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Cannabinoid type 2 receptors as a therapeutic target for substance use disorders

大麻素 2 型受体作为物质使用障碍的治疗靶点

基本信息

批准号：
10606224
负责人：
Lawrence Michael Carey IV
金额：
$ 0.84万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-02-01 至 2023-02-20
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10606224
关键词：
Acceleration Address Agonist Behavior CNR1 gene CNR2 gene COVID-19 pandemic Cessation of life Clinical Clinical Trials Cocaine Communication Cues Dependence Development Disease Drug abuse Drug usage Epidemic Evaluation Fentanyl Food Foundations Grant Health Health Personnel Human Impaired cognition Individual Infusion procedures Injections Laboratories Macaca mulatta Medication Management Methamphetamine Modeling Monkeys Mus National Institute of Drug Abuse Nicotine Opiate Addiction Opioid Opioid Analgesics Opioid agonist Opioid replacement therapy Overdose Pain Pathologic Pharmaceutical Preparations Physical Dependence Policies Population Postdoctoral Fellow Procedures Public Health Relapse Research Research Personnel Research Training Rewards Risk Rodent Safety Self Administration Solid Stimulant Structure Substance Use Disorder Sucrose Testing Therapeutic Toxic effect Training Translations Treatment Efficacy Twin Multiple Birth Ventilatory Depression Withdrawal abuse liability antagonist cannabinoid receptor career career development cocaine self-administration combat compliance behavior conditioned place preference design drug of abuse effective therapy fentanyl self-administration high risk interest model organism mortality nonhuman primate novel opioid abuse opioid overdose opioid use opioid use disorder overdose death polysubstance abuse polysubstance use post-doctoral training preclinical study preference prescription opioid response responsible research conduct side effect skills stimulant abuse stimulant use stimulant use disorder substance use treatment synthetic opioid therapeutic target treatment strategy vigilance

项目摘要

Project Summary Drug abuse remains a significant, and escalating, public health problem as rates of drug abuse and overdose deaths have been accelerating incessantly over the last decade. While opioids have primarily driven this catastrophic expansion in overdose deaths, a resurgence in mortality associated with the use of stimulant drugs, and the co-abuse of opioids and stimulant drugs, is evident in recent years. While treatment options for the management of opioid use disorder exist, they are plagued by poor patient compliance or are themselves opioid agonists and therefore possess a high risk for dependence, abuse, and death. For stimulant use disorder, there are currently no approved treatment options. The shortcomings of currently available treatments for opioid use disorder, and the total lack of any treatment options for stimulant use disorder, clearly indicate the need for novel options to reduce the abuse-related effects of opioid and stimulant drugs. Cannabinoid type 2 (CB2) receptor agonists are one potential target that have demonstrated some promise in combating the abuse-related effects of both opioids and stimulant drugs. However, humans rarely use drugs in isolation indicating the preclinical study of candidate treatments for substance use disorders on single drugs of abuse does not accurately reflect the way drugs are used by humans and may not represent their therapeutic potential in real world scenarios. Therefore, the research proposed in this application aims to examine the effects of CB2 receptor agonists on the abuse-related effects of opioids, stimulants, and opioid/stimulant mixtures. These studies will examine the therapeutic potential of CB2 receptor agonists on 2 of the most problematic aspects of substance use disorders: drug taking behavior, and relapse. Studies in Aim 1 will examine the effects of CB2 receptor agonists on the self-administration of fentanyl, methamphetamine, and fentanyl/methamphetamine mixtures in a food versus drug choice procedure. Studies in Aim 2 will examine the effects of CB2 receptor agonists on the reinstatement of responding previously reinforced by fentanyl, methamphetamine, and fentanyl/methamphetamine mixtures. These studies will provide the foundation for future research into the therapeutic utility of CB2 receptor agonists on other problematic effects of opioid, stimulant, and polysubstance use disorders including their effects on physical dependence and withdrawal, drug taking behavior in physically dependent subjects, and the ventilatory depressant effects of opioids. Moreover, the postdoctoral training plan proposed in this application encompasses the acquisition of vital new scientific skills in addition to other structured activities designed to facilitate the applicants transition from postdoctoral trainee to independent investigator.

项目总结