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

描述(由申请人提供)：大麻，或大麻，是世界上最常用的非法药物，其滥用比率在过去25年中有所上升。事实上，在美国，与大麻接触有关的疾病患者的比例是其他任何非法药物患者的两倍。使用水平的增加主要发生在青春期和青春期，从公共卫生的角度来看，这一点令人担忧，因为这也是神经发育的关键时期。这一事实进一步强调了这种恐惧 大麻可能成为一种入门药物，因为它的使用可能使个人容易滥用其他非法药物。此外，大麻的效力(β-9-四氢大麻酚(？9-THC)的浓度)在美国现在超过10%(1983年为4%)，这可能会对正常的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，彻底了解其对神经功能的长期影响至关重要。大麻和相关的植物大麻素通过激活中枢大麻素受体(CB1R)发挥作用。现在公认的是，反复接触大麻会导致耐受性、依赖性的发展，并在停止使用时出现戒断综合征。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。静息状态默认模式网络和“任务积极”控制网络可能依赖于一个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，本研究的目的是考察长期使用大麻、急性戒断和持续戒断对默认模式和控制脑网络的影响。将使用功能磁共振成像(FMRI)评估大麻依赖者在基线(照常吸烟)、短暂(48小时)确认戒烟(最有可能发生大麻戒断)和长期(4周)确认戒断后的默认模式网络和控制网络。健康对照个体的样本也将被评估。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，并将为神经网络在积极使用大麻、戒断和长期戒断过程中的地位和功能提供新的线索。

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.