Case study: Melatonin

[gwern]

I discuss melatonin’s effects on sleep & its safety; I segue into the general benefits of sleep and the severely disrupted sleep of the modern Western world, the cost of melatonin use and the benefit (eg. enforcing regular bedtimes), followed by a basic cost-benefit analysis of melatonin concluding that the net profit is large enough to be worth giving it a try barring unusual conditions or very pessimistic safety estimates.

Full essay: http://​​www.gwern.net/​​Melatonin

[clockbackward]

Your argument essentially amounts to the following:

1. Melatonin significantly improves sleep quality.

2. It has no side effects.

3. It has low cost.

If all of these are true, then who wouldn’t want to take it? However, you spend a lot of time on discussing point 3, but little on points 1 and 2, which are arguably the most important. How do you know that Melatonin really improves sleep quality so much? Is it just based on your personal experience (and perhaps that of other people you know)? If so, that is not convincing, as large scale randomized controlled studies are generally the only way to reliably tell if a medicine works. There are too many complicating factors like individual differences between people, the placebo effect, random fluctuation, reversion to the mean, difficulty in remembering how we felt in the past, etc. to rely on anecdotes.

Another point that your article does not address is the fact that there is a difference between a medicine having no known side effects, and a medicine ACTUALLY having no side effects. Any time that you take medicine you are taking a risk of a reaction that is unknown, or which failed to be uncovered in any studies that were done on it. For example, it is probably unknown whether a decade of Melatonin use (rather than just one or two years) causes problems of any kind. This sort of danger is unfortunately difficult to quantify, but I believe deserves at least some mention.

[Paul Crowley]

spend a lot of time on discussing point 3 This is by far the biggest failing of the post, it grates hugely. It’s cheap, we get it.

[Bugmaster]

Upvoted for truth. The original article basically amounts to saying, “There’s this drug that will totally improve your life, guaranteed, with no side effects, trust me ! Now go ahead and ingest it.” Ummm yeah that’s great, but I think I’ll wait for some long-term studies to tell me things like this:

• What are the long-term side effects of the drug ?

• How will this drug interact with any other drugs I might be taking ?

• What is the correct dose for me personally ? What are the consequences of an accidental overdose ?

• Overall, how likely is this drug to kill or cripple me ?

Until those questions are answered, I’m not taking this drug, regardless of how cheap it is.

[mattnewport]

It sounds interesting but I’m a little wary of your one line dismissal of any potential side effects without reference. To the best of my knowledge the function of sleep is still not completely understood and the long term effects of reduced sleep are not known. A suggestion to take any kind of supplement every day for the rest of your life places a fairly high bar on safety. Taking melatonin to overcome jet-lag seems very likely to be safe but I’m more wary of using it on an ongoing daily basis.

Do you have any references to support the claim that there are no long term side effects of daily use?

[gwern]

I did link to Wikipedia for a reason; see http://​​en.wikipedia.org/​​wiki/​​Melatonin#Availability_and_safety . But besides AngryParsley’s link, there’s

• http://​​www.ahrq.gov/​​Clinic/​​epcsums/​​melatsum.htm

• http://​​jbr.sagepub.com/​​cgi/​​content/​​abstract/​​12/​​6/​​673

• http://​​linkinghub.elsevier.com/​​retrieve/​​pii/​​S0387760498000722

• http://​​www.springerlink.com/​​index/​​D5U5L315J8X79105.pdf

Given the unanimous results of safety in the short-term, positive results in long-term child use, the exploitation of a regular physiological process, the long track-record of melatonin use, and the lack of evidence for any long-term harm, I think I’d say the onus is on any doomsayers.

(No doubt there’s a witty Eliezerism or post on the topics of negative results and burdens of proof, but offhand I can’t think of it.)

[mattnewport]

It took large scale randomized studies to establish the negative health effects of vitamin supplements/​antioxidants and HRT both of which appeared safe in the short term, exploited a regular physiological process and had a long track record of use. I’d want to see a large randomized study of the long term effects of melatonin use in adults to establish the long term effects of melatonin use in adults.

The Wikipedia link you give merely concludes that “evidence suggests that melatonin is safe with short-term use, three months or less”. From your other links:

The findings of this review suggest that exogenous melatonin is a relatively safe substance when used in the short term, over a period of days or weeks, and is safe at relatively high doses and in various formulations. However, the safety of exogenous melatonin when used in the long-term, over months and years, remains unclear.

There are no published long-term safety data on the use of melatonin for whatever purpose, assuming long term to mean more than 6 months of daily medication. In the light of its physiological role in animals, the potential deleterious effects include inhibition of reproductive function, delayed timing of puberty, and influence (when taken during pregnancy and lactation) on the circadian status of the fetus and neonate and on future development. Its interactions with other medications are virtually unexplored. For most positive effects published, there also exist negative reports.

There is evidence to suggest that melatonin is not effective in treating most primary sleep disorders with short-term use (4 weeks or less); however, additional large-scale RCTs are needed before firm conclusions can be drawn. There is some evidence to suggest that melatonin is effective in treating delayed sleep phase syndrome with short-term use. There is evidence to suggest that melatonin is safe with short-term use (3 months or less).

The evidence you present for the benefits of melatonin is also weak and the Wikipedia article is fairly circumspect about the benefits of melatonin. The first review you link to states:

Melatonin decreased sleep onset latency (SOL) in normal sleepers (weighted mean difference (WMD): −3.9 min; 95- percent CI: −5.3 min., −2.6 min.). The magnitude of this effect appears to be clinically insignificant. There was evidence of possible publication bias in the selection of studies that were analyzed; we found a greater number of studies reporting positive results compared to negative results.

and

Melatonin increased sleep efficiency in normal sleepers (WMD: 2.3 percent; 95-percent CI: 0.7 percent, 3.9 percent), and this effect was dependent on the timing of sleep, such that the effect of melatonin was greater in daytime sleepers (daytime sleep: WMD: 8.0 percent; 95- percent CI: 1.0 percent, 15.0 percent; night-time sleep: WMD: 1.2 percent; 95-percent CI: 0 percent, 2.4 percent). The magnitude of this effect appears to be clinically insignificant. There was considerable evidence of possible publication bias in the selection of studies analyzed; we found a greater number of studies reporting positive results compared to negative results.

and

Generally, these studies were of low-to-moderate quality.

Nowhere have in these links do I see any evidence supporting your key claim that melatonin allows for the benefits of 8 hours of sleep in 7 hours.

I think your post spent too much time discussing the relatively uninteresting topic of the cost of melatonin and not enough on the evidence for safety or efficacy. Based on the discussion and the further research you and others have linked I’m not persuaded enough by the evidence for safety or efficacy to adopt melatonin for long term use, but I may try it out for jet lag or other short term sleep difficulties.

[AngryParsley]

I’d want to see a large randomized study of the long term effects of melatonin use in adults to establish the long term effects of melatonin use in adults.

How big a study do you need before you’ll judge something as safe? You selected two examples of a class of therapies that “appeared safe in the short term, exploited a regular physiological process and had a long track record of use.”

From the wikipedia article on the HRT study:

The risk in current users was increased about 1.2 fold; for every 1000 women using HRT, 2.6 developed ovarian cancer over 5 years, compared with 2.2 in those not taking HRT.

The reason huge studies were required to find issues with HRT is because HRT so rarely causes issues. The question you should be asking is: If it is known that a drug is safe in the short term, exploits a regular physiological process, and has a long track record of use, what is the chance that it is harmful in the long term (and to what degree)? The two examples you pointed out are not the entire data set. Your behavior is extremely risk-averse compared to other choices you make daily.

[mattnewport]

How big a study do you need before you’ll judge something as safe?

I don’t think it makes sense to ask that question in isolation. When judging whether some risk is worth taking I’d generally look at both the evidence for the potential risks and for the potential benefits. I focused on the potential risks in my original post but the reason I’m not convinced that taking melatonin on a long term basis is justified is that the evidence for the benefits is also weak. If there was extremely strong evidence for the claimed benefits of taking melatonin over the long term then I might consider the risks of long term side effects worth taking. My position at the moment is that the balance of evidence suggests that the risk/​reward proposition is not compelling for long term use of melatonin, though as I have said I may well try it next time I have a transatlantic flight to counter jetlag.

The question you should be asking is: If it is known that a drug is safe in the short term, exploits a regular physiological process, and has a long track record of use, what is the chance that it is harmful in the long term (and to what degree)?

I don’t think that’s the right question. The right question is whether the evidence for benefits outweighs the evidence for harm. I used to take vitamin supplements because the risk/​reward based on the available evidence seemed compelling. In light of more recent large scale studies that show no long term benefits and some evidence of long term harm I no longer take vitamin supplements.

Your behavior is extremely risk-averse compared to other choices you make daily.

I am not risk-averse in general, in fact I think I probably have a higher than average risk tolerance in general. I probably require a higher risk/​reward payoff for any kind of long term use of supplements or drugs than the average North American however.

[AngryParsley]

Here’s the longest-term study I could find: http://​​www.ncbi.nlm.nih.gov/​​pubmed/​​19486273

Basically, children taking melatonin for several years didn’t develop any problems. Melatonin is also used by blind people quite a bit, since without it their circadian rhythms are longer than 24 hours.

[mattnewport]

I believe it’s not generally considered valid to apply results from medical studies on adults to children. I’m not sure if the reverse applies.

[AngryParsley]

The fact that the study was on children certainly doesn’t help the validity when applied to adults, but I think you’re being overly risk-averse. Melatonin’s mechanism of action is pretty well understood, and it occurs in the body already. The long-term effects would have to be very bad to outweigh the advantages of a regular sleep schedule and an extra hour of wakefulness every day. That’s assuming melatonin works, of course.

