[crdrost]

PSA that melatonin use was way out of control before this study was even published.

Sleep aid melatonin is shipped in pills containing ridiculous amounts of the stuff—I’ve seen 10, 12, and 20mg myself, Amazon has a 40mg fast dissolve and 60mg gummies.

This spikes your blood amount with 100x-1000x of your natural cycle of melatonin. Why? Because melatonin is not, repeat not, the signaling molecule that makes you sleepy. It responds to light levels and triggers the cascade of other molecules that make you sleepy, several hours after it peaks. So that's why the 100x overdose—you are trying to kick those secondary mechanisms into overdrive, “hey everyone it is black as the abyss of hell I guess we gotta sleep!!”, because Americans taking melatonin want to pop one just before bed and have it knock them out.

And it does that for like 2 or 3 days before your body starts down-regulating all of its sensitivities to those melatonin byproducts. Nerve cells like to be tickled, not zapped, when you shock them like this they react angrily.

You want to use melatonin to reinforce circadian rhythm and fight jet lag, you do it with amounts in the ~100 micrograms range, slow release if you can find it, and you take that at sunset and let it reinforce your normal cycle. If you're looking for an acute sleep aid, take a walk, get fresh air, drink water, and if those don't help pop a Benadryl/Unisom (it's the same drug either way). If you have doctor’s orders of course follow those, but if you're just trying to self-medicate that’s how you do it.

Absolutely unsurprising that punching your sleep apparatus in the gut once every day for five years increases some sort of stress on your heart.

[canjobear]

In grad school I got to attend a talk by one of the researchers who was involved in the discovery of melatonin as a sleep aid for humans. He said that his team had hoped for it to become a prescription medicine dosed at 500 mcg, because anything higher gave paradoxical effects and actually made sleep worse. But it ended up being classified as a supplement in the US rather than a drug, so they had no way to control the dosage on the market.

The other useful thing I learned is that melatonin isn't primarily involved in falling asleep, its main function as a hormone is in staying asleep. I've started taking it sporadically if I wake up in the middle of the night, to make sure I get back to a deep sleep and stay there, and it seems to be super effective for this.

[BobbyTables2]

I suspect each brand tries to put more to out-compete with other brands.

People look at multivitamins and think “more is better”. Unfortunately they are stuffed with ingredients that can’t be absorbed well together, but do result in higher sales…

[tlavoie]

I've taken it rarely, but not found it to be a panacea on the night I'm having trouble sleeping. That is, if it isn't already early when I take it, I'm positively trashed for the morning after. The next night is when I find that taking one early helps in catching up.

[richbell]

> He said that his team had hoped for it to become a prescription medicine dosed at 500 mcg, because anything higher gave paradoxical effects and actually made sleep worse.

Tangentially, I'm reminded of this interview around ~31m.

TL;DR they found something that promoted deeper sleep, but people didnt necessary feel "well rested", and so it was shelved for something that subjectively improved sleep but actually reduced the quality of sleep.

https://youtu.be/UWhk2LMDwCc?t=31m

[PaulKeeble]

There was a collection of studies about a decade ago that seemed to determine the optimal use of Melatonin was about 350 micrograms taken about 1 hour before bed. The ideal was also slow release which was the best you could do to match the bodies process currently. The doses you can buy are far too high even the 1.5mg ones.

[wincy]

I buy 300mcg for me and my kids, it’s a fantastic sleep aid. Thanks to Scott Alexander talking about it.

[elcritch]

It can be difficult to find low dose melatonin unfortunately. Especially in slow release.

Often kids sleep tablets are better. Also kids chewable gummies can be cut in half to get an effective dosage. I've not found a good long release version of those.

[getpost]

> you take that at sunset and let it reinforce your normal cycle

Yes, the way Michael Grandner explains it in this podcast[0], melatonin is an ancient molecule that signals, "it is dark." If you give it to nocturnal species, it wakes them up!

