, Volume 112, Issue 4, pp 490–496 | Cite as

Effect of pharmacological daytime doses of melatonin on human mood and performance

  • Andrew B. Dollins
  • Harry J. Lynch
  • Richard J. Wurtman
  • Mei Hua Deng
  • Karl U. Kischka
  • Ray E. Gleason
  • Harris R. Lieberman
Original Investigations


Melatonin (10, 20, 40, or 80 mg, PO) or placebo was administered at 1145 hours on five separate occasions to 20 healthy male volunteers and the effects on serum melatonin levels, mood, performance, and oral temperature were monitored. Subjects were studied between 0930 and 1700 hours. A battery of interactive computer tasks designed to assess performance and mood was completed, oral temperature was measured, and blood samples were taken for serum melatonin radioimmunoassay. The areas under the time-melatonin concentration curve (AUC) varied significantly in proportion to the various melatonin doses. Compared with placebo treatment, all melatonin doses significantly decreased oral temperature, number of correct responses in auditory vigilance, response latency in reaction time, and self-reported vigor. Melatonin also increased self-reported fatigue, confusion, and sleepiness.

Key words

Human Melatonin Mood Performance Reaction time Vigilance Fatigue Circadian Sleep Alertness 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Arendt J, Broadway J (1987) Light and melatonin as zeitgebers in man. Chronobiol Int 4:273–282PubMedGoogle Scholar
  2. Arendt J, Borbely AA, Franey C, Wright J (1984) The effect of chronic, small doses of melatonin given in the late afternoon on fatigue in man: a preliminary study. Neurosci Lett 45:317–321CrossRefPubMedGoogle Scholar
  3. Arendt J, Aldhous M, Marks V (1986) Alleviation of jet-lag by melatonin: preliminary results of controlled double-blind trial. Br Med J 292:1170Google Scholar
  4. Armstrong SM, Cassone VM, Chesworth MJ, Redman JR, Short, RV (1986) Synchronization of mammalian circadian rhythms by melatonin. In: Wurtman RJ, Waldhauser F (eds) Melatonin in humans. Proceedings of the First International Conference on Melatonin in Humans. J Neurol Transm 21(suppl):375–394Google Scholar
  5. Banderet LE, Lieberman HR (1989) Treatment with tyrosine, a neurotransmitter precursor, reduces environmental stress in humans. Brain Res Bull 22:759–762CrossRefPubMedGoogle Scholar
  6. Brown GM, Grota LJ, Pulido O, Burns TG, Niles LP, Snieckus V (1983) Application of immunologic techniques to the study of pineal indoleamines. Pineal Res Rev 1:207–246Google Scholar
  7. Brzezinski A, Seibel MM, Lynch HJ, Deng MH, Wurtman RJ (1987) Melatonin in preovulatory follicular fluid. J Clin Endocrinol Metab 64:865–867PubMedGoogle Scholar
  8. Cagnacci A, Elliott JA, Yen SSC (1992) Melatonin: a major regulator of the circadian rhythm of core temperature in humans. J Clin Endocrinol Metab 75:447–452CrossRefPubMedGoogle Scholar
  9. Claustrat B, Brun J, David M, Sassolas G, Chazot G (1992) Melatonin and jet lag: confirmatory result using a simplified protocol. Biol Psychiatry 32:705–711CrossRefPubMedGoogle Scholar
  10. Dollins AB, Lynch HJ, Wurtman RJ, Deng MH, Lieberman HR (1993) Effects of illumination on human nocturnal serum melatonin levels and performance. Physol Behav 53:153–160CrossRefGoogle Scholar
  11. Hamilton M (1967) Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol 6:278–296PubMedGoogle Scholar
