This project within the P20 application is: Neural Effects of Chronic Cannabis Exposure in HumanAdolescents. The overall hypothesis is that dysregulation of frontal cortex function by cannabis use impairsexecutive cognitive function, thereby increasing vulnerability to cannabis dependence. As adolescence ischaracterized by ongoing brain development, this may be a particularly vulnerable period. Thus, brainfunctioning will be characterized in human adolescents ages 15-17 to evaluate brain and behavioralabnormalities associated with chronic cannabis use using neuropsychological testing and functionalmagnetic resonance imaging (fMRI).Cannabis users (n=30) and demographically similar normal controls (n=30) will be free from psychiatric orneurological problems or substantial other substance involvement, and users will have >200 lifetimesexposures to cannabis. All youths will receive (1) neuropsychological testing focused on inhibition, verballearning, and other executive functions as well as (2) fMRI during an inhibitory task previously shown toactivate prefrontal regions, and during administration of Cambridge Neuropsychological Test AutomatedBattery (CANTAB) tasks that involve frontal regions and have non-human primate analogs. Then, youths willundergo a 28-day monitored abstinence period involving coming to the research site 9 times in 28 days forprovision of an observed sample for urine drug screening. Each week, a brief battery of repeatable CANTABtests will be administered, and subjective ratings of cannabis withdrawal, mood state, cortisol, and sleepquality will be collected. On the 27 day, subjects will repeat the full neuropsychological battery, and on the28th 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 ofcannabis exposure, data will be contrasted directly with similar measures administered in Dr. Mason'sproject within this P20 application. Results will also be compared to those of adolescent non-human primatesand rodents from the Center projects of Drs. Taffe and Parsons, respectively. Together, these projects andthe infrastructure and training of the Center will help identify mechanisms for vulnerability to cannabisdependence, and characterize the potential neurotoxic abnormalities associated with chronic heavy cannabisuse in youth.
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