The hormone melatonin, produced by the pineal gland, is a sleep facilitator with circadian action. In the normal case, the inner clock in the suprachiasmatic nuclei (SCN) sends an “on” signal to the pineal gland sometime in the evening a couple of hours before we feel ready for sleep, and an “off” signal shortly before we wake up, after which the hormone washes out of the bloodstream and is absent until the following night.

Melatonin also talks back to the SCN, and influences its timing.  This has inspired the use of melatonin tablets to “trick” the inner clock, when it is running late, to shift earlier. In turn, sleep onset shifts earlier, which can help people who are unable to fall asleep in time.  But it is not a sleeping pill: it acts most powerfully taken hours before bedtime in a tiny dose that does not force sleep onset, but rather nudges the circadian clock, and its sleep onset signal, earlier.

It is helpful to think of melatonin administration just like light therapy, but taken at opposite times of day.  In fact, both methods used together form a powerful circadian control signal that can move sleep earlier or later, depending on the sleeper’s goal.

REFERENCES

Books

  • Arendt J. Melatonin and the Mammalian Pineal Gland. Berlin, Springer Verlag, 1994.
  • Czeisler CA, Turek FW (eds.). Melatonin, Sleep, and Circadian Rhythms. Journal of Biological Rhythms 1997;12:707ff.

Reviews

Arendt J. Melatonin and human rhythms. Chronobiology International 2006:23;21-37.
Gordon N. The therapeutics of melatonin: a paediatric perspective. Brain and Development 2000;22:213-217.
Macchi MM, Bruce JN. Human pineal physiology and functional significance of melatonin. Frontiers in Neuroendocrinology 2004;25:177-95.
Scheer FA, Czeisler CA. Melatonin, sleep, and circadian rhythms. Sleep Medicine Reviews 2005;9:5-9.

Studies

Lewy AJ, Wehr TA, Goodwin FK, Newsome DA, Markey SP. Light suppresses melatonin secretion in humans. Science 1980;210:1267-1269.
Lewy AJ, Ahmed S., Latham Jackson JM, Sack RL. Melatonin shifts human circadian rhythms according to a phase-response curve. Chronobiology International 1992:9;380-392.
Jan JE, Hamilton D, Seward N, Fast DK, Freeman RD, Laudon M. Clinical trials of controlled-release melatonin in children with sleep-wake cycle disorders.  Journal of Pineal Research 2000;29:34-39.
Zhdanova IV, Wurtman RJ, Regan MM, Taylor JA, Shi JP, Leclair OU. Melatonin treatment for age-related insomnia. Journal of Clinical Endocrinology and Metabolism 2001;86:4727-4730.
Smits MG, Nagtegaal EE, van der Heijden J, Coenen AM, Kerkhof GA. Melatonin for chronic sleep onset insomnia in children: A randomized placebo-controlled trial. Journal of Child Neurology 2001;16:86-92.
Zhdanova IV, Tucci V. Melatonin, Circadian Rhythms, and Sleep. Current Treament Options in Neurolology 2003;5:225-229.
Mundey K, Benloucif S, Harsanyi K, Dubocovich ML, Zee PC. Phase-dependent treatment of delayed sleep phase syndrome with melatonin. Sleep 2005;28:1271-1278.
Terman M,  Hakala JC, Cooper TB, Bogner RH, Sricharoon K, Terman JS, Macchi MM, Winokur A, Oren DA. Controlled release melatonin in a physiological washout profile: Final report to the Sleep Research Society Foundation, 2007.
Van der Heijden KB, Smits MG, Van Someren EJ, Ridderinkhof KR, Gunning WB. Effect of melatonin on sleep, behavior, and cognition in ADHD and chronic sleep-onset insomnia. Journal of the American Academy of Child and Adolescent Psychiatry 2007;46:233-241.
Burgess HJ, Revell VL, Eastman CI. A three pulse phase response curve to three milligrams of melatonin in humans. Journal of Physiology 2008;586:639-647.