Sensitivity to Cannabis Effects and Cue Reactivity as Markers of a Developing Disorder in Adolescents

对大麻效应的敏感性和提示反应性作为青少年发育障碍的标志

• 批准号: 10586397
• 负责人: Hayley Treloar Padovano
• 金额: $ 66.29万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-15 至 2028-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10586397
• 关键词: Acceleration; Accounting; Acute; Address; Adolescence; Adolescent; Affect; Age; Behavioral; Blood Pressure; Brain; Cannabis; Cellular Phone; Clinical; Cues; DSM-V; Data; Development; Dimensions; Disease; Drug usage; Ecological momentary assessment; Environment; Etiology; Formulation; Goals; Growth; Health; Heart Rate; Human; Hypersensitivity; Incubated; Individual; Individual Differences; Inhalation; Intoxication; Laboratories; Life; Longitudinal Studies; Measurable; Measurement; Measures; Modeling; Monitor; National Institute of Drug Abuse; Oils; Oral; Pattern; Pharmaceutical Preparations; Physiological; Predisposition; Process; Protocols documentation; Public Health; Reaction; Reporting; Research; Rewards; Risk; Science; Severities; Societies; Standardization; Statutes and Laws; Symptoms; System; Teenagers; Testing; Time; age effect; age related; biological sex; cannabis administration; cannabis craving; cannabis cue; cohort; craving; cue reactivity; design; drug reward; epidemiology study; incentive salience; indexing; innovation; longitudinal design; marijuana use; marijuana use disorder; motivational processes; neural; pleasure; preclinical study; prevent; preventive intervention; prospective; prospective test; public health priorities; public health relevance; recruit; response; theories; trend

PROJECT SUMMARY Cannabis use disorder (CUD) is a significant public health concern with origins in adolescence. Cannabis use escalates during the teenage years, and early cannabis use predicts the development of later problems. Leading etiological theories suggest that repeated cannabis use as the brain develops produces changes in reward systems. Over time, these instrumental brain changes alter cannabis effects and increase the incentive salience of cannabis cues, ultimately conferring risk for CUD. This longitudinal study pairs ecological momentary assessment (EMA) in the natural environment and a gold-standard human laboratory (HLAB) paradigm to monitor changes in subjective cannabis effects, cue reactivity, and CUD symptoms across the formative adolescent years. Leveraging smartphone (EMA) reports in natural settings allows for studying adolescents’ reactions to the typically higher potency THC products and varied formulations (e.g., oils, edibles) favored by teenagers. The use of an accelerated longitudinal design allows for charting development from ages 13 to 19 through multicohort assessments completed in a shorter timeframe. We aim to recruit 224 adolescents (ages 13 to 16 at study outset, n = 56 per age cohort) who endorse cannabis use in the past month. Adolescents will complete a baseline HLAB protocol with follow-ups at 1, 2, and 3 years. Each yearly assessment point will also include a 28-day measurement burst of EMA in daily life. Multiple domain latent growth curve modeling will: (Aim 1) characterize age-related changes in sensitivity to rewarding cannabis effects over adolescence (ages 13 to 19); (Aim 2) test prospective relations of CUD symptom progression with change in sensitivity to rewarding cannabis effects; and (Aim 3) test prospective relations of CUD progression with responses to cannabis cues in the natural environment and HLAB. The proposed longitudinal study extends the investigative team’s prior research showing cross-sectional associations of CUD severity with subjective cannabis effects and cue reactivity among adolescents. Our proposal is highly innovative, as well-studied etiological CUD constructs are assessed across adolescence in real-world and laboratory settings using well-operationalized, multidimensional assessments. Further, disaggregating individual differences in change from overall age trends through an accelerated longitudinal design is a sensitive approach that is distinctively innovative. Our proposal addresses a key priority identified by the NIDA Epidemiology Research Branch by efficiently combining the advantages of longitudinal research with behavioral and laboratory-based measures to inform understanding of CUD etiology (NOT-DA-19-066). This proposal will support efforts to prevent the progression of an incubating or emerging CUD by enhancing scientific understanding of the trajectory to more severe harms. Providing new empirical evidence of malleable processes that can serve as targets of preventative interventions has power to reduce the magnitude of societal ramifications of CUD.

项目摘要 大麻使用障碍（CUD）是青少年起源的重要公共卫生问题。大麻使用 在青少年时期和早期大麻使用预测后来的问题的发展。领导 病因理论表明，随着大脑的发展，重复使用大麻会产生奖励的变化 系统。随着时间的流逝，这些工具性大脑会改变大麻的影响并增加激励显着性 大麻提示，最终赋予CUD风险。这个纵向研究对生态瞬间 自然环境中的评估（EMA）和金标准的人类实验室（HLAB）范式 监视格式的主题大麻效应，提示反应性和CUD符号的变化 青春期。在自然设置中利用智能手机（EMA）报告可以研究青少年 对通常较高效力的THC产品和各种配方（例如油，食品）的反应 青少年。加速纵向设计的使用允许绘制从13岁到19岁的开发 通过在较短的时间范围内完成的多轴心评估。我们的目标是招募224名青少年（13岁 在研究一开始，至16岁，每个年龄段的n = 56）在过去一个月中认可大麻的使用。青少年会 完成一项基线HLAB方案，其随访时间为1、2和3年。每个年度评估点也将 在日常生活中包括28天的EMA测量。多个领域潜在的增长曲线建模将：（目标 1）表征与年龄相关的对青春期大麻效应的敏感性的变化（13至13岁 19）; （目标2）测试CUD症状的前瞻性关系，随着对奖励的敏感性而变化 大麻效应； （目标3）测试CUD进展的前瞻性关系与对大麻线索的反应 自然环境和HLAB。拟议的纵向研究扩展了调查团队的先前 研究表明，CUD严重程度与主观大麻效应的横截面关联和提示 青少年的反应性。我们的建议具有很高的创新性，并且经过充分研究的病因学结构是 使用良好的多维，在现实世界和实验室环境中对青少年进行评估 评估。此外，分解从总年龄趋势的变化中的个体差异。 加速纵向设计是一种敏感的方法，具有明显的创新性。我们的提议解决了 NIDA流行病学研究分支确定的关键优先级是有效地结合了 纵向研究采用行为和实验室的措施，以告知对CUD病因的理解 （NOT-DA-19-066）。该建议将支持防止孵化或新兴的努力 通过增强对轨迹的科学理解来造成更严重的伤害。提供新的经验 可以用作预防干预目标的可延展过程的证据有能力减少 CUD的社会后果的幅度。