The Effect of Cannabis Use on Human Cerebellar Function

大麻使用对人类小脑功能的影响

基本信息

批准号：
7389798
负责人：
PATRICK David SKOSNIK
金额：
$ 17.63万
依托单位：
TRUSTEES OF INDIANA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-30 至 2009-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7389798
关键词：
Acute Adolescence Adolescent Adult Agonist Air American Anterior Architecture Area Attention Auditory Behavioral Biochemical Biological Assay Blinking Brain CNR1 gene Cannabinoids Cannabis Cannabis sativa plant Carboxylic Acids Cell Communication Cerebellar cortex structure Cerebellum Chronic Clinical Cognition Computer information processing Concept Formation Condition Conditioned Stimulus Cytoplasmic Granules DSM-IV Data Disease Disruption Down-Regulation Drug usage Drug user Electrodes Electroencephalography Endocannabinoids Exhibits Eye Female Fiber Fingers Fright Future Gait Glutamates Human Illicit Drugs Imaging Techniques Individual Individual Differences Interview Intoxication Knowledge Learning Left Length Lobule Magnetic Resonance Imaging Marijuana Mass Chromatography Measures Mediating Methodology Methods Motor Movement Nature Neurons Neuropsychological Tests Neurosciences Numbers Operative Surgical Procedures Outcome Paranoia Patient Self-Report Pattern Perceptual distortions Performance Personal Satisfaction Pharmaceutical Preparations Play Posture Preclinical Drug Evaluation Presynaptic Terminals Procedures Process Property Psychophysiology Public Health Purkinje Cells Questionnaires Rate Reaction Time Reading Research Role Running Short-Term Memory Spectrometry Stimulus Structure Substance Abuse Detection Synapses System Techniques Testing Tetrahydrocannabinol Thinking Time Time Perception Translational Research United States Urine addiction base behavior measurement cannabinoid receptor classical conditioning cognitive function conditioning critical developmental period granule cell inclusion criteria indexing interest male neurodevelopment neuroimaging novel presynaptic psychologic receptor relating to nervous system response theories translational approach urinary young adult

项目摘要

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

描述（由申请人提供）：大麻或 Cannabis sativa 是美国最常用的非法药物。使用水平的增加发生在青春期和成年早期，从公共卫生的角度来看，这是令人担忧的，因为这些也是神经发育的关键时期。大麻可能充当入门毒品，因为使用大麻可能会使个人滥用其他非法药物，这一事实进一步加剧了这种担忧。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，但目前缺乏数据来检验大麻的使用对大脑功能状态的影响。小脑是一种充满大麻素受体的神经计时结构。因此，当前提案的总体目标是检查当前的大麻使用者是否在小脑介导的经典眨眼调节（EBC）和节奏手指敲击方面表现出异常。此外，将使用磁共振成像（MRI）来评估这些缺陷的结构相关性。据推测，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（条件反射越来越少且不合时宜）。在有节奏的手指敲击任务中，预计大麻使用者将表现出增加的敲击可变性和增加的敲击率。据预测，由于长期内源性大麻素补偿机制，长期大麻使用者将表现出小脑体积减少，并且这些体积变化将与 EBC 和节奏手指敲击表现相关。最后，假设 EBC、节奏手指敲击和小脑体积的缺陷将与大麻使用的数量和时间（包括尿液中 THC 代谢物的水平）相关。总而言之，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。项目叙述