Melatonin: Much More Than You Wanted To Know

[I am not a sleep spe­cial­ist. Please con­sult with one be­fore mak­ing any drastic changes or try­ing to treat any­thing ser­i­ous.]

Van Geijlswijk et al de­scribe sup­ple­mental melatonin as “a chro­n­o­bi­otic drug with hyp­notic prop­er­ties”. Using it as a pure hyp­notic – a sleep­ing pill – is like us­ing an AK-47 as a club to bash your en­emies’ heads in. It might work, but you’re fail­ing to ap­pre­ci­ate the full power and sub­tlety avail­able to you.

Melatonin is a neur­o­hor­mone pro­duced by the pineal gland. In a nor­mal cir­ca­dian cycle, it’s low­est (un­detect­able, less than 1 pg/​ml of blood) around the time you wake up, and stays low through­out the day. Around fif­teen hours after wak­ing, your melatonin sud­denly shoots up to 10 pg/​ml – a pro­cess called “dim light melatonin on­set”. For the next few hours, melatonin con­tin­ues to in­crease, maybe as high as 60 or 70 pg/​ml, mak­ing you sleepier and sleepier, and pre­sum­ably at some point you go to bed. Melatonin peaks around 3 AM, then de­clines un­til it’s un­detect­ably low again around early morn­ing.

Is this what makes you sleepy? Yes and no. Sleep­i­ness is a com­bin­a­tion of the cir­ca­dian cycle and the so-called “Pro­cess S”. This is an un­ne­ces­sar­ily sin­is­ter-sound­ing name for the fact that the longer you’ve been awake, the sleepier you’ll be. It seems to be partly reg­u­lated by a mo­lecule called ad­en­osine. While you’re awake, the body pro­duces ad­en­osine, which makes you tired; as you sleep, the body clears ad­en­osine away, mak­ing you feel well-res­ted again.

In healthy people these pro­cesses work to­gether. Cir­ca­dian rhythm tells you to feel sleepy at night and awake dur­ing the day. Pro­cess S tells you to feel awake when you’ve just risen from sleep (nat­ur­ally the morn­ing), and tired when you haven’t slept in a long time (nat­ur­ally the night). Both pro­cesses agree that you should feel awake dur­ing the day and tired at night, so you do.

When these pro­cesses dis­agree for some reason – night shifts, jet lag, drugs, ge­net­ics, play­ing Civil­iz­a­tion un­til 5 AM – the sys­tem fails. One pro­cess tells you to go to sleep, the other to wake up. You’re never quite awake enough to feel en­er­gized, or quite tired enough to get rest­ful sleep. You find your­self ly­ing in bed toss­ing and turn­ing, or wak­ing up while it’s still dark and not be­ing able to get back to sleep.

Melatonin works on both sys­tems. It has a weak “hyp­notic” ef­fect on Pro­cess S, mak­ing you im­me­di­ately sleepier when you take it. It also has a stronger “chro­n­o­bi­otic” ef­fect on the cir­ca­dian rhythm, shift­ing what time of day your body con­siders sleep to be a good idea. Ef­fect­ive use of melatonin comes from un­der­stand­ing both these ef­fects and us­ing each where ap­pro­pri­ate.

1. Is melatonin an ef­fect­ive hyp­notic?

Yes.

That is, tak­ing melatonin just be­fore you want to get to sleep, does help you get to sleep. The evid­ence on this is pretty un­an­im­ous. For primary in­som­nia, two meta-ana­lyses – one by Brzez­in­ski in 2005 and an­other by Fer­ra­ci­oli-Oda in 2013 – both find it safe and ef­fect­ive. For jet lag, a meta-ana­lysis by the usu­ally-skep­tical Co­chrane Col­lab­or­a­tion pro­nounces melatonin “re­mark­ably ef­fect­ive”. For a wide range of primary and sec­ond­ary sleep dis­orders, Bus­cemi et al say in their ab­stract that it doesn’t work, but a quick glance at the study shows it ab­so­lutely does and they are in­cor­rectly un­der-re­port­ing their own res­ults. The Psy­chi­at­ric Times agrees with me on this: “Res­ults from an­other study re­por­ted as neg­at­ive ac­tu­ally demon­strated a stat­ist­ic­ally sig­ni­fic­ant pos­it­ive res­ult of a de­crease in sleep latency by an av­er­age of 7.2 minutes for melatonin”.

