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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Exploratory Grants (P20)
Project #
5P20DA024194-03
Application #
7878048
Study Section
Special Emphasis Panel (ZDA1)
Project Start
Project End
Budget Start
2009-07-01
Budget End
2010-06-30
Support Year
3
Fiscal Year
2009
Total Cost
$230,613
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Taffe, Michael A; Creehan, Kevin M; Vandewater, Sophia A (2015) Cannabidiol fails to reverse hypothermia or locomotor suppression induced by ?(9) -tetrahydrocannabinol in Sprague-Dawley rats. Br J Pharmacol 172:1783-91
Taffe, M A (2015) Drug abuse scientists should use social media to engage the public because their primary translational product is information. Drug Alcohol Depend 154:315-9
Irimia, Cristina; Polis, Ilham Y; Stouffer, David et al. (2015) Persistent effects of chronic ?9-THC exposure on motor impulsivity in rats. Psychopharmacology (Berl) 232:3033-43
Jacobus, Joanna; Squeglia, Lindsay M; Sorg, Scott F et al. (2014) Cortical thickness and neurocognition in adolescent marijuana and alcohol users following 28 days of monitored abstinence. J Stud Alcohol Drugs 75:729-43
Hanson, Karen L; Thayer, Rachel E; Tapert, Susan F (2014) Adolescent marijuana users have elevated risk-taking on the balloon analog risk task. J Psychopharmacol 28:1080-7
Wright Jr, M Jerry; Vandewater, Sophia A; Taffe, Michael A (2013) Cannabidiol attenuates deficits of visuospatial associative memory induced by ?(9) tetrahydrocannabinol. Br J Pharmacol 170:1365-73
Wetherill, Reagan; Tapert, Susan F (2013) Adolescent brain development, substance use, and psychotherapeutic change. Psychol Addict Behav 27:393-402
Mahmood, O M; Goldenberg, D; Thayer, R et al. (2013) Adolescents' fMRI activation to a response inhibition task predicts future substance use. Addict Behav 38:1435-41
Wright Jr, M J; Vandewater, S A; Parsons, L H et al. (2013) ?(9)Tetrahydrocannabinol impairs reversal learning but not extra-dimensional shifts in rhesus macaques. Neuroscience 235:51-8
Taffe, M A (2012) ?9-Tetrahydrocannabinol attenuates MDMA-induced hyperthermia in rhesus monkeys. Neuroscience 201:125-33

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