NEURAL EFFECTS OF CHRONIC CANNABIS EXPOSURE IN HUMAN ADOLESCENTS

P20应用程序中的该项目是：人类慢性大麻暴露的神经效应 青少年。总的假设是，使用大麻导致额叶皮质功能失调， 执行认知功能，从而增加对大麻依赖的脆弱性。青春期是 由于大脑正在发育，这可能是一个特别脆弱的时期。因此，大脑 功能将在15-17岁的人类青少年中进行表征，以评估大脑和行为 使用神经心理学测试和功能测试与慢性大麻使用相关的异常 磁共振成像（fMRI）。 大麻使用者（n=30）和人口统计学上相似的正常对照（n=30）将无精神病或 神经系统问题或实质性的其他物质参与，并且用户将有>200个寿命 接触大麻所有的青少年将接受（1）神经心理学测试，重点是抑制，言语 学习和其他执行功能，以及（2）功能磁共振成像在抑制任务，以前显示， 激活前额叶区域，并在剑桥神经心理测试自动化管理过程中 电池（CANTAB）任务，涉及额叶区域，并有非人类灵长类动物的类似物。年轻人将 接受28天的监测禁欲期，包括在28天内9次前往研究中心， 提供用于尿液药物筛查的观察样本。每周，一组可重复的CANTAB 将进行测试，并对大麻戒断、情绪状态、皮质醇和睡眠进行主观评级 质量将被收集。在第27天，受试者将重复完整的神经心理成套测试， 第28天，参与者将获得相同的fMRI协议。 MANCOVA将对比各组之间和不同时间的测试表现和前额叶脑反应， 控制潜在的混淆。评估在持续时间和慢性化方面的发育差异， 大麻暴露，数据将直接与梅森博士的类似措施进行对比。 P20应用程序中的项目。结果也将与青少年非人类灵长类动物的结果进行比较 和啮齿类动物分别来自塔菲博士和帕森斯博士的中心项目。这些项目和 该中心的基础设施和培训将有助于确定对大麻的脆弱性机制 依赖，并表征与慢性重度大麻相关的潜在神经毒性异常 使用在青年。

This project within the P20 application is: Neural Effects of Chronic Cannabis Exposure in Human Adolescents. The overall hypothesis is that dysregulation of frontal cortex function by cannabis use impairs executive cognitive function, thereby increasing vulnerability to cannabis dependence. As adolescence is characterized by ongoing brain development, this may be a particularly vulnerable period. Thus, brain functioning will be characterized in human adolescents ages 15-17 to evaluate brain and behavioral abnormalities associated with chronic cannabis use using neuropsychological testing and functional magnetic resonance imaging (fMRI). Cannabis users (n=30) and demographically similar normal controls (n=30) will be free from psychiatric or neurological problems or substantial other substance involvement, and users will have >200 lifetimes exposures to cannabis. All youths will receive (1) neuropsychological testing focused on inhibition, verbal learning, and other executive functions as well as (2) fMRI during an inhibitory task previously shown to activate prefrontal regions, and during administration of Cambridge Neuropsychological Test Automated Battery (CANTAB) tasks that involve frontal regions and have non-human primate analogs. Then, youths will undergo a 28-day monitored abstinence period involving coming to the research site 9 times in 28 days for provision of an observed sample for urine drug screening. Each week, a brief battery of repeatable CANTAB tests will be administered, and subjective ratings of cannabis withdrawal, mood state, cortisol, and sleep quality will be collected. On the 27 day, subjects will repeat the full neuropsychological battery, and on the 28th day, participants will be given the same fMRI protocol. MANCOVA will contrast test performance and prefrontal brain response between groups and across time, controlling for potential confounds. To evaluate developmental differences in duration and chronicity of cannabis exposure, data will be contrasted directly with similar measures administered in Dr. Mason's project within this P20 application. Results will also be compared to those of adolescent non-human primates and rodents from the Center projects of Drs. Taffe and Parsons, respectively. Together, these projects and the infrastructure and training of the Center will help identify mechanisms for vulnerability to cannabis dependence, and characterize the potential neurotoxic abnormalities associated with chronic heavy cannabis use in youth.