Ex­pert con­sensus gen­er­ally fol­lows the meta-ana­lyses: melatonin works. I find cau­tious en­dorse­ments by the Mayo Clinic and John Hop­kins less im­press­ive than its less-than-com­pletely-neg­at­ive re­view on Science-Based Medi­cine, a blog I can usu­ally count on for a hit job on any di­et­ary sup­ple­ment.

The con­sensus stresses that melatonin is a very weak hyp­notic. The Bus­cemi meta-ana­lysis cites this as their reason for de­clar­ing neg­at­ive res­ults des­pite a stat­ist­ic­ally sig­ni­fic­ant ef­fect – the sup­ple­ment only made people get to sleep about ten minutes faster. “Ten minutes” sounds pretty pathetic, but we need to think of this in con­text. Even the strongest sleep med­ic­a­tions, like Am­bien, only show up in stud­ies as get­ting you to sleep ten or twenty minutes faster; ef=“ht­tps://​ww<em>w.nytimes.com/​2007/​10/​23/​health/​23drug.html”>this New York Times art­icle says that “viewed as a group, [newer sleep­ing pills like Am­bien, Lun­esta, and Sonata] re­duced the av­er­age time to go to sleep 12.8 minutes com­pared with fake pills, and in­creased total sleep time 11.4 minutes.” I don’t know of any stat­ist­ic­ally-prin­cipled com­par­ison between melatonin and Am­bien, but the dif­fer­ence is hardly (pun not in­ten­ded) day and night.

Rather than say “melatonin is crap”, I would ar­gue that all sleep­ing pills have meas­ur­able ef­fects that vastly un­der­per­form their sub­ject­ive ef­fects. The linked art­icle spec­u­lates on one reason this might be: people have low aware­ness around the time they get to sleep, and a lot of people’s per­cep­tion of whether they’re in­som­niac or not is more anxi­ety (or some­times lit­er­ally dream) than real­ity. This is pos­sible, but I also think of this in terms of an­ti­de­press­ant stud­ies, which find sim­il­arly weak ob­ject­ive ef­fects des­pite pa­tients (and doc­tors) who swear by them and say they changed their lives. If I had to guess, I would say that the stud­ies in­clude an awk­ward com­bin­a­tion of sick and less-sick people and con­fuse re­spon­ders and non-re­spon­ders. Maybe this is spe­cial plead­ing. I don’t know. But if you think any sleep­ing pill works well, melatonin doesn’t ne­ces­sar­ily work much worse than that.

Sleep latency stat­ist­ics are hard to com­pare to one an­other be­cause they’re so de­pend­ent on the study pop­u­la­tion. If your sub­jects take an hour to fall asleep, per­haps melatonin could shave off thirty-four minutes. But if your sub­jects take twenty minutes to fall asleep, then no sleep­ing pill will ever take off thirty-four minutes, and even an amaz­ing sleep­ing pill might struggle to make fif­teen. I can­not dir­ectly com­pare the people who say melatonin gives back ten minutes to the people who say melatonin gives back thirty-four minutes to the people who say Am­bien gives back twelve, but my totally un­prin­cipled guess is that melatonin is about a third as strong as Am­bien. It also has about a hun­dred times fewer side ef­fects, so there’s def­in­itely a place for it in sleep medi­cine.

2. What is the right dose of melatonin?

0.3 mg.

“But my local drug­store sells 10 mg pills! When I asked if they had any­thing lower, they looked through their stock­room and were even­tu­ally able to find 3 mg pills! And you’re say­ing the cor­rect dose is a third of a mil­li­gram?!”

Yes. Most ex­ist­ing melatonin tab­lets are around ten to thirty times the cor­rect dose.

Many early stud­ies were done on eld­erly people, who pro­duce less en­do­gen­ous melatonin than young people and so are con­sidered es­pe­cially re­spons­ive to the drug. Several lines of evid­ence de­term­ined that 0.3 mg was the best dose for this pop­u­la­tion. Elderly people given doses around 0.3 mg slept bet­ter than those given 3 mg or more and had fewer side ef­fects (Zh­dan­ova et al 2001). A meta-ana­lysis of dose-re­sponse re­la­tion­ships con­curred, find­ing a plat­eau ef­fect around 0.3 mg, with doses after that hav­ing no more ef­fic­acy, but worse side ef­fects (Brzez­in­ski et al, 2005). And doses around 0.3 mg cause blood melatonin spikes most sim­ilar in mag­nitude and dur­a­tion to the spikes seen in healthy young people with nor­mal sleep (Vural et al, 2014).

