, Volume 100, Issue 2, pp 222–226 | Cite as

Sleep laboratory investigations on hypnotic properties of melatonin

  • F. Waldhauser
  • B. Saletu
  • I. Trinchard-Lugan
Original Investigations


Melatonin (MLT), a pineal hormone, has some sedative and hypnotic properties. To explore this effect further 20 young, healthy volunteers exposed to artificial insomnia participated in a double-blind, placebo controlled, parallel group design study. They slept in a sleep laboratory for several consecutive nights and were polygraphically monitored and subjected to a battery of psychometric tests and standardized self-report questionnaires each morning. One night all subjects received only placebo (21:00 hours) and on a second night half of them were subjected to placebo and half to MLT. On the later night blood MLT levels were measured. Polygraphic recordings revealed that MLT at bedtime decreased the time the subjects were awake before sleep onset (P<0.025), sleep latency (P<0.05), and the number of awakenings during the total sleep period (P<0.025), and increased sleep efficiency (P<0.05). In addition, it decreased sleep stage 1 (P<0.05) and increased sleep stage 2 (P<0.025). On the morning following the treatment most objective and subjective measures for awakening quality showed a trend towards improvement after MLT. One hour after its oral administration, serum MLT rose to a high pharmacological level (25817 pg/ml; median), but individual peak serum MLT levels varied by a factor of 300. From the data collected it is concluded that a single pharmacological dose of MLT exerts a hypnotic effect by accelerating sleep initiation, improving sleep maintenance and altering sleep architecture in a similar manner to anxiolytic sedatives; objective and subjective measures for awakening qualitiy indicate good tolerance of one dose of MLT without hangover problems on the following morning. Oral administration of crystalline MLT, however, results in high interindividual differences in absorption.