[taryneast]

Endorphins are chemicals that occur naturally in the body, with a mechanism that is pretty well understood. Yet taking opioids regularly is not good for you.

You cannot assume health-benefits simply because it already occurs in the body.

There may well be benefits, but they must be proved independently of simply understanding the natural mechanism.

[thomblake]

These supplements are unlikely to help a balanced diet, there is little evidence they do, and there are studies which have indicated actual harm from the consumption of multivitamins

What I’d really like to see is a study comparing unhealthy diets plus multivitamins to just the unhealthy diet.

[Kaj_Sotala]

Without having looked at the actual studies in detail, it seems that even several of the “no benefit” studies report multivitamins to be beneficial when one does have an otherwise unhealthy diet.

Wikipedia:

Similarly, a 2006 report for the United States Department of Health and Human Services concluded that “regular supplementation with a single nutrient or a mixture of nutrients for years has no significant benefits in the primary prevention of cancer, cardiovascular disease, cataract, age-related macular degeneration or cognitive decline.”[16] However, the report noted that multivitamins have beneficial effects in people with poor nutritional status, vitamin D and calcium can help prevent fractures in older people, and that zinc and antioxidants can help prevent age-related macular degeneration in people at a high risk of developing this disease.

In 2007 the United Kingdom Food Standards Agency published an updated set of recommendations for eating a healthy diet.[17] The recommendations stated that pregnant women should take extra folic acid and iron and that older people might need extra vitamin D and iron. However, the report advised that “Vitamin and mineral supplements are not a replacement for good eating habits” and stated that supplements are unnecessary for healthy adults who eat a balanced diet.

From the cited New York Times article:

But a balanced diet typically provides an adequate level of these nutrients, and today many popular foods are fortified with extra vitamins and minerals. As a result, diseases caused by nutrient deficiency are rare in the United States.

In any event, most major vitamin studies in recent years have focused not on deficiencies but on whether high doses of vitamins can prevent or treat a host of chronic illnesses.

(I’ll keep taking my multivitamins, as my diet certainly isn’t balanced.)

[A1987dM]

I take multivitamins as a backup plan of sorts so that I don’t have to worry too much about whether my diet is balanced.

[Liron]

Pfff, 5959% is nothing. You can get a banana for 15 cents and it’ll keep you from dying of starvation. So let’s say you value the next 50 years of your life at $7.25 an hour… That’s a return of 28419037481114.5%!

Seriously do you have a good link for where to buy melatonin?

[gwern]

Pfff, 5959% is nothing. You can get a banana for 15 cents and it’ll keep you from dying of starvation. So let’s say you value the next 50 years of your life at $7.25 an hour… That’s a return of 28419037481114.5%!

Yes, but you have to keep buying them; leggo my bananos, you damn dirty ape!

Seriously do you have a good link for where to buy melatonin?

I’d rather not be perceived as advertising. I was concerned about mentioning Tommy Health at all, actually. As I said, it’s very widely available. If you want an online link, Amazon is as good a place to buy through as any.

[Jonathan_Graehl]

I tried it for a few weeks and didn’t notice any major difference. I think I’ll try again on this recommendation. Perhaps my endogenous melatonin is already sufficient, or I was a lazy self-monitor.

I would summarize:

(1) In your personal experience, 1.5mg of melatonin 30 min before sleeping makes you feel 8-hours rested after 7-hours of sleep (but 9mg is harmful)

(2) that dosage has negligible cost

That’s all you really needed to say.

It’s jarring to me that you so meticulously analyze the cost of dosing with melatonin; once I know a cost is below some low threshold, I prefer not to think about it at all. I’d rather you took the same care into performing some objective tests of mental capability on varying amounts of sleep, so that it really means something when you say you gain an hour of wakefulness. Of course, I’d want this blinded as well, but I doubt you have convincing placebo pills available; besides, I don’t mind taking something in hope of accruing some real and placebo benefits.

If your experience is typical, then the only reason people shouldn’t be dosing melatonin is if there’s some long-term health detriment (I don’t have any mechanism in mind; it seems unlikely).

[Jack]

For me, the ability to force myself to go to bed is by far the most important claim made in this post.

[SilasBarta]

I’ve long had trouble going to sleep, and it’s not an issue of refusing to go to bed, but rather, that I can’t seem to just fall asleep like everyone else. My mind just won’t shut down. OTC sleeping pills don’t work on me: all they do is make me really drowsy but just as unable to fall asleep, which is a sucky feeling.

Recently, I started going on a prescription medication that works like a charm, in that predictably makes me sleepy, and actually fall asleep, and, on occasion, lets me wake up refreshed in the morning. However, it’s relatively expensive, even with insurance.

Based on this TL post, I’m going to try melatonin, and if it does the same thing in terms of making me fall asleep, that alone would be worth it.

[NancyLebovitz]

If you don’t mind, what’s the prescription medication?

[SilasBarta]

Seroquel aka Quetiapine (which unfortunately is prescribed for a lot of things other than insomnia, but only serves to knock me out in about an hour).

[gwern]

Based on this TL post, I’m going to try melatonin, and if it does the same thing in terms of making me fall asleep, that alone would be worth it.

And?

[SilasBarta]

Unfortunately, it turns out it’s never been able to make me go to sleep, anywhere near as well as the prescription. Though it does make me wake up earlier (restfully).

(Sorry for the delay, I guess I just haven’t been logging in as much, lately!)

[gwern]

Though it does make me wake up earlier (restfully).

So you are still using it?

[SilasBarta]

Yes, though I hope to one day not need it. I’m trying to use smaller amounts as time goes by.

[[deleted]]

Welcome back! I missed you.

[SilasBarta]

Thanks! It’s good to feel appreciated!

I’ve also moved to the SF Bay area, capital of LW.

[gwern]

BTW, I did wind up measuring sleep over 6 months of on/​off melatonin, so I now have more than intuition for the 1-hour claim (which turns out to be more like 50 minutes): http://​​www.gwern.net/​​Zeo#melatonin-analysis

[Jonathan_Graehl]

Very impressive followup. I’ve skimmed that.

My less meticulous conclusion is that melatonin makes me wake earlier and easier with light (maybe in general, but I don’t wake by alarm). I haven’t bothered to check whether that means I actually slept better (in terms of improving my performance/​mood going forward), but I consider it a good sign.

[gwern]

So you are still using it?

[Jonathan_Graehl]

About 2 in every 7 days—when I feel like my past night’s misadventures might make it hard for me to sleep and wake properly. So no, not really. If I lived alone, I’d probably be more regimented and go for ⁷⁄₇ with some tiny dose (because stable habits that can be tweaked gradually are reassuring).

Based on my experience, I’d recommend it if you want to wake up “naturally” with the light but your recent sleep history (e.g. jet lag) wouldn’t permit that. Otherwise, I’ve been too sloppy to know precisely what it does for me (I can feel a large dose, such that I’d guarantee it’s not only placebo).

[gwern]

It’s jarring to me that you so meticulously analyze the cost of dosing with melatonin; once I know a cost is below some low threshold, I prefer not to think about it at all.

That’s great for you—if you feel convinced, you save all the time I spent researching & writing this. But how do you know the cost is below that threshold? Because I did so meticulously analyze it.

More to the point, I don’t analyze everything like this. Once I calculated the cost per night was below 10 cents and the benefit above half an hour, my mind was made up. Everything after that was for a hopefully educational ‘case study’ for readers, and to make the conclusion as strong as possible.

I’d rather you took the same care into performing some objective tests of mental capability on varying amounts of sleep, so that it really means something when you say you gain an hour of wakefulness. Of course, I’d want this blinded as well, but I doubt you have convincing placebo pills available; besides, I don’t mind taking something in hope of accruing some real and placebo benefits.

I do have visually convincing placebos (some vitamin B supplements), but part of the problem is there’s no way I can fool myself—I know what the onset feels like with and without melatonin.

Although it wouldn’t be a bad idea to take some measurements on the Dual N-back test; I would like to know the saving more precisely than ‘more than half and hour and less than 2’. :)

[Alicorn]

I was prescribed melatonin for a sleep complaint some years ago and noticed no detectable improvement: I didn’t get to sleep more easily, wake up less during the night, or feel more refreshed in the morning. What might explain this?

[DanArmak]

I’ve been prescribed melatonin recently myself, and it’s not helping me much. Here are my theories on the subject.

Melatonin is good for (at least) one thing: if you don’t fall asleep naturally, either at all or at a convenient time, taking melatonin can help fix that. (“Naturally” here means you feel tired and sleepy and genuinely want to go to sleep, so you don’t need to invest will to do so.)

A high level of melatonin tells your body to fall asleep. If you take melatonin at a time during the day when your body produces melatonin already, then the extra-high level may not make any difference. In other words, if the reason you had trouble falling asleep isn’t low levels of melatonin but some unrelated physiological problem, then there’s no point in raising levels.

The second possible scenario is what I appear to have. I have a natural sleep schedule that’s at odds with the day cycle. Left alone (e.g. during summer break), I wil go to sleep at 2am and wake up at noon. If I take melatonin at 10pm, I can fall asleep at 11. But my body still produces its own melatonin until noon, so I don’t wake up earlier—the net effect is that I sleep 14 hours and wake up tired.

The doctor said if I keep taking melatonin at a fixed time every day for half a year, my body may adjust its own melatonin-producing cycle to match. More likely it won’t, but there’s no alternative treatment that I know of. So far I’ve bee taking it for one month with only modest (possibly statistically-insignificant) improvement.

BTW, my prescribed dose is 5mg daily, higher than usual. The doctor said there are still no side effects ever reported, even with higher dosages. He’s a sleep expert, not a GP, so that has some credibility.

I’m interested in hearing more ideas, stories, …

[Alicorn]

I have a friend with this disorder, which sounds like what you describe. Pretty much what you have to do with that is be nocturnal.

