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 饮酒在年轻人中很普遍，而且有问题，他们比成年人更容易饮酒 使用酒精，患上酒精使用障碍(AUD)，并遭受与酒精有关的持久不良后果。尽管 明确需要针对青少年的AUD治疗，既定的心理社会和行为干预提供 疗效有限，很少有青年实现持续戒酒或戒酒。药物疗法 在支持成人物质使用障碍治疗结果方面发挥了关键作用，但到目前为止，还没有药物治疗 用于青少年AUD的药物值得FDA批准。安全有效的辅助药物的开发 需要治疗青少年AUD以改善治疗结果，并有可能减少长期 青少年使用的后果。大麻二酚(CBD)--大麻中的主要植物大麻素 植物，是一种潜在的治疗青少年AUD的候选药物。作为一个年轻人，它特别有吸引力 治疗选择，因为它是不醉人的，似乎一般耐受性良好，并且没有表现出 滥用责任。CBD在中枢神经系统内有许多潜在的靶点，可能会缓解症状 通过调节谷氨酸能、GABA能、多巴胺能、阿片能和内源性大麻素 小路。临床前研究表明，CBD影响一系列饮酒行为(例如，减少酒精含量 寻求和摄取；减轻戒断、复发、焦虑和冲动的症状)，以及最近的临床工作 已经表明CBD有可能减少支持酒精和大麻共同使用的成年人的酒精摄入量。 建立慢性阻塞性肺疾病对青少年的急性神经代谢、神经行为和心理生理影响 在启动更大规模的试验之前，AUD将是药物治疗开发管道中至关重要的第一步。 此应用程序的目标是通过以下方式测试CBD作为治疗青少年AUD的潜在有效候选药物 利用了解发育情况的神经成像方法(磁共振波谱和功能 核磁共振)和基于实验室的酒精线索反应程序。为了实现这一目标，本研究将使用随机、 双盲，受试者内交叉设计。按照平衡顺序，35名青年(14-24岁)相遇 AUD的标准将接受600毫克CBD或安慰剂配合标准膳食(以调节CBD吸收 率)，在神经成像和行为评估范例之前三个小时，以13天的洗涤为间隔 句号。这一建议与跨NIH倡议一致，该倡议旨在确定神经知情的新物质使用 对年轻人的治疗。这些发现将弥补药物治疗中的一个关键的翻译鸿沟(“死亡之谷”)。 为青少年开发AUD，推进CBD严格神经行为早期疗效测试的方法学。 通过这项研究建立的效果可能为更大规模的临床试验铺平道路，并最终改善 患有澳门氏症的年轻人的长期结果。