Other stud­ies were done on blind people, who are es­pe­cially sens­it­ive to melatonin since they lack light cues to en­train their cir­ca­dian rhythms. This is a little bit of a dif­fer­ent in­dic­a­tion, since it’s be­ing used more as a chro­n­o­bi­otic than a sleep­ing pill, but the res­ults were very sim­ilar: lower doses worked bet­ter than higher doses. For ex­ample, in Lewy et al 2002, nightly doses of 0.5 mg worked to get a blind sub­ject sleep­ing nor­mally at night; doses of 20 mg didn’t. They reas­on­ably con­clude that the 20 mg is such a high dose that it stays in their body all day, de­feat­ing the point of a hor­mone whose job is to sig­nal night­time. Other stud­ies on the blind have gen­er­ally con­firmed that doses of around 0.3 to 0.5 mg are op­timal.

There have been dis­ap­point­ingly few stud­ies on sighted young people. One such, At­ten­bur­row et al 1996 finds that 1 mg works but 0.3 mg doesn’t, sug­gest­ing these people may need slightly higher doses, but this study is a bit of an out­lier. Another Zh­dan­ova study on 25 year olds found both to work equally. And Pires et al study­ing 22-24 year olds found that 0.3 mg worked bet­ter than 1.0. I am less in­ter­ested in judging the 0.3 mg vs. 1.0 mg de­bate than in point­ing out that both num­bers are much lower than the 3 – 10 mg doses found in the melatonin tab­lets sold in drug­stores.

UpToDate, the gold stand­ard re­search data­base used by doc­tors, agrees with these low doses. “We sug­gest the use of low, physiolo­gic doses (0.1 to 0.5 mg) for in­som­nia or jet lag (Grade 2B). High-dose pre­par­a­tions raise plasma melatonin con­cen­tra­tions to a supra­physiolo­gic level and al­ter nor­mal day/​night melatonin rhythms.” Mayo Clinic makes a sim­ilar re­com­mend­a­tion: they re­com­mend 0.5 mg. John Hop­kins’ ex­perts al­most agree: they say “less is more” but end up chick­en­ing out and re­com­mend­ing 1 to 3 mg, which is well above what the stud­ies would sug­gest.

Based on a bunch of stud­ies that either fa­vor the lower dose or show no dif­fer­ence between doses, plus clear evid­ence that 0.3 mg pro­duces an ef­fect closest to nat­ural melatonin spikes in healthy people, plus UpToDate usu­ally hav­ing the best re­com­mend­a­tions, I’m in fa­vor of the 0.3 mg num­ber. I think you could make an ar­gu­ment for any­thing up to 1 mg. Anything bey­ond that and you’re def­in­itely too high. Ex­cess melatonin isn’t grossly dan­ger­ous, but tends to pro­duce tol­er­ance and might mess up your chro­n­o­bi­o­logy in other ways. Based on an­ec­dotal re­ports and the im­plaus­ib­il­ity of be­com­ing tol­er­ant to a nat­ural hor­mone at the dose you nat­ur­ally have it, I would guess suf­fi­ciently low doses are safe and ef­fect­ive long term, but this is just a guess, and most guidelines are cau­tious in say­ing any­thing after three months or so.

3. What are cir­ca­dian rhythm dis­orders? How do I use melatonin for them?

Cir­ca­dian rhythm dis­orders are when your cir­ca­dian rhythm doesn’t match the nor­mal cycle where you want to sleep at night and wake up in the morn­ing.

The most pop­u­lar cir­ca­dian rhythm dis­order is “be­ing a teen­ager”. Teen­agers’ melatonin cycle is nat­ur­ally shif­ted later, so that they don’t want to go to bed un­til mid­night or later, and don’t want to wake up un­til eight or later. This is an ob­vi­ous mis­match with school start­ing times, lead­ing to teen­agers either not get­ting enough sleep, or get­ting their sleep at times their body doesn’t want to be asleep and isn’t able to use it prop­erly. This is why every reput­able sleep sci­ent­ist and rel­ev­ant sci­entific body keeps telling the pub­lic school sys­tem to start later.