Key words

Melatonin Sleep Behavior Performance Sleep laboratory 


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  1. Aldhous M, Franey C, Wright I, Arendt J (1985) Plasma concentrations of melatonin in man following oral absorption of different preparations. Br J Clin Pharmacol 19:517–521PubMedGoogle Scholar
  2. Anton-Tay F (1974) Melatonin: effects on brain research. Adv Biochem Psychopharmacol 11:315–324PubMedGoogle Scholar
  3. Anton-Tay F, Diaz JL, Fernandez-Guardiola A (1971) On the effect of melatonin upon human brain; its possible therapeutic implications. Life Sci 10:841–850CrossRefGoogle Scholar
  4. Arendt J, Borbely AA, Franey C, Wright J (1984) The effects of chronic, small doses of melatonin given in the late afternoon on fatigue in man: a preliminary study. Neurosci Lett 45:317–321CrossRefPubMedGoogle Scholar
  5. Barchas JD, Da Costa F, Spector S (1967) Acute pharmacolgy of melatonin. Nature 214:919–920PubMedGoogle Scholar
  6. Cramer H, Rudolph J, Consbruch U, Kendel K (1974) On the effects of melatonin on sleep and behavior in man. Adv Biochem Psychopharmacol 11:187–191PubMedGoogle Scholar
  7. Fünfgeld EW (1966) Vigorimeter: Zur Kraftmessung der Hand und zur Simulationsprüfung. Dtsch Med Wochenschr 49:2214–2216Google Scholar
  8. Grünberger J (1977) Psychodiagnostik des Alkoholkranken. Methodischer Beitrag zur Bestimmung der Organizität in der Psychiatrie. Maudrich, WienGoogle Scholar
  9. Grünberger J, Linzmayer L, Saletu B (1984) Klinische Psychodiagnostik mit Hilfe psychophysiologischer Verfahren. Wien Med Wochenschr 134:21–35Google Scholar
  10. Hishikawa Y, Cramer H, Kuholo W (1969) Natural and melatonin-induced sleep in young chickens — a behavioral and electrographic study. Exp Brain Res 7:84–94CrossRefPubMedGoogle Scholar
  11. Holmes SW, Sudgen D (1982) Effects of melatonin on sleep and neurochemistry in the rat. Br J Pharmacol 76:95–101PubMedGoogle Scholar
  12. Lane EA, Moss HB (1985) Pharmacokinetics of melatonin in man: first pass hepatic metabolism. J Clin Endocrinol Metab 61:1214–1216PubMedGoogle Scholar
  13. Lieberman HR, Waldhauser F, Garfield G, Lynch HJ, Wurtman RJ (1984) Effects of melatonin on human mood and performance. Brain Res 323:201–207CrossRefPubMedGoogle Scholar
  14. Marczynski TJ, Yamaguchi N, Ling GM, Grodzinska L (1964) Sleep induced by the administration of melatonin (5-metoxy N-acetyltryptamine) to the hypothalamus of unrestrained cats. Experientia 20:436–437CrossRefGoogle Scholar
  15. Nicholson AN, Borland RG, Stone BM (1979) Effects of benzodiazepines on sleep and on performance: studies in healthy man. In: Priest RG, Pletscher A, Ward J (eds) Sleep research. MTP Press, Lancaster, pp 109–122Google Scholar
  16. Rechtshaffen A, Kales A (1968) A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects. Braine information service, Los AngelesGoogle Scholar
  17. Rickels K (1983) Clinical trials on hypnotics. J Clin Psychopharmacol 3:133–139PubMedGoogle Scholar
  18. Saletu B (1976) Psychopharmaka, Gehirntätigkeit und Schlaf. Karger, BaselGoogle Scholar
  19. Saletu B, Grünberger J (1981) Traffic noise-induced sleep disturbances and their correction by an anxiolytic sedative, OX 373. Neuropsychobiology 7:302PubMedGoogle Scholar
  20. Saletu B, Grünberger J, Sieghart W (1985) Nocturnal traffic noise, sleep, and quality of awakening: neurophysiologic, psychometric and receptor activity changes after quazepam. Clin Neuropharmacol 8:74Google Scholar
  21. Saletu B, Pakesch G (1987a) Recent advances in the clinical pharmacology of benzodiazepines, Part II: Pharmacodynamics. Hum Psychopharmacol 2:61–84CrossRefGoogle Scholar
  22. Saletu B, Kindshofer G, Anderer P, Grünberger J (1987b) Short-term sleep laboratory studies with cinolazepam in situational insomnia induced by traffic noise. Int J Clin Pharmacol Res 7:407–418PubMedGoogle Scholar
  23. Saletu B, Wessely P, Grünberger J, Schultes M (1987c) Erste klinische Erfahrungen mit einem neuen schlafanstoßenden Benzodiazepine, Cinolzepam, mittels eines Selbstbeurteilungsbogens für Schlaf- und Aufwachqualität (SSA). Neuropsychiatrie 1:169–176Google Scholar
  24. Vollrath L, Semm P, Gammel G (1981) Sleep induction by intranasal application of melatonin. Bioscience 29:327–329Google Scholar
  25. Waldhauser F, Waldhauser M, Lieberman HJ, Deng MH, Lynch HJ, Wurtman RJ (1984a) Bioavailability of melatonin in humans. Neuroendocrinology 39:307–313PubMedGoogle Scholar
  26. Waldhauser F, Lynch HJ, Wurtmann RJ (1984b) Melatonin in human body fluids: clinical significance. In: Reiter RJ (ED) The pineal gland. Raven Press, New York, pp 345–369Google Scholar
  27. Von Zerssen D, Koeller DM, Rey ER (1970) Die Befindlichkeitskala (Bf-S), ein einfaches Instrument zur Objektivierung von Befindlichkeitsstörungen, insbesondere im Rahmen von Längsschnittuntersuchungen. Arzneimittelforschung 20:915PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • F. Waldhauser
    • 1
  • B. Saletu
    • 2
  • I. Trinchard-Lugan
    • 1
  1. 1.Department of PediatricsUniversity of ViennaViennaAustria
  2. 2.Department of PsychiatryUniversity of ViennaViennaAustria

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