Melatonin entrains free-running blind people according to a physiological dose-response curve

Abstract

The specific circadian role proposed for endogenous melatonin production was based on a study of sighted people who took low pharmacological doses (500 μg) of this chemical signal for the "biological night": the magnitude and direction of the induced phase shifts were dependent on what time of day exogenous melatonin was administered and were described by a phase-response curve that turned out to be the opposite of that for light. We now report that lower (physiological) doses of up to 300 μg can entrain (synchronize) free-running circadian rhythms of 10 totally blind subjects that would otherwise drift later each day. The resulting log-linear dose-response curve in the physiological range a..