When a this kind of late sleep sched­ule per­sists into adult­hood or be­comes too dis­tress­ing, we call it Delayed Sleep Phase Disorder. People with DSPD don’t get tired un­til very late, and will nat­ur­ally sleep late if given the chance. The weak ver­sion of this is “be­ing a night owl” or “not be­ing a morn­ing per­son”. The strong ver­sion just looks like in­som­nia: you go to bed at 11 PM, toss and turn un­til 2 AM, wake up when your alarm goes off at 7, and com­plain you “can’t sleep”. But if you can sleep at 2 AM, con­sist­ently, re­gard­less of when you wake up, and you would fall asleep as soon as your head hit the pil­low if you first got into bed at 2, then this isn’t in­som­nia – it’s DSPD.

The op­pos­ite of this pat­tern is Ad­vanced Sleep Phase Disorder. This is most com­mon in the eld­erly, and I re­mem­ber my grand­father hav­ing this. He would get tired around 6 PM, go to bed by 7, wake around 1 or 2 AM, and start his day feel­ing fresh and alert. But the weak ver­sion of this is the per­son who wakes up at 5 each morn­ing even though their alarm doesn’t go off un­til 8 and they could really use the ex­tra two hours’ sleep. These people would prob­ably do fine if they just went to bed at 8 or 9, but the de­mands of work and a so­cial life make them feel like they “ought” to stay up as late as every­one else. So they go to bed at 11, wake up at 5, and com­plain of “ter­minal in­som­nia”.

Fin­ally, there’s Non-24-Hour-Sleep Disorder, where some­how your bio­lo­gical clock ended up deeply and un­shake­ably con­vinced that days on Earth are twenty-five (or whatever) hours long, and de­cides this is the hill it wants to die on. So if you nat­ur­ally sleep 11 – 7 one night, you’ll nat­ur­ally sleep 12 – 8 the next night, 1 to 9 the night after that, and so on un­til either you make a com­plete 24-hour cycle or (more likely) you get so tired and con­fused that you stay up 24+ hours and break the cycle. This is most com­mon in blind people, who don’t have the visual cues they need to re­mind them­selves of the 24 hour day, but it hap­pens in a few sighted people also; Eliezer Yudkowsky has writ­ten about his struggles with this con­di­tion.

Melatonin ef­fect­ively treats these con­di­tions, but you’ve got to use it right.

The gen­eral heur­istic is that melatonin drags your sleep time to­wards the dir­ec­tion of when you take the melatonin.

So if you want to go to sleep (and wake up) earlier, you want to take melatonin early in the day. How early? Van Geijlswijk et al sums up the re­search as say­ing it is most ef­fect­ive “5 hours prior to both the tra­di­tion­ally de­term­ined [dim light melatonin on­set] (cir­ca­dian time 9)”. If you don’t know your own melatonin cycle, your best bet is to take it 9 hours after you wake up (which is pre­sum­ably about seven hours be­fore you go to sleep).

What if you want to go to sleep (and wake up) later? Our un­der­stand­ing of the melatonin cycle strongly sug­gests melatonin taken first thing upon wak­ing up would work for this, but as far as I know this has never been form­ally in­vest­ig­ated. The best I can find is re­search­ers say­ing that they think it would hap­pen and be­ing con­fused why no other re­searcher has in­vest­ig­ated this.

And what about non-24-hour sleep dis­orders? I think the goal in treat­ment here is to ad­vance your phase each day by tak­ing melatonin at the same time, so that your sleep sched­ule is more de­pend­ent on your own sup­ple­mental melatonin than your (screwed up) nat­ural melatonin. I see con­flict­ing ad­vice about how to do this, with some people say­ing to use melatonin as a hyp­notic (ie just be­fore you go to bed) and oth­ers say­ing to use it on a typ­ical phase ad­vance sched­ule (ie nine hours after wak­ing and seven be­fore sleep­ing, plaus­ibly about 5 PM). I think this one might be com­plic­ated, and a qual­i­fied sleep doc­tor who un­der­stands your per­sonal rhythm might be able to tell you which sched­ule is best for you. Eliezer says the lat­ter re­gi­men had very im­press­ive ef­fects for him (search “Last but not least” here). I’m in­ter­ested in hear­ing from the MetaMed re­searcher who gave him that re­com­mend­a­tion on how they knew he needed a phase ad­vance sched­ule.

Does melatonin used this way cause drowsi­ness (eg at 5 PM)? I think it might, but prob­ably such a min­imal amount com­pared to the non-sleep-con­du­cive­ness of the hour that it doesn’t re­gister.

