Melatonin

• ANATOMY OR SYSTEM AFFECTED: Brain, endocrine system, glands

DEFINITION: A substance produced by the pineal gland that has been used as a controversial therapeutic agent

Structure and Functions

Melatonin, also known as N-acetyl-5-methoxytryptamine, is a hormone found in a wide variety of living organisms. In vertebrates (animals with backbones), including humans, it is produced by the pineal gland. The pineal gland is located deep within the center of the brain. Although it is inside the brain, it is considered part of the endocrine system rather than the nervous system. In humans, the pineal gland is a gray or white organ less than one centimeter long and shaped like a pine cone.

The pineal gland produces varying amounts of melatonin in response to changes in light. Light inhibits the production of melatonin, and darkness stimulates it. In some small animals, light reaches the pineal gland directly through the skull. In larger animals, including humans, information about lightness and darkness is transmitted by the nervous system from the eyes to the suprachiasmatic nucleus, a cluster of nerve cells in a region of the brain known as the hypothalamus. The suprachiasmatic nucleus regulates the secretion of melatonin by the pineal gland.

Melatonin is believed to be involved in regulating the sleep cycle in response to changes in light. Because the amount of melatonin produced by the pineal gland declines sharply at puberty, it is believed to be involved in the development of the reproductive system. Because melatonin production continues to decline with age, some researchers believe that it is associated with the process of aging.

Disorders and Diseases

Disorders of melatonin production other than its normal decline with age are rare. Tumors of the pineal gland may reduce melatonin production. Some evidence suggests that this may lead to premature aging. Children with tumors of the pineal gland may reach puberty at a very early age.

Some researchers suggest that the normal decline in melatonin production with age is associated with diseases of older adults. Animal studies suggest that loss of melatonin is associated with increased cell damage. Melatonin is believed to act as an antioxidant, a substance that protects cells from free radicals, which are produced when cells use oxygen. Cell damage has been linked to a large number of diseases of older patients, including various forms of cancer, heart disease, and Alzheimer’s disease.

Based on this evidence, melatonin has been used to treat and prevent a wide variety of illnesses. In the 1990s, melatonin became widely used in the United States. Because it was classified as a dietary supplement rather than as a drug, it was available without a prescription and with little government regulation. While some researchers suggested caution until more was known about melatonin, others suggested taking small daily doses of the hormone to slow down the aging process. Popular books such as The Melatonin Miracle (1995), by Walter Pierpaoli, William Regelson, and Carol Colman, claim that melatonin can stimulate the immune system, prevent cancer and heart disease, improve sexual relations, reduce the effects of stress, act as a contraceptive, and add years to the human life span. Critics argue that these claims are greatly exaggerated. There remains a lack of peer-reviewed, rigorous, academic studies supporting many of these claims.

The least controversial suggested use for melatonin is as a sleeping aid. Human studies have indicated that melatonin is safe and effective for this use. Unlike many other sleeping pills, melatonin seems to have no effect on normal sleep patterns and few side effects. Melatonin has also been shown to be effective in treating jet lag, the difficulty that travelers have adjusting to a new time zone. In the twenty-first century, melatonin is widely available and comes in several forms, including pills, liquids, and gummies. Melatonin may also be used to help with problems with sleep in children, though a doctor’s advice should be sought before administration.

Critics of routine melatonin use point out that little is known about its long-term effects. They also point to evidence that some people may experience short-term side effects such as nightmares, headaches, daytime sleepiness, and mild depression. A major concern is the lack of regulation of melatonin products, leading to the possibility that other unknown substances may be present.

Even the most optimistic proponents of melatonin suggest certain precautions. Many products contain more melatonin than researchers believe is necessary, leading to the possibility of a greater risk of side effects with no increase in benefit. Melatonin should only be taken at bedtime to avoid unwanted sleepiness. It should not be used by pregnant women because its effect on the fetus is unknown. Because it is believed to stimulate the immune system, melatonin should be avoided in people with severe allergies, autoimmune disorders, or cancer of the immune system.

Perspective and Prospects

The pineal gland was known to exist in ancient times. It was first described scientifically by the Greek physician Galen in the second century. The French philosopher René Descartes (1596–1650) suggested that it was the location of the human soul. The true function of the pineal gland remained unknown until the middle of the twentieth century.

Melatonin was discovered in 1958 and first described as a hormone in 1963. Research into its effects began in the 1970s and 1980s. Interest in this hormone increased dramatically in 1995, with the publication of several books and articles publicizing its possible benefits. Research on melatonin continued for many years, particularly in regard to its long-term effects.

Into the mid-2020s, many early claims about melatonin as an anti-aging or disease-preventing miracle hormone had been discredited. Melatonin continued to be widely used and well-studied as a treatment for sleep disorders and jet lag, and sometimes prescribed for children with neurodevelopmental conditions. While generally safe in the short term, concerns remained about inconsistent supplement quality and a lack of long-term safety data, making medical guidance important for routine use.

Bibliography

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Goodman, H. Maurice. Basic Medical Endocrinology. 4th ed., Academic, 2009.

Holt, Richard I. G., and Neil A. Hanley. Essential Endocrinology and Diabetes. 6th ed., Blackwell, 2012.

“Melatonin: Questions, Facts, Mysteries.” University of California, Berkeley, Wellness Letter, vol. 16, no. 8, 2000, pp. 1–2.

Olcese, James, editor. Melatonin After Four Decades: An Assessment of Its Potential. Kluwer, 1999.

Pandi-Perumal, S. R., and Daniel P. Cardinali, editors. Melatonin: Biological Basis of Its Function in Health and Disease. Landes Bioscience, 2006.

Summer, Jay Vera. “Can You Take Melatonin While Pregnant?” Sleep Foundation, 15 July 2025, www.sleepfoundation.org/melatonin/pregnancy. Accessed 17 Aug. 2025.

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Watson, Ronald R. Melatonin in the Promotion of Health. 2nd edition., CRC, 2012.

Yan, Tyler, and Ran D. Goldman. "Melatonin for Children with Autism Spectrum Disorder." Canadian Family Physician, vol. 66, no. 3, 2020, p. 183-185. PubMed Central, pmc.ncbi.nlm.nih.gov/articles/PMC8302336/. Accessed 17 Aug. 2025.