Acute Marijuana Effects on Regional Cerebral Blood Flow

描述(申请人提供)：该项目寻求持续的资金，以探索急性和长期使用大麻对局部脑血流量(RCBF)和认知功能的影响。增加对大麻对人类大脑影响的认识具有重要的公共健康影响，因为它是美国最常用的非法药物(目前估计，美国每周或更频繁地使用大麻的人数超过700万)。在经历了整个20世纪70年代末和80年代的下降之后，大麻在年轻人中的流行率在90年代初飙升，并一直居高不下，这再次引发了人们对潜在健康风险的担忧。该项目在最初的资助期内的具体目标是：1)研究大脑系统中调节因偶尔吸烟MJ而严重受损的认知功能的rCBF变化，以及2)确定经常、长期(即长期)使用MJ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进展。简而言之，我们发现MJ的直接影响在我们最初的四项研究中都是重复的。吸食大麻导致腹侧前脑广泛区域的rCBF增加，包括眼眶额叶皮质、前扣带回、岛叶和颞极以及小脑。在枕叶皮质和听觉皮质，rCBF持续下降，但更多的是以任务依赖的方式。我们发现，在听觉注意任务中，吸烟的MJ对行为或激活模式的影响相对较小。然而，在一组偶尔使用的用户中，记忆任务的性能受到了损害，rCBF也发生了显著变化。长期吸食MJ后没有表现出记忆障碍，这表明他们已经对药物的认知影响产生了耐受性，但他们确实表现出了与偶尔服用安慰剂和MJ后不同的rCBF差异。 这里提出的研究利用带有[150]水的正电子发射计算机断层扫描和认知任务来评估大麻对小脑-皮质回路的影响。我们将评估吸食大麻对慢性使用者和偶尔吸食者的小脑功能的急性影响，这些任务已经被证明激活了正常志愿者的小脑。除了标准的图像减影分析外，相关技术还将评估小脑与其他大脑区域的“功能连接”。我们还将使用由腹侧前脑区域介导的认知任务来评估小脑-皮质回路，我们发现吸食大麻后，腹侧前脑区域的rCBF显著增加。我们还将利用最近发现的激活奖赏回路的PET方案来评估大麻对长期和偶尔吸食大麻的人大脑这些区域的影响。最后，需要自定节奏的时间和其他假定的小脑功能的认知任务将被用来评估长期吸食大麻的人小脑灌流不足的功能后果。

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.