# How melatonin puts the brain to sleep — and what we still don’t know
A review published in the Journal of Family Medicine and Primary Care lays out what decades of research have established about melatonin’s role in sleep — and where the evidence still falls short.
Melatonin is a neurohormone produced by the pineal gland. Its synthesis runs through a two-step enzymatic pathway: serotonin gets converted by AANAT (arylalkylamine N-acetyltransferase), then by HIOMT (hydroxyindole-O-methyltransferase) into melatonin. The whole process is clocked by the suprachiasmatic nucleus (SCN) in the hypothalamus. Light suppresses production; darkness triggers it. That makes melatonin one of the most reliable biochemical markers of where someone’s internal clock stands.
Once released, melatonin acts on two G-protein-coupled receptors — MT1 and MT2 — found throughout the SCN and other brain regions. MT1 activation quiets SCN neuronal firing and promotes sleep onset. MT2 receptors are more involved in shifting the circadian phase. Together, they help you fall asleep, stay asleep, and stay aligned with the day-night cycle.
The review also flags melatonin’s side roles: antioxidant, anti-inflammatory, and chronobiotic — meaning it can actively shift the timing of biological rhythms, not just mark them.
## What the evidence says about using it
Exogenous melatonin is widely used for circadian rhythm sleep-wake disorders, jet lag, shift work, and insomnia — especially in older adults, whose natural production drops with age.
Short-term safety looks fine. The problem is everything else. Over-the-counter doses vary wildly between countries. There are no regulatory standards tying dose to indication. And almost no long-term data exists on whether chronic use affects the body’s own melatonin production, reproductive function, or other hormonal systems. The review’s authors call for dose-response studies with proper follow-up — the kind that barely exist right now.
## Why it matters
Melatonin is one of the most-used sleep aids in the world. Circadian disruption has been linked to metabolic disease, cardiovascular risk, and mood disorders. Yet the gap between how many people take melatonin and how much we actually know about using it properly remains wide.
This review is a narrative synthesis, not a meta-analysis — so it cannot quantify effect sizes across studies. Many of the trials it draws on used different dosing protocols, which makes cross-study comparisons difficult. The authors flag this as a recurring weak point in the field.
## Bottom line
Melatonin is central to circadian sleep-wake timing through the SCN–MT1/MT2 receptor axis. It works for circadian misalignment and insomnia. But the questions that matter most for everyday use — how much, for how long, and with what downstream effects — are largely unanswered.
**Source:** Wani PD. “Melatonin and sleep: Exploring its role in regulating the circadian rhythm and sleep-wake cycle.” *Journal of Family Medicine and Primary Care* 15(3):1057-1062, 2026. DOI: 10.4103/jfmpc.jfmpc_150_25.