Advancing Varenicline as a Treatment for Cannabis Use Disorder

推进伐尼克兰治疗大麻使用障碍

• 批准号: 9249775
• 负责人: Kevin M Gray
• 金额: $ 82.74万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-15 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9249775
• 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; Placebo Control; Placebos; Population; Prefrontal Cortex; Process; Research; Rewards; Safety; Short-Term Memory; System; Testing; Thalamic structure; Tobacco Use Cessation; United States; Urine; alcohol use disorder; base; blood oxygenation level dependent response; clinical effect; cognitive function; craving; cue reactivity; drug development; follow-up; illicit drug use; improved; marijuana use; marijuana use disorder; meetings; mesolimbic system; neural circuit; neuromechanism; receptor; research clinical testing; restoration; tobacco abstinence; varenicline; week trial

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。尽管大麻的使用很普遍并且 大麻素的基础科学研究十分发达，药物开发也取得了进展 大麻使用障碍（CUD）受到限制。 Varenicline，一种选择性烟碱型 nACH 受体部分激动剂 α4β2 亚型和 α7 亚型的完全激动剂，可以说是最有效的药物疗法 促进戒烟，并且还显示出治疗酒精使用障碍的前景。伐尼克兰 可能通过多种机制改善大麻使用结果，包括与中边缘的相互作用 多巴胺系统，增强认知功能，恢复抑制控制。然而，迄今为止， 伐尼克兰尚未在专门寻求 CUD 治疗的个体中进行评估。在这个UG3/UH3 应用中，我们建议快速而彻底地评估伐尼克兰对 CUD 的效用，以潜在地推进 伐尼克兰通过 FDA 的药物开发审批管道。在 UG3 组件中，我们将进行 为期六周的安慰剂对照伐尼克兰治疗 CUD 的概念验证临床试验，与治疗前和治疗后配对 评估涉及大麻提示反应和抑制控制的认知功能和神经回路 阐明伐尼克兰治疗 CUD 的药效学。如果 UG3 组件的里程碑 如果满足的话，UH3 项目将是一项动力充足的为期 12 周的临床试验，并进行后续全面评估 伐尼克兰在此人群中的疗效。