The Effect of Cannabis Use on Human Cerebellar Function

描述（由申请人提供）：大麻，或大麻，是美国最常用的非法药物。青少年和青年时期的使用水平增加，从公共卫生的角度来看，这是令人关切的，因为这些时期也是神经发育的关键时期。由于大麻的使用可能使个人易于滥用其他非法药物，大麻可能成为入门毒品，这一事实进一步强调了这种担忧。众所周知，大麻中的活性成分-9-四氢大麻酚（THC）会导致短期记忆和注意力等认知功能异常，但关于大麻使用对小脑功能状态影响的数据却很少，小脑是一种充满大麻素受体的神经定时结构。因此，当前提案的总体目标是检查当前大麻使用者是否表现出小脑介导的经典眨眼条件反射（EBC）和手指节拍的异常。此外，这些缺陷的结构相关性评估将使用磁共振成像（MRI）来确定。假设在EBC范式中，与对照组相比，大麻使用者将表现出较差的学习表现（更少和更多的不良时间条件反应）。在有节奏的手指敲击任务中，预测大麻使用者将表现出更高的敲击变异性和更高的敲击率。研究还预测，由于长期内源性大麻素代偿机制，慢性大麻使用者将表现出小脑体积的减少，这些体积的变化将与EBC和手指敲击的节奏表现相关。最后，假设EBC的缺陷、有节奏的手指敲击和小脑体积将与大麻使用的数量和长度相关，包括尿中四氢大麻酚代谢物的水平。综上所述，来自这些研究的数据将进一步加深我们对大麻素系统的理解，这将有助于阐明最常用的滥用药物之一的作用机制。项目的叙述

DESCRIPTION (provided by applicant): Marijuana, or Cannabis sativa, is the most commonly used illicit drug in the United States. Increased levels of use occur during adolescence and young adulthood, which is of concern from a public health perspective, since these are also critical periods of neural development. This fear is further underscored by the fact that cannabis may act as a gateway drug, since its use may predispose individuals to abuse other illicit drugs. While it is well known that the active ingredient in cannabis, -9-tetrahydrocannabinol (THC) causes abnormalities in cognitive functions such as short-term memory and attention, there are a paucity of data examining the effect of cannabis use on the functional state of the cerebellum, a neural timing structure that is replete with cannabinoid receptors. Therefore, the overall aim of the current proposal is to examine whether current cannabis users demonstrate abnormalities in cerebellar-mediated classical eye blink conditioning (EBC) and paced finger tapping. In addition, assessments of the structural correlates of these deficits will be determined using magnetic resonance imaging (MRI). It is hypothesized that during the EBC paradigm cannabis users will demonstrate poorer learning performance (less and more poorly timed conditioned responses) as compared to controls. During the paced finger tapping tasks, it is predicted that cannabis users will exhibit increased tapping variability and increased tapping rates. It is also predicted that chronic cannabis users will exhibit decreased cerebellar volumes due to long-term endocannabinoid compensatory mechanisms, and that these volumetric changes will correlate with EBC and paced finger tapping performance. Finally, it is hypothesized that deficits in EBC, paced finger tapping, and cerebellar volume will correlate with the amount and length of cannabis use, including urinary levels of THC metabolites. Taken together, data from these studies will further our understanding of the cannabinoid system, which will help elucidate the mechanism of action of one of the most commonly used drugs of abuse.Project Narrative