Melatonin
Properties
| State | Solid (white to off-white crystalline powder) |
| Color | White to off-white |
| Solubility | Slightly soluble in water (1 g/L); soluble in ethanol and DMSO |
| Melting Point | 116-118°C |
| Boiling Point | Decomposes before boiling |
About Melatonin
Melatonin is the indoleamine the pineal gland makes from serotonin every night when the suprachiasmatic nucleus tells it that the lights are out. The biosynthesis is a two-step trim from serotonin: aralkylamine N-acetyltransferase (AANAT) acetylates the primary amine to N-acetylserotonin, then HIOMT methylates the 5-OH to give the 5-methoxy group. Pineal output peaks somewhere around 2-4 a.m. at roughly 60-70 pg/mL plasma in a healthy adult and falls back to ~10 pg/mL by sunrise. The on/off switch is light at 460-480 nm hitting melanopsin in the intrinsically photosensitive retinal ganglion cells, and the pathway runs retina → SCN → paraventricular nucleus → superior cervical ganglion → pineal. That's why a glance at a phone screen at 11 p.m. delays melatonin onset by 60-90 minutes in most people. Pharmacologically, melatonin binds MT1 and MT2 receptors with Kd around 100 pM, and unlike a benzodiazepine it does not sedate by enhancing GABA — it shifts the circadian phase, which is why it works for jet lag and shift work but is hit-or-miss for ordinary insomnia. The over-the-counter US market sells about 3 mg per pill on average, which is roughly 30x the physiological peak; clinical sleep medicine increasingly recommends 0.3-0.5 mg taken 4-6 hours before target bedtime for circadian phase-shifting.
Where you'll encounter it
If you have ever flown JFK to Heathrow on a redeye, landed at 7 a.m. local with the sun blasting, and wondered whether to take the 5 mg melatonin gummy in your bag — you have run into the dosing problem nobody tells you about. The high doses sold in the US (3-10 mg) raise plasma melatonin to ~1000x physiological levels for hours, which is more about hitting receptors hard than about restoring the natural curve. Sleep researchers like Charmane Eastman have shown 0.3-0.5 mg works as well or better for phase-shifting, with less morning grogginess. In the lab, melatonin shows up in dim-light melatonin onset (DLMO) assays — researchers measure salivary melatonin every 30 minutes under <30 lux red light to find each subject's true circadian phase, the gold-standard chronotype measurement.
Common Uses
- OTC supplement for jet-lag phase shifting (0.3-0.5 mg dose, 4-6 h before target bedtime)
- Adjunct treatment for delayed sleep-wake phase disorder and shift-work disorder
- Dim-light melatonin onset (DLMO) assays for circadian-phase research
- Free-radical scavenger in oxidative-stress and neuroprotection research
- Adjuvant in chemotherapy clinical trials for solid tumors
Safety Information
Not classified as hazardous under GHS. Common side effects at 1-5 mg supplement doses include daytime sleepiness (~15% of users), morning grogginess, vivid dreams, and headache. Long-term safety data beyond ~6 months are thin. Drug interactions: warfarin (additive bleeding risk via CYP1A2 inhibition), fluvoxamine (8x plasma melatonin from CYP1A2 inhibition), nifedipine (reduced antihypertensive effect), and immunosuppressants. Pediatric use only with sleep specialist oversight — case reports of seizures in children with neurological conditions. Pregnancy category not established; avoid. Supplement melatonin is not held to drug-grade manufacturing standards in most markets, so independent assays have found 70-470% of labeled dose across brands.
This safety summary is for educational reference only and may not be complete. It is not a substitute for Safety Data Sheets (SDS), medical advice, or professional chemical safety guidance. Always consult appropriate SDS and qualified professionals before handling chemicals. We deliberately do not publish occupational exposure limits or other regulatory thresholds: those values are revised over time and differ between jurisdictions, so the only correct source is the current SDS and the regulations that apply where you work.