The Effect of Cannabis Use on Human Cerebellar Function

大麻使用对人类小脑功能的影响

• 批准号: 7500650
• 负责人: Sharlene D Newman
• 金额: $ 20.73万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7500650
• 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

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，或大麻，是美国最常用的非法药物。青少年和青年期吸毒水平增加，从公共卫生角度来看，这是一个令人关切的问题，因为这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，因此大麻可能成为一种入门药物，这一事实进一步突出了这种担心。虽然众所周知，大麻中的活性成分-9-四氢大麻酚（THC）会导致认知功能异常，如短期记忆和注意力，但很少有数据研究大麻使用对小脑功能状态的影响，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）和手指敲击的异常。此外，将使用磁共振成像（MRI）确定这些缺陷的结构相关性评估。据推测，在EBC范式大麻用户将表现出较差的学习性能（更少和更差的时间条件反射）相比，控制。在有节奏的手指敲击任务期间，预测大麻使用者将表现出增加的敲击可变性和增加的敲击速率。据预测，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减少，并且这些体积变化将与EBC和节奏手指敲击性能相关。最后，据推测，EBC，手指敲击和小脑体积的缺陷将与大麻使用的数量和长度相关，包括THC代谢物的尿液水平。总之，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。

项目成果

Examining the effects of former cannabis use on cerebellum-dependent eyeblink conditioning in humans.

检查以前使用大麻对人类小脑依赖性眨眼调节的影响。

• DOI: 10.1007/s00213-011-2556-1
• 发表时间: 2012
• 期刊: Psychopharmacology
• 影响因子: 3.4
• 作者: Steinmetz,AdamB;Edwards,ChadR;Vollmer,JenniferM;Erickson,MollyA;O'Donnell,BrianF;Hetrick,WilliamP;Skosnik,PatrickD
• 通讯作者: Skosnik,PatrickD

Cerebellar-dependent learning as a neurobehavioral index of the cannabinoid system.

小脑依赖性学习作为大麻素系统的神经行为指标。

• DOI: 10.1615/critrevneurobiol.v19.i1.30
• 发表时间: 2007
• 期刊: Critical reviews in neurobiology
• 作者: Edwards,ChadR;Skosnik,PatrickD
• 通讯作者: Skosnik,PatrickD

Striatal D(2)/D(3) receptor availability is inversely correlated with cannabis consumption in chronic marijuana users.

• DOI: 10.1016/j.drugalcdep.2012.07.016
• 发表时间: 2013-02-01
• 期刊: DRUG AND ALCOHOL DEPENDENCE
• 影响因子: 4.2
• 作者: Albrecht, Daniel S.;Skosnik, Patrick D.;Vollmer, Jennifer M.;Brumbaugh, Margaret S.;Perry, Kevin M.;Mock, Bruce H.;Zheng, Qi-Huang;Federici, Lauren A.;Patton, Elizabeth A.;Herring, Christine M.;Yoder, Karmen K.
• 通讯作者: Yoder, Karmen K.