Cannabis Toxicology in Relation to Neurocognitive Outcomes in Adolescents

大麻毒理学与青少年神经认知结果的关系

• 批准号: 10563133
• 负责人: Natasha E Wade
• 金额: $ 19.14万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-15 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10563133
• 关键词: Abstinence; Acute; Adolescence; Adolescent; Adult; Age; Age Years; Agonist; Attention; Award; Behavior; Binding; Biological Availability; Brain; CNR1 gene; Cannabinoids; Cannabis; Categories; Chemical Exposure; Chemicals; Child; Classification; Clinical; Cognition; Cognitive; Complement; Consumption; Data; Development; Dose; Drops; Drug Kinetics; Eating; Ensure; Environment; Environmental Exposure; Exhibits; Exposure to; Flowers; Frequencies; Funding; Genetic; Goals; Hair; Household; Human; Individual; Intoxication; Investigation; Knowledge; Learning; Legal Status; Length; Link; Literature; Male Adolescents; Mass Spectrum Analysis; Measurable; Measurement; Measures; Memory; Mentorship; Methodology; Methods; Modeling; Monitor; National Institute of Drug Abuse; Neurocognition; Neurocognitive; Outcome; Parents; Participant; Patient Self-Report; Pattern; Performance; Pharmaceutical Preparations; Plants; Policies; Population; Predisposition; Protocols documentation; Receptor Signaling; Reporting; Research; Research Personnel; Sampling; Scientist; Short-Term Memory; Smoke; THC concentration; THC exposure; Tetrahydrocannabinol; Time; Toxicology; Training; Urinalysis; Variant; Work; Youth; adolescent substance use; behavior influence; behavior measurement; career; cognitive development; cognitive function; cognitive performance; cognitive task; cohort; critical period; early adolescence; emerging adult; endogenous cannabinoid system; environmental tobacco smoke; environmental tobacco smoke exposure; experience; follow-up; improved; marijuana use; marijuana user; neurodevelopment; novel; open data; risk perception; secondhand cannabis smoke; statistics; substance use; tool; verbal; young adult

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.

项目摘要/摘要。虽然大麻效力、使用方法(例如， 虽然已经出现了花卉(可食用)和政策，但年轻人的高使用量仍然相对稳定。此外, 儿童接触二手大麻的比率正在上升。这种大麻植物含有120多种 大麻类成分，包括精神活性成分β-9-四氢大麻酚(THC) 与言语记忆、注意力和工作记忆的缺陷有关；然而，这些的持久性 其影响仍然存在争议。频率、使用方法和效力的不同可能会导致不同的 大麻的代谢量。到目前为止，研究主要依赖于自我报告，尽管存在潜在的错误- 参与者的报告和对大麻使用间歇性(而不是剂量或模式)的依赖，几乎 没有调查二手烟接触的研究。这些限制可能解释了先前在 大麻认知文献。K08提案的主要目的是促进跨学科的专业知识在 使用坚固的生物样本(毛发)检查大麻类分析物水平的毒理学，以评估认知能力 相互关联。使用毛发可以改进对两者之间关系的方法学研究 大麻使用、二手烟暴露和潜在的认知影响。毛发分析的扩展在 青少年脑认知发展(ABCD)研究将为青少年提供新的和重要的知识 关于大麻-认知联系的科学文献，澄清了先前两者的不同结果 与青少年使用大麻相关的负面和无效认知功能变化，并检查 二手烟的影响。因果推理模型将被用来确定 头发中THC及其代谢物水平对老年人横断面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进行测量，时间为 建议的项目，当ABU参与者的年龄在13-14岁到17-18岁之间。这样做的目的是 项目与NIDA的战略资金计划是一致的，因为这项工作将衡量 在易受伤害的年轻人口中环境和直接接触大麻。额外的培训 提供给韦德博士，特别是大麻毒理学，二手烟暴露，青春期早期， 和统计数据，将补充她之前在物质使用、神经认知和新兴成年人方面的经验。 一个由专家组成的指导团队将在这些独特的领域之间架起桥梁，以提高我们对 暴露(个人使用或环境暴露)对青少年认知发展的影响。在 此次获奖结束后，韦德博士将实现她作为跨学科临床医生的职业独立目标。 在大麻毒理学和认知学方面有专长的科学家，提交的R01就是例证。最后， 资助对更多头发样本的分析也将有利于ABCD的开放科学模型，因为所有数据 收集的数据将通过年度精心策划的ABCD数据发布提供给世界各地的研究人员。