[DanArmak]

I’ve been nocturnal since I’ve started attending university, but it makes for a lonely life. I’d rather fix it if possible.

[Larks]

The plus side I’ve found is there are radically less distractions around at 1am, so I can often get more work done between 11pm and 2am than I can in the whole afternoon. Last night I managed to complete an entire application form for an internship with BP, whereas in the day all I’d managed was half a page of geometry notes.

Possibly even more importantly, mindlessly hitting refresh on facebook is not an acceptable activity at 2am, whereas earlier in the day it is, so if I am awake then, it’s because I’m actually working.

[CannibalSmith]

Move to another time zone.

[Alicorn]

That wouldn’t help for the long term; circadian clocks, even wonky circadian clocks, are set by cycles of daylight and darkness.

[DanArmak]

Indeed. If I moved to the US, after a few weeks I would adjust.

One solution is to create an artificial light & dark cycle that’s earlier than the actual daily cycle where I live. That would work—as long as I never left my room.

[Alicorn]

Surely you wouldn’t have to stay in your room 24 hours a day? You could go outside when the light and dark of your artificial cycle and the natural cycle coincided, couldn’t you? I don’t know how sensitive human clocks are—maybe going out at nine a.m. right after you woke up when you’re trying to fool yourself into “thinking” it’s noon would create problems having to do with the exact location of the sun—but it seems like there would be a window there.

[DanArmak]

You’re right, of course. I’ll do the calculations.

Assume I want to shift my sleep cycle 4 hours ahead (i.e. wake up 4 hours earlier, 8am instead of noon).

We currently have sunrise and sunset roughly at 6:30 and 17:00 local time. I assume for simplicity that this remains constant and also ignore DST.

I’ll want to simulate sunrise at 2:30 am and sunset at 13:00. So assuming the sun is “properly up” (high enough) starting at 7am, I can go outside from 7am-1200 and again after sunset at 1700. I have to stay at home during the night (for artificial lighting starting at 2:30) and during the artificial darkness period, 1300-1700.

This might actually be workable if there aren’t too many interruptions. Hmm...

One thing I don’t yet know is how exactly artificial lighting affects the body’s sleep cycle; how the body reacts to it differently than darkness and also differently than sunlight.

I’ll have to think about this some more.

[pdf23ds]

I have exactly the same problem. I also tried Lunesta and Ambien, which didn’t really work, and Rozarem, which is supposed to be quite similar to melatonin, and had similar but stronger effects. Nothing that worked. I also tried bright light therapy, which didn’t seem to work at all, and was very inconvenient. At the moment I’m on a free sleep schedule, which seems to cycle completely every 2-3 weeks. (I’m not sure because I’ve never kept a sleep diary.) That’s only currently possible because I’m unemployed.

[MichaelGR]

The second possible scenario is what I appear to have. I have a natural sleep schedule that’s at odds with the day cycle. Left alone (e.g. during summer break), I wil go to sleep at 2am and wake up at noon. If I take melatonin at 10pm, I can fall asleep at 11. But my body still produces its own melatonin until noon, so I don’t wake up earlier—the net effect is that I sleep 14 hours and wake up tired.

If the melatonin works for the “falling asleep” part of the problem, why not simply use an alarm clock to wake yourself up after your desired number of hours of sleep?

[Kutta]

Melatonin is best for sleep quality improvement with people who are above 40 as endogenous melatonin production usually starts to decrease from 30. You’re much younger than that, so sleep disturbances are less likely to be caused by low night melatonin levels (so supplementary melatonin is less likely to be a significant remedy).

[randallsquared]

For at least some of us, the decrease in sleep is a boon. I’m only 36, and over the past 4-5 years I’ve had a very noticeable decrease in sleep, without any apparent side effects. It’s not uncommon for me to sleep six hours and wake up refreshed before the alarm clock goes off, which is wonderful for someone who used to have to budget at least 8 hours a day for sleep.

[AngryParsley]

It could be that you weren’t taking enough. Another major factor is your bedtime routine. Exercise, bright lighting, and other stimulating activities (video games, emotionally-engaging movies) can discourage sleep.

[lsparrish]

Too low of a dosage for your body’s tolerance level could explain it.

[wedrifid]

Too much is just as likely. Melatonin’s response curve is weird.

[gwern]

Is it? It seemed like a normal enough U-curve as far as I knew.

[wedrifid]

Is it? It seemed like a normal enough U-curve as far as I knew.

It varies drastically from person to person. The effective dose has varied by a factor of 60 even among people I’ve designed cognitive/​nutritional stacks for and varies even more so in the general case.

The inverted U is also different to the way it is usually used. Usually things have benefits to a certain level but then disadvantages start weighing them down if the dose gets too high. The cognitive enhancement from stimulants like caffeine for example reaches a peak then declines along that specific metric. But you certainly don’t go back towards normal in the obvious effects. You’re totally wired. With melatonin some will get a drastic alteration in their sleep behavior at 0.5 mg while a mega dose of 100 mg is not incredibly disruptive. For a hormone and especially a hormone with mind altering effects you can’t usually get away with that.

[gwern]

I meant more in the way of clinical evidence, than anecdotes; I’ve never tried 100mg or heard of trying it before (my 1 9mg experience being sufficiently unpleasant to deter me from higher doses), so I guess I have to take your word for it on the claim of it not being incredibly disruptive.

[wedrifid]

so I guess I have to take your word for it on the claim of it not being incredibly disruptive.

You could take my word for it that large doses are not found to be incredibly disruptive (even in the long term) in clinical studies either.

[whpearson]

Did you get a proper explanation for your sleep complaint?

[Alicorn]

Nope. A tentative hypothesis is sleep apnea, since my dad had that, but how well I sleep is extremely inconsistent (some nights I get excellent sleep, some nights I wake up a dozen times and am a zombie all the next day) and seems to correlate better with whether I’ve set an alarm than with any of the factors that are supposed to affect sleep apnea.

[LauraABJ]

Do you have a study that confirms your ‘melatonin subtracts an hour’ theory you could link to? My husband uses melatonin and can still easily spend 12 hours in bed. I’ve avoided using it, since I don’t have difficulty actually falling asleep and I didn’t want to sleep longer as a result of using it. You should probably argue that everyone should try using melatonin for a week or so, since the potential gains are large, not that everyone who doesn’t use it is being foolish. The whole argument falls apart if your base assertion is wrong, and you provide no evidence that the effect melatonin has on you generalizes to everyone. That being said, I am glad you shared this information.

[gwern]

Do you have a study that confirms your ‘melatonin subtracts an hour’ theory you could link to?

Not really, unfortunately, but I do have more than a subjective impression; see http://​​lesswrong.com/​​lw/​​1lt/​​case_study_melatonin/​​5w76

You should probably argue that everyone should try using melatonin for a week or so, since the potential gains are large, not that everyone who doesn’t use it is being foolish.

Yes, this probably can be expressed nicely as a “value of information” problem. I’ve done that.

[gwern]

Since I wrote this post, the following comments have come in. If I missed any, please PM or reply with links. The following entries are compiled from LessWrong, #lesswrong, gwern.net, Reddit, or Google+, generally in relation to this melatonin essay; I classify as using/​positive anyone who is using melatonin or will likely use melatonin in the future for any reason (eg. daily use counts, but so does using it for jetlag), and as negative/​null anyone who is no longer using it for any reason (eg. found a better way to induce vivid dreams, or found it made them sleep better but this interfered with their diabetes-related medical devices).

Using/​positive:

• AndrewHickey

• AngryParsley

• Bongo

• D_Malik

• HughRistik

• James_Miller

• JenniferRM

• Jonathan_Graehl

• Matt_Simpson

• Nick_Tarleton

• Vaniver

• betterthanwell

• daenerys (2)

• fiddlemath

• hegemonicon

• jimmy

• knb

• orthonormal

• simplicio

• timtyler

• wallowinmaya

• wedrifid

• wilkox

• Eliezer Yudkowsky

• jacob_cannell

• SilasBarta

• gwern

• Kingoftheinternet

• Gustaff88

• Marius van Voorden

• TB

• willabtsm

• herman_gill

• bore902

• bronzehydra

• bkgood

• keflexxx

• urdude

• 00000000000000000000

• whatarepuppy

• Erik de Castro Lopo

• Johan Tibell

• Boyd Smith

• Antoine Latter

• Carter Schonwald

• Michael O’Kelly

• Boxo (#lesswrong; IRC entries may be inflated by multiple nicks whose unity I didn’t recognize)

• Grognor *

• Jonii^ *

• Kiba *

• LunkAlarm *

• Tene *

• ToyKeeper *

• buymcdonalds *

• clone_of_saturn *

• cwillu *

• drethelin *

• efm *

• flowp *

• jandrog *

• klfwip *

• nialo *

• nshepperd

• papermachine *

• puritan *

• quintopia *

• realitygrill *

• roxton *

• rsaarelm *

• WashIrving *

• jbeshir *

• Siod *

• docl *

• Eratyx *

Not using/​mixed/​negative:

• AdeleneDawner

• Alicorn

• DanArmak

• Liron

• NancyLebovitz

• Nic_Smith

• PhilGoetz

• RichardKennaway

• RobinReborn

• Tyrrell_McAllister (2)

• alasarod

• blueberry

• eirenicon

• pdf23ds

• prismattic

• jimrandomh

• Jacopo Santelli

• TwoChe

• Ashley Yakeley

• Matthew Graves

• Lemmih (#lesswrong)

• Logos01 *

• Philippa *

• Tetsuo55 *

• folktheory *

• ivan *

• kanzure *

• Dodek *

Unknown:

• AdeleneDawner

• CasioTheSane

• Curiouskid

• Cyan

• Ralith

• SoullessAutomaton

• handoflixue

• kevin

• nazgulnarsil

• shokwave

• philh

[Eliezer Yudkowsky]

I am microdosing, 300mcg plain + 300mcg time-release, both from LEF. Currently trying doubling the time-release dosage to see if that works better. More than 400mcg up-front did not work well. In general, people trying melatonin are advised to try microdoses.

