Effect of inducing nocturnal serum melatoninconcentrations in daytime on sleep, mood, body temperature, andperformance.

We examined effects of very low doses of melatonin(0.1-10 mg, orally) or placebo, administered at 1145 h, on sleep latency andduration, mood, performance, oral temperature, and changes in serum melatoninlevels in 20 healthy male volunteers. A repeated-measure double-blind Latinsquare design was used. Subjects completed a battery of tests designed to assessmood and performance between 0930 and 1730 h. The sedative-like effects ofmelatonin were assessed by a simple sleep test: at 1330 h subjects were asked tohold a positive pressure switch in each hand and to relax with eyes closed whilereclining in a quiet darkened room. Latency and duration of switch release,indicators of sleep, were measured. Areas under the time-melatonin concentrationcurve varied in proportion to the different melatonin doses ingested, and the0.1- and 0.3-mg doses generated peak serum melatonin levels that were within thenormal range of nocturnal melatonin levels in untreated people. All melatonindoses tested significantly increased sleep duration, as well as self-reportedsleepiness and fatigue, relative to placebo. Moreover, all of the dosessignificantly decreased sleep-onset latency, oral temperature, and the number ofcorrect responses on the Wilkinson auditory vigilance task. These data indicatethat orally administered melatonin can be a highly potent hypnotic agent; theyalso suggest that the physiological increase in serum melatonin levels, whichoccurs around 2100 h daily, may constitute a signal initiating normal sleeponset.