[0] https://www.youtube.com/watch?v=AQF_eopP1ys

[eurleif]

>Benadryl/Unisom (it's the same drug either way)

Are you sure about this? Everything I can find says Benadryl is diphenhydramine, and Unisom is doxylamine. (Both linked to increased dementia risk, for what it's worth.)

[pogue]

Yes, I would use first generation antihistamines like those sparingly as they are anticholergenic. It's more of a long term concern rather than for occasional use.

For the low dose melatonin, Life Extension brand sells patented MicroActive formula of fast release/slow release melatonin in a 1.5mg dosage and a 6 hour time released 300mcg version. It's a quality brand and those are the dosage ranges I would recommend sticking around.

I have seen the insanely high 30mg+ amounts being sold and that's ridiculous. If you need that much, there's other factors going on. I would look into reducing caffeine intake, doing proper sleep hygiene (google it), and talk to a doctor/get a referral to a sleep specialist if it's an ongoing thing.

But, also look into l-theanine, glycine/magnesium glycinate, valerian root extract, passionflower, lemon balm and things of that sort for occasional sleeplessness or trouble falling asleep. (Visit examine.com & ergo-log.com and search for these ingredients on there to see all the references, how they work, and for more info.)

Natural isn't necessarily better, but I would recommend those any day over Z drugs, antihistamines and a lot of other rx sleep drugs. Make sure you're buying a quality brand though.

Finally, please don't give melatonin to children...

Parents give kids more melatonin than ever, with unknown long-term effects https://arstechnica.com/health/2025/04/melatonin-for-kids-sa...

[grimpy]

There are two kinds of Unisom: diphenhydramine and doxylamine succinate.

[pedalpete]

Can you point to a source about the body down-regulating melatonin?

I also thought this was the case, but everything I've seen suggests that taking melatonin does not alter the natural production of melatonin.

You are correct about everything else though.

[a2dam]

It doesn't. There's some minor evidence, but it's very quickly reversed.

[crdrost]

I mean it's understudied, but at the very least you have [1], children given high doses daily of melatonin developed delayed sleep/wake cycles when measured by DLMO (the time of day that your endogenous melatonin starts to rise) and that “Nearly all children who temporarily discontinued melatonin experienced a delay in sleep onset time,” both of which strongly suggest downregulation is happening. (Usually endogenous melatonin skews earlier with melatonin supplementation, see [2].)

Similar inefficacies have been seen clinically e.g. in [3] and are (caution, anecdata) widespread on the internet, with "melatonin doesn't work" being a popular search term with tons of articles about it. An honest to goodness test seems to have been done at [4] where they made sleep disturbance symptoms "disappear" by resuming treatment at a lower dosage, but instead of blaming the neurons they are blaming the liver, saying that it got overloaded and couldn't clear melatonin out of the bloodstream anymore in some patients—I just want to include that as a plausible alternative explanation so that you don't take my words as gospel truth or anything. I’m trained as a physicist, not a physician, and there is this meme of people with physics degrees thinking that everybody else’s field is their expertise and like I want to be deliberately self conscious about my limitations here.

[1]: PDF Warning: https://www.herbogeminis.com/revista/IMG/pdf/melatonin-adhd....

[2]: https://academic.oup.com/sleep/article-abstract/33/12/1605/2...

[3]: https://www.psychiatrist.com/jcp/effects-exogenous-melatonin...

[4]: https://pubmed.ncbi.nlm.nih.gov/20576063/

[happymellon]

I visited my in-laws a couple of weeks ago.

From streetlights everywhere, emergency vehicles blasting sirens at all hours, trains blasting horns (miles away but are still audible), its no surprise that Americans are struggling to sleep if this is your environment.

Melatonin isn't going to fix that.

[nerdsniper]

https://slatestarcodex.com/2018/07/10/melatonin-much-more-th...

[temp0826]

I know someone with a condition (I don't recall the name of it) but it actually calls for these massive doses of melatonin (up to 100 mg). The vast majority of people wanting to use it should start LOW- as in 0.25-0.5 mg.

[DANmode]

Accurate.

After 1-3mg, you’re doing yourself a disservice.

At least, for sleep purposes. I cannot comment on its use as an antioxidant.