The impact of marijuana use on brain and cognitive function in HIV-infected patients

项目总结/摘要 这一修改后的R03提案是为一个NIDA赞助的艾滋病科学跟踪奖的研究过渡（A- START; PA-15 - 290）。A-START计划的主要目标是支持新的和早期的职业生涯 艾滋病毒/艾滋病药物滥用研究领域的调查人员，特别是那些目前 该计划的重点是药物滥用或艾滋病毒/艾滋病，现在谁希望扩大他们的计划和研究 这两个领域的交集。当前提案的PI是一名早期职业调查员， 2014年8月，第一个R01奖授予了一项多模式神经影像学研究，该研究探讨了艾滋病毒感染如何调节 与年龄相关的认知能力下降从那以后，他得到了一份行政补充，以扩大招生 研究R01项目中的性别差异，并作为合作伙伴参与了其他成功的赠款， 调查员PI坚定地致力于神经艾滋病研究的职业生涯，并通过A-START将 将他的研究计划扩展到艾滋病毒/艾滋病药物滥用的神经生物学和神经心理学， 长期关注药物滥用如何影响HIV相关神经认知功能障碍的发生率和严重程度 紊乱这类疾病是艾滋病最常见的神经系统并发症， 估计在所有艾滋病毒感染者中占35 - 70%，针对此类合并症的研究 艾滋病研究办公室将其确定为最优先事项（见NOT-OD-15 - 137）。 该项目的主要研究目标是量化独特的神经心理学和神经生物学 艾滋病毒感染者长期滥用大麻的后果。为此，我们将从人口统计学角度研究- 匹配HIV感染者和未感染者的重度、轻度和非大麻使用者。所有参与者将 接受神经心理学测试、高分辨率结构神经成像和动态功能成像 脑磁图（MEG）脑磁图是一种新兴的方法，直接量化神经生理 活动，并可以产生高空间精度和毫秒级时间分辨率的功能图。数据 将通过PI的R01项目收集HIV感染者和未感染者的轻度和非使用者群体， 它使用相同的神经心理学和成像方法，但认为大量使用是一种排斥， 的搜索.重要的是，只有四项研究检查了大麻滥用对认知功能的影响， 这些研究报告了混合的结果。此外，迄今为止还没有研究评估大脑 在这一领域的结构或功能。因此，艾滋病病毒感染者滥用大麻的后果依然存在 很大程度上是未知的，这是特别令人担忧的，因为我们进入了大麻合法化的时代。总之，这 A-START项目将：（a）提供有关艾滋病毒相关的神经影像学和神经心理学数据， 神经认知障碍可能受到慢性大麻使用的影响，（B）对是否 神经系统并发症的严重程度与大麻消费的程度（重对轻）有关， 及（c）作为主要研究员开始有关爱滋病病毒/爱滋病的药物滥用研究的跳板。

Project Summary/Abstract This amended R03 proposal is for a NIDA-sponsored, AIDS-Science Track Award for Research Transition (A- START; PA-15-290). The primary goal of the A-START program is to support the entry of new and early career investigators into the area of drug abuse research in HIV/AIDS, particularly those whose current research program focuses on either drug abuse or HIV/AIDS, and who now wish to expand their program and study the intersection of these two areas. The PI of the current proposal is an early career investigator who received his first R01 award in August 2014 for a multimodal neuroimaging study examining how HIV-infection modulates age-related cognitive decline. Since then, he has received an administrative supplement to expand enrollment and examine sex differences in the R01 project, and been involved in other successful grants as a co- investigator. The PI is strongly committed to a career in neuroAIDS research, and through an A-START will expand his research program into the neurobiology and neuropsychology of drug abuse in HIV/AIDS, with a long-term focus on how substance abuse affects the incidence and severity of HIV-associated neurocognitive disorders. Such disorders are the most common neurological complication of HIV disease, with prevalence estimates ranging from 35-70% of all HIV-infected patients, and research targeting such comorbidities has been identified as a top priority by the Office of AIDS Research (see NOT-OD-15-137). The primary research goals of this project are to quantify the unique neuropsychological and neurobiological consequences of chronic marijuana abuse in HIV-infected patients. To this end, we will study demographically- matched groups of HIV-infected and uninfected heavy, light, and non-users of marijuana. All participants will undergo neuropsychological testing, high-resolution structural neuroimaging, and dynamic functional imaging with magnetoencephalography (MEG). MEG is an emerging method that directly quantifies neurophysiological activity and can produce functional maps with high spatial precision and millisecond temporal resolution. Data for the HIV-infected and uninfected light and non-user groups will be collected through the PI’s R01 project, which uses the same neuropsychological and imaging methods, but considers heavy use to be an exclusion criteria. Importantly, only four studies have examined the impact of marijuana abuse on cognitive function in HIV-infected patients, and these studies reported mixed results. Further, no study to date has evaluated brain structure or function in this area. Thus, the consequences of marijuana abuse in HIV-infected patients remain largely unknown, which is especially concerning as we enter an era of marijuana legalization. In summary, this A-START project will: (a) provide seminal neuroimaging and neuropsychological data on how HIV-associated neurocognitive disorders may be affected by chronic marijuana use, (b) contribute novel insight into whether the severity of neurological complications connects with the extent of marijuana consumption (heavy vs. light), and (c) serve as a springboard for the PI to begin drug abuse research in HIV/AIDS.