Acute Marijuana Effects on Regional Cerebral Blood Flow

描述（由申请人提供）：本项目寻求持续资助，以探索急性和慢性大麻使用对区域脑血流量（rCBF）和认知功能的影响。增加对大麻对人类大脑影响的了解具有重要的公共卫生意义，因为它是美国最常用的非法药物（目前估计，在美国，超过700万人每周或更频繁地使用大麻）。在经历了20世纪70年代末和80年代的下降之后，20世纪90年代初，青少年吸食大麻的流行率飙升，并一直保持在令人不安的高位，重新引发了对潜在健康风险的担忧。在最初的资助期内，该项目的具体目标是：1)研究偶尔吸食MJ的大脑系统中调节认知功能的rCBF变化，以及2)确定定期、长期（即慢性）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得到了重复。吸食大麻导致前脑腹侧广阔区域rCBF增加，包括眶额叶皮质、前扣带、脑岛和颞极以及小脑。减少的rCBF持续出现在枕叶皮层，也在听觉皮层，但以更依赖于任务的方式。我们发现，在听觉注意力任务中，吸烟MJ对行为或激活模式的影响相对较小。然而，一组偶尔使用的人在记忆任务上的表现受到损害，rCBF也发生了显著变化。长期服用者在吸烟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rCBF差异，这与服用安慰剂和MJ的临时组不同。

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.