fMRI and Cognition in Adolescent Cannabis Users

描述(申请人提供)：相关性：大麻是美国最常用的非法药物，6%的高中生报告每月吸食大麻20次。神经成熟在青春期继续，表现为灰质减少和白质增加，包括大麻素受体密集分布的区域(如额叶、海马体、纹状体和小脑)。然而，很少有研究研究青春期大量使用大麻与随后的大脑发育之间的关系。纵向研究对于确定以前观察到的异常是在使用大麻之前还是由大麻素暴露引起的至关重要。描述：在这项申请中，我们建议招募78名青少年，以增加R21 DA15228项目(PI：Tapert)招募的90名青少年的队列，并在最初评估1.5年和3年后对这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(检查脑体积)和扩散成像(探测脑白质完整性)。在三年的随访期内，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名吸食大量大麻的人和42名不吸食大麻的人，他们是通过两个当地学区招募的，方法与R21 DA15228相同。在基线水平上，所有参与者的年龄为16-18岁，没有精神、学习、神经和医学疾病，接触酒精、尼古丁和其他药物的时间有限。在用户中，晚发型(16岁以后)的现任用户、早发型(小于或等于15岁)的现任用户、早发性(小于或等于15岁)的前任用户将被列为招募目标。在每次成像治疗之前，青少年将接受为期28天的戒毒期监测，每3-4天提供一次尿样，并提供头发样本进行药物毒理学(如R21 DA15228所示)。目的：当前应用的目的是：(1)复制戒除28天后长期大量吸食大麻和人口统计学上相似的非吸毒者之间中枢神经系统差异的初步结果；(2)确定早期大量使用大麻(而不是持续时间)是否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三年期间大脑成像和认知测试测量的变化；以及(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。所有分析将控制发病前因素(即，药物使用障碍的家族史和个性)、教育参与(即，就学)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).