Melatonin
Melatonin
Melatonin is an endogenous neurohormone produced by the pineal gland that regulates the sleep-wake cycle and circadian rhythms. It is widely used as a supplement to improve sleep onset latency, manage jet lag, and support circadian rhythm disorders such as delayed sleep phase syndrome. At higher doses, it is also investigated for its antioxidant and immunomodulatory properties.
Mechanism of Action
Melatonin primarily acts as an agonist at MT1 and MT2 G-protein coupled receptors in the suprachiasmatic nucleus of the hypothalamus, suppressing wakefulness signals and promoting sleep onset. MT1 receptor activation inhibits neuronal firing to reduce alertness, while MT2 activation helps phase-shift circadian rhythms. Melatonin also acts as a direct free radical scavenger and upregulates antioxidant enzymes such as superoxide dismutase and glutathione peroxidase, independent of receptor binding.
Evidence by Health Goal(18 goals)
Dosing Protocols
30-60 minutes before desired sleep time
Lower doses (0.5-1mg) are often as effective as higher doses for sleep onset and carry fewer next-day grogginess side effects. Start at 0.5mg and titrate up only if needed. Doses above 5mg are generally not recommended for routine sleep use.
15-30 minutes before desired sleep time
Sublingual administration results in faster absorption and earlier peak plasma concentrations compared to oral, which may be advantageous for sleep onset difficulties. Allows for lower effective doses due to bypassing first-pass metabolism.
Safety & Side Effects
Melatonin has an excellent short-term safety profile and is one of the most widely used sleep supplements globally; however, long-term effects of pharmacological doses remain understudied, and it is classified as a prescription medication in several countries including the UK, Germany, and Australia for doses above 2mg. Use with caution in children, pregnant or breastfeeding individuals, and those with autoimmune conditions, as melatonin can modulate immune function.
Possible Side Effects
- !Morning grogginess or next-day sedation, particularly at doses above 3mg
- !Dizziness or lightheadedness shortly after administration
- !Headache, especially with higher doses or prolonged use
- !Nausea or mild gastrointestinal discomfort
- !Vivid or unusual dreams
- !Hormonal effects with long-term high-dose use, including potential suppression of endogenous melatonin production
- !Mild hypothermia or drop in core body temperature
Interactions
- -Potentiates CNS depressants including benzodiazepines, Z-drugs, and alcohol, increasing sedation risk
- -May enhance anticoagulant effects of warfarin and other blood thinners, increasing bleeding risk
- -Can lower blood pressure additively - use caution with antihypertensive medications
- -Fluvoxamine (SSRI) significantly increases melatonin plasma levels by inhibiting CYP1A2 metabolism, risking excessive sedation
- -May diminish efficacy when combined with beta-blockers, which suppress endogenous melatonin secretion
Cost & Where to Buy
Melatonin is widely available over-the-counter in the US and is one of the most affordable supplements. Cost varies by dose, brand quality, and formulation (immediate-release vs. extended-release). Extended-release and sublingual formulations trend toward the higher end of pricing.
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