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N-Acetyl-5-methoxytryptamine (also known as melatonin) is a hormone of the tryptamine class. It is found in animals, plants, fungi, and bacteria. In animals, it functions as a hormone that anticipates the daily onset of darkness;[1] it may have different functions in other organisms but evidently it plays a role in the regulation of the circadian rhythm of several biological functions.[2]


Melatonin is a non-selective melatonin receptor agonist, acting at both the MT1 receptor and the MT2 receptor.

Melatonin is comprised of a monoamine chain attached to an indole ring at the third carbon. A monoamine chain is made up of an amine group attached to an ethane chain. This monoamine chain can be found in many neurotransmitters, including histamine, dopamine, adrenaline, and noradrenaline. It is also found in many psychoactive substances such as members of the tryptamine and phenethylamine chemical classes. Melatonin, being a tryptamine, shares many structural properties with psychedelic substances. However, it lacks their associated psychedelic effects[3]. Where many tryptamines have a group bonded to the ethylamine, melatonin has an acetyl group.

Roles in humans

Melatonin plays crucial role in many different process within the human body. Some of the important ones are listed below. 

Light dependence

Production of melatonin by the pineal gland is inhibited by light and permitted by darkness. For this reason melatonin has been called “the hormone of darkness” and its onset each evening is called the Dim-Light Melatonin Onset (DLMO). Secretion of melatonin, and its level in the blood, peaks in the middle of the night, and gradually falls during the second half of the night, with normal variations in timing according to an individual’s chronotype.

Until recent history, humans in temperate climates were exposed to only about six hours of daylight in the winter. In the modern world, artificial lighting reduces darkness exposure to typically eight hours or less per day all year round. Even low light levels inhibit melatonin production to some extent, but over-illumination can create significant reduction in melatonin production. Since it is principally blue light that suppresses melatonin,[4] wearing glasses that block blue light[5] in the hours before bedtime may avoid melatonin loss. Use of blue-blocking goggles the last hours before bedtime has also been advised for people who need to adjust to an earlier bedtime, as melatonin promotes sleepiness.

Reduced melatonin production has been proposed as a likely factor in the significantly higher cancer rates in night workers,[24] and the effect of modern lighting practice on endogenous melatonin has been proposed as a contributory factor to the larger overall incidence of some cancers in the developed world.[6] As inadequate as blood concentrations may be in brightly lit environments, some scientists now believe that a person’s overnight output of melatonin can be further jeopardized each time he or she interrupts his or her sleep and turns on a bright light (suggesting that using a less-bright nightlight would be safer). Others suggest that such short exposures do no harm.[7]

Circadian Rhythm

A circadian rhythm is any biological process that displays an endogenous, entrainable oscillation of about 24 hours. These rhythms are driven by a circadian clock, and rhythms have been widely observed in plants, animals, fungi and cyanobacteria. The term circadian comes from the Latin circa, meaning “around” (or “approximately”), and diem or dies, meaning “day”. The formal study of biological temporal rhythms, such as daily, tidal, weekly, seasonal, and annual rhythms, is called chronobiology. Although circadian rhythms are endogenous (“built-in”, self-sustained), they are adjusted (entrained) to the local environment by external cues called zeitgebers, commonly the most important of which is daylight.

The melatonin signal forms part of the system that regulates the circadian cycle by chemically causing drowsiness, but it is the central nervous system that controls the daily cycle in most components of the paracrine and endocrine systems[8][9] rather than the melatonin signal (as was once postulated).

In his book “Spirit Molecule” Dr. Rick Strassman writes :

“We have a good understanding of how the body regulates melatonin production. It is the “hormone of darkness.” Light turns off melatonin production, both during daylight hours and in the presence of artificial light during night time hours. The longer the night time dark hours, the more melatonin. The greater the daylight hours, the less melatonin. Besides indicating whether it is day or night, the patterns of melatonin production also inform the animal about the time of year. These longer term melatonin effects help prepares for the appropriate seasonal responses—pregnancy in spring or fall, hibernation during the winter, or fat loss in summer.”[10]


Many supplemental melatonin users have reported an increase in the vividness or frequency of dreams. Extremely high doses of melatonin (50mg) dramatically increased REM sleep time and dream activity in both narcoleptics and those without narcolepsy.[14]