[gwern]

In general, people trying melatonin are advised to try microdoses.

That’s definitely something I noticed in the anecdotes: people with positive experiences seem to mention switching to 1mg doses and not experimenting.

I’m going to strengthen the language in my melatonin essay dealing with dosage, and add some reminders to myself to do more blind experiments with differing doses when I run out of my current melatonin pill mixes.

[John_Maxwell]

I’m going to strengthen the language in my melatonin essay dealing with dosage, and add some reminders to myself to do more blind experiments with differing doses when I run out of my current melatonin pill mixes.

Any updates on this?

[gwern]

Not yet. My five-fold sleep experiment was originally supposed to be long done by now, but I put the lithium part on hold to run another long experiment, and so it hasn’t finished yet. Hopefully I’ll be able to start by 2014.

[laakeus]

I’m interested in knowing how you came up with the conclusion that it reduces your sleep need (or bed time) by one hour?

I can understand that taking melatonin would reduce bed time if it made you fall asleep faster, but personally I’ve had no trouble falling asleep quickly so there would basically be no difference. (In fact, I’ve experienced an opposite effect with the couple of times I’ve taken melatonin.)

It takes a lot more than just casual observations to conclude that there are other effects. Basically you’d need to measure your sleep debt some way and compare its development when taking the drug and when not. Unfortunately there is no direct way to measure sleep debt so it will require quite extensive tests to make any decisive conclusions about this hypothesis.

If you already have this data, please share it. If not, I’d be happy if you took a step back and really tried to measure and confirm this claim.

One final note is that current research has demonstrated that sleep has an important part in memory consolidation. If supplemental melatonin really does cut sleep need, it will necessary have effects on memory consolidation too. (For example, motor memory consolidation happens in REM and NREM-2 phases that most probably would be cut if daily sleep need was reduced.)

[randallsquared]

I’ve had no trouble falling asleep quickly so there would basically be no difference. (In fact, I’ve experienced an opposite effect with the couple of times I’ve taken melatonin.)

For people who actually have trouble falling asleep, or wanting to fall asleep, this is definitely a concern. When I was researching melatonin a few years ago, one of the problems I read was that if you fight off the effects of getting sleepy long enough, you’ll actually find it more difficult to sleep afterwards (that night, I mean). This was the reason I chose to avoid it after a few tests at that time: I didn’t feel I could afford the risk of accidentally pushing through the sleepiness and getting almost no sleep in a given night.

[gwern]

See http://​​lesswrong.com/​​lw/​​1lt/​​case_study_melatonin/​​5w76

[tut]

I looked up melatonin in FASS. The only melatonin based drug that’s legal in Sweden is called Cirkadin. It has 2mg of melatonin per pill. It is a prescription drug, and only recommended for patients who are older than 55.

There are some side effects. Common ones are headaches, inflammation of the throat (lasting 1-2 days, they don’t say if that’s alltogether or after you quit melatonin), back pain and weakness (asteni). That’s probably the real cost of using it.

Melatonin induces CYP3a in vitro. If it does that in the blood as well it will decrease the effects of several other drugs. It also increases the effects of some sedatives, and the effects of melatonin is influenced by several other drugs. So if you are on some important medication, talk to your doctor before taking melatonin.

Also, if you have liver problems melatonin will stay in your blood much longer than in gwern’s, so you will be drowsy the day after you use it.

[CronoDAS]

I don’t care how long I spend asleep. I just hate going to bed, and I hate getting up.

[Wei Dai]

I just hate going to bed, and I hate getting up.

Me too, and I’d love to know what that’s about. It’s a small, but puzzling form of irrationality.

[pete22]

Same here, and I agree it’s puzzling. Especially not wanting to go to bed. With most of my behaviors that don’t have an obvious motivation, I can think it through and figure out what’s going on, but not with this one.

I wonder if it’s a latent anti-bedtime reaction from childhood?

[PhilGoetz]

Speaking of which, why do all “good” American parents enforce bedtimes? I would think that if they enforced the getting-up time, the kids would take care of the getting-to-sleep part on their own.

[Alicorn]

This does not work with teenagers, in whom bedtimes are practically unenforceable, but whose need to get to school in a timely fashion does a reasonable job of imposing a getting-up time. They are chronically sleep deprived. Smaller children, I imagine, have even less of a chance of managing the feat.

[cousin_it]

...Woah. Thanks to your comment, I just remembered vividly how much my school years sucked.

[AdeleneDawner]

Don’t teenagers have brain-chemistry that makes them have trouble getting to sleep at a reasonable hour? I’m not finding a good reference, but I remember reading that, and that the effect doesn’t apply to children.

[gwern]

Roughly one-quarter of the kids fell into the borderline-acceptable category, meaning they reported eight hours of shuteye nightly. The overwhelming majority fell short — with 30.2 percent reporting seven hours, 22.8 percent slumbering closer to six hours, 10 percent catching a mere five hours of sleep, and 5.9 percent claiming to nod off for no more than four hours most weeknights. Just the thought makes me yawn. Certainly, schools don’t help the situation by starting classes earlier for teens than they do for younger kids — even though puberty and other developmental changes lead to adolescents needing more sleep than grade schoolers, not less.
But there could be other issues.
Like what share of teens don’t get enough sleep because they’re naturally night owls (like me) and find almost anything before 2 or 3 a.m. more interesting than slumber? http://​​www.sciencenews.org/​​view/​​generic/​​id/​​53220/​​title/​​Vast_majority_of_teens_are_sleep-deprived

The circadian link is to a gatewayed article; you can find a public copy at http://​​www.thefreelibrary.com/​​Sleepy+teens+haven%27t+got+circadian+rhythm.-a0134623686

In an attempt to reset the students’ daily biological clocks Biological clocks, or circadian rhythms, so that they would be more alert in daytime and go to bed earlier, the researchers exposed some students in their classrooms to especially bright light between 8 a.m. and 10 a.m. Other students were exposed to muted red lighting. But the bright light neither changed students’ sleep patterns nor improved their scores on tests of mood, vigor, and cognitive function cognitive function Neurology Any mental process that involves symbolic operations–eg, perception, memory, creation of imagery, and thinking; CFs encompasses awareness and capacity for judgment .

[byrnema]

I remember. It was a very high-profile study that asserted a phase-delay in the teenage sleep cycle. The study was cited for a while in arguments to shift the school day later by a couple hours.

[AdeleneDawner]

That’s it. Thanks!

[PhilGoetz]

That makes sense—but let me add that the idea that it is a myth that bedtimes must be enforced fits another observation: parents also seem to believe that they have to persuade or force their children to eat; yet in big families where no one can make sure everyone eats, all the children learn quickly to eat on their own.

[Blueberry]

parents also seem to believe that they have to persuade or force their children to eat

They do? I would be very surprised at parents who believed this. Eating satisfies a natural desire and feels good. Sleeping means stopping the fun thing you’re doing and lying down in a dark room; why would kids want to do that?

[scotherns]

I have two kids. If left to their own devices, they would eat the tastiest things on their plate, then stop (then complain about being hungry an hour later). They would never eat anything remotely healthy, and subsist entirely on chocolate if given the choice.

Since we have evolved to value fat and sugar as being the tastiest substances, children do have to be taught/​persuaded to eat healthy food.

They also do need to be told when to go to bed. The times at which we have tried to let them set their own bed times have resulted in them trying to stay awake as long as they possibly can, until they fall asleep in the middle of whatever they were doing. They almost never voluntarily go to bed, no matter how obviously tired they are.

[PhilGoetz]

Eat a meal with a family with a single child. In many cases, the parents will spend much of the meal ordering or pleading with the child to eat their food. Then eat a meal with a family with 6 or more children. That probably won’t happen.

I do know one kid who really won’t eat on his own; if you don’t coax him into eating, he won’t eat enough. But that’s unusual.

[pdf23ds]

They just want an hour or so to themselves before bed, if that.

[AdeleneDawner]

It seems like it’s a near/​far problem, at least in part—it’d take a few weeks, perhaps even a month or two, for the kids to figure it out, and in the meantime the parents will be inconvenienced by having to deal with cranky kids, and also probably having to stay up later than they’d prefer to.

I suspect most parents don’t give it enough thought to realize that the situation would be temporary (well, not counting the possibility that the kids could settle into an inconveniently late bedtime) and the lesson would be valuable, though, or they don’t believe that their kids would figure it out at all.

[NancyLebovitz]

Could you guys be more specific about what you hate about going to bed and about getting up? I don’t even know whether you’ve all got the same problem.

[pete22]

Let’s say it’s midnight, I’m tired, and I’m home alone with nothing better to do. I know I have to get up early and I’ll feel better /​ be more productive the next day in direct proportion to how much sleep I get. I still just don’t want to go to bed. It requires real force of will not to stay up and find something else to do, even if it just amounts to reading random stuff online or otherwise killing time.

I’ve gotten better at just making myself go to bed anyway in that situation, but I don’t know why it should take any effort in the first place. Going to sleep should – at least occasionally—be my most attractive alternative, even from a short-term perspective. But for some reason it never feels that way.

I don’t have insomnia, nightmares, apnea or any other condition (that I know of) that would make sleep/​bed unpleasant – so at least in my case the act of sleep itself doesn’t seem to be a factor.

[John_Maxwell]

Use cron to make your browser open a new tab once a minute starting at midnight that says “GET TO BED!”

