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

项目摘要/摘要 这项修改后的R03提案是为了设立由NIDA赞助的艾滋病-科学轨道研究过渡奖(A- 开始；PA-15-290)。A-Start计划的主要目标是支持新职业和早期职业的进入 艾滋病毒/艾滋病药物滥用研究领域的调查员，特别是那些目前研究 该计划的重点是药物滥用或艾滋病毒/艾滋病，他们现在希望扩大他们的计划，研究 这两个区域的交叉点。目前提案的PI是一名早期职业调查员，他收到了他的 2014年8月，首次获得R01奖，表彰一项研究艾滋病毒感染如何调节的多模式神经成像研究 与年龄相关的认知衰退。从那时起，他就收到了扩大招生规模的行政补助 并在R01项目中检查性别差异，并作为联合 调查员。PI坚定地致力于神经艾滋病研究的事业，并通过A-Start将 将他的研究项目扩展到艾滋病毒/艾滋病药物滥用的神经生物学和神经心理学领域， 长期关注药物滥用如何影响艾滋病毒相关神经认知的发生率和严重程度 精神错乱。这种疾病是艾滋病毒疾病最常见的神经系统并发症， 据估计，所有艾滋病毒感染患者的比例从35%到70%不等，针对这种并存的研究已经 被艾滋病研究办公室确定为最优先事项(见NOT-OD-15-137)。 这个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进行研究- 将感染艾滋病毒的人与未感染的人、吸食大麻的人、吸食少量大麻的人和不吸食大麻的人进行配对。所有参与者将 接受神经心理测试、高分辨率结构神经成像和动态功能成像 脑磁图(MEG)检查。脑磁图是一种直接量化神经生理学的新兴方法。 并可以生成具有高空间精度和毫秒时间分辨率的功能地图。数据 对于感染和未感染艾滋病毒的用户组，将通过PI的R01项目收集光和非用户组， 它使用相同的神经心理学和成像方法，但认为过度使用是一种排除 标准。重要的是，只有四项研究考察了滥用大麻对老年人认知功能的影响 这些研究报告的结果好坏参半。此外，到目前为止还没有研究评估大脑 这一地区的结构或功能。因此，艾滋病毒感染者滥用大麻的后果仍然存在。 这在很大程度上是未知的，随着我们进入大麻合法化时代，这一点尤其令人担忧。总而言之，这是 A-START项目将：(A)提供有关艾滋病毒如何与 神经认知障碍可能会受到长期使用大麻的影响，(B)对是否有新的洞察力 神经系统并发症的严重程度与吸食大麻的程度(重度与轻度)有关， 以及(C)作为非政府组织开始艾滋病毒/艾滋病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.