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%的高中生报告每月使用大麻超过20次。神经成熟在青春期以灰质减少和白色物质增加的形式继续，包括在大麻素受体密集分布的区域（例如，额叶、海马、纹状体和小脑）。然而，很少有研究探讨青少年时期大量使用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否早于大麻使用或由大麻素暴露引起至关重要。产品描述：在本申请中，我们计划招募78名青少年，以添加到项目R21 DA 15228中招募的90名青少年队列中（PI：Tapert），并对这168名青少年进行相同的神经心理学测试，功能性磁共振成像，（功能磁共振成像;工作记忆、抑制和学习任务），MRI（以检查脑体积）和扩散成像（以探测白色物质完整性）。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。参与者将是126名重度大麻使用者和42名非使用者，他们将使用与R21 DA 15228相同的方法通过当地两个学区招募。在基线时，所有参与者年龄为16-18岁，无精神病、学习、神经和医学疾病，并且有限暴露于酒精、尼古丁和其他药物。在使用者中，迟发性（16岁以后）当前使用者、早发性（小于或等于15岁）当前使用者和早发性（小于或等于15岁）前使用者将成为招募的目标。在每次成像之前，青少年将接受28天的监测禁欲期，每3-4天提供一次尿液样本和一次用于药物毒理学的头发样本（如R21 DA 15228所述）。目的：本申请的目的是：（1）复制慢性重度大麻使用者和人口统计学上相似的非使用者之间在戒断28天后CNS差异的初步发现;（2）确定是否早发性大麻依赖性神经元性疾病（CNS）。（与持续时间相反）大量使用大麻与中枢神经系统功能异常有关;（3）确定大麻使用的频率和强度是否可以预测3年内大脑成像和认知测试指标的变化;以及（4）评估执行功能任务中的FMRI反应模式是否可以预测随后的物质使用。所有分析将控制发病前因素（即，物质使用障碍的家族史和个性），教育参与（即，出席）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).