Melatonin isn’t the only way to ad­vance or delay sleep phase. Here is a handy cheat sheet of re­search find­ings and the­or­et­ical pre­dic­tions:

TO TREAT DELAYED PHASE SLEEP DISORDER (ie you go to bed too late and wake up too late, and you want it to be earlier)

– Take melatonin 9 hours after wake and 7 be­fore sleep, eg 5 PM

– Block blue light (eg with blue-blocker sunglasses or f.lux) after sunset

– Ex­pose your­self to bright blue light (sun­light if pos­sible, dawn sim­u­lator or light boxes if not) early in the morning

– Get early morn­ing exercise

– Beta-block­ers early in the morn­ing (not gen­er­ally re­com­men­ded, but if you’re tak­ing beta-block­ers, take them in the morn­ing)

TO TREAT ADVANCED PHASE SLEEP DISORDER (ie you go to bed too early and wake up too early, and you want it to be later)

– Take melatonin im­me­di­ately after waking

– Block blue light (eg with blue-blocker sunglasses or f.lux) early in the morning

– Ex­pose your­self to bright blue light (sun­light if pos­sible, light boxes if not) in the even­ing.

– Get late even­ing exercise

– Beta-block­ers in the even­ing (not gen­er­ally re­com­men­ded, but if you’re tak­ing beta-block­ers, take them in the even­ing)

These don’t “cure” the con­di­tion per­man­ently; you have to keep do­ing them every day, or your cir­ca­dian rhythm will snap back to its nat­ural pat­tern.

What is the cor­rect dose for these in­dic­a­tions? Here there is a lot more con­tro­versy than the hyp­notic dose. Of the nine stud­ies van Geijlswijk de­scribes, seven have doses of 5 mg, which sug­gests this is some­thing of a stand­ard for this pur­pose. But the only study to com­pare dif­fer­ent doses dir­ectly (Mun­dey et al 2005) found no dif­fer­ence between a 0.3 and 3.0 mg dose. The Co­chrane Review on jet lag, which we’ll see is the same pro­cess, sim­il­arly finds no dif­fer­ence between 0.5 and 5.0.

Van Geijlswijk makes the im­port­ant point that if you take 0.3 mg seven hours be­fore bed­time, none of it is go­ing to be re­main­ing in your sys­tem at bed­time, so it’s un­clear how this even works. But – well, it is pretty un­clear how this works. In par­tic­u­lar, I don’t think there’s a great well-un­der­stood physiolo­gical ex­plan­a­tion for how tak­ing melatonin early in the day shifts your cir­ca­dian rhythm seven hours later.

So I think the evid­ence points to 0.3 mg be­ing a pretty good dose here too, but I wouldn’t blame you if you wanted to try tak­ing more.

4. How do I use melatonin for jet lag?

Most stud­ies say to take a dose of 0.3 mg just be­fore (your new time zone’s) bed­time.

This doesn’t make a lot of sense to me. It seems like you should be able to model jet lag as a cir­ca­dian rhythm dis­order. That is, if you move to a time zone that’s five hours earlier, you’re in the ex­act same po­s­i­tion as a teen­ager whose cir­ca­dian rhythm is set five hours later than the rest of the world’s. This sug­gests you should use DSPD pro­tocol of tak­ing melatonin nine hours after wak­ing /​ five hours be­fore DLMO /​ seven hours be­fore sleep.

My guess is for most people, their new time zone bed­time is a couple of hours be­fore their old bed­time, so you’re get­ting most of the ef­fect, plus the hyp­notic ef­fect. But I’m not sure. Maybe tak­ing it earlier would work bet­ter. But given that the new light sched­ule is already work­ing in your fa­vor, I think most people find that tak­ing it at bed­time is more than good enough for them.

5. I try to use melatonin for sleep, but it just gives me weird dreams and makes me wake up very early

This is my ex­per­i­ence too. When I use melatonin, I find I wake the next morn­ing with a jolt of en­ergy. Al­though I usu­ally have to grudgingly pull my­self out of bed, melatonin makes me wake up bright-eyed, smil­ing, and ready to face the day ahead of me…

…at 4 AM, in­vari­ably. This is why des­pite my in­terest in this sub­stance I never take melatonin my­self any­more.

There are many people like me. What’s go­ing on with us, and can we find a way to make melatonin work for us?

