Impact of Marijuana Exposure on Brain Maturation

描述（由申请人提供）：这是根据PA-06-001编写的申请的第二次修订。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）和扩散张量成像（DTI），以非侵入性方式测量大脑结构和化学物质，在大麻滥用的神经成像方面开展独立的研究生涯。该计划将允许候选人，一名神经科学家，启动与了解青少年滥用大麻及其作为“门户”药物的潜在作用有关的技术复杂的研究。这一目标将通过严格的培训计划来实现，将根据候选人的目标和经验量身定制的教学和研究组成部分相结合。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MR扫描仪;该项目的导师以应用这些尖端技术研究药物成瘾机制而闻名。在他们的监督下，候选人将评估经常使用大麻的青少年以及年龄和性别匹配的非大麻暴露受试者，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级指标。我们假设：1）在大麻暴露的受试者中，灰质体积相对于白色物质体积的比例将较低。2)多个区域的谷氨酸盐和肌醇（神经胶质标志物）浓度降低。3)皮质醇增加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，以成功成为一名独立的研究人员，致力于研究大脑在大脑仍在成熟的关键青少年时期对大麻暴露的反应。

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.