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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.

项目概要药物滥用仍然是一个重大且不断升级的公共卫生问题，因为药物滥用率和过去十年中，服药过量导致的死亡人数不断增加。虽然阿片类药物主要驱动服药过量死亡人数灾难性增加，与使用兴奋剂相关的死亡率再次上升近年来，阿片类药物和兴奋剂药物的共同滥用现象很明显。虽然治疗方案阿片类药物使用障碍的管理是存在的，他们受到患者依从性差的困扰，或者本身就是阿片类激动剂，因此具有依赖性、滥用和死亡的高风险。对于兴奋剂使用障碍，目前没有批准的治疗方案。目前阿片类药物治疗的缺点使用障碍，以及完全缺乏任何兴奋剂使用障碍的治疗选择，清楚地表明需要减少阿片类药物和兴奋剂药物滥用相关影响的新选择。 2 型大麻素 (CB2) 受体激动剂是一个潜在的靶点，在对抗与滥用相关的疾病方面已显示出一些希望。阿片类药物和兴奋剂药物的作用。然而，人类很少单独使用药物，这表明针对单一滥用药物的物质使用障碍候选治疗方法的临床前研究并不准确反映人类使用药物的方式，可能无法真实代表其治疗潜力世界情景。因此，本申请提出的研究旨在检验CB2受体的作用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影响。这些研究将检查 CB2 受体激动剂对物质的两个最有问题的方面的治疗潜力使用障碍：吸毒行为和复发。目标 1 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/甲基苯丙胺混合物自我给药的影响食物与药物的选择程序。目标 2 的研究将检查 CB2 受体激动剂对恢复之前通过芬太尼、甲基苯丙胺和甲基苯丙胺强化的反应芬太尼/甲基苯丙胺混合物。这些研究将为未来的研究奠定基础 CB2 受体激动剂对阿片类药物、兴奋剂和多物质的其他问题影响的治疗效用使用障碍，包括其对身体依赖和戒断的影响、身体上的吸毒行为依赖性受试者，以及阿片类药物的通气抑制作用。此外，博士后培养计划本申请中提出的除其他技能外还包括获得重要的新科学技能旨在促进申请人从博士后实习生过渡到独立的结构化活动研究者。