laboratories Liver Microsomes Measures Metabolic Biotransformation Molecular Molecular Profiling Mus Nature New Zealand Parents Peripheral Pharmacology Physiological Plasma Process Proliferating Public Health Reporting Research Respiration Rodent Route Sampling Site Smoker Smoking Stimulus Structure Structure-Activity Relationship System Temperature Tetrahydrocannabinol Time Toxic effect Toxicology Training Universities Work abuse liability addiction liability cannabimimetics cannabinoid receptor drug discrimination endogenous cannabinoid system heart function in vivo indexing insight intraperitoneal male member multidisciplinary natural hypothermia non-cannabinoid psychologic pulmonary function substance use synthetic cannabinoid vaper vaping

项目摘要

PROJECT SUMMARY Synthetic cannabinoids (SC) produce psychological effects resembling those of 9-tetrahydrocannabinol (THC) but are usually more potent and efficacious. Notably, the use of these substance is often associated with greater toxicity. Clusters of severe adverse reactions and death have been reported internationally, including in the U.S. and New Zealand. The global nature of SC abuse argues for an international approach to addressing the problem. To this end, one overall goal of this project is to strengthen a nascent international collaboration initiated among laboratories in the U.S. (RTI International) and New Zealand (University of Otago). Through this collaborative and multi-disciplinary effort, we will determine molecular and pharmacokinetic mechanisms that may underlie differences in the in vivo effects of chemically diverse SC related to their abuse potential and to their toxicological effects in peripheral systems. A foundational hypothesis for this proposed work is that the both the behavioral effects and the toxicological effects associated with SC use are related to their differential interactions with the endogenous cannabinoid system, as compared to THC and other partial CB1 receptor agonists. This hypothesis will be evaluated through systematic study of the SAR of SC and the mechanisms underlying their central and peripheral actions (i.e., their molecular fingerprints). This work will enhance ability to predict which new compounds are likely to have toxicological effects when – or before – they appear and will provide a scientific basis for evaluation of potential health concerns associated with use of these compounds. This research also will increase knowledge of the structure-activity relationships at cannabinoid receptors, resulting in deepened understanding of endocannabinoid system functioning.

项目概要合成大麻素 (SC) 产生类似于 9-四氢大麻酚 (THC) 的心理效应但通常更有效。值得注意的是，这些物质的使用通常会带来更大的效果。包括美国在内的国际上已报告了一系列严重不良反应和死亡事件。和新西兰。 SC 滥用的全球性要求采取国际方法来解决这一问题。为此，该项目的总体目标是加强新生的国际合作。美国（RTI International）和新西兰（奥塔哥大学）的实验室通过该项目发起。通过协作和多学科的努力，我们将确定分子和药代动力学机制可能是化学成分多样化的 SC 体内效应差异的基础，与其滥用潜力有关，并且与它们对周围系统的毒理学作用。这项拟议工作的基本假设是两者。与 SC 使用相关的行为效应和毒理学效应与其差异有关与 THC 和其他部分 CB1 受体相比，与内源性大麻素系统的相互作用该假设将通过对 SC 的 SAR 及其机制的系统研究来评估。这项工作将增强其中枢和外围行为的基础（即分子指纹）。预测哪些新化合物在出现时或出现之前可能会产生毒理学效应为评估与使用这些化合物相关的潜在健康问题提供科学依据。这项研究还将增加对大麻素受体结构-活性关系的了解，从而加深了对内源性大麻素系统功能的了解。