RESEARCH MONOGRAPH · KDC-MN-149

Melatonin

May 9, 2026 Kodiac biolabs Research Revised May 30, 2026 2 min read

Our opinion on this compound

74/100

Established hormone where the popular use dose is roughly 10 to 100 times what the physiology calls for

Melatonin is one of the more abused-by-marketing molecules on the supplement market. The pharmacology is actually pretty straightforward: indolamine secreted by the pineal gland under SCN-driven circadian control, peaks in early biological night, acts primarily through MT1 and MT2 receptors. Physiologic peak plasma concentrations are in the 50 to 200 picomolar range. The doses sold over the counter (typically 3 to 10 mg) produce plasma concentrations of 1000-fold or more above physiologic, which is genuinely strange dosing.

The interesting research on melatonin is mostly about chronobiology and phase-shifting effects, where appropriately-timed low doses (0.3 to 0.5 mg) can shift circadian phase as effectively as higher doses without the next-morning grogginess and without the dose-response saturation problems that the bigger doses introduce. Brzezinski's work, the Lewy lab, and the Czeisler group have published on this for decades. The right dose is small and the timing matters more than the amount.

What we like: as a phase-shifting tool melatonin works. The MT1/MT2 receptor pharmacology is well-mapped, the SCN circadian biology is textbook, and the clinical literature on jet lag and circadian rhythm sleep disorders is reasonable. Underappreciated angle: melatonin also has direct antioxidant effects at higher doses that may be separate from the receptor-mediated chronobiology effects, which is a different research area entirely.

What we dont like: the popular use of high-dose melatonin as a sleep aid misses what the molecule actually does. It's not a sedative-hypnotic. The supraphysiologic doses cause receptor desensitization at MT1 and can paradoxically worsen sleep architecture, particularly suppressing REM sleep in some studies. The product market also has notorious quality issues, with multiple analyses showing actual content ranging from 17 percent to over 400 percent of labeled dose, which is genuinely embarrassing for a pharmaceutical-grade compound.

Mechanism: MT1 and MT2 well-mapped, downstream effects on SCN neuronal firing increasingly well-characterized. Antioxidant effects are more speculative.

Sourcing: cheap, easy to make, but the OTC supplement market is famously inconsistent. Pharmaceutical-grade and research-grade vendors are reliable; cheap consumer products are not.

Established workhorse, misused at popular doses.

Evidence: 85
Mechanism: 85
Reliability: 65
Safety: 75
Sourcing: 60
Value: 80
Signal: 65
Staying power: 75

Plain-language summary Intrigue 65 / 100

Melatonin is the sleep hormone produced by the pineal gland in response to darkness. Supplementation is used for circadian rhythm disorders, jet lag, and sleep onset. The optimal dose is much lower than typically sold (0.3 mg, not 5-10 mg). Not stocked by Kodiac. This monograph is provided for research and educational reference.

Intrigue 0–100 blends mechanism novelty, evidence strength, and translational potential. Kodiac editorial, not peer-reviewed.

Endogenous indolamine hormone

An endogenous pineal hormone synthesized from serotonin, the master circadian regulator and a widely-used sleep supplement.

Abstract

Melatonin (N-acetyl-5-methoxytryptamine; CAS 73-31-4; molecular formula C13H16N2O2; molecular weight 232.28) is an endogenous indolamine synthesized in the pineal gland from serotonin via N-acetylation and 5-methoxylation. Endogenous melatonin secretion peaks during darkness and is the principal hormonal signal of biological night. Supplementation is widely used for sleep onset, jet lag, and shift work sleep. Mechanism is MT1 and MT2 melatonin receptor agonism; the compound also has direct antioxidant activity. Pharmacokinetics: plasma half-life 30 to 50 minutes; oral bioavailability variable (15 to 50 percent). Reported research dose ranges in the literature are described in the source publications.

Mechanism of action

MT1/MT2 melatonin receptor agonist. Direct antioxidant. Master circadian phase regulator.

Reported research dose ranges

Reported research dose ranges in the literature.

References

Brzezinski A. Melatonin in humans. N Engl J Med 1997.

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KDC-MN-149

The full reference document is provided strictly for research use only. It reports research dose ranges from the published literature, not instructions for use in humans or animals.

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FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.

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Melatonin

Abstract

Mechanism of action

Reported research dose ranges

References

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Abstract

Mechanism of action

Reported research dose ranges

References

Read the full monograph

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