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.

项目总结 大麻使用障碍(CUD)是一个重大的公共卫生问题，起源于青春期。吸食大麻 在青少年时期，吸食大麻的风险逐渐上升，早期吸食大麻预示着以后的问题的发展。先导 病因学理论表明，随着大脑发育，重复使用大麻会导致奖赏的变化 系统。随着时间的推移，这些工具性的大脑变化改变了大麻的影响，并增加了激励的显著程度 大麻线索，最终给CUD带来风险。这项纵向研究配对了生态瞬间 自然环境评估(EMA)和黄金标准的人类实验室(HLAB)范例 监测整个形成期的主观大麻效应、线索反应性和CUD症状的变化 青春期。在自然环境中利用智能手机(EMA)报告可以研究青少年的 对通常更高效力的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从13岁到19岁的图表开发 通过在较短的时间内完成多队列评估。我们的目标是招募224名青少年(13岁 在研究开始时，每个年龄组56人)在过去一个月内支持使用大麻。青少年会 完成基线HLAB方案，并在1年、2年和3年进行跟踪。每个年度评估点还将 包括日常生活中EMA的28天测量突发。多域潜在增长曲线建模将：(AIM 1)描述青春期(13岁至20岁)对奖励大麻效果的敏感性与年龄相关的变化 19)；(目标2)检验CUD症状进展与奖赏敏感度变化的预期关系 大麻效应；以及(目标3)测试CUD进展与对大麻线索的反应的预期关系 自然环境和HLAB。拟议的纵向研究扩展了调查小组之前的 研究表明CUD严重程度与主观大麻效果和线索的横截面关联 青少年的反应性。我们的建议是高度创新的，因为经过充分研究的病因学CUD结构是 在现实世界和实验室环境中评估青春期，使用可操作性好的多维 评估。此外，根据总体年龄趋势分解个体差异变化通过 加速纵向设计是一种敏感的方法，具有明显的创新性。我们的建议针对的是 NIDA流行病学研究分部通过有效结合以下优势确定的关键优先事项 以行为和实验室为基础的纵向研究，以了解CUD病因学 (非-DA-19-066)。这项提案将支持防止正在孵化或出现的 通过加强对走向更严重危害的轨迹的科学理解，消除对妇女的歧视。提供新的经验 可以作为预防性干预目标的可塑性过程的证据有能力减少 CUD的社会影响的大小。