Reply to the comment on ‘Melatonin as a hypnotic: Con’

Abstract

We agree that the soporific effects of melatonin are subtle, however, Dr Zhdanova’s review and reply to our commentary both fail to consider the fact that previous melatonin studies have been unable to reproduce anything like a natural dose, timing, and profile at the requisite site of action, compared with its endogenous nocturnal secretion. The whole premise of her review thus relies on the likely untestable hypothesis that exogenous melatonin acts like endogenous melatonin. Even the few studies that have attempted to reproduce ‘endogenous’ levels by intravenous administration were still conducted during the day when endogenous production was basal. At the very least, that there are time-of-day effects suggest that sensitivity to administered daytime melatonin at its site(s) of action is different to that during the phase of endogenous nocturnal production. Specifically, daytime injection of melatonin to normal nocturnal levels in the blood and saliva of young adults produces significant thermoregulatory changes without subjective soporific effects. 1 Sus