Neurobehavioral effects of cannabidiol in youth alcohol use disorder

大麻二酚对青少年酒精使用障碍的神经行为影响

• 批准号: 10629333
• 负责人: Lindsay Squeglia
• 金额: $ 17.87万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10629333
• 关键词: Acute; Addictive Behavior; Adjuvant Analgesic; Adolescence; Adolescent; Adult; Affect; Age; Alcohol abuse; Alcohol consumption; Alcohols; Alternative Medicine; Anterior; Anxiety; Behavior Therapy; Behavior assessment; Behavioral; Brain; Cannabidiol; Cannabis; Cannabis sativa plant; Central Nervous System; Cessation of life; Clinical; Clinical Trials; Crossover Design; Data; Development; Double-Blind Method; Endocannabinoids; Functional Magnetic Resonance Imaging; Glutamates; Goals; Happiness; Healthcare Systems; Heart Rate; Heavy Drinking; Hour; Human; Impulsivity; Intervention; Investigation; Magnetic Resonance Spectroscopy; Measures; Methodology; Methods; Neurotransmitters; Outcome; Pathway interactions; Persons; Pharmaceutical Preparations; Pharmacotherapy; Placebos; Play; Procedures; Psychophysiology; Randomized; Relapse; Research; Rewards; Safety; Signal Transduction; Societies; Standardization; Substance Use Disorder; Symptoms; System; Techniques; Testing; Time; Treatment outcome; United States National Institutes of Health; Withdrawal Symptom; Work; Youth; absorption; abuse liability; alcohol abstinence; alcohol behavior; alcohol craving; alcohol cue; alcohol related consequences; alcohol related problem; alcohol seeking behavior; alcohol use disorder; alcohol use initiation; cost; critical period; cue reactivity; drinking behavior; efficacy testing; efficacy trial; evidence base; gamma-Aminobutyric Acid; improved; in vivo; neural; neurobehavioral; neuroimaging; neuromechanism; novel; optimism; phytocannabinoid; pre-clinical; psychosocial; response; saliva secretion; screening; substance use treatment; therapeutic target; underage drinking; young adult

PROJECT SUMMARY/ABSTRACT Alcohol use is prevalent and problematic among youth, who are more likely than adults to initiate alcohol use, develop alcohol use disorder (AUD), and suffer lasting adverse alcohol-related consequences. Despite the clear need for youth-targeted AUD treatments, established psychosocial and behavioral interventions offer limited efficacy, with very few youth achieving sustained alcohol abstinence or reduction. Pharmacotherapies play a key role in bolstering substance use disorder treatment outcomes in adults, but to date, no medications for AUD in youth have merited FDA approval. The development of safe and effective adjunctive medications to treat adolescent AUD is needed to improve treatment outcomes and to potentially reduce the long-term consequences of adolescent use. Cannabidiol (CBD), one of the main phytocannabinoids in the Cannabis sativa plant, is a potentially promising candidate pharmacotherapy for youth AUD. It is particularly appealing as a youth treatment option since it is non-intoxicating, appears generally well-tolerated, and demonstrates no signal of abuse liability. CBD has many potential targets within the central nervous system that may mitigate the symptoms of AUD via modulation of the glutamatergic, GABAergic, dopaminergic, opioidergic, and endocannabinoid pathways. Preclinical work has shown that CBD affects an array of drinking behaviors (e.g., reduces ethanol seeking and intake; mitigates symptoms of withdrawal, relapse, anxiety, and impulsivity), and recent clinical work has indicated CBD's potential to reduce alcohol intake within adults who endorse alcohol and cannabis co-use. Establishing the acute neurometabolic, neurobehavioral, and psychophysiological effects of CBD in youth with AUD will be a critical first step in the pharmacotherapy development pipeline before initiating larger scale trials. The goal of this application is to test CBD as a potentially effective candidate medication for youth AUD by leveraging developmentally informed neuroimaging methods (magnetic resonance spectroscopy and functional MRI) and lab-based alcohol cue reactivity procedures. To accomplish this goal, this study will use a randomized, double-blind, within-subjects crossover design. In counterbalanced order, 35 youth (ages 14-24) who meet criteria for AUD will receive 600 mg of CBD or placebo with a standardized meal (to modulate CBD absorption rates) three hours before a neuroimaging and behavioral assessment paradigm, separated by a 13-day washout period. This proposal is consistent with the trans-NIH initiative to identify neurally-informed novel substance use treatments for youth. Findings will bridge a critical translational gap (“the valley of death”) in pharmacotherapy development for youth AUD, advancing methodology for rigorous neural-behavioral early efficacy testing of CBD. Effects established through this study could pave the way to a larger-scale clinical trial and, ultimately, improved long-term outcomes for young people suffering from AUD.

项目摘要/摘要 在青年中，饮酒很普遍，有问题，他们比成年人更有可能启动酒精 使用，发展饮酒障碍（AUD），并遭受持久的广告与酒精有关的后果。尽管有 明确需要针对青年的AUD治疗，已建立的社会心理和行为干预措施提供 效率有限，很少有青年实现持续的酒精戒酒或减少。药物治疗 在加强成年人的药物使用障碍治疗结果方面发挥关键作用，但迄今为止没有药物 对于年轻人来说，AUD值得FDA批准。开发安全有效的辅助药物 需要治疗青少年AUD来改善治疗结果并有可能减少长期 青少年使用的后果。大麻二酚（CBD），大麻sativa中的主要植物大麻素 植物是青年AUD的潜在承诺候选药物治疗。年轻时特别有吸引力 治疗选项由于没有毒性，因此看起来很容易耐受，并且没有证明 虐待责任。 CBD在中枢神经系统内有许多潜在的靶标，可以减轻症状 通过调节谷氨酸能，GABA能，多巴胺能，阿片类法和内源性大麻素的调节 途径。临床前工作表明，CBD会影响一系列饮酒行为（例如，减少乙醇 寻求和摄入；减轻戒断，退休，动画和冲动的症状）以及最近的临床工作 已经表明，CBD有可能减少认可酒精和大麻共同使用的成年人中的酒精摄入量。 建立CBD对年轻人的急性神经代谢，神经行为和心理生理影响 在启动大规模试验之前，AUD将是药物治疗开发管道的关键第一步。 该应用的目的是测试CBD作为对青年AUD的潜在有效候选药物 利用开发的知情神经影像学方法（磁共振光谱和功能 MRI）和基于实验室的酒精提示反应性程序。为了实现这一目标，本研究将使用随机， 双盲主题内部跨界设计。以平衡的顺序，35名青年（14-24岁）见面 AUD的标准将获得600毫克的CBD或安慰剂，并带有标准餐（调节CBD Abusetion 费率）在神经影像和行为评估范式之前的三个小时，被13天的冲洗分开 时期。该提案与识别自然信息的新型物质使用的Trans-NIH计划一致 青年治疗。调查结果将弥合药物治疗中的关键翻译差距（“死亡谷”） 青年AUD的开发，进步的方法论，用于严格的CBD神经行为早期效率测试。 通过这项研究建立的效果可以为大规模临床试验铺平道路，并最终改善 患有AUD的年轻人的长期结局。