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：(改编自申请者摘要)：青少年使用大麻情况 我们社会中的人仍然是一个问题。正是这种非法药物才是 这是当今年轻人最常用的。据估计，全球固定用户超过 一亿人。然而，我们仍然知之甚少。 人类使用它的神经生物学后果。很明显，一个更好的 了解其在人脑中的作用将有助于发展 创新应对大麻使用和滥用增加的方法。在… 目前，大麻在人脑中起作用的功能部位有 人们对此知之甚少。作为人类重大技术进步的结果 脑功能成像，现在可以直接检查 大麻及其对人脑的长期使用。这样做的长期目标是 该项目是为了阐明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 那些与药物的醉人和 自我管理特性及其对认知和知觉的损害 运动行为。这个项目将完全在有经验的人身上进行 大麻吸毒者。功能性磁共振成像(FMRI)将被用作 所有研究中的成像方式。功能磁共振成像是磁共振成像的一种特殊应用 它允许检查大脑的功能活动而不使用 X射线或电离辐射。其出色的时间(秒)和空间(2-4 Mm)分辨率允许在受试者内进行虚拟的实时大脑成像 目前其他非侵入性或微创的设计是不可能的 侵入性手术。该项目有四个具体目标：1)确定 FMRl变化的神经元和非神经元(血管)机制 A9-THC诱导的信号。这将通过使用两个动脉脊椎来实现 基于标记的血流灌注研究，并首次通过Gd-DTPA血容量图。 这些结果将扩大我们对地球动力学的基本理解。 大麻素对脑神经和血管功能的影响及其应用 对目标2、3和4的研究进行分析和解释)至 使用粗体成像进一步量化A9-THC的作用以确定其 人脑内的药效学特性及其在时间上的联系 和强度对观察到的静脉注射的生理和行为行为 ^9-THC。3)测定^9-THC促进脑功能活动的能力 使用知觉-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 长期大量吸食和停止吸食大麻对局部神经元的影响 比较神经元对任务激活和急性药物反应的反应性 挑战作为使用和/或退出的功能。现建议货柜码头处理费 在人类大脑的活动中产生明显的变化，无论是在休息时还是在 在执行认知和知觉-运动任务期间， 可使用fmrl测量血液氧合、流量和体积，它是 进一步假设，这种独特的行为和生理效应 人类中的THC和大麻是由于大脑区域的独特模式造成的 在急性给药后被激活和/或被抑制，并且这些 反应将是具体的剂量和时间。圆满完成 这些研究将增加我们对大麻在 并可能提出新的策略，以应对其在 我们的青春。