Default Mode and Control Brain Networks in Cannabis Dependence, and Abstinence

大麻依赖和禁欲中的默认模式和控制大脑网络

• 批准号: 8583789
• 负责人: PATRICK David SKOSNIK
• 金额: $ 21.29万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8583789
• 关键词: Abstinence; Acute; Adolescence; Applications Grants; Back; Biological Neural Networks; Brain; Budgets; Cannabinoids; Cannabis; Cannabis Smoking; Cannabis sativa plant; Chronic; Cognitive; Cognitive deficits; Consumption; Data; Dependence; Development; Disease; Down-Regulation; Endocannabinoids; Equilibrium; Exhibits; Exposure to; Fright; Functional Magnetic Resonance Imaging; Funding; Glutamates; Hour; Human; Illicit Drugs; Image; Image Analysis; Individual; Light; Long-Term Effects; Magnetic Resonance Imaging; Marijuana; Marijuana Dependence; Measures; Medial; National Institute of Drug Abuse; Neuraxis; Neurobiology; Neurocognition; Neurophysiology - biologic function; Performance; Pharmaceutical Preparations; Play; Positron-Emission Tomography; Prefrontal Cortex; Property; Public Health; Residual state; Rest; Sampling; Seeds; Self Perception; Short-Term Memory; Smoking; Study Section; Substance Withdrawal Syndrome; System; Tetrahydrocannabinol; Time; United States; Withdrawal; base; blood oxygen level dependent; cannabinoid receptor; critical period; design; endogenous cannabinoid system; information processing; innovation; mind control; neurodevelopment; neuroimaging; neurophysiology; neurotransmission; novel; operation; public health relevance; receptor; relating to nervous system; young adult

DESCRIPTION (provided by applicant): Marijuana, or Cannabis sativa, is the most commonly used illicit drug worldwide, and rates of its abuse have increased during the past twenty-five years. In fact, in the United States, individuals with disorders related to cannabis exposure are two times higher than for any other illicit drug. Increased levels of use primarily 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. In addition, the potency of cannabis (concentration of delta-9-tetrahydrocannabinol (? 9-THC)), is now exceeding 10% in the U.S. (compared to 4% in 1983), which could have unforeseen consequences for normal brain function. Given the vast number of individuals who consume cannabis on a regular basis, a thorough understanding of its long-term effects on neural function is vitally important. Cannabis and associated phytocannabinoids exert their effects through the activation of central cannabinoid receptors (CB1R). It is now well-established that repeated exposure to cannabis results in the development of tolerance, dependence, and a withdrawal syndrome upon cessation of use. Long-term cannabinoid exposure also induces a decrease in the number of CB1Rs. However, the functional implications of these changes remain unclear. The resting-state default mode network and "task-positive" control network may be dependent on an intact endocannabinoid system, which could be compromised by heavy cannabis use. Therefore, the purpose the proposed study is to examine the effects of chronic cannabis use, acute withdrawal, and sustained abstinence on default mode and control brain networks. Functional magnetic resonance imaging (fMRI) will be used to evaluate the default mode network and control network in cannabis-dependent individuals at baseline (smoking as usual), following brief (48 hour) confirmed abstinence (when cannabis withdrawal is most likely to occur), and after prolonged (4 weeks) confirmed abstinence. A sample of healthy control individuals will also be assessed. It is anticipated that data from this study will elucidate the neurobiological consequences of chronic cannabis consumption and its effect on brain function, and will shed new light on the status and function of neural networks during active cannabis use, withdrawal, and prolonged abstinence.

描述（由申请人提供）：大麻或大麻Sativa是全球最常用的非法药物，其滥用率在过去的二十五年中有所提高。实际上，在美国，与大麻暴露有关的疾病的个体是任何其他非法药物的两倍。利用水平的提高主要发生在青春期和成年期间，这是从公共卫生的角度关注的，因为这也是神经发育的关键时期。事实进一步强调了这种恐惧 该大麻可以用作门户药物，因为它的使用可能会使个体容易滥用其他非法药物。此外，在美国，大麻的效力（Delta-9-四氢大麻酚的浓度（？9-THC））现在超过10％（相比之下，1983年为4％），这可能会对正常脑功能产生不可预见的后果。鉴于定期食用大麻的人数大量的人对其对神经功能的长期影响的彻底了解至关重要。大麻和相关的植物大麻素通过激活中央大麻素受体（CB1R）发挥作用。现在，重复接触大麻会导致耐受性，依赖性和戒断综合征在停止使用后的发展。长期大麻素的暴露也会导致CB1RS数量减少。但是，这些变化的功能含义尚不清楚。静止状态默认模式网络和“任务阳性”控制网络可能取决于完整的内源性内源性系统，该系统可能会因大麻使用而损害。因此，拟议的研究的目的是检查慢性大麻使用，急性戒断和持续戒酒对默认模式和控制脑网络的影响。功能磁共振成像（fMRI）将用于评估大麻依赖性个体（如往常一样吸烟）的默认模式网络和控制网络，此后经过短暂的（48小时）确认的节制（最有可能发生大麻的情况），以及延长（4周）确认了戒烟。还将评估健康对照者的样本。可以预料，这项研究的数据将阐明慢性大麻消耗及其对脑功能的影响的神经生物学后果，并将在主动大麻使用，戒断和长期戒酒期间对神经网络的状态和功能进行新的启示。