fMRI and Cognition in Adolescent Cannabis Users

描述（由申请人提供）：相关性：大麻是美国最常用的非法药物，6%的高中毕业生报告每月使用大麻20次。神经成熟在青春期以灰质减少和白质增加的形式继续进行，包括在大麻素受体密集分布的区域（如额叶、海马、纹状体和小脑）。然而，很少有研究调查了青春期大量吸食大麻与随后的大脑发育之间的关系。纵向研究对于确定先前观察到的异常是在大麻使用之前还是由大麻素暴露引起的至关重要。描述：在本申请中，我们建议招募78名青少年加入到R21 DA15228项目（PI: Tapert）招募的90名青少年队列中，并在初步评估后1.5年和3年对这168名青少年进行相同的神经心理测试、功能磁共振成像（FMRI；工作记忆、抑制和学习任务）、MRI（检查脑容量）和弥散成像（探测白质完整性）。在3年的随访期内，每6个月进行一次简短的访谈，以评估大麻、酒精、尼古丁和其他药物的使用和学术参与情况。参与者将是126名重度大麻使用者和42名非使用者，通过两个当地学区招募，使用与R21 DA15228相同的方法。在基线时，所有参与者的年龄为16-18岁，无精神、学习、神经和医学障碍，并限制酒精、尼古丁和其他药物的接触。在用户中，将针对晚发（16岁以后）的现有用户、早发（小于等于15岁）的现有用户和早发（小于等于15岁）的前用户进行招募。在每次成像之前，青少年将经历28天的监测戒断期，每3-4天提供尿液样本和头发样本用于药物毒理学（如R21 DA15228）。目的：当前应用的目的是：(1)重复慢性重度大麻使用者和人口统计学上相似的非使用者在禁欲28天后中枢神经系统差异的初步发现；(2)确定早起（而不是持续时间）大量使用大麻是否与中枢神经系统功能异常有关；(3)确定大麻使用频率和强度是否能预测3年内脑成像和认知测试指标的变化；(4)评估执行功能任务期间的FMRI反应模式是否可以预测随后的物质使用。所有分析都将控制发病前因素（即物质使用障碍和人格的家族史）、教育参与（即出勤）和其他物质使用（即酒精、尼古丁和其他药物）。

DESCRIPTION (provided by applicant): Relevance: Marijuana is the most commonly used illicit drug in the U.S., and 6 percent of high school seniors report using marijuana >20 times per month. Neuromaturation continues during adolescence in the form of gray matter decreases and white matter increases, including in regions with dense distributions of cannabinoid receptors (e.g., frontal lobe, hippocampus, striatum, and cerebellum). However, few studies have examined the relationship between heavy marijuana use during adolescence and subsequent brain development. Longitudinal studies are essential to determine if previously observed abnormalities predate cannabis use or are caused by cannabinoid exposure. Description: In this application, we propose to recruit 78 adolescents to add to a cohort of 90 adolescents recruited in project R21 DA15228 (PI: Tapert), and follow these 168 teens with the same neuropsychological tests, functional magnetic resonance imaging (FMRI; working memory, inhibition, and learning tasks), MRI (to examine brain volume), and diffusion imaging (to probe white matter integrity) 1.5 and 3 years after the initial assessment. Brief interviews will be conducted each 6 months over the 3-year follow-up period to assess marijuana, alcohol, nicotine, and other drug use and academic involvement. Participants will be 126 heavy marijuana users and 42 non-users, recruited through two local school districts using the same approach as in R21 DA15228. At baseline, all participants will be age 16-18, free from psychiatric, learning, neurological, and medical disorders, and with limited exposure to alcohol, nicotine, and other drugs. Among users, late onset (after age 16) current users, early onset (less than or equal to 15) current users, and early onset (less than or equal to 15) former users will be targeted for recruitment. Prior to each imaging session, youths will undergo a 28-day monitored abstinence period by providing urine samples every 3-4 days and a hair sample for drug toxicology (as in R21 DA15228). Aims: Aims of the current application are to: (1) replicate preliminary findings of CNS differences between chronic heavy marijuana users and demographically similar non-users after 28 days of abstinence; (2) determine whether early onset (as opposed to duration) of heavy marijuana use is associated with abnormal CNS functioning; (3) determine if frequency and intensity of marijuana use predicts changes in brain imaging and cognitive test measures over a 3-year period; and (4) evaluate if FMRI response patterns during executive functioning tasks can predict subsequent substance use. All analyses will control for premorbid factors (i.e., family history of substance use disorders and personality), educational involvement (i.e., attendance), and other substance use (i.e., alcohol, nicotine, and other drugs).