Melatonin

CAS Number	73-31-4 (verified against PubChem CID 896)
Molecular Formula / MW	C13H16N2O2 / 232.28 g/mol
Chemical Class	Indoleamine — N-acetyl-5-methoxytryptamine; derived from serotonin, itself from tryptophan
Source	Endogenously synthesised by the pineal gland under darkness; commercial material is synthetic
Receptors	MT1 and MT2 G-protein-coupled receptors
Typical Standardisation	Melatonin by HPLC; 99% is the standard commercial grade
Regulatory Note	Regulatory status varies sharply by market — a supplement in the US, a prescription medicine in much of the EU, UK, and elsewhere
Buy from Herbuno	Melatonin 99% Powder →

Name origin: Melatonin was named for its effect on melanophores — it lightens the skin of amphibians by aggregating melanin granules, which is how it was first detected and isolated from bovine pineal glands in 1958. Chemically it is N-acetyl-5-methoxytryptamine, an indoleamine synthesised from serotonin, which is itself synthesised from tryptophan. Its human function turned out to have nothing to do with skin colour. Traditional use: None, and no ethnobotanical narrative should be constructed. Melatonin is an endogenous hormone, isolated in 1958 and characterised through the second half of the 20th century. Research trajectory: The critical conceptual point, which this page will hammer because the market ignores it, is that melatonin is a chronobiotic — a signal that communicates darkness and entrains circadian phase — and not a hypnotic in the sense that a benzodiazepine or Z-drug is. It is the body’s clock signal, not its off switch. Reading the clinical literature through the hypnotic frame produces disappointment; reading it through the chronobiotic frame makes it cohere. Regulatory note: Melatonin’s regulatory status differs radically between markets — freely sold as a supplement in the United States, but a prescription-only medicine in the UK, much of the EU, Japan, and Australia. This is a material compliance issue, not a footnote.

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Evidence for Melatonin Applications

The effect size for general insomnia is real but small, and honest reporting requires saying so. A meta-analysis of nineteen randomized placebo-controlled trials involving 1,683 subjects with primary sleep disorders found melatonin significantly reduced sleep latency — by a weighted mean difference of 7.06 minutes (95% CI 4.37–9.75) — and increased total sleep time by 8.25 minutes (95% CI 1.74–14.75) (Ferracioli-Oda 2013). Seven minutes faster to sleep and eight minutes more sleep is statistically significant and clinically modest. Anyone selling melatonin as a powerful sleep aid is misrepresenting the data. Claim strength: Moderate (small effect).

But the effect is dramatically larger where the problem is circadian rather than insomnia — and this is the whole point. A meta-analysis found melatonin decreased sleep onset latency by a weighted mean difference of 11.7 minutes overall, but with the reduction far greater in people with delayed sleep phase syndrome (38.8 minutes; 95% CI 27.3–50.3) than in people with insomnia (7.2 minutes; 95% CI 2.4–12.0) — and the authors noted the former result appears to be clinically important, with no evidence of adverse effects (Buscemi 2005). A fivefold difference in effect between circadian disorder and insomnia is the single most useful fact on this page. Claim strength: Moderate to High (circadian indications).

Timing matters more than dose, and the market has this backwards. Dose-response meta-analysis has found that melatonin gradually reduces sleep onset latency and increases total sleep time, peaking at around 4 mg/day — with meta-regression showing that the time between administration and the sleep episode was a significant predictor of sleep onset latency. Because melatonin acts by phase-shifting the circadian clock, when it is taken determines the direction and magnitude of the shift. A high dose at the wrong time is worse than a low dose at the right one. Yet the market has drifted toward 5, 10, and even 20 mg products — doses far above physiological levels, above the meta-analytic optimum, and unsupported by dose-response data. Claim strength: Moderate.

The efficacy picture also differs by population, and the honest summary is uncomfortable for the adult supplement market. In non-comorbid chronic insomnia, subgroup analysis has found melatonin significantly effective for sleep onset latency and total sleep time in children and adolescents — while in the adult group, melatonin was not significantly effective for sleep onset latency, total sleep time, or sleep efficiency. Meanwhile, network meta-analyses consistently note that none of these interventions is superior to cognitive-behavioural therapy for insomnia, which remains first-line. Claim strength: Emerging (adult chronic insomnia).