[wedrifid]

I have at times set cron to shut down the PC, with a 1 minute countdown. It worked wonders. It did cut down on productivity somewhat. Working 25 hours straight actually does get a lot of stuff done!

[SoullessAutomaton]

This is my experience as well, for the most part.

The only times I recall “going to bed” feeling like a good idea is when I’ve been so far into exhausted sleep deprivation that base instincts took over and I found myself doing so almost involuntarily.

Even in those cases, my conscious mind was usually confabulating wildly about how I wasn’t actually going to sleep, just lying down for a half a moment, not sleeping at all… right up until I pretty much passed out.

It’s rather vexing.

[AdeleneDawner]

Would you guys mind terribly if I picked your brains?

The kind of experience you’re describing is described fairly often in autistic communities. There’s a few variations, generally falling into the categories of sensory processing or executive dysfunction issues. The former category would include not experiencing, or noticing that you’re experiencing, ‘tiredness’, even when your body is acting tired in a way that others would notice (e.g. yawning, stretching, body language). The second case involves not being able to stop whatever activity you’re engaged in and go to bed, even though you recognize (perhaps briefly, before being drawn back into what you’re doing) that you are tired and it would be a good idea. (This isn’t quite the same as ‘I’ll do one more part, and then go to bed’ in that it’s less conscious and therefore harder to break out of—in many cases it takes a significant effort of will to stop your body from automatically taking the next step in what you’re doing, even if you’ve actually decided not to take that next step.)

I’m curious to find out if those issues are also experienced by people who aren’t autistic—perhaps to a lesser degree, or with different explanations than the ones that I mentioned. Do the issues I described sound like what you’re experiencing? Are they close, or similar in some interesting way?

[SoullessAutomaton]

The former category would include not experiencing, or noticing that you’re experiencing, ‘tiredness’, even when your body is acting tired in a way that others would notice (e.g. yawning, stretching, body language).

I’m not sure if this is what you’re talking about, but I’ve long distinguished two aspects of “tiredness”. One is the sensation of fatigue, exhaustion, muddled thinking, &c.--physical indicators of “I need sleep now”.

The second is the sensation of actually being sleepy, in the sense of reduced energy, body relaxation, and a general feeling that going to bed sounds like a fine plan.

I almost always notice the former, but unless accompanied by the latter (often not the case), acting on it by going to bed requires a conscious decision. Usually, the sleepiness will appear after I’m lying down, but at times I’ve been unable to clear my mind of activity and will lie in bed for two or more hours, unable to sleep despite being extremely tired.

If I’m deeply involved in something and not feeling “sleepy” I can easily fail to notice the fatigue (along with hunger and various other non-urgent physical sensations).

The second case involves not being able to stop whatever activity you’re engaged in and go to bed, even though you recognize (perhaps briefly, before being drawn back into what you’re doing) that you are tired and it would be a good idea.

In my case it’s more garden-variety procrastination; going to sleep is just one more thing that I know I should do but don’t really want to, because it’s boring.

I’m curious to find out if those issues are also experienced by people who aren’t autistic—perhaps to a lesser degree, or with different explanations than the ones that I mentioned. Do the issues I described sound like what you’re experiencing? Are they close, or similar in some interesting way?

My experience mostly reduces to a disconnect between a non-critical physical need and the desire to fulfill it, generally to an extent proportional to how much mental activity is bouncing around my conscious mind (the default state being “too much”).

As a final note, besides the melatonin not making me sleepy, neither ethanol nor caffeine seems to have an appreciable effect on whether I can get to sleep (though both will reduce the quality of any sleep).

[AdeleneDawner]

Thanks for the datapoint.

I’m not sure if this is what you’re talking about...

I almost always notice the former...

If I’m deeply involved in something and not feeling “sleepy” I can easily fail to notice the fatigue (along with hunger and various other non-urgent physical sensations).

That doesn’t sound like the experience I was trying to describe, which is of not noticing sleepiness or fatigue at all, even when not doing something engaging. The ‘not noticing’ caveat is there because some autistics won’t automatically notice those sensations, but can consciously check to see if they’re occurring, and get into the habit of doing so. (The issue can apply to hunger, too.)

[SoullessAutomaton]

If you’re actually collecting datapoints, not just using the term semi-metaphorically, it may help to add that I’ve been diagnosed with (fairly moderate) ADHD; if my experience is representative of anything, it’s probably that.

[wedrifid]

I’m curious to find out if those issues are also experienced by people who aren’t autistic—perhaps to a lesser degree, or with different explanations than the ones that I mentioned. Do the issues I described sound like what you’re experiencing? Are they close, or similar in some interesting way?

How will you distinguish between a non-autistic ‘experiencing an autistic associated experience to a lesser degree’ and, well, someone experiencing a lesser degree of autism? Considering the context I am not sure if a “I notice that too” from a LessWrong poster would inform me much at all about how much prevalence independent of the causal factors behind autistism.

My experience, for what it is worth:

The former category would include not experiencing, or noticing that you’re experiencing, ‘tiredness’, even when your body is acting tired in a way that others would notice (e.g. yawning, stretching, body language).

My main experience of ‘tiredness’ is metacognitive awareness of impaired cognitive function. For example, I’ll notice that my verbal expression and spelling becomes impaired and the names of things elude me and then conclude that I am tired. I don’t feel ‘sleepy’. Note that now that I have discovered melatonin I actually can feel tired (if I take ~6 mg). This was quite a novelty! I also seemed to have developed somewhat more awareness of other ‘tiredness’ indicators such as yawning over recent years (late 20s).

The above applies to hunger as well, for most part.

The second case involves not being able to stop whatever activity you’re engaged in and go to bed, even though you recognize (perhaps briefly, before being drawn back into what you’re doing) that you are tired and it would be a good idea.

Spot on.

[AdeleneDawner]

How will you distinguish between a non-autistic ‘experiencing an autistic associated experience to a lesser degree’ and, well, someone experiencing a lesser degree of autism?

I’m not sure that those categories are naturally distinguishable, actually—there’s a fair bit of controversy over whether there’s a smooth spectrum between very autistic individuals and very NT individuals, and such datapoints could be taken as evidence for that theory. Whether the NT-leaning-toward-autistic portion of that spectrum (assuming it exists, which I believe it does) manifests in single examples of significant autistic-type experiences in otherwise NT people vs. multiple slightly autistic-leaning traits (or both) is also interesting.

I tend not to spell that kind of thing out unless asked, though—not everyone reacts well to overt suggestions that they might be autistic-leaning because of some trait. ‘NT with a quirk’ is much more palatable.

[Blueberry]

The second case involves not being able to stop whatever activity you’re engaged in and go to bed, even though you recognize (perhaps briefly, before being drawn back into what you’re doing) that you are tired and it would be a good idea. (This isn’t quite the same as ‘I’ll do one more part, and then go to bed’ in that it’s less conscious and therefore harder to break out of—in many cases it takes a significant effort of will to stop your body from automatically taking the next step in what you’re doing, even if you’ve actually decided not to take that next step.)

This sounds like me. Not just for going to bed, but for anything I need to do. Do you have links to descriptions or discussions of this experience? Have people found any way of dealing with it? I’m probably slightly on the autism spectrum.

ETA: I’ve also heard this described as ADD or OCD.

[AdeleneDawner]

This is my go-to article on the subject. I can probably dig up some more things later, if you’re interested. (I’m about to go to bed.) Mostly it’s more worked-around than overcome, but there are resources out there on how to work around it, and I’ll make a point of trying to find some of them if you want.

Executive dysfunction is part of ADD, too, so I wouldn’t be surprised to hear of it being an element of that. My understanding of OCD is that the mechanism behind the issue isn’t the same, but I could easily be wrong; I haven’t done as much research on OCD.

[Blueberry]

Thanks! Yes, please dig up more on that! (Guess you didn’t go to bed right away.) I’d love to see resources for how to work around it.

[Tyrrell_McAllister]

I definitely have those kinds of experiences. I don’t believe that I’m autistic.

[PhilGoetz]

Going to bed is a little like dying. Someone slightly other wakes up in the morning.

[gwern]

Because I can’t stop my compulsive quoting...

 "I lay me down and slumber
 And every morn revive.
 Whose is the night-long breathing
 That keeps a man alive?"

-- XIII, More Poems, A.E. Housman (1859 – 1936)

[Wei Dai]

Going to bed is a little like dying. Someone slightly other wakes up in the morning.

Good point. For example, last night just before going to bed, I was totally absorbed in Eliezer’s latest story. But when I woke up this morning, I forgot about wanting to finish the story, and started doing other things. (Eventually I came upon the open tab and finished it.)

BTW, if anyone hasn’t read that story yet, you should keep this page handy as a reference, otherwise it’s pretty hard to understand.

[[deleted]]

/​.

[AngryParsley]

Thanks for posting this. You’ve done a good job of explaining how melatonin is insanely cost-effective. I do want to mention some caveats for anyone who is interested in trying melatonin.

I use melatonin nightly. I admit it’s effective, but it’s no panacea. You can’t drink a cup of coffee, then take some melatonin and expect to fall right asleep. It can also help to keep the lights low for about 30 minutes before bed time. Finally, one side-effect of melatonin is that I often have very vivid dreams. I don’t know of any studies confirming this, but there are quite a few anecdotes.

[jimmy]

I’ve done an informal polling of my friends whom I’ve introduced to melatonin, and the majority of them noticed more vivid dreams without me mentioning it.

I use it only occasionally, but the effect it has on my dreams is too large to fake (and I noticed it before ever hearing that it was supposedly a common side effect)

[gwern]

I’ve noticed it too, but I didn’t really think it germane to a cost-benefit evaluation. More dreams is a mixed blessing in general—unless one wants to do lucid dreaming, which is an entirely different kettle of fish, and this little essay covers enough as it is.

