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: 6662707
• 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 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6662707
• 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）：年轻人使用大麻 我们社会中的人仍然是一个问题。这是非法药物， 这是当今年轻人最常用的方法。据估计，全球经常使用者超过 一亿人。然而，我们仍然知之甚少。 神经生物学的后果。很明显，一个更好的 了解它在人脑中的作用将有助于发展 创新的方法来应对大麻使用和滥用的增加。在 目前，大麻在人脑中作用的功能部位是 不太了解。由于人类的重大技术进步， 功能性脑成像，现在可以直接检查 大麻及其对人类大脑的长期使用。长期目标是 该项目旨在阐明A9-四氢大麻酚（THC）的作用部位， 大麻的主要精神活性成分，在人脑中，并确定 这些机制与药物的致醉作用有关， 自我管理的性质及其对认知和知觉的损害 运动行为该项目将完全由经验丰富的人进行 吸食大麻的人功能性磁共振成像（FMRI）将被用作 所有研究中的成像模式。功能磁共振成像是磁共振成像的一种特殊应用 允许检查功能性大脑活动而不使用 X射线或电离辐射。其出色的时间（秒）和空间（2-4 mm）分辨率允许虚拟的“真实的时间”脑成像 这些设计是目前其他非侵入性或微创技术无法实现的， 侵入性手术该项目有四个具体目标：1）确定 fMR 1变化的神经元和非神经元（血管）机制 由A9-THC诱导的信号。这将通过使用动脉旋转 基于标记的灌注研究和首过Gd-DTPA血容量标测。 这些结果将扩大我们对生物力学的基本理解， 大麻素对脑神经元和血管功能的影响，并将应用于 分析和解释目标2、3和4的研究。2)到 使用BOLD成像进一步量化A9-THC作用，以确定其 药效学特性在人脑内，并将它们及时联系起来 观察到的静脉注射的生理和行为作用的强度 ^9-THC。3)为了确定^9-THC对大脑功能活动的影响， 使用感知运动和认知任务来激活特定的大脑区域 含有大麻素受体作为实验探针。4)确定 重度、慢性大麻使用和停止对局部神经元的影响 通过比较神经元对任务激活和急性药物 质疑作为使用和/或撤回的函数。建议THC 在人类大脑的活动中产生明显的变化，无论是在休息时， 在执行认知和感知运动任务时， 使用fMRI测量血氧、流量和体积是可测量的。 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 急性给药后激活和/或抑制，并且这些 反应将是剂量和时间特异性的。圆满完成 这些研究将增加我们对大麻作用位点的了解， 人类，并可能表明新的战略，以处理其日益增加的使用， 我们的青春