Melatonin as a medication and supplement

Melatonin is a naturally occurring hormone produced in the brain that is also used as a dietary supplement and medication. As a hormone, melatonin is released by the pineal gland and is involved in sleep–wake cycles. As a supplement and medication, it is often used for the short-term treatment of disrupted sleep patterns such as from jet lag or shift work, and is typically taken orally.

Side effects from melatonin supplements are minimal at low doses for short durations (the studies reported that side effects occurred about equally for both melatonin and placebo). Side effects of melatonin are rare but may occur in 1 to 10 patients out of 1,000. 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. Its use is not recommended during pregnancy or breastfeeding or for those with liver disease.

Melatonin acts as an agonist of the melatonin MT₁ and MT₂ receptors, the biological targets of endogenous melatonin. 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. Immediate-release melatonin has a short elimination half-life of about 20 to 50 minutes. Prolonged-release melatonin used as a medication has a half-life of 3.5 to 4 hours.

Melatonin was discovered in 1958. It is sold over-the-counter in Canada and the United States; in the United Kingdom, it is a prescription-only medication. In Australia and the European Union, it is indicated for difficulty sleeping in people over the age of 54. Slenyto is a prolonged-release melatonin medicine used in the E.U. to treat insomnia in children and adolescents with autism spectrum disorder, neurogenetic disorders, or ADHD. 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. It was approved for medical use in the European Union in 2007. Besides melatonin, certain synthetic melatonin receptor agonists like ramelteon, tasimelteon, and agomelatine are also used in medicine. In 2023, it was the 164th most commonly prescribed medication in the United States, with more than 3 million prescriptions.