This bro-sci­ence site has an un­cited the­ory. Melatonin is known to sup­press cortisol pro­duc­tion. And cortisol is in­versely cor­rel­ated with ad­ren­aline. So if you’re nat­ur­ally very low cortisol, melatonin spikes your ad­ren­aline too high, pro­du­cing the “wake with a jolt” phe­nomenon that I and some other people ex­per­i­ence. I like the way these people think. They un­der­stand in­di­vidual vari­ab­il­ity, their model is bio­lo­gic­ally plaus­ible, and it makes sense. It’s also prob­ably wrong; it has too many steps, and noth­ing in bio­logy is ever this el­eg­ant or sens­ible.

I think a more parsi­mo­ni­ous the­ory would have to in­volve cir­ca­dian rhythm in some way. Even an 0.3 mg dose of melatonin gives your body the ab­so­lute max­imum amount of melatonin it would ever have dur­ing a nat­ural cir­ca­dian cycle. So sup­pose I want to go to bed at 11, and take 0.3 mg melatonin. Now my body has a melatonin peak (usu­ally as­so­ci­ated with the very middle of the night, like 3 AM) at 11. If it as­sumes that means it’s really 3 AM, then it might de­cide to wake up 5 hours later, at what it thinks is 8 AM, but which is ac­tu­ally 4.

I think I have a much weaker cir­ca­dian rhythm than most people – at least, I take a lot of naps dur­ing the day, and fall asleep about equally well whenever. If that’s true, maybe melatonin acts as a su­per­stim­u­lus for me. The nor­mal tend­ency to wake up feel­ing re­freshed and alert gets ex­ag­ger­ated into a sud­den ir­res­ist­able jolt of awake­ness.

I don’t know if this is any closer to the truth than the ad­ren­aline the­ory, but it at least fits what we know about cir­ca­dian rhythms. I’m go­ing to try to put some ques­tions about melatonin re­sponse on the SSC sur­vey this year, so start try­ing melatonin now so you can provide use­ful data.

What about the weird dreams?

From a HuffPo art­icle:

Dr. Ra­fael Pelayo, a Stan­ford University pro­fessor of sleep medi­cine, said he doesn’t think melatonin causes vivid dreams on its own. “Who takes melatonin? Someone who’s hav­ing trouble sleep­ing. And once you take any­thing for your sleep, once you start sleep­ing more or bet­ter, you have what’s called ‘REM re­bound,’” he said.

This means your body “catches up” on the sleep phase known as rapid eye move­ment, which is char­ac­ter­ized by high levels of brain-wave activ­ity.

Normal sub­jects who take melatonin sup­ple­ments in the con­trolled set­ting of a sleep lab do not spend more time dream­ing or in REM sleep, Pelayo ad­ded. This sug­gests that there is no in­her­ent prop­erty of melatonin that leads to more or weirder dreams.

Okay, but I usu­ally have nor­mal sleep. I take melatonin some­times be­cause I like ex­per­i­ment­ing with psy­cho­tropic sub­stances. And I still get some really weird dreams. A Slate journ­al­ist says he’s been tak­ing melatonin for nine years and still gets crazy dreams.

We know that REM sleep is most com­mon to­wards the end of sleep in the early morn­ing. And we know that some parts of sleep struc­ture are re­spons­ive to melatonin dir­ectly. There’s a lot of de­bate over ex­actly what melatonin does to REM sleep, but given all the re­ports of altered dream­ing, I think you could pull to­gether a case that it has some role in sleep ar­chi­tec­ture that pro­motes or in­tens­i­fies REM.

6. Does this re­late to any other psy­chi­at­ric con­di­tions?

Prob­ably, but this is all still spec­u­lat­ive.

Seasonal af­fect­ive dis­order is the clearest sus­pect. We know that the sea­sonal mood changes don’t have any­thing to do with tem­per­at­ure; they seem to be based en­tirely on winter hav­ing shorter (vs. sum­mer hav­ing longer) days.

There’s some evid­ence that there are two sep­ar­ate kinds of winter de­pres­sion. In one, the late sun­rises train people to a late cir­ca­dian rhythm and they end up phase-delayed. In the other, the early sun­sets train people to an early cir­ca­dian rhythm and they end up phase-ad­vanced. Plaus­ibly SAD also in­volves some com­bin­a­tion of the two where the cir­ca­dian rhythm doesn’t know what it’s do­ing. In either case, this can make sleep non-cir­ca­dian-rhythm-con­gru­ent and so less ef­fect­ive at do­ing whatever it is sleep does, which causes mood prob­lems.