[jimmy]

I’d say it’s worth mentioning, though not worth spending many words on.

Some people I’ve talked to won’t take it because they don’t want any more nightmares than they already have.

[jacob_cannell]

I’ve been using melatonin for years now. I recommended it as part of my health article a while back.

When I started I was careful to always take a <1mg dose. More recently (due to laziness really) I have just been taking whatever dose I found at the store without bothering to break the tablets apart.

Your article reminded me that the current 3mg tabs I have are probably too much. This dose still works fine for me, but I have noticed a higher incidence of headaches which could be connected.

PS, good work on your site gwern, I find your research useful.

[Tyrrell_McAllister]

My rule of thumb is melatonin subtracts an hour. That is: if one slept for 7 hours, one awakes as refreshed as if one had slept for 8 hours (and so on).

That’s the opposite of my impression. I used melatonin for several months because it made it so easy to get to sleep. But I found that I needed to get a full 8 hours of sleep to wake up refreshed. I attributed that to some vague notion that the melatonin needed that much time to work its way through my system. At any rate, waking up after less than 8 hours seemed harder than it does without melatonin. That was my very unscientific impression.

For that reason, I was glad when I found a mental trick that let me get to sleep as easily as I could with melatonin.

[gwern]

Perhaps you were taking a too-large dose? Or taking it in some way that took a long time to be absorbed?

[Bongo]

Melatonin trip report:

I’ve used melatonin for two weeks now. Taking 1.5mg consistently puts me to sleep within an hour. Also gives me vivid dreams. Makes it easier to go to sleep at the same time every night. Does not make it easier or harder to get up in the morning.

Verdict: melatonin is worth it.

[Richard_Kennaway]

3. Melatonin supplements just doesn’t work on you, period.

• Possible, but unlikely. This isn’t some mental trick—it’s a fundamental fact of mammalian biology.

The presence of melatonin in the body and its function there may be fundamental, but that does not make the effect of supplements equally fundamental. The role of vitamins is also fundamental, but you yourself cite evidence that vitamin supplementation for all is a bad idea. I don’t see anything in what you have written to suggest that melatonin supplementation for all should be any different.

FWIW, I have tried melatonin—last night, in fact, 3mg—and observed no effect. I did not fall asleep more quickly (I was still awake three hours later, at 01:40); I woke at a typical time; my waking lethargy was, if anything, slightly more than usual; my dreams were typical.

I’ll give it a few more goes with a reduced dose (from further reading, 3mg seems excessive), but real science is supposed to work every time.

ETA: 1mg had the same lack of effect.

[PhilGoetz]

The gains I have laid out are significant enough I consider it irrational for someone not to use it, unless:

You forgot

1. You are like Phil, and melatonin has no observable effect on you.

(Pretend that 1 is a 9. It is. Honestly. It just shows up as a 1.)

[arundelo]

To get

9. List item 9

do:

9\. List item 9

[randallsquared]

You can use

\9.

\9. to produce this.

[timtyler]

My own brief “M” review: http://​​timtyler.org/​​melatonin/​​

[gwern]

I think your review shows that melatonin as a recreational drug is kind of silly. :)

[timtyler]

I took it after hanging around with some LE folk. Interesting—but the side effects were serious enough for me to stop quickly. Maybe I will try it again when I am quite a bit older.

[Kevin]

I have a friend that took abusive levels of melatonin in a futile effort to conquer insomnia. He said laying in bed on 9mg of melatonin without falling asleep was like dreaming while you’re awake.

Instead of the 3rd eye analogy, I would describe melatonin as altering your thought patterns to be more conducive to sleep. The types of nonsense thoughts you have right before you fall asleep come sooner on melatonin.

[Cyan]

I’m going to get some melatonin as soon as possible.

[Cyan]

I’ve been taking 1.5 mg of melatonin every night for the past two weeks (except for last night). It’s hard to say exactly what effect it had, because it’s confounded with another major change in my sleep habits. It seemed to me that it moved my energy levels towards “a little bit sluggish” relative to what I counterfactually expected had I not taken the melatonin. So if I had a good night’s sleep, I seemed less energetic than I ought, and if I had very little sleep, I seemed more alert than I ought.

On Sunday night (Jan 17) , I got 5 hours of sleep and felt terrible on Monday. On Monday night I got 6.25 hours of sleep and felt very marginal on Tuesday. Last night I got 4.75 hours of sleep—but I forgot to take the melatonin. Today I feel far better than I ought to on such little sleep. I’m going to neglect the melatonin again tonight and see what tomorrow brings.

ETA: Also, I noticed no change in the vividness or lucidity of my dreams relative to my baseline of rarely remembering any dreams for longer than 30 seconds after waking up.

[whpearson]

I tried to get some just know. But it turns out in the UK you can only get melatonin on prescription.

[gwern]

Since the big criticism of this article was lack of proof of safety, which is a negative and rather hard to prove (who’s going to pay for a long-term study of safety when there are lots of reasons to think there is no problem and bigger fish to fry?), I’ve given a try of the opposite—showing that melatonin supplementation improves health; see the last paragraph of http://​​www.gwern.net/​​Melatonin#use

If our computer use is massively cutting our melatonin secretion and lack of melatonin causes noticeable health problems in the most studied group (shift workers), then it seems straightforward to me that supplementation back to the baseline will improve health.

(Quickly looking, none of my refs give specific total secretion amounts, so I can’t be sure that taking say 1.5mg exactly counteracts an average 50% fall, but it doesn’t seem likely that 1.5mg or 3mg will overshoot by a grotesque & harmful amount.)

[Kevin]

Do you have any evidence that melatonin is not addictive or habit forming? I have not read the studies you have linked; do they explicitly suggest this?

My understanding is that taking melatonin regularly will cause your body to naturally produce less melatonin, especially when taken in the 3mg dosage. Most doctors recommend a dosage of 1mg as that is closer to the body’s natural amounts of melatonin.

Anyways, I think it’s worth trying melatonin for one of the side effects, weird, vivid, possibly lucid dreams. Or possibly just increased dream recall.

[jimrandomh]

I tried melatonin for the first time last night after reading this article. I will report back my results in two weeks.

[Mass_Driver]

Where’s the report? It’s been more than two months. :-)

[jimrandomh]

The outcome was an abort for a reason that’s not generally applicable. (Using melatonin prevented me from waking up in response to high or low blood sugar, which matters only for diabetics like me, but is an absolute showstopper, since failing to wake up in response to low blood sugar could be fatal.)

[NancyLebovitz]

On the one hand, it’s not generally applicable, but on the other, you’re probably not the only diabetic reading LW.

[Mass_Driver]

Sorry to hear it! Better luck next time you go pharma-spleunking.

[nshepperd]

Ah, only just saw this. That’s a shame. But for the benefit of anyone else reading this, I’m also a insulin dependent diabetic, and so far I’ve observed that on melatonin I do still wake up in response to low blood sugar. Therefore this may be a thing that varies between individuals.

[gwern]

Miscellaneous note: Mentally, I find it easier to try to write for a non-LW audience, hence the tedious explanation & justification of the minimum wage assumption.

[CannibalSmith]

Well written and convincing article. Good job!

[eirenicon]

I have delayed-phase sleep disorder—I would say I “suffer” from it but it’s really only a problem when a 3-10 sleep schedule is out of the question (as it is now, since I currently work 9-5). It’s simply impossible for me to fall asleep before 2 or 3 am unless I am extremely tired. In addition, I’m a light sleeper, and have never been able to sleep while traveling or, in fact, whenever I’m not truly horizontal. I took melatonin to help with this for a couple years (at a recommended 0.3 mg dose), and it worked extremely well. However, I experienced unusually vivid dreams, and would often wake up feeling groggy. Ultimately, I switched to taking 50 mg 5-HTP an hour or two before bed. The result is that I fall sleep as easily as with melatonin, but wake up feeling far more refreshed. I usually clock 7 hours of sleep a night now, and have brighter and more productive days.

The best sleep aid I’ve ever used isn’t a legal one, though. Luckily, it’s widely available here in Canada...

[sboo]

as 5-HTP is metabolized to melatonin, i wonder how much of the effect comes from melatonin itself.

[SoullessAutomaton]

Consider me another data point for “found no obvious effect”. I took a 3mg dose nightly for a couple weeks and didn’t notice it doing much of anything. It might have made me feel a bit drowsy, but only briefly, and to a sufficiently small degree that I considered a biased perception due to wondering if I’d feel sleepier to be a more plausible hypothesis.

In either case, it certainly did not produce enough drowsiness to make “going to sleep” seem unusually appealing, and going to bed after taking it remained a conscious, deliberate exercise of will; on at least one occasion “procrastination” won out and I stayed up anyway with no appreciable difficulty.

Nevertheless, intermittent insomnia and restless sleep in recent weeks has convinced me to try again. Current, extremely subjective impressions are that it might be marginally improving sleep quality, but seems to do little for countering insomnia.

[taw]

And what evidence do you have that it works the way you say without side effects… ? My self-experiments with Provigil say that nothing can reduce my long term need to sleep without severely deteriorating my mental capacity. Plural of anecdote being data...

[gwern]

And what evidence do you have that it works the way you say without side effects… ?

Feel free to go through WP, all the studies linked in various places on this page, and every study that 2 seconds on Google & Google Scholar would turn up, and explain them all away.

My self-experiments with Provigil say that nothing can reduce my long term need to sleep without severely deteriorating my mental capacity.

I never said you needed less sleep. I said you needed less time for sleep; they’re not the same thing. Not every minute spent in bed ‘sleeping’ is actual sleep, nor every minute asleep of equal value & quality; to quote myself:

I am unsure whether its effect is to put one to sleep faster, or to do that and also deepen sleep, but melatonin does it well.

