Acute Marijuana Effects on Regional Cerebral Blood Flow

大麻对局部脑血流的急性影响

• 批准号: 6905505
• 负责人: Daniel S. O Leary
• 金额: $ 36.88万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6905505
• 关键词: acute disease /disorder; attention; behavior test; behavioral /social science research tag; brain circulation; brain imaging /visualization /scanning; cannabinoids; clinical research; cognition; human subject; magnetic resonance imaging; marijuana abuse; memory disorders; neurochemistry; positron emission tomography; psychological tests; psychomotor reaction time; psychopharmacology; reinforcer; time perception

DESCRIPTION (provided by applicant): This project seeks continuing funding to explore the effects of acute and chronic marijuana use on regional cerebral blood flow (rCBF) and cognitive function. Increased knowledge of marijuana's impact on the human brain has important public health implications since it is the most commonly used illegal drug in the United States (current estimates are that over seven million people use cannabis weekly or more often in the US). Following declines throughout the late 1970s and the 1980s, the prevalence of marijuana use among youth skyrocketed in the early 1990s, and has remained disturbingly high, renewing concerns about potential health risks. The specific aims of the project during the initial funding period were: 1) to study rCBF changes in brain systems mediating cognitive functions that are acutely impaired by smoking MJ in occasional users, and 2) to determine if regular, long-term (i.e., chronic) use alters the acute response of the brain to MJ. We have made a great deal of progress towards achieving these aims. In brief, we found direct effects of MJ that replicated in all four of our initial studies. Smoking marijuana resulted in increased rCBF in an extensive region of the ventral forebrain that included orbital frontal cortex, anterior cingulate, insula, and temporal poles as well as in the cerebellum. Decreased rCBF was consistently found in occipital cortex, and also in auditory cortices, but in a more task-dependent manner. We found that smoking MJ had relatively little effect on behavior, or on the pattern of activation, during an auditory attention task. However, performance on memory tasks was impaired in a group of occasional users, and rCBF was also significantly changed. Chronic users did not show memory impairment after smoking MJ, suggesting that they had developed tolerance to the cognitive effects of the drug, but they did show rCBF differences that differed from the occasional group after both placebo and MJ. The studies proposed here utilize PET with [15O]water and cognitive tasks to assess marijuana's effects on cerebellar-cortical circuitry. We will assess the acute effects of smoking marijuana on cerebellar function in chronic and occasional users during tasks that have been shown to activate the cerebellum in normal volunteers. In addition to standard image subtraction analyses, correlational techniques will assess the "functional connectivity" of the cerebellum with other brain regions. We will also assess cerebellar-cortical circuitry using cognitive tasks that are mediated by ventral forebrain areas that we found to have dramatic increases in rCBF after smoking marijuana. We will also utilize a PET protocol that we recently found to activate reward circuitry to assess the effects of marijuana on these brain regions in chronic and occasional users. Finally, cognitive tasks requiring self-paced timing and other putative cerebellar functions will be used to assess the functional consequences of cerebellar hypoperfusion in chronic users of marijuana.

描述（由申请人提供）：该项目寻求持续资金来探索急性和慢性大麻使用对区域脑血流（RCBF）和认知功能的影响。人们对大麻对人脑的影响的了解增加具有重要的公共卫生影响，因为它是美国最常用的非法药物（目前的估计是，超过700万人每周或在美国使用大麻）。在整个1970年代末和1980年代下降之后，1990年代初期大麻使用率的普遍性，并且对潜在的健康风险仍然令人不安，更新的担忧。该项目在初始资金期间的具体目的是：1）研究脑系统中的RCBF变化，介导了认知功能，而认知功能会因偶尔使用MJ而严重损害，而2）确定常规的长期（即慢性）是否会改变大脑对MJ的急性反应。我们在实现这些目标方面取得了很大的进步。简而言之，我们发现MJ的直接影响在我们所有的四项初始研究中都复制了。吸烟大麻导致腹侧前脑广泛区域的RCBF增加，其中包括轨道额叶皮层，前扣带回，岛状和颞杆以及小脑。 RCBF的减少始终在枕皮层和听觉皮层中发现，但以任务依赖的方式发现。我们发现，在听觉注意任务期间，吸烟MJ对行为或激活模式的影响相对较小。但是，在一组偶尔的用户中，内存任务的性能受到了损害，RCBF也发生了重大变化。慢性使用者在吸烟MJ后没有显示出记忆力障碍，这表明他们已经对药物的认知效应产生了宽容，但他们确实显示出RCBF的差异与安慰剂和MJ后偶尔的组不同。 这里提出的研究利用[15o]水和认知任务的PET评估大麻对小脑皮层电路的影响。我们将在任务中评估吸烟大麻对慢性和偶尔使用者小脑功能的急性影响，这些任务已被证明会激活正常志愿者的小脑。除了标准图像减法分析外，相关技术还将评估小脑与其他大脑区域的“功能连通性”。我们还将使用腹侧前脑区域介导的认知任务来评估小脑皮质回路，我们发现吸烟大麻后RCBF的增加幅度急剧增加。我们还将利用一种宠物协议，该协议最近发现该协议激活奖励电路，以评估大麻对慢性和偶尔用户中这些大脑区域的影响。最后，需要自定进度的时间和其他假定小脑功能的认知任务将用于评估大麻长期使用大麻使用者的小脑灌注不足的功能后果。