Sack R L, Lewy A J, Blood M L, Stevenson J, Keith L D
Department of Psychiatry, School of Medicine, Oregon Health Sciences University, Portland 97201.
J Biol Rhythms. 1991 Fall;6(3):249-61. doi: 10.1177/074873049100600305.
The purpose of this study was to test the phase-shifting and entraining effects of melatonin in human subjects. Five totally blind men were found in a previous study to have free-running endogenous melatonin rhythms. Their rhythms were remarkably stable, so that any deviation from the predicted phase was readily detectable. After determination of their free-running period and phase, they were given exogenous melatonin (5 mg) at bedtime (2200 hr) for 3 weeks, in a double-blind, placebo-controlled trial. The effects on the endogenous melatonin rhythm were assessed at intervals ranging from several days to 2 weeks. Exogenous administration of melatonin phase-advanced their endogenous melatonin rhythms. In three of the subjects, cortisol was shown to be phase-shifted in tandem with the melatonin rhythm. A sixth subject [one of the coauthors (JS)] was previously found to have free-running cortisol and temperature rhythms and was plagued by recurrent insomnia and daytime sleepiness. He had tried unsuccessfully to entrain his rhythms for over 10 years. After he took melatonin (7 mg at 2100 hr), his insomnia and sleepiness resolved. Determination of his endogenous melatonin rhythm after about a year of treatment demonstrated endogenous rhythms that appeared normally entrained. The treatment of blind people with free-running rhythms has many advantages for demonstrating chronobiological effects of hormones or drugs.
本研究的目的是测试褪黑素对人类受试者的相位移动和同步化作用。在先前的一项研究中发现，五名全盲男性具有自由运转的内源性褪黑素节律。他们的节律非常稳定，因此任何与预测相位的偏差都很容易被检测到。在确定他们的自由运转周期和相位后，在一项双盲、安慰剂对照试验中，他们在就寝时间（22:00）服用外源性褪黑素（5毫克），持续3周。在几天到2周的间隔时间内评估对内源性褪黑素节律的影响。外源性给予褪黑素使他们的内源性褪黑素节律提前。在三名受试者中，皮质醇与褪黑素节律同步发生相位移动。第六名受试者[共同作者之一（JS）]先前被发现具有自由运转的皮质醇和体温节律，并饱受复发性失眠和日间嗜睡之苦。他试图使自己的节律同步化超过10年，但未成功。在他服用褪黑素（21:00时7毫克）后，他的失眠和嗜睡症状得到缓解。在大约一年的治疗后对他的内源性褪黑素节律进行测定，结果显示内源性节律似乎正常同步。对具有自由运转节律的盲人进行治疗，对于证明激素或药物的生物钟效应具有许多优势。