Either effect might be the reason, or both of them together.

[taw]

Which studies do you find particularly convincing? Cochrane has only meta-analysis of short-term melatonin use for jet lag, which I don’t doubt.

Which studies show that melatonin allows long term reduction in need for sleep, and that this sleep reduction has no negative consequences?

Saying you need “less time for sleep” only applies to people who have difficulties falling asleep, and needs some evidence anyway.

[AdeleneDawner]

I have a job that doesn’t require me to be awake at any particular time, and my sleep schedule varies quite a bit (in the way that you’d expect; my average day is ~25 hours). I just purchased some melatonin tablets (this brand/​dosage). Other than having heard it recommended as a sleep aid before, and having heard that it’s not effective for everyone, I know nothing about it but what’s in this post, which should minimize any psychosomatic effects. What’s the most useful datapoint(s) that I could provide to the community?

Edit: Found a more accurate link to the pills I have.

[gwern]

I’d like to know how hard you find it to wake up, how groggy you feel, and if possible, your performance on any mental benchmarks you might have.

(If you don’t have any existing benchmarks, you can find a ton of examples at http://​​lesswrong.com/​​lw/​​1gl/​​how_to_test_your_mental_performance_at_the_moment/​​ Obviously you should spend some time on your chosen benchmark & familiarize yourself before you begin popping the pills.)

[Nic_Smith]

I stopped taking melatonin because I’d wake up extremely groggy. Although I also have a (bad?) habit of covering my eyes with a pillow or the corner of a blanket AND I have a light blocking shade in my room, so I was basically waking up in complete darkness. One thing I considered to counteract this was plugging a lamp into a “vacation” timer and having it fire up around 7a or 8a or so. I think I’ll stop at the hardware store and give the whole setup, melatonin and all, another try after reading this post.

[gwern]

Here’s a thought: use the melatonin and wrap a scarf around your head before going to bed, but leave the shade up or loose. The melatonin & scarf will put you to sleep, and sunrise around 6 or 7 will slowly wake you up, since by then the melatonin will have run out and your scarf will have come off.

[Nic_Smith]

Thanks for the suggestion. Actually, for the last couple of days, I’ve been taking about half the dose I tried last year, and I’ve had the shade open a bit—the little bit of light it lets in at night doesn’t seem to bug me as much as it used to. It seems to be working in terms of moving the time I wake up a bit each day, and not so much grogginess. I know Less Wrong isn’t Erowid, but I think my experience trying melatonin sublingually, which is something that was suggested in one of the other comments, might be interesting—IT BURNS! And now the underside of my tongue itches, which is not even something I knew was possible before. As a guess, this is my fault, as a quick search shows there are actually lozenges that are meant to be taken this way, instead of the usual swallowed tablets.

[jimmy]

I take it occasionally (mainly when I need to shift my sleep schedule back a few hours very quickly), but have kept from taking it nightly due to worries of tolerance and such.

Have you noticed any tolerance or know of any studies that cover this?

The metastudy I saw mentioned many studies finding no effect due to large doses causing tolerance effects (and recomended doses of no more than 1mg, IIRC).

I also never heard of the ‘subtract an hour’ part, nor have I noticed it on my own (though I use it in times when it’d be harder to notice). Has anyone else noticed this effect or are there studies talking about it?

I mainly take it sublingually (0.75mg), which kicks in much more quickly than orally which helps if you can’t plan a half hour in advance. I sometimes notice the effects in two minutes this way.

[gwern]

Have you noticed any tolerance or know of any studies that cover this?

I’ve seen neither. I take pretty much the same dose I did way back in my early teens when I started. But I’ll admit, I haven’t looked very hard for the latter.

A quick Google Scholar search only turns up a few hits for ‘melatonin tolerance’ which cover tolerance of melatonin itself; one says

Sleep maintenance and initiation were further improved following the 2-month 1-mg sustained-release melatonin treatment, indicating that tolerance had not developed. After cessation of treatment, sleep quality deteriorated. Our findings suggest that for melatonin-deficient elderly insomniacs, melatonin replacement therapy may be beneficial in the initiation and maintenance of sleep. http://​​www.ncbi.nlm.nih.gov/​​pubmed/​​8552931

Or in one primate study:

Daily administration of a 5-μg/​kg dose for 4 weeks or gradually escalating melatonin doses (5-320 μg/​kg over a 3-week period) did not result in the development of tolerance or sensitization to the effect of melatonin on sleep initiation or sleep period. http://​​cat.inist.fr/​​?aModele=afficheN&cpsidt=13688537

And here’s some Times coverage:

On the other hand, says Wyatt, people don’t seem to build up a tolerance to melatonin, and even small amounts, like the 0.3-mg dose used in the study, are effective. Studies show also that melatonin is safe for adults, at least in the short term, with few side effects. http://​​www.time.com/​​time/​​magazine/​​article/​​0,9171,1191851,00.html

But on the other hand, a regular Google search will turn up several people complaining of tolerance. (Whether you believe any of them or write them off as freaks, exaggerators, victims of fake melatonin, or whatever, is up to you.)

[jimmy]

Thanks for the reply. I didn’t mean to make you do the leg work for me.

But on the other hand, a regular Google search will turn up several people complaining of tolerance. (Whether you believe any of them or write them off as freaks, exaggerators, victims of fake melatonin, or whatever, is up to you.)

I think I’ll believe them, but think they’re taking too much. The metastudy I read a while ago (couldn’t find it in a couple minutes, but I’ll look harder if you want to see it) said that people were taking too much (>1mg) because there was a patent or something on using it at <1mg doses where it worked best. This led to people developing tolerances and the studies reflecting this. All the studies you listed were with lower doses of melatonin, so it makes sense that they didn’t.

I guess I’ll try taking it regularly now.

[snul]

I attempted to use melatonin on myself in a pseudo-study and wrote about it here: http://​​lesswrong.com/​​r/​​discussion/​​lw/​​ngj/​​open_thread_april_4_april_10_2016/​​d7s5

[mattnewport]

I’m a bit skeptical about this but it’s an interesting idea and seems relevant to this discussion. It might even be a useful way of making any self-tests of melatonin slightly more scientific. I haven’t tried it myself yet.

Sleep Cycle Analyzes Your Sleep Patterns for a Better Wake-Up

[gwern]

I’ve seen a lot of those things (Hacker News has in the past week been discussing some new product which doesn’t use a cellphone but you wear on your wrist as a band). I’m not sure how good their data is.

I do plan to get a Zeo (from Zeo Inc., since they seem to provide much better data on your sleep (such as what stage you are in, which would be very important if one wanted to run polyphasic experiments) - but I’m torn between that and SNP/​DNA testing from 23AndMe to learn about how effective modafinil might be for me.

EDIT: I got a Zeo and have been happily running experiments, see http://​​lesswrong.com/​​lw/​​1lt/​​case_study_melatonin/​​5w76 ; so now I guess I need to figure out what the right price to me for SNP testing is. And also how to legally get it where I am...

[gwern]

To follow up, my first sleep experiment with the Zeo was using melatonin on/​off; the results seem to confirm my 1-hour rule of thumb: http://​​www.gwern.net/​​Zeo#melatonin-analysis

[NancyLebovitz]

I’ve taken melatonin a few times—it put me to sleep, though I think the onset of sleepiness was more like an hour after taking it. If I overrode the mild sleepiness, the melatonin’s effect was lost,.

I’ve heard that people’s natural production of melatonin declines with age, so there may be an age below which the pills don’t make a huge difference for most people.

[gwern]

I’ve taken melatonin a few times—it put me to sleep, though I think the onset of sleepiness was more like an hour after taking it.

Sure, that’s possible. Maybe your formulation simply took a long time; if I chew my pills, they act that much faster since they have that much more surface-area. No surprise there. I’ve seen time-delayed version as well.

I’ve heard that people’s natural production of melatonin declines with age, so there may be an age below which the pills don’t make a huge difference for most people.

This too is possible. I was reading some of the child studies, and an infant or young child produces impressive amounts; supplementing wouldn’t do much. (I also tried some on one; he reported sleeping a little bit better but nothing he would’ve noticed if I hadn’t asked him.)

[John_Maxwell]

“It really amazes me that melatonin is available in any pharmacy,” Bentley said. “It is a powerful hormone, and yet people don’t realize that it’s as ‘powerful’ as any steroid. I’m sure that many people who take it wouldn’t take steroids so glibly. It could have a multitude of effects on the underlying physiology of an organism, but we know so little about how it interacts with other hormone systems.”

Popular supplement melatonin found to have broader effects in brain than once thought (2005)

[wedrifid]

Bentley said. “It is a powerful hormone, and yet people don’t realize that it’s as ‘powerful’ as any steroid. I’m sure that many people who take it wouldn’t take steroids so glibly.

Unless the quality of the remainder of the article uses an entirely different caliber of reasoning than what you have chosen to excerpt here it should be dismissed as drivel. The (by clear implication, anabolic) steroids that Bentley attempts to equate to melatonin have clear effects that need to be managed or accepted. There has been enough research and practical use of melatonin to reliably establish that whatever the effects of melatonin are they less significant than the effects of anabolic steroids.

[sboo]

right: Worst Argument In The World.

[gwern]

“So in conclusion: be afraid, be very afraid.”

[John_Maxwell]

I’m confused… did you update at all on the possibility of harms from long-term melatonin use after reading the article?

[gwern]

No. Your excerpt was a poor exposition of the standard precautionary principle I regard as entirely useless.

Reading your link now, I have even less reason to pay attention to it. It’s a random press release about a presumably small unreplicated animal study in a species I don’t know to be particularly germane to humans (eg. chimps) about changes of unclear importance in a body system with no human analogues (“In birds, switching off GnRH causes the gonads—testes and ovary—to shrink as part of the birds’ yearly cycle.”) with doses potentially high enough to be completely irrelevant to human supplementation (injecting melatonin?). I haven’t even read the study!

