Efficacy of melatonin treatment in a phase advance model of insomnia

褪黑激素是松果体在夜间产生的一种荷尔蒙。它的释放时间是受控制的 通过昼夜节律计时系统。它的计时可以通过暴露在光中通过 从眼睛到视交叉上核的多突触通路，也就是生物钟。 据报道，外源性褪黑素补充剂对人类有两种作用：一种催眠作用 (促进睡眠)和时间生物学(重置昼夜节律)，从而影响这两个 相互作用以调节睡眠和清醒的神经生物系统。褪黑激素补充剂有 据报道，它是治疗昼夜节律睡眠障碍的有效方法，包括轮班工作 许多盲人遭受睡眠障碍、时差反应、睡眠延迟综合症和睡眠障碍。 个人。然而，在最近的一项荟萃分析中，这些报告中的绝大多数被排除在外 因为它们不是随机对照试验。结论是褪黑素不是 对时差和倒班工作相关的睡眠抱怨有效。鉴于普遍存在的， 不加控制地、非处方地使用褪黑激素治疗一般的睡眠症状 在人群中，褪黑素的随机对照试验对于评估其疗效至关重要。 一过性失眠。 目前的提案将在一个阶段测试褪黑素的计时生物效应和促进睡眠的效果 失眠模型的研究进展。受试者将在服用褪黑激素或安慰剂之前服用 计划的睡眠时段提前了几个小时，模拟了向东旅行。在……下面 这些条件、低的睡眠压力和生物钟的计时使睡眠变得特别 很难。我们将测量睡眠和由昼夜节律控制的多种生理节律 褪黑素或安慰剂给药，并使用精确的分析方法来确定 褪黑素对睡眠和人类昼夜节律系统的影响。这项研究将提供重要的 关于褪黑素作用机制的信息，这将是褪黑素使用的关键 作为一种治疗昼夜节律睡眠障碍的药物。

Melatonin is a hormone produced by the pineal gland at night. The timing of its release is controlled by the circadian timing system. Its timing can be suppressed or reset by exposure to light through a multisynaptic pathway from the eye through the suprachiasmatic nucleus, the master circadian clock. Exogenous melatonin supplementation has been reported to act in two ways in humans: as a soporific (sleep-promoting) and a chronobiotic (to reset circadian phase), thus affecting both of the neurobiologic systems that interact to regulate sleep and wakefulness. Melatonin supplements have been reported to be an effective treatment for circadian rhythm sleep disorders, including shift work dyssomnia, jet-lag, delayed sleep phase syndrome, and sleep disruption suffered by many blind individuals. However, in a recent meta-analysis, the vast majority of these reports were excluded because they were not randomized controlled trials. The conclusion was that melatonin is not efficacious for sleep complaints associated with jetlag and shift work. In view of the widespread, uncontrolled, over-the-counter use of melatonin for treating sleep complaints in the general population, a randomized controlled trial of melatonin is essential to evaluate efficacy in treatment of transient insomnia. The current proposal will test the chronobiotic and sleep promoting effects of melatonin in a phase advance model of insomnia. Subjects will be administered either melatonin or placebo before a scheduled sleep episode which is advanced by several hours, simulating eastward travel. Under these conditions, low sleep pressure and the timing of the circadian clock make sleep particularly difficult. We will measure sleep and multiple physiologic rhythms controlled by the circadian after melatonin or placebo administration, and use precise analytic methods to determine the impact of melatonin on sleep and the human circadian timing system. This study will provide important information regarding the mechanism of action of melatonin that will be critical for the use of melatonin as a treatment for circadian rhythm sleep disorders.