Melatonin

Melatonin is a hormone produced mainly by the pineal gland in humans and other vertebrates. In humans, it derives from serotonin through two enzymatic steps catalyzed by arylalkylamine N-acetyltransferase (AANAT) and hydroxyindole O-methyltransferase (HIOMT). Synthesis follows a circadian pattern: darkness stimulates production, while light suppresses it. Melatonin levels rise in the evening, peak during the night, and decline toward morning.

Role and mechanism: Melatonin communicates night length to the body and helps regulate the sleep-wake cycle. It acts mainly through MT1 and MT2 receptors in the brain and other tissues, influencing circadian timing and sleep propensity. Beyond sleep, melatonin has antioxidant properties and has been explored for immune and metabolic effects; evidence varies by outcome and condition.

Clinical use and regulation: In many countries, melatonin is sold as an over-the-counter dietary supplement or as a prescription drug, with regulatory status differing by jurisdiction. It is commonly used for jet lag, shift work sleep disorder, and some instances of primary or circadian-related insomnia, particularly in blind individuals. Dosing and timing depend on the indication and patient factors.

Safety and interactions: Short-term use is generally well tolerated in adults, with drowsiness, headaches, dizziness, and gastrointestinal symptoms reported. The safety of long-term use, effects on children or adolescents, pregnancy, and lactation are less certain. Potential interactions include anticoagulants, antidiabetic drugs, immunosuppressants, and certain antidepressants; use should be discussed with a clinician, especially in individuals with medical conditions or those taking other medications.

Pharmacokinetics and timing: Melatonin is rapidly absorbed with a relatively short half-life. Because circadian responses depend on dosing time, timing is important for therapeutic effects; for jet lag, taking melatonin near target sleep time at the destination is commonly advised, whereas for shift work, timing must align with the intended sleep window.