Cannabis Toxicology in Relation to Neurocognitive Outcomes in Adolescents

项目总结/摘要。虽然大麻效力发生了重大变化，但使用方法（例如， 虽然在这些领域（花卉、食用品）和政策的影响下，年轻人的高使用率保持相对稳定。此外，本发明还提供了一种方法， 儿童接触二手大麻的比率正在上升。大麻植物含有超过120 大麻素成分，其中δ-9-四氢大麻酚（THC）是一种精神活性成分， 与言语记忆、注意力和工作记忆的缺陷有关;然而，这些缺陷的持续存在， 影响仍然存在争议。频率、使用方法和效力的差异可能会导致 大麻代谢的指标迄今为止的研究主要依赖于自我报告，尽管潜在的错误- 参与者的报告和依赖大麻使用的偶发性（而不是剂量或模式）， 没有研究调查二手接触。这些限制可以解释先前的不一致， 大麻认知文献本K 08提案的主要目的是促进跨学科的专业知识， 毒理学检查大麻素分析物水平使用稳健的生物样品（头发），以评估认知 相互关联使用毛发可以改进方法学研究， 大麻使用，二手烟暴露和潜在的认知影响。毛发分析在 青少年大脑认知发展（ABCD）研究将为青少年大脑认知发展研究增添新的重要知识。 关于大麻-认知联系的科学文献，澄清了两者先前的不一致结果 与使用大麻的青少年相关的负面和零认知功能变化，并检查 二手大麻烟的影响。因果推理模型将用于确定 头发中THC及其代谢物水平对儿童横向和纵向认知功能的影响 ABCD队列的子样本。认知和物质使用将每年测量一次， 建议的项目，当ABCD参与者年龄在13-14岁和17-18岁之间。其目的是 项目与NIDA的战略资助计划一致，因为这项工作将衡量 在脆弱的年轻人口中环境和直接接触大麻。的额外培训 提供给韦德博士，特别是在大麻毒理学，二手烟暴露，青春期早期， 和统计学，将补充她以前在物质使用，神经认知和新兴成人方面的经验。 一个由专家组成的导师团队将在这些独特的领域之间架起桥梁，以提高我们对 THC暴露（个人使用或环境暴露）对青少年认知发展的影响。在 这个奖项的结论，韦德博士将满足她的职业独立作为一个跨学科的临床目标 具有大麻毒理学和认知方面专门知识的科学家，例如提交了R 01。最后 对额外头发样本的分析的资助也将有利于ABCD的开放科学模型，因为所有数据 收集的数据将通过年度策划的ABCD数据发布提供给全球研究人员。

PROJECT SUMMARY/ABSTRACT. While significant changes in cannabis potency, methods of use (e.g., flower, edibles) and policy have occurred, high levels of use by youth remain relatively constant. In addition, rates of secondhand cannabis exposure in children is increasing. The cannabis plant contains over 120 cannabinoid constituents, with delta-9-tetrahydrocannabinol (THC), a psychoactive constituent, most associated with deficits in verbal memory, attention, and working memory; however, the persistence of these effects remains controvertible. Differences in frequency, method of use, and potency may produce variation in measures of cannabis metabolized. Research to-date has primarily relied on self-report, despite potential mis- reporting by participants and reliance on episodic (rather than dose or patterns) of cannabis use, and almost no research investigating secondhand exposure. Such limitations may explain prior inconsistencies in the cannabis-cognition literature. The primary aim of this K08 proposal is to facilitate interdisciplinary expertise in toxicology to examine cannabinoid analyte levels using a robust biosample (hair) to assess cognitive correlates. The use of hair allows for improved methodological investigation of the relationship between cannabis use, secondhand smoke exposure, and potential cognitive impact. Expansion of hair analysis in the Adolescent Brain Cognitive Development (ABCD) study will add novel and important knowledge to the scientific body of literature regarding the cannabis-cognition link, clarifying prior discrepant results of both negative and null cognitive function changes associated with cannabis using adolescents, and examining the influence of second-hand cannabis smoke. Causal inference models will be used to determine the influence of THC and its metabolite levels from hair on cross-sectional and longitudinal cognitive function among a subsample of the ABCD cohort. Cognition and substance use will be measured annually for the length of the proposed project, when ABCD participants are between the ages of 13-14 and 17-18 years. The aims of this project are consistent with NIDA's strategic funding plans, as this work would measure behavioral sequelae of environmental and direct exposure of cannabis in a vulnerable, young population. The additional training afforded to Dr. Wade, particularly in cannabis toxicology, secondhand smoke exposure, early adolescence, and statistics, would complement her prior experience in substance use, neurocognition, and emerging adults. A mentorship team of experts will bridge these unique fields to improve our understanding of the effects of THC exposure (personal use or environmental exposure) on adolescent cognitive development. At the conclusion of this award, Dr. Wade will meet her goal of career independence as an interdisciplinary clinical scientist with expertise in cannabis toxicology and cognition, exemplified by submission of an R01. Finally, the funding of analysis of additional hair samples will also benefit the open-science model of ABCD, as all data collected will be available to researchers worldwide through the annual curated ABCD data release.