EFFECTS OF THC ON REGIONAL BRAIN ACTIVITY : A FMRI STUDY

THC 对区域大脑活动的影响：一项 FMRI 研究

• 批准号: 6378716
• 负责人: ALAN S BLOOM
• 金额: $ 33.64万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-29 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6378716
• 关键词: bioimaging /biomedical imaging; cannabinoids; cardiovascular pharmacology; cerebrovascular system; clinical research; cognition; drug withdrawal; functional magnetic resonance imaging; human subject; marijuana abuse; neuropharmacology; pharmacokinetics; psychomotor function; psychopharmacology

DESCRIPTION: (Adapted from applicant's abstract): The use of marijuana by young people in our society continues to be a problem. It is the illicit drug that is most commonly used by youths today. Estimates of worldwide regular users exceed one hundred million individuals. However we still know little of the neurobiological consequences of its use by humans. It is clear that a better understanding of its actions in the human brain will benefit the development of innovative methods to deal with the increase in marijuana use and abuse. At present, functional sites for the action of marijuana in the human brain are poorly understood. As a result of significant technological advances in human functional brain imaging, it is now possible to directly examine the effects of marijuana and its chronic use on the human brain. The long range goal of this project is to elucidate sites of action A9-tetrahydrocannabinol (THC), the major psychoactive constituent of marijuana, in human brain and to determine those that are mechanistically related to the drug's intoxicating and self-administration properties and its impairment of cognitive and perceptual motor behavior. This project will be conducted entirely on experienced human marijuana users. Functional magnetic resonance imaging (FMRI) will be used as the imaging modality in all studies. fMRI is a specialized application of MRI that permits an examination of functional cerebral activity without the use of X-rays or ionizing radiation. Its excellent temporal (seconds) and spatial (2-4 mm) resolution permits virtual "real time' brain imaging and within subjects designs that are not possible with other current non-invasive or minimally invasive procedures. This project has four specific aims: 1) To determine the neuronal and non-neuronal (vascular) mechanisms underlying the changes in fMRl signal induced by A9-THC. This will be accomplished by using both arterial spin labeling based perfusion studies and first pass Gd-DTPA blood volume mapping. These results will expand our basic understanding of the dynamics of cannabinoid effects on brain neuronal and vascular function and will be applied to the analysis and interpretation of the studies from Aims 2, 3 and 4. 2) To further quantify A9-THC action using BOLD imaging to determine its pharmacodynamic properties within the human brain and to relate them in time and intensity to observed physiological and behavioral actions of intravenous ^9-THC. 3) To determine the ability of ^9-THC to aRer functional brain activity using perceptual-motor and cognitive tasks that activate specific brain regions containing cannabinoid receptors as experimental probes. 4) To determine the effects of heavy, chronic marijuana use and cessation on regional neuronal responsivity by comparing neuronal responses to task activation and acute drug challenge as a function of use and/or withdrawal. It is proposed that THC produces distinct changes in the activity of the human brain, both at rest and during the performance of cognitive and perceptual-motor tasks that are measurable using fMRl measures of blood oxygenation, flow and volume, It is further hypothesized that the unique behavioral and physiological effects of THC and marijuana in humans is due to unique patterns of brain regions activated and/or inhibited following acute drug administration, and that these responses will be both dose and time specific. The successful completion of these studies will increase our knowledge of the locus of marijuana action in humans and may indicate new strategies for dealing with its increasing use in our youth.

描述：（改编自申请人的摘要）：Young使用大麻 我们社会中的人们仍然是一个问题。是非法药物是 今天最常用的年轻人使用。全球常规用户的估计超过 一亿个人。但是我们仍然对 人类使用的神经生物学后果。很明显，更好 了解其在人脑中的行动将有益于 处理大麻使用和滥用的创新方法。在 现在，大麻在人脑中作用的功能部位是 理解不佳。由于人类的显着技术进步的结果 功能性大脑成像，现在可以直接检查 大麻及其在人脑上的长期使用。远距离目标 项目将阐明作用位点A9四氢大麻酚（THC）， 大麻的主要精神活性成分，在人脑中，并确定 那些与药物的醉人和 自我管理的属性及其认知和感知的损害 运动行为。该项目将完全按照经验丰富的人类进行 大麻使用者。功能磁共振成像（fMRI）将用作 所有研究中的成像方式。 fMRI是MRI的专业应用 这允许检查功能性大脑活动，而无需使用 X射线或电离辐射。它极好的时间（秒）和空间（2-4 MM）分辨率允许虚拟“实时”大脑成像和主体内部 其他当前非侵入性或最小的设计是不可能的 侵入性程序。该项目具有四个具体目标：1）确定 FMRL变化的背后的神经元和非神经元（血管）机制 由A9-THC诱导的信号。这将通过使用两种动脉旋转来实现 基于标记的灌注研究和首次通过GD-DTPA血量映射。 这些结果将扩大我们对动态的基本理解 大麻素对脑神经元和血管功能的影响，将应用 分析和解释目标2、3和4。2） 进一步使用粗体成像来量化A9-THC动作以确定其 人脑中的药效学特性并随着时间的推移将其关联 静脉内观察到的生理和行为作用的强度 ^9-thc。 3）确定 ^9-THC对ARER功能性脑活动的能力 使用感知运动和认知任务来激活特定的大脑区域 包含大麻素受体作为实验探针。 4）确定 重型大麻使用和停止对区域神经元的影响 通过比较对任务激活和急性药物的神经元反应的反应性 挑战是使用和/或提款的函数。有人提出THC 在静止和 在执行认知和感知运动任务的过程中 可以使用FMRL测量血液氧合，流量和体积的测量 进一步假设，独特的行为和生理影响 人类中的THC和大麻是由于大脑区域的独特模式 急性药物给药后激活和/或抑制 响应既是剂量又是特定时间的。成功完成 这些研究将增加我们对大麻作用源的了解 人类，可能表明应对其日益使用的新策略 我们的青年。