[9][12] As a supplement, it is often used for the attempted short-term treatment of disrupted sleep patterns, such as from jet lag or shift work, and is typically taken orally.

[17][8] They may include somnolence, headaches, nausea, diarrhea, abnormal dreams, irritability, restlessness, insomnia, anxiety, migraine, lethargy, hyperactivity, dizziness, hypertension, abdominal pain, heartburn, mouth ulcers, dry mouth, hyperbilirubinaemia, dermatitis, night sweats, pruritus, rash, dry skin, pain in the extremities, symptoms of menopause, chest pain, glycosuria (sugar in the urine), proteinuria (protein in the urine), abnormal liver function tests, weight gain, mood swings, aggression, and grogginess after awakening.

[21] It is thought to activate these receptors in the suprachiasmatic nucleus of the hypothalamus in the brain to regulate the circadian clock and sleep–wake cycles.

[18] The U.S. Food and Drug Administration (FDA) treats melatonin as a dietary supplement and, as such, has not approved it for any medical uses.

[26][27] There is no good evidence that melatonin helps treat insomnia and its attempted use for this purpose is recommended against by the American Academy of Sleep Medicine.

[31] Melatonin is a safer alternative than clonazepam in the treatment of REM sleep behavior disorder – a condition associated with the synucleinopathies like Parkinson's disease and dementia with Lewy bodies.

[35] A 2020 Cochrane review found no evidence that melatonin helped sleep problems in people with moderate to severe dementia due to Alzheimer's disease.

[36] A 2019 review found that while melatonin may improve sleep in minimal cognitive impairment, after the onset of Alzheimer's disease it has little to no effect.

[38] A prolonged-release 2 mg oral formulation of melatonin sold under the brand name Circadin is approved for use in the European Union in the short-term treatment of insomnia in people age 55 and older.

[41] Several inhalation-based melatonin products with a wide range of doses are being sold but the safety remains to be evaluated.

[40] The American Academy of Sleep Medicine (AASM) said that the melatonin content in unregulated (without a USP verified mark) supplements can diverge widely from the claimed amount; a study found that the melatonin content ranged from one half to four times the stated dose.

[15][20] Melatonin appears to cause very few side effects as tested in the short term, up to three months, at low doses.

[clarification needed][dubious – discuss] Two systematic reviews found no adverse effects of exogenous melatonin in several clinical trials, and comparative trials found the adverse effects headaches, dizziness, nausea, and drowsiness were reported about equally for both melatonin and placebo.

[citation needed] Low doses of melatonin are usually sufficient to produce a hypnotic effect in most people.

[46] There is emerging evidence that the timing of taking exogenous melatonin in relation to food is also an important factor.

[49] In autoimmune disorders, evidence is conflicting whether melatonin supplementation may ameliorate or exacerbate symptoms due to immunomodulation.

Extremely high doses of melatonin increased REM sleep time and dream activity in people both with and without narcolepsy.

The American Academy of Sleep Medicine says there is little evidence that melatonin supplementation is effective in treating insomnia in healthy children.

[8] CYP1A2 inducers like cigarette smoking, carbamazepine, and rifampicin may reduce melatonin exposure due to induction of CYP1A2.

[6][7] Melatonin is rapidly absorbed and distributed, reaching peak plasma concentrations after 60 minutes of administration, and is then eliminated.

[62] The New England Journal of Medicine editorialized in 2000: "With these recent careful and precise observations in blind persons, the true potential of melatonin is becoming evident, and the importance of the timing of treatment is becoming clear.

[8] Melatonin is categorized by the US Food and Drug Administration (FDA) as a dietary supplement, and is sold over-the-counter in both the US and Canada.

[64][69] Melatonin is the most popular over-the-counter sleep remedy in the United States, resulting in sales in excess of US$400 million during 2017.

[77][78][79] There have also been studies trying to prove the effectiveness of melatonin in relation to epilepsy, dysmenorrhea, delirium, and tinnitus, but little to no beneficial role has been found.

Melatonin and its metabolites protect organisms from oxidative stress by scavenging reactive oxygen species which are generated during exposure.