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. The supplement is unregulated by FDA in the US, 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.