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.

项目摘要药物滥用仍然是一个重大且升级的公共卫生问题，作为药物滥用率和在过去的十年中，过量死亡一直在不断加速。阿片类药物主要是驱动的过量死亡中的这种灾难性扩张，与使用兴奋剂有关的死亡率复兴近年来，药物以及阿片类药物和刺激性药物的共同滥用。而治疗选择存在阿片类药物使用障碍的管理，它们受到差的患者依从性的困扰，或者自己是阿片类药物激动剂，因此具有依赖，虐待和死亡的高风险。对于刺激使用障碍，目前没有批准的治疗选择。阿片类药物当前可用治疗的缺点使用障碍以及完全缺乏刺激使用障碍的任何治疗选择，清楚地表明需要减少阿片类药物和刺激药物的滥用相关作用的新颖选择。大麻素2型（CB2）受体激动剂是一个潜在的目标，它在打击与滥用有关的方面表现出了一些希望阿片类药物和兴奋剂的作用。但是，人类很少在孤立地使用药物，表明对单一滥用药物的药物使用障碍候选治疗的临床前研究没有准确地反映了人类使用药物的方式，并且可能不会代表其实际潜力世界情景。因此，本应用程序中提出的研究旨在检查CB2受体的影响激动剂对阿片类药物，兴奋剂和阿片类药物/兴奋剂混合物的滥用相关作用。这些研究会检查CB2受体激动剂在两个最有问题的物质方面的治疗潜力使用疾病：吸毒行为和复发。 AIM 1中的研究将检查CB2受体的影响激动剂对芬太尼，甲基苯丙胺和芬太尼/甲基苯丙胺混合物的自我施用食物与药物选择程序。 AIM 2中的研究将检查CB2受体激动剂对恢复先前由芬太尼，甲基苯丙胺和芬太尼/甲基苯丙胺混合物。这些研究将为未来研究的基础 CB2受体激动剂对阿片类药物，兴奋剂和polysubstance的其他有问题影响的治疗效用使用疾病，包括对身体依赖和戒断的影响，物理上的药物行为依赖的受试者以及阿片类药物的通气抑郁作用。此外，博士后培训计划在本申请中提出的建议还包括对重要的新科学技能的获得旨在促进申请人从博士后学员到独立的结构化活动研究者。