Many psychoactive drugs, such as LSD and cocaine, increase melatonin synthesis.[15] It has been suggested that nonpolar (lipid-soluble) indolic hallucinogenic drugs emulate melatonin activity in the awakened state and that both act on the same areas of the brain.[14] It has been suggested that psychotropic drugs be readmitted in the field of scientific inquiry and therapy.[15] If so, melatonin may be prioritized for research in this reemerging field of psychiatry.[16]

Anti Oxidant

Besides its primary function as synchronizer of the biological clock, melatonin may exert a powerful anti-oxidant activity. In many lower life forms, it serves only this purpose.[11] Melatonin is a powerful antioxidant that can easily cross cell membranes and the blood-brain barrier.[12] In animal models, melatonin has been demonstrated to prevent the damage to DNA by some carcinogens, stopping the mechanism by which they cause cancer.[13]



[1].Hardeland R, Pandi-Perumal SR, Cardinali DP. Melatonin. Int J Biochem Cell Biol. 2006 Mar;38(3):313-6. Epub 2005 Sep 27.

[2]. Altun A, Ugur-Altun B (2007). Melatonin: therapeutic and clinical utilization. Int. J. Clin. Pract. 61 (5): 835–45.

[3].TIHKAL: The Continuation by Alexander T Shulgin , Ann Shulgin , Dan Joy. 1997.

[4]. Brainard GC, Hanifin JP, Greeson JM, Byrne B, Glickman G, Gerner E, Rollag (August 15,2001). Action spectrum for melatonin regulation in humans: evidence for a novel circadian photoreceptor.. J Neurosci. 15;21 (16): 6405-12. PMID: 11487664.

[5]. Kayumov L, Casper RF, Hawa RJ, Perelman B Chung SA, Sokalsky S, Shipiro (May 2005). Blocking low-wavelength light prevents nocturnal melatonin suppression with no adverse effect on performance during simulated shift work.. J Clin Endocrinol Metab. 90 (5): 2755-61. PMID: 15713707.

[6]. Pauley S (2004). Lighting for the human circadian clock: recent research indicates that lighting has become a public health issue.. Med Hypotheses 63 (4): 588-96. PMID 1532500.

[7].Harder B (Jan 2006). Bright Lights, Big Cancer: Melatonin-depleted blood spurs tumor growth.. Science News 169 (1): 8 – 10.

[8]. Richardson G (2005). The human circadian system in normal and disordered sleep.. J Clin Psychiatry 66 Suppl 9: 3 – 9; quiz 42-3. PMID 16336035.

[9]. Perreau-Lenz S, Pévet P, Buijs R, Kalsbeek A (2004). The biological clock: the bodyguard of temporal homeostasis.. Chronobiol Int 21 (1): 1 – 25. PMID 15129821.

[10]. Rick Strassman. DMT: The Spirit Molecule: A Doctor’s Revolutionary Research into the Biology of Near-Death and Mystical Experiences. Jan 2001.

[11]. Lewis, Alan (1999). Melatonin and the Biological Clock, pp. 23, McGraw-Hill.

[12]. Sessa, Ben (2005). Can psychedelics have a role in psychiatry once again?. The British Journal of Psychiatry: 457 – 458. PMID 15928353.

[13]. Sessa, Ben (2005). Endogenous psychoactive tryptamines reconsidered: an anxiolytic role for dimethyltryptamine.. Med Hypotheses 5 (64): 930-7. PMID 15780487.

[14]. Dun-Xian Tan, Lucien C. Manchester, Maria P. Terron, Luis J. Flores, Russel J. Reiter (2007). One molecule, many derivatives: a never-ending interaction of melatonin with reactive oxygen and nitrogen species?. Journal of Pineal Research 42 (1): 28 – 42. PMID 17198536.

[15]. Hardeland R (2005). Antioxidative protection by melatonin: multiplicity of mechanisms from radical detoxification to radical avoidance.. Endocrine 27 (2): 119-30. PMID 16217125.

[16]. Karbownik M, Reiter R, Cabrera J, Garcia J (2001). Comparison of the protective effect of melatonin with other antioxidants in the hamster kidney model of estradiol-induced DNA damage.. Mutat Res 474 (1 – 2): 87 – 92. PMID 11239965.



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