Where melatonin has the clearest and least contested standing is in circadian disruption: jet lag, shift work, delayed sleep-wake phase disorder, and non-24-hour sleep-wake disorder in blind individuals, where it has been shown to regulate sleep-wake patterns. This is a mechanistically coherent, well-defined application set, and it is where a formulator can stand on solid ground. It is also, notably, not where most melatonin is sold. Claim strength: Moderate to High.

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Dosage & Formulator Specification

Herbuno carries Melatonin 99% powder. Buyers must confirm the regulatory status of melatonin in their destination market before purchasing: it is a dietary supplement in the United States but a prescription-only medicine in the UK, much of the EU, Japan, and Australia. This is a material compliance requirement and Herbuno will discuss it at enquiry.

Dose-response meta-analysis places the optimum at around 4 mg/day, with efficacy for sleep onset latency and total sleep time peaking there — a finding that sits awkwardly against a market drifting toward 5, 10, and 20 mg products. Physiological nocturnal melatonin levels correspond to considerably lower doses still, and doses in the 0.3–1 mg range have been used effectively for circadian phase-shifting. Timing is the variable that matters most: because melatonin phase-shifts the circadian clock, the interval between administration and the intended sleep episode determines the effect, and this should be reflected in label guidance rather than left to the consumer to guess.

Analytical verification should specify melatonin by HPLC (99% standard) against a certified reference standard, with related-substance and residual-solvent profiling, since commercial melatonin is synthetic and impurity profile is a function of synthetic route. Content uniformity deserves particular attention for this ingredient: independent analyses of commercial melatonin products have repeatedly found actual content diverging substantially from label claim, in both directions. For a hormone with dose- and timing-sensitive effects, that is a meaningful quality failure rather than a rounding error.

Melatonin is well tolerated in the short term, with meta-analyses reporting no evidence of significant adverse effects; drowsiness, headache, dizziness and vivid dreams are the most commonly reported. Several cautions warrant clear statement. It is a hormone, and long-term safety data — particularly regarding effects on the reproductive axis in children and adolescents, a population in which it is widely and increasingly used — is genuinely limited; this deserves candour rather than reassurance. Next-day sedation and impaired driving are plausible, especially at the supraphysiological doses now common. Melatonin is metabolised primarily by CYP1A2, so interaction with fluvoxamine and other CYP1A2 inhibitors can markedly raise exposure. Interaction with anticoagulants and with immunosuppressants has been reported. And the regulatory position — prescription-only in many markets — exists precisely because these are not trivial considerations.

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Frequently Asked Questions — Melatonin

How much does melatonin actually help with sleep?
Less than the market implies. A meta-analysis of 19 trials in primary sleep disorders found it reduced sleep latency by about 7 minutes and increased total sleep time by about 8 minutes. Statistically significant, clinically modest. Anyone selling it as a powerful sleep aid is misrepresenting the data.

Then when does melatonin work well?
When the problem is circadian rather than insomnia — and the difference is roughly fivefold. One meta-analysis found sleep onset latency reduced by 38.8 minutes in delayed sleep phase syndrome versus only 7.2 minutes in insomnia. Jet lag, shift work, delayed sleep-wake phase disorder, and non-24-hour rhythm in blind individuals are where it stands on solid ground.

Is more melatonin better?
No. Dose-response meta-analysis found efficacy peaking at around 4 mg/day — yet the market has drifted to 5, 10, and even 20 mg products, far above physiological levels and unsupported by dose-response data. Timing matters more than dose: because melatonin phase-shifts the clock, when you take it determines the effect.

Is melatonin legal to sell everywhere?
No, and this is a material compliance issue. It is a dietary supplement in the United States but a prescription-only medicine in the UK, much of the EU, Japan, and Australia. Buyers must confirm the regulatory status in their destination market before purchasing.

Related compounds: Valerenic Acids, Bacoside A, Magnolol, Apigenin

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Claim-strength scale – High = multiple human RCTs; Moderate = limited trials or strong preclinical convergence; Emerging = early-stage lab or animal data.

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