Melatonin shifts human orcadian rhythms according to a phase-response curve

Alfred J. Lewy, Saeeduddin Ahmed, Jeanne M.Latham Jackson, Robert L. Sack

Research output: Contribution to journalArticlepeer-review

653 Scopus citations


A physiological dose of orally administered melatonin shifts circadian rhythms in humans according to a phase-response curve (PRC) that is nearly opposite in phase with the PRCs for light exposure: melatonin delays circadian rhythms when administered in the morning and advances them when administered in the afternoon or early evening. The human melatonin PRC provides critical information for using melatonin to treat circadian phase sleep and mood disorders, as well as maladaptation to shift work and transmeridional air travel. The human melatonin PRC also provides the strongest evidence to date for a function of endogenous melatonin and its suppression by light in augmenting entrainment of circadian rhythms by the light-dark cycle.

Original languageEnglish (US)
Pages (from-to)380-392
Number of pages13
JournalChronobiology International
Issue number5
StatePublished - 1992


  • Circadian phase shifts
  • Circadian phase sleep and mood disorders
  • Dim light melatonin onset (DLMO)
  • Melatonin administration
  • Phase-response curve (PRC)

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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