Impact of Marijuana Exposure on Brain Maturation

描述（由申请人提供）：这是针对PA-06-001所写申请的第二次修订。它描述了一个系统的5年培训计划，通过使用磁共振成像（MRI）技术，包括结构MRI，磁共振波谱（MRS）和弥散张量成像（DTI）来非侵入性测量大脑结构和化学，启动大麻滥用神经成像的独立研究事业。这个计划将允许候选人，一个神经科学家，发起相关的技术复杂的研究，以了解青少年滥用大麻及其作为“入门”药物的潜在作用。这一目标将通过严格的培训计划来实现，该计划结合了针对候选人目标和经验量身定制的教学和研究组成部分。夏威夷大学（UH）提供了一个理想的培训环境：UH拥有全新的最先进的3特斯拉研究专用磁共振扫描仪；这个项目的导师们以应用这些尖端技术来研究药物成瘾的机制而闻名。在他们的监督下，候选人将评估经常使用大麻的青少年和年龄和性别匹配的非大麻暴露对象，使用体内MRI， MRS和DTI来测量大脑结构和化学，以及认知能力和皮质醇水平的二次测量。我们假设：1)大麻暴露者脑灰质体积相对于脑白质体积的比例会降低。2)多个区域谷氨酸和肌醇（神经胶质标记物）浓度降低。皮质醇升高和认知能力下降与大脑结构和化学物质的变化有关。该奖项将为PI提供受保护的时间，使其能够成功地成为一名独立的研究者，致力于研究大脑在青春期对大麻暴露的反应，那时大脑仍在发育。

DESCRIPTION (provided by applicant): 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.