This is a second revision of an application written in response to PA-06-001. It describes a systematic 5- year training plan to launch an independent research career in neuroimaging of marijuana abuse through the use of magnetic resonance imaging (MRI) techniques, including structural MRI, magnetic resonance spectroscopy (MRS), and diffusion tensor imaging (DTI) to non-invasively measure brain structure and chemistry. This plan will allow the candidate, a neuroscientist, to initiate technologically sophisticated research of relevance to understanding marijuana abuse in adolescents and its potential role as a """"""""gateway"""""""" drug. This goal will be achieved through a rigorous training plan, integrating didactic and research components tailored to the candidate's goals and experience. The University of Hawaii (UH) provides an ideal training environment: UH is home to a brand new state-of-the-art 3 Tesla research dedicated MR scanner;and the mentors of this project are renowned for the application of these cutting-edge technologies to study mechanisms of drug addiction. Under their supervision, the candidate will evaluate adolescents with regular marijuana use and age and gender matched non-marijuana exposed subjects, using in vivo MRI, MRS, &DTI to measure of brain structure and chemistry, as well as secondary measures of cognitive abilities and cortisol levels. We hypothesize: 1) The proportion of gray matter volume relative to white matter volume will be lower in marijuana exposed subjects. 2) Multiple regions will have decreased glutamate and myo-inositol (glial marker) concentrations. 3) Increased cortisol and poorer cognitive performance will correlate with changes in brain structure and chemistry. This award would provide the PI with protected time to successfully become an independent investigator dedicated to the study of the brain's response to marijuana exposure during the critical adolescent years when the brain is still maturing.
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