ACUTE MARIJUANA EFFECTS ON REGIONAL CEREBRAL BLOOD FLOW

描述：(申请人摘要) 众所周知，吸食大麻会严重损害人类认知的各个方面， 急性改变全局和局部脑血流量(RCBF)，并导致 长期使用者中更轻微但永久性的认知功能障碍。 然而，人们对大脑认知功能的变化知之甚少 是由吸食大麻引起的。本项目调查急性rCBF 吸食大麻引起的认知功能障碍及相关变化 偶尔和长期使用这种物质的人。 用[150]水的正电子发射断层扫描(PET)将被用于测量 完成注意和记忆任务的志愿者的rCBF 之前的研究表明，吸食大麻会产生强烈的影响。 还将获得高分辨率磁共振(MR)图像，用于 每个受试者。MR地标将用于放置共同配准的PET图像 到立体定位坐标空间进行图像减影和统计 映射分析。具体的假设也将通过测量rCBF来检验 在追踪MR图像的感兴趣区域内。 要使用的特定PET激活范例来自于 我们之前已经开发了研究注意力和记忆的方法。我们 因此对这些任务激活的大脑区域有一定的了解 在精神分裂症患者中观察到正常和异常的rCBF模式 认知障碍。 使用双盲设计的初步研究将提供基本的定量 关于大麻在rCBF上的时间进程和定位的信息。 两项研究随后将使用双盲设计，偶尔使用 在PET成像过程中，大麻执行注意力和记忆任务。一 进一步的研究将评估吸食大麻与吸食大麻的急性影响 长期吸食大麻的人服用安慰剂以测量rCBF 与我们小组发现的记忆缺陷相关的变化 这样的人。 我们的普遍假设是，吸食大麻会减弱 正常认知特征的rCBF的任务特异性模式 功能。也就是说，激活区域在空间上将更小 大麻后的程度和程度较低，与 认知能力较差。我们假设这种衰减将是 在长期吸食大麻的人中，这一比例明显更高。更具体 将对注意力和记忆任务的地区性假设进行测试。 这些研究将是第一次提供有关大脑的信息 与急性但严重的认知损害相关的机制 通过在临时吸食者中吸食大麻。这也将是第一项研究 提供有关rCBF和认知功能的急性变化的信息 吸食大麻引起的功能在慢性疾病后变得更加严重 使用这种物质。

DESCRIPTION: (Applicant's Abstract) Smoking marijuana is known to acutely impair aspects of human cognition, to acutely change global and regional cerebral blood flow (rCBF), and to cause more subtle but permanent cognitive dysfunction in long-term users. However, little is known about changes in the brain's cognitive functions that are caused by smoking marijuana. This project investigates acute rCBF changes and associated cognitive dysfunction caused by smoking marijuana in both occasional and chronic users of the substance. Positron Emission Tomography (PET) with [15O] water will be used to measure rCBF in volunteer subjects performing attention and memory tasks that previous research has shown to be acutely effected by smoking marijuana. High resolution magnetic resonance (MR) images will also be obtained for each subject. MR landmarks will be used to place co-registered PET images into stereotaxic coordinate space for image subtraction and statistical mapping analyses. Specific hypotheses will also be tested by measuring rCBF within regions of interest traced upon the MR image. The specific PET activation paradigms to be used are drawn from those that we have previously developed to investigate attention and memory. We therefore have knowledge of brain regions activated by these tasks in normals, and abnormal rCBF patterns observed in schizophrenic patients with cognitive impairment. An initial study using a double-blind design will provide basic quantitative information about the time course and localization of marijuana on rCBF. Two studies will then use a double-blind design with occasional users of marijuana performing attention and memory tasks during PET imaging. One further study will assess the acute effects of smoking marijuana versus placebo in individuals who are chronic users of marijuana to measure rCBF changes associated with the deficits in memory that our group has found in such individuals. Our general hypothesis is that smoking marijuana will attenuate the task-specific pattern of rCBF that is characteristic of normal cognitive function. That is, that areas of activation will be smaller in spatial extent and lower in magnitude following marijuana, in conjunction with poorer cognitive performance. We hypothesize that this attenuation will be significantly greater in long-term users of marijuana. More specific regional hypotheses will be tested for the attention and memory tasks. These studies will be the first to provide information about the brain mechanisms associated with the acute but severe cognitive impairment caused by smoking marijuana in casual users. It will also be the first study to provide information about whether the acute changes in rCBF and cognitive function caused by smoking marijuana become more severe following chronic use of this substance.