Dosage
The appropriate dose can vary enormously from person to person. Dr. Pierpaoli, a leading melatonin researcher, has successfully used dosages ranging from 0.1 to 200 mg. That’s a 2000-fold difference between the lowest dose and the highest! Several intelligent melatonin users we know started by taking 3 mg at 11 p.m., and then adjusted the dose from there. If they found that they slept well but were drowsy in the morning, they cut the dose in half. If they found the dose had little or no sleep-inducing effect, they increased the dose by 3 mg each night until they got the desired effect. We have received reports from one person who gets good results from less than one milligram, and several from people who use in the vicinity of 20 mg. Most people get good results with doses between 3 and 10 mg.
Precautions
Timing may be crucial for the most effective use of melatonin. Individual differences in the absorption and metabolism of melatonin may account for the differences in size and timing of the resulting melatonin pulse. A good illustration of this effect is found in the experiences of Dr. Tzischinsky [1992] of the medical university in Haifa, Israel. Dr. Tzischinsky treated an 18-year-old blind man suffering from chronic sleep disturbances. Presumably, the young man’s blindness prevented sunlight from cueing his circadian rhythm. He suffered from daytime fatigue, often falling asleep during the day, but was awake at night. After two unsuccessful treatment regimens with 5 mg and 10 mg melatonin administered at bedtime (10 - 10:30 p.m.), Dr. Tzischinsky tried a third regimen of only 5 mg administered at 8 p.m. for three weeks. This approach resulted in a successful resolution of the man’s sleep disturbances.
This observation (and others like it) demonstrate the importance of not only adjusting the dosage but also the time of the dose. Melatonin seems to be much more critical in this regard than other smart drugs. One melatonin user reports that he gave himself terrible jet-lag by absent-mindedly taking melatonin at 3 a.m. after staying up late. He recovered from this error, resetting his circadian rhythm back to normal with melatonin at 10 p.m. the following evening, but not before he had to spend an entire day in jet-lag hell for his mistake.
References
Arendt J, Aldhous M and Marks V. Alleviation of jet-lag by melatonin: Preliminary results of controlled double-blind trial. Brit Med J 292: 1170, 1986.
Belokrylov GA, Morozov VG, Khavinson VH, et al. The action of low molecular extracts from heterological thymus, pineal and hypothalamus on the immune response in mice. Biull Eksp Biol Med 81: 202-4, 1976.
Brown GM. Psychoneuroendocrinology of depression. Psychiatr J Univ Ott 14(2): 344-8; Jun 1989. Discussion follows article.
Claustrat B, Brun J, David M, Sassolas G and Chazot G. Melatonin and jet-lag: Confirmatory result using a simplified protocol. Biol Psychiatry (USA) 32(8): 705-11, 1992.
Dilman VM, Anisimov VN, and Ostroumova MN. Increase in lifespan of rats following polypeptide pineal extract treatment. Exp Pathology 17: 539-45, 1979.
Dilman VM. Improvement of cell-mediated immunity after pineal gland extract treatment. Vopr Oncol (Problems of Oncology) 7: 70-72, 1977.
Lieberman HR, Waldhauser F, Garfield G, et al. Effects of melatonin on human mood and performance. Brain Res (Netherlands) 323(2): 201-7, 1984.
Lissoni P, Barni S, Crispino S, Tancini G and Fraschini F. Endocrine and immune effects of melatonin therapy in metastatic cancer patients. Eur J Cancer Clin Oncol (United Kingdom) 25(5): 789-95, 1989.
Lovely RH. Recent studies in the behavioral toxicology of ELF electric and magnetic fields. Prog Clin Biol Res 257: 327-47, 1988.
Maestroni GJ, Conti A and Pierpaoli W. Pineal melatonin, its fundamental immunoregulatory role in aging and cancer. Ann N Y Acad Sci 521: 140-8, 1988.
Maurizi CP. The therapeutic potential for tryptophan and melatonin: possible roles in depression, sleep, Alzheimer’s disease and abnormal aging. Med Hypotheses 31(3): 233-42, March 1990.
Nair NPV, Hariharasubramanian N, Pilapil C, Issac I, and Thavundayil JX. Plasma melatonin—an index of brain aging in humans? Biological Psychiatry 21: 141-50, 1986.
Neville K and McNaughton N. Anxiolytic-like action of melatonin on acquisition but not performance of DRL. Pharmacol Biochem Behav 24(6): 1497-502, June 1986.
Ostroumova MN and Vasiljeve IA. Effect or polypeptide pineal extract on fat-carbohydrate metabolism. Probl Endokrinol 22: 66-9, 1976.
Ovanesov KB. Vliianie ostrogo i khronicheskogo vvedeniia melatonina na pereobuchenie krys v U-obraznom labirinte i ikh chuvstvitel’nost’ k galoperidolu [The effect of the acute and chronic administration of melatonin on the relearning of rats in a Y maze and their sensitivity to haloperidol]. Farmakol Toksikol 53(2): 15-7, Mar-Apr 1990.
Pierpaoli W, Changxian VI and Dall’aza A. Aging—Postponing effect of circadian melatonin: Experimental evidence, significance and possible mechanism. Intern J Neuroscience 51: 334-342, 1990.
Pierpaoli W and Maestroni GJM. Melatonin: A principal neuroimmunoregulatory and anti-stress hormone: Its anti-aging effects. Immunol Lett (Netherlands) 16(3-4): 355-61, 1987.
Regelson W and Pierpaoli W. Melatonin: a rediscovered antitumor hormone? Cancer Investig 5: 379-385, 1987.
Sandyk R, Anninos PA and Tsagas N. Age-related disruption of circadian rhythms: possible relationship to memory impairment and implications for therapy with magnetic fields. Int J Neurosci (England) 59(4): 259-62, Aug 1991.
Skene DJ, Vivien-Roels B, Sparks DL, Hunsaker JC, Pevet P, Ravid D and Swaab DF. Daily variation in the concentration of melatonin and 5-methoxytryptophol in the human pineal gland: effect of age and Alzheimer’s disease. Brain Res 528(1): 170-4, 24 Sept 1990.
Souetre E, Salvati E, Krebs B, Belugou JL and Darcourt G. Abnormal melatonin response to 5-methoxypsoralen in dementia. Am J Psychiatry 146(8): 1037-40, Aug 1989.
Tasca C, Damian E and Stefaneanu L. Disappearance of aortic lesions in the rabbits with experimental atheromatosis after pineal extraction administration. Rev Roum d’Endocr 11: 209-13, 1974.
Tohgi H, Abe T, Takahashi S, Kimura M, Takahashi J and Kikuchi T. Concentrations of serotonin and its related substances in the cerebrospinal fluid in patients with Alzheimer-type dementia. Neurosci Lett (Ireland) 141(1): 9-12, 1992.
Tzischinsky O, Pal I, Epstein R, Dagan Y and Lavie P. The importance of timing in melatonin administration in a blind man. J Pineal Res (Denmark) 12(3): 105-8, 1992.