Advancing Varenicline as a Treatment for Cannabis Use Disorder

推进伐尼克兰治疗大麻使用障碍

基本信息

批准号：
10004604
负责人：
Kevin M Gray
金额：
$ 98.17万
依托单位：
MEDICAL UNIVERSITY OF SOUTH CAROLINA
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：
2016-09-15 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10004604
关键词：
Abstinence Adverse event Agonist Anterior Basic Science Cannabinoids Cannabis Clinical Trials Corpus striatum structure Cues Development Dorsal Evaluation Frequencies Individual Measures Mediating Memory Neurocognition Outcome Patient Self-Report Pharmaceutical Preparations Pharmacodynamics Pharmacotherapy Placebos Population Prefrontal Cortex Process Research Rewards Safety Short-Term Memory System Testing Thalamic structure Tobacco Use Cessation United States Urine alcohol abuse therapy alcohol use disorder base blood oxygenation level dependent response clinical effect cognitive enhancement cognitive function craving cue reactivity drug development follow-up illicit drug use improved marijuana use marijuana use disorder mesolimbic system neural circuit neuromechanism receptor research clinical testing restoration tobacco abstinence varenicline week trial

项目摘要

ABSTRACT Cannabis is the most commonly used illicit drug in the United States. Although cannabis use is widespread and basic science research on cannabinoids is well-developed, advancements in medication development for cannabis use disorder (CUD) have been limited. Varenicline, a selective nicotinic nACH receptor partial agonist of the α4β2 subtype and a full agonist of the α7 subtype, is arguably the most effective pharmacotherapy for promoting tobacco abstinence, and has also shown promise for the treatment of alcohol use disorder. Varenicline may improve cannabis use outcomes through multiple mechanisms, including interaction with the mesolimbic dopamine system, enhancement of cognitive functioning, and restoration of inhibitory control. To date, however, varenicline has not been evaluated in individuals specifically seeking treatment for CUD. In this UG3/UH3 application, we propose to rapidly yet thoroughly assess the utility of varenicline for CUD to potentially advance varenicline through the FDA's drug development approval pipeline. In the UG3 component, we will conduct a six-week, placebo-controlled proof-of-concept clinical trial of varenicline for CUD, paired with pre- and post- evaluations of cognitive functioning and neural circuitry involved in cannabis cue reactivity and inhibitory control to elucidate the pharmacodynamics of varenicline as a treatment for CUD. If milestones of the UG3 component are met, the UH3 project will be an adequately powered 12-week clinical trial with follow-up to fully assess the efficacy of varenicline in this population.

抽象的大麻是美国最常用的非法药物。尽管大麻的使用是广泛的，并且关于大麻素的基础科学研究已经发达，在药物开发方面取得了进步大麻使用障碍（CUD）受到限制。 Varenicline，一种选择性的烟碱NACH受体部分激动剂的α4β2亚型和α7亚型的完整激动剂可以说是最有效的药物治疗促进烟草禁欲，还表现出对治疗酒精疾病的有望。 varenicline 可以通过多种机制改善大麻的使用结果，包括与中唇的相互作用多巴胺系统，增强认知功能以及抑制性控制的恢复。但是，迄今为止在专门寻求CUD治疗的个体中，尚未评估Varenicline。在这个UG3/UH3中应用，我们建议快速但彻底评估Varenicline的cud效用 Varenicline通过FDA的药物开发批准管道。在UG3组件中，我们将进行六周的安慰剂对照概念验证的cud临床试验，与前后对参与大麻提示反应性和抑制性控制的认知功能和神经回路的评估为了阐明varenicline的药物宏观动力学作为CUD的治疗方法。如果UG3组件的里程碑被满足，UH3项目将是一项足够动力的12周临床试验，并随访，以完全评估 Varenicline在该人群中的功效。