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

项目摘要 大麻使用障碍（CUD）是一个重要的公共卫生问题，起源于青少年。大麻使用 在青少年时期，大麻的滥用会加剧，早期使用大麻预示着以后问题的发展。领导 病因学理论表明，随着大脑发育，反复使用大麻会产生奖励的变化。 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效果，并增加了激励的显着性 大麻线索，最终赋予CUD的风险。这项纵向研究对生态瞬时 评估（EMA）在自然环境和黄金标准的人类实验室（HLAB）范式， 监测主观大麻效应，线索反应和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产物和不同制剂的反应（例如，油、食用品）， 青少年加速纵向设计的使用允许从13岁到19岁的图表发展 通过在较短时间内完成的多队列评估。我们的目标是招募224名青少年（13岁 研究开始时为16人，每个年龄组n = 56人），他们在过去一个月内支持大麻使用。青少年将 完成基线HLAB方案，并在1年、2年和3年进行随访。每个年度评估点还将 包括日常生活中28天EMA测量突发。多域潜在增长曲线建模将：（目的 1)描述青春期（13岁至18岁）对奖励大麻效应的敏感性的年龄相关变化。 （目的2）测试CUD症状进展与奖励敏感性变化的前瞻性关系 大麻的影响;（目的3）测试CUD进展与大麻线索反应的前瞻性关系， 自然环境和HLAB。拟议的纵向研究扩展了调查小组先前的 研究显示CUD严重程度与主观大麻效应和线索的横截面关联 青少年的反应。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 使用可操作性强、多维度的方法，在现实世界和实验室环境中对青春期进行评估 评估。此外，通过一项研究，从总体年龄趋势中分解变化的个体差异， 加速纵向设计是一种敏感的方法，具有独特的创新性。我们的建议针对一个 NIDA流行病学研究分支通过有效结合以下优势确定的关键优先事项： 采用行为和实验室测量的纵向研究，以了解CUD病因 （NOT-DA-19-066）。这项建议将支持防止孵化或出现的疾病进展的努力。 通过提高对CUD运动轨迹的科学认识，使其危害更加严重。提供新的经验 有证据表明，可作为预防性干预措施目标的可塑性过程， CUD的社会影响的程度。

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.