  12. Hindmarch I (1980) Psychomotor function and psychoactive drugs. Br J Clin Pharmacol 10:189–209PubMedGoogle Scholar
  13. Hoddes E, Dement W, Zarcone V (1973) Quantification of sleepiness: a new approach. Psychophysiology 10:431–436PubMedGoogle Scholar
  14. James SP, Mendelson WB, Sack DA, Rosenthal NE, Wehr TA (1987) The effect of melatonin on normal sleep. Neuropsychopharmacology 1:41–44CrossRefPubMedGoogle Scholar
  15. James SP, Sack DA, Rosenthal NE, Mendelson WB (1990) Melatonin administration in insomnia. Neuropsychopharmacology 3:19–23PubMedGoogle Scholar
  16. Johanson CE, Uhlenhuth EH (1980) Drug preference and mood in humans: diazepam. Psychopharmacology 71:269–273Google Scholar
  17. Johnson LC, Chernick DA (1982) Sedative-hypnotics and human performance. Psychopharmacology 76:101–113CrossRefPubMedGoogle Scholar
  18. Jones DM, Smith AP, Broadbent DE (1979) Effects of moderate intensity noise on the Bakan vigilance task. J Appl Psychol 64:627–634CrossRefPubMedGoogle Scholar
  19. Joy JE, Losee-Olson S, Turek FW (1989) Single injections of triazolam, a short-acting benzodiazepine, lengthen the period of the circadian activity rhythm in golden hamsters. Experientia 45:152–154CrossRefPubMedGoogle Scholar
  20. Lewy AJ, Sack RL, Latham JM (1991) Melatonin and the acute suppressant effect of light may help regulate circadian rhythms in humans. Adv Pineal Res 5:285–193Google Scholar
  21. Lewy AJ, Ahmed S, Jackson JML, Sack RL (1992) Melatonin shifts human circadian rhythms according to a phase-response curve. Chronobiol Int 9:380–392PubMedGoogle Scholar
  22. Lieberman HR, Corkin S, Spring BJ, Growdon JH, Wurtman RJ (1984a) Mood, performance and pain sensitivity: changes induced by food constituents. J Psychiatr Res 17:135–145CrossRefGoogle Scholar
  23. Lieberman HR, Waldhauser F, Garfield G, Lynch HJ, Wurtman RJ (1984b) Effects of melatonin on human mood and performance. Brain Res 323:201–207CrossRefPubMedGoogle Scholar
  24. Lieberman HR, Garfield GS, Waldhauser F, Lynch HJ, Wurtman RJ (1985) Possible behavioral consequences of light-induced changes in melatonin availability. In: Wurtman RJ, Baum MJ, Potts JT Jr (eds) The medical and biological effects of light. Ann NY Acad Sci 453:242–252PubMedGoogle Scholar
  25. Lieberman HR, Wurtman JJ, Chew B (1986) Changes in mood after carbohydrate consumption may influence snack choices of obese individuals. Am J Clin Nutr 44:772–778PubMedGoogle Scholar
  26. Lieberman HR, Wurtman RJ, Emde GG, Roberts C, Coviella ILG (1987) The effects of low doses of caffeine on human mood and performance. Psychopharmacology 92:308–312CrossRefPubMedGoogle Scholar
  27. MacFarlane JG, Cleghorn JM, Brown GM, Streiner DL (1991) The effects of exogenous melatonin on the total sleep time and daytime alertness of chronic insomniacs: a preliminary study. Biol Psychiatry 30:371–376CrossRefPubMedGoogle Scholar
  28. McNair PM, Lorr M, Droppleman LF (1971) Profile of mood states manual. Educational and Industrial Testing Service, San DiegoGoogle Scholar
  29. Morton DJ, Naik D (1989) Effect of oral melatonin at various dose levels on blood pressure of normotensive humans. Med Sci Res 17:837Google Scholar
  30. Nickelsen T, Demisch L, Demisch K, Radermacher B, Schoffling K (1989) Influence of subchronic intake of melatonin at various times of the day on fatigue and hormonal levels: a placebo-controlled, double-blind trial. J Pineal Res 6:325–334PubMedGoogle Scholar