How does sun­rise time af­fect the av­er­age per­son, who is rarely awake for the sun­rise any­way and usu­ally sleeps in a dark room? I think your brain sub­con­sciously “no­tices” the time of the dawn even if you are asleep. There are some weird path­ways lead­ing from the eyes to the nuc­leus gov­ern­ing cir­ca­dian rhythm that seem in­de­pend­ent of any other kind of vis­ion; these might be keep­ing tabs on the sun­rise if even a little out­side light is able to leak into your room. I’m basing this also on the claim that dawn sim­u­lat­ors work even if you sleep through them. I don’t know if people get sea­sonal af­fect­ive dis­order if they sleep in a com­pletely en­closed spot (eg un­der­ground) where there’s no con­ceiv­able way for them to mon­itor sun­rise times.

Bright light is the stand­ard treat­ment for SAD for the same reason it’s the stand­ard treat­ment for any other cir­ca­dian phase delay, but shouldn’t melatonin work also? Yes, and there are some pre­lim­in­ary stud­ies (pa­per, art­icle) show­ing it does. You have to be a bit care­ful, be­cause some people are phase-delayed and oth­ers phase-ad­vanced, and if you use melatonin the wrong way it will make things worse. But for the stand­ard phase-delay type of SAD, nor­mal phase ad­van­cing melatonin pro­tocol seems to go well with bright light as an ad­di­tional treat­ment.

This model also ex­plains the oth­er­wise con­fus­ing tend­ency of some SAD suf­fer­ers to get de­pressed in the sum­mer. The prob­lem isn’t amount of light, it’s cir­ca­dian rhythm dis­rup­tion – which sum­mer can do just as well as winter can.

I’m also very sus­pi­cious there’s a strong cir­ca­dian com­pon­ent to de­pres­sion, based on a few lines of evid­ence.

First, one of the most clas­sic symp­toms of de­pres­sion is awaken­ing in the very early morn­ing and not be­ing able to get back to sleep. This is con­fus­ing for de­pressed people, who usu­ally think of them­selves as very tired and need­ing to sleep more, but it def­in­itely hap­pens. This fits the pro­file for a cir­ca­dian rhythm is­sue.

Se­cond, agomelat­ine, a melatonin ana­logue, is an ef­fect­ive (ish) an­ti­de­press­ant.

Third, for some reason stay­ing awake for 24+ hours is a very ef­fect­ive de­pres­sion treat­ment (al­beit tem­por­ary; you’ll go back to nor­mal after sleep­ing). This seems to sort of be a way of telling your cir­ca­dian rhythm “You can’t fire me, I quit”, and there are some com­plic­ated sleep depriva­tion /​ cir­ca­dian shift pro­to­cols that try to lever­age it into a longer-last­ing cure. I don’t know any­thing about this, but it seems pretty in­ter­est­ing.

Fourth, we checked and de­pressed people def­in­itely have weird cir­ca­dian rhythms.

Last of all, bi­polar has a very strong cir­ca­dian com­pon­ent. There aren’t a whole lot of life­style changes that really work for pre­vent­ing bi­polar mood epis­odes, but one of the big ones is keep­ing a steady bed and wake time. So­cial rhythms ther­apy, a rare ef­fect­ive psy­cho­ther­apy for bi­polar dis­order, re­volves around train­ing bi­polar people to con­trol their cir­ca­dian rhythms.

The­or­ies of why cir­ca­dian rhythms mat­ter so much re­volve either around the idea of pro-cir­ca­dian sleep – that sleep is more res­tor­at­ive and ef­fect­ive when it matches the cir­ca­dian cycle – or the idea of mul­tiple cir­ca­dian rhythms, with the body func­tion­ing bet­ter when all of them are in sync.

7. How can I know what the best melatonin sup­ple­ment is?

Lab­door has done pur­ity tests on vari­ous brands and has ranked them for you. All the ones they high­light are still ten to thirty times the ap­pro­pri­ate dose (also, stop call­ing them things like “Triple Strength!” You don’t want your med­ic­a­tions to be too strong!). As usual, I trust Nootrop­ic­sDe­pot for things like this – and sure enough their melatonin (avail­able on Amazon) is ex­actly 0.3 mg. God bless them.