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 Cannabis sativa 是全世界最常用的非法药物，其滥用率在过去二十五年中有所增加。事实上，在美国，患有与大麻接触相关疾病的人是任何其他非法药物的两倍。使用水平的增加主要发生在青春期和成年早期，从公共卫生的角度来看，这值得关注，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 大麻可能会成为一种入门毒品，因为使用大麻可能会使个人滥用其他非法药物。此外，大麻的效力（δ-9-四氢大麻酚 (? 9-THC) 的浓度）目前在美国已超过 10%（1983 年为 4%），这可能会对正常大脑功能产生不可预见的后果。鉴于大量定期吸食大麻的人，彻底了解大麻对神经功能的长期影响至关重要。大麻和相关植物大麻素通过激活中枢大麻素受体（CB1R）发挥作用。现在已经证实，反复接触大麻会导致耐受性、依赖性，并在停止使用后出现戒断综合症。长期接触大麻素也会导致 CB1R 数量减少。然而，这些变化的功能影响仍不清楚。静息态默认模式网络和“任务积极”控制网络可能依赖于完整的内源性大麻素系统，该系统可能会因大量使用大麻而受到损害。因此，拟议研究的目的是检查长期使用大麻、急性戒断和持续戒断对默认模式和控制大脑网络的影响。功能性磁共振成像（fMRI）将用于评估大麻依赖个体在短暂（48小时）确认戒断（最有可能发生大麻戒断时）后基线（照常吸烟）的默认模式网络和控制网络，并在长期（4周）确认禁欲后。还将评估健康对照个体的样本。预计这项研究的数据将阐明长期吸食大麻的神经生物学后果及其对大脑功能的影响，并将为主动使用大麻、戒断和长期禁欲期间神经网络的状态和功能提供新的线索。