  31. Nicholson AN, Pascoe PA, Spencer MB, Stone BM, Roehrs T, Roth T (1986) Sleep after transmeridian flights. Lancet 8517:1205–1208CrossRefGoogle Scholar
  32. Petrie K, Conaglen JV, Thompson L, Chamberlain K (1989) Effect of melatonin on jet lag after long haul flights. BMJ 298:705–707PubMedGoogle Scholar
  33. Reiter RJ (1988) Neuroendocrinology of melatonin. In: Miles A, Philbrick DRS, Thompson C (eds) Melatonin clinical perspectives. Oxford University Press, Oxford New York Tokyo, pp 1–42Google Scholar
  34. Reiter RJ (1991) Melatonin: the chemical expression of darkness. Mol Cell Endocrinol 79:C153-C158CrossRefPubMedGoogle Scholar
  35. Rosenthal NE, Genhart M, Sack DA, Skewer RG, Wehr TA (1987) Seasonal affective disorder and its relevance for the understanding and treatment of bulimia. In: Hudson JI, Pope HG Jr (eds) The psychobiology of bulimia. American Psychiatric Press, Washington DC, pp 205–228Google Scholar
  36. Sack RL, Lewy AJ, Blood ML, Stevenson J, Keith LD (1991) Melatonin administration to blind people: phase advances and entrainment. J Biol Rhythms 6:249–261PubMedGoogle Scholar
  37. Smith A (1967) Consistent sex differences in a specific (decoding) test performance. Ed Psychol Meas 27:1077–1083Google Scholar
  38. Smith AP, Tyrrell DAJ, Al-Nakib W, Coyle KB, Donovan CB, Higgins PG, Willman JS (1987) Effects of experimentally induced respiratory virus infections and illness on psychomotor performance. Neuropsychobiology 18:144–148PubMedGoogle Scholar
  39. Van Reeth O, Turek FW (1989) Administrering triazolam on a circadian basis entrains the activity rhythm of hamsters. Am J Physiol 256:R639-R645PubMedGoogle Scholar
  40. Vollrath L, Semm P, Gammel G (1981) Sleep induction by intranasal application of melatonin. Adv Biosci 29:327–329Google Scholar
  41. Waldhauser F, Weiszenhacher G, Frisch H, Zeitlhuber U, Waldhauser M, Wurtman RJ (1984) Fall in nocturnal serum melatonin during prepuberty and pubescence. Lancet 1:362–365CrossRefPubMedGoogle Scholar
  42. Waldhauser F, Saletu B, Trinchard-Lugan, I (1990) Sleep laboratory investigations of hypnotic properties of melatonin. Psychopharmacology 100:222–226CrossRefPubMedGoogle Scholar
  43. Wilkinson RT (1968) Sleep deprivation: performance tests for partial and selective sleep deprivation. In: Reiss BF, Abt LA (eds) Progress in clinical psychology. Grune & Stratton, New York, pp 28–43Google Scholar
  44. Wilkinson RT (1969) Some factors influencing the effect of environmental stressors on performance. Psychol Bull 72:260–272PubMedGoogle Scholar
  45. Wilkinson RT, Houghton D (1975) Portable four-choice reaction time test with magnetic tape memory. Behav Res Methods Instrum 7:441–446Google Scholar
  46. Winer, BJ (1971) Statistical principles in experimental design, 2nd edn. McGraw-Hill, New York, pp 384–388Google Scholar
  47. Wurtman RJ, Axelrod J, Kelly DE (1968) The pineal. Academic Press, New YorkGoogle Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • Andrew B. Dollins
    • 1
  • Harry J. Lynch
    • 1
  • Richard J. Wurtman
    • 1
  • Mei Hua Deng
    • 1
  • Karl U. Kischka
    • 1
  • Ray E. Gleason
    • 1
  • Harris R. Lieberman
    • 1
  1. 1.Department of Brain and Cognitive Sciences, and The Clinical Research CenterMassachusetts Institute of TechnologyCambridgeUSA

Personalised recommendations