Treatment of Cannabinoid Withdrawal in Rhesus Monkeys

恒河猴大麻素戒断的治疗

• 批准号: 7113218
• 负责人: Lance R McMahon
• 金额: $ 35.64万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7113218
• 关键词: Cannabis; Macaca mulatta; adrenocorticotropic hormone; amines; behavioral /social science research tag; behavioral medicine; cannabinoids; corticotropin releasing factor; cortisol; drug abuse chemotherapy; drug addiction antagonist; drug administration rate /duration; drug withdrawal; hormone inhibitor; hypothalamic pituitary adrenal axis; inhalation drug abuse; inhalation drug administration; placebos; psychopharmacology; substance abuse related behavior

DESCRIPTION (provided by applicant): Marijuana dependence and withdrawal are increasingly reported, yet adequate treatment options have not been identified. This R01 will expand upon a compelling line of investigation demonstrating that drug discrimination can be used to quantify the behavioral effects of the cannabinoid antagonist SR 141716A in monkeys receiving delta9-THC. Dependence will be established with delta9-THC and withdrawal characterized by directly observable signs, drug discrimination, and neuroendocrine response. Aim 1 will examine a role for cannabinoid and monoamines in the discriminative stimulus effects of delta9-THC withdrawal, induced both by SR 141716A and by temporary discontinuation of A9-THC treatment. Studies will examine a role for cannabinoids and monoamines in the directly observable signs of withdrawal induced by SR 141716A. Collectively, studies in Aim 1 will examine the relative contribution of cannabinoids and monoamines across different indices of withdrawal and will test the hypothesis that monoamines attenuate discriminative measures and not other indices of withdrawal. Aim 2 will examine a role for hypothalamic pituitary adrenal activity (indexed by cortisol and ACTH) in the acute and chronic effects of delta9-THC and will examine a role for CRH antagonists in modifying delta9-THC withdrawal. Drug discrimination will be used in Aim 3 to characterize the subjective effects of inhaled marijuana smoke which represents the predominant route of administration in humans. Studies will examine modification of the discriminative stimulus effects of inhaled marijuana smoke by cannabidiol and cannabinol and blockade of these discriminative stimulus effects by cannabinoid antagonists. A likely future direction will be to characterize dependence that occurs to inhaled marijuana smoke. This application will address a need for understanding the behavioral, pharmacologic, and neuroendocrine determinants of cannabinoid dependence and will examine test compounds for modification of cannabinoid withdrawal and acute marijuana action.

描述（由申请人提供）：大麻依赖和戒断的报道越来越多，但尚未确定适当的治疗方案。该 R01 将扩展一系列令人信服的研究，证明药物歧视可用于量化大麻素拮抗剂 SR 141716A 对接受 delta9-THC 的猴子的行为影响。使用 delta9-THC 会建立依赖性，并以直接可观察到的体征、药物辨别和神经内分泌反应为特征进行戒断。目标 1 将研究大麻素和单胺在由 SR 141716A 和暂时停止 A9-THC 治疗引起的 delta9-THC 戒断的区别刺激效应中的作用。研究将检验大麻素和单胺在 SR 141716A 诱导的可直接观察到的戒断症状中的作用。总的来说，目标 1 的研究将考察大麻素和单胺对不同戒断指数的相对贡献，并将检验单胺减弱歧视性措施而不是其他戒断指数的假设。目标 2 将研究下丘脑垂体肾上腺活动（以皮质醇和 ACTH 为索引）在 delta9-THC 的急性和慢性影响中的作用，并将研究 CRH 拮抗剂在改变 delta9-THC 戒断中的作用。目标 3 中将使用药物歧视来描述吸入大麻烟雾的主观影响，大麻烟雾代表了人类的主要给药途径。研究将研究大麻二酚和大麻酚对吸入大麻烟雾的辨别性刺激作用的改变以及大麻素拮抗剂对这些辨别性刺激作用的阻断。未来可能的方向是描述吸入大麻烟雾的依赖性。该申请将解决了解大麻素依赖的行为、药理学和神经内分泌决定因素的需求，并将检查用于修饰大麻素戒断和急性大麻作用的测试化合物。