Combine all the conditionals here (the smallness and lack of replication alone knocks down the chance this means anything about anything to well under 50%), and I don’t see why I would update at all (not being an AI or anything which can represent degrees of belief with 64-bit floats).

If anything, I think this sort of study is a good example of why animal studies should be ignored in discussing supplements.

[John_Maxwell]

Good points.

Have there been any meta-analyses of how well supplement studies on animals tend to transfer to humans?

[gwern]

On the general topic of animal model external validity & translation to humans (with obvious relevance to supplements & nootropics), here are the major systematic reviews, meta-analyses, and articles criticizing the routine failures of animal models to provide any meaningful information about dangers or benefits in humans, and documenting the even lower quality of animal experiments than usual in (human) medicine or psychology:

• “Nimodipine in animal model experiments of focal cerebral ischemia: a systematic review”, Horn 2001; review

• “Wound healing in cell studies and animal model experiments by Low Level Laser Therapy; were clinical studies justified? A systematic review”, Lucas et al 2002; meta-analysis

• “Does animal experimentation inform human healthcare? Observations from a systematic review of international animal experiments on fluid resuscitation”, Roberts et al 2002; meta-analysis

• “Systematic reviews of animal experiments”, Sandercock & Roberts 2002

• “Meta-analysis of the effects of endothelin receptor blockade on survival in experimental heart failure”, Lee et al 2003; meta-analysis

• “Where is the evidence that animal research benefits humans?”, Pound et al 2004; review

• “The use of animal models in the study of complex disease: all else is never equal or why do so many human studies fail to replicate animal findings?”, Williams et al 2004; essay

• “The future of teratology research is in vitro”, Bailey et al 2005; review

• “How good are rodent models of carcinogenesis in predicting efficacy in humans? A systematic review and meta-analysis of colon chemoprevention in rats, mice and men”, Corpet & Pierre 2005; meta-analysis

• “Surveying the literature from animal experiments”, Lemon & Dunnett 2005; essay

• “Systematic review and meta-analysis of the efficacy of FK506 in experimental stroke”, Macleod et al 2005; meta-analysis

• “Systematic review and meta-analysis of the efficacy of melatonin in experimental stroke”, Macleod et al 2005; meta-analysis

• “Methodological quality of animal studies on neuroprotection in focal cerebral ischaemia”, van der Worp et al 2005; review

• “Nitric oxide synthase inhibitors in experimental ischemic stroke and their effects on infarct size and cerebral blood flow: a systematic review”, Willmot et al 2005; meta-analysis

• “A systematic review of nitric oxide donors and L-arginine in experimental stroke; effects on infarct size and cerebral blood flow”, Willmot et al 2005; meta-analysis

• “Translation of Research Evidence From Animals to Humans”, Hackam 2006; review “1,026 experimental treatments in acute stroke”, O’Collins et al 2006; review

• “A Systematic Review of Systematic Reviews and Meta-Analyses of Animal Experiments with Guidelines for Reporting”, Peters 2006; review

• “Translating animal research into clinical benefit”, Hackam 2007; essay

• “Systematic Reviews of Animal Experiments Demonstrate Poor Human Clinical and Toxicological Utility”%20641-659.pdf), Knight 2007; review

• “Comparison of treatment effects between animal experiments and clinical trials: systematic review”, Perel et al 2007; review

• “How can we improve the pre-clinical development of drugs for stroke?”, Sena et al 2007; essay

• “Systematic Reviews of Animal Experiments Demonstrate Poor Contributions to Human Healthcare”%2089-96.pdf), Knight 2008; essay

• “Evidence-Based Data From Animal and Human Experimental Studies on Pain Relief With Antidepressants: A Structured Review”, Fishbain et al 2008; review

• “Are animal models as good as we think?”, Wall & Shani 2008; essay

• “Publication bias in reports of animal stroke studies leads to major overstatement of efficacy”, Sena et al 2010; meta-analysis

• “Can Animal Models of Disease Reliably Inform Human Studies?”, Worp 2010; essay

• “Human relevance of pre-clinical studies in stem cell therapy: systematic review and meta-analysis of large animal models of ischaemic heart disease”, van der Spoel et al 2011; meta-analysis

I spent the day reading up on the topic. The transfer or replication rates range from around 40% on the upper end to zero in some cases involving as many as hundreds of attempts to transfer. The methodological quality of the animal studies are usually terrible with hardly any blinding and randomization rare (and when it is done, one author indicates that researchers surveyed would say it was done as informally as grabbing random mice/​rats out of the cages), and the publication biases at play seem to be even larger than in human studies.

(Reading the papers, I found myself disturbed by the ethical implications: when human studies fall to publication bias, ‘all’ that does is waste many millions of dollars and impede the progress of science and substantially inconvenience many subjects and put them at risk; but when at least a third of all animal experiments never get written up, and half of chimpanzee medical/​biological studies never get cited when they do get published, that means that the billions of animals gone through every few years are mutilated and tortured and killed for absolutely nothing at all. This makes me much more sympathetic to the NIH’s recent retirement of its research chimpanzees.)

There are some interesting examples, though; from one of the links:

In animal models of acute ischemic stroke, about 500 “neuroprotective” treatment strategies have been reported to improve outcome, but only aspirin and very early intravenous thrombolysis with alteplase (recombinant tissue-plasminogen activator) have proved effective in patients, despite numerous clinical trials of other treatment strategies [8],[9].

From the toxicology paper:

“Karnofsky’s Law, which states ‘Anything can be teratogenic if given in the right dose, to the right species, at the right time’. If every single drug, chemical and indeed substance can be teratogenic in some particular animal at some specific dose, then to produce a positive result one need only find a suitably sensitive species and administer a suitably high dose (Scialli, 1992). This may well explain the inclusion of various everyday substances, some of which are intrinsic components of the mother’s body and/​or the developing conceptus and which are essential for life itself, in the list of teratogens in ’Dangerous Properties of Industrial Materials@ (Lewis, 1989). These include drinking water (Turbow et al., 1971) and table salt (Nishimura and Miyamoto, 1969); oxygen; sugars in the form of sucrose and lactose; palm oil, corn oil and nutmeg oil; other naturally occurring food constituents such as cholesterol and papain (prevalent in pineapples); vitamins such as A, D2, K, B7 and B12 (the B vitamins are frequently found in pregnancy supplements); naturally occurring and essential hormones such as estradiol, progesterone and various prostaglandins; the amino acid methionine, and the DNA constituent adenine.”

From my appendix:

Animal models such as mice can simply be irrelevant to humans, leading to cases like <150 sepsis clinical trials all failing—because the drugs worked in mice but humans have a completely different set of genetic reactions to inflammation.

(I imagine that the latter is particularly relevant; how many thousands of mouse studies on inflammation were part of the evidence base for those <150 clinical trials? Probably quite a few. And it seems that they all are essentially irrelevant to anything in humans. Now, imagine the translation rate for bird to primate, based on a bird system which doesn’t even exist in humans...)

[John_Maxwell]

Thanks for doing all this research! You should make a page on gwern.net, you’re wasting your talents going in to this kind of depth in an ancient comments thread ;)

[gwern]

Perish the thought of there being any waste!

[gwern]

I don’t know of any good meta-analysis or review, aside from some quick searching turning up “Translation of Research Evidence From Animals to Humans” & “Can Animal Models of Disease Reliably Inform Human Studies?” which seems to be narrower than one would want (examining treatment for specific issues in animal models translating to successful treatment in humans, which is much more likely to translate than your press release).

There are some interesting examples, though; from the second link:

In animal models of acute ischemic stroke, about 500 “neuroprotective” treatment strategies have been reported to improve outcome, but only aspirin and very early intravenous thrombolysis with alteplase (recombinant tissue-plasminogen activator) have proved effective in patients, despite numerous clinical trials of other treatment strategies [8],[9].

From my appendix:

Animal models such as mice can simply be irrelevant to humans, leading to cases like <150 sepsis clinical trials all failing—because the drugs worked in mice but humans have a completely different set of genetic reactions to inflammation.

(I imagine that the latter is particularly relevant; how many thousands of mouse studies on inflammation were part of the evidence base for those <150 clinical trials? Probably quite a few. And it seems that they all are essentially irrelevant to anything in humans. Now, imagine the translation rate for bird to primate, based on a bird system which doesn’t even exist in humans...)

[A1987dM]

I suspect it might also depend, among other things, on how closely related those animals are to us. I would likely take your study more seriously if it was done on mammals, and even more so if it was done on primates.

[John_Maxwell]

A few cautions: Melatonin is considered generally safe for short-term use. However, there have been concerns about risks of bleeding (especially in people taking blood-thinners like warfarin). There also is increased risk of seizure, particularly in children with brain disorders.

http://​​www.webmd.com/​​vitamins-and-supplements/​​lifestyle-guide-11/​​natural-good-sleep-tips-on-melatonin-valerian

Also, risky for diabetics?

[gwern]

First link doesn’t include any citations, so...

[DanielLC]

I’m confused on why the value of an hour isn’t just your hourly wage. If you value your time more, you’d be working less. If you value your time less, you’d be working more. Since you clearly spend exactly as much time working as you do, you value your free time that much.

Then again, that only works if you value the time you’re trying to fall asleep or are asleep the same as you value work.

Back on topic: I’ve heard that taking melatonin makes your body produce less of it, though doing so the the point of having less total melatonin seems unlikely, and even if it’s only a slight increase, it’s only a few cents. Also, I didn’t exactly hear it from a reliable source.

[thomblake]

I’m confused on why the value of an hour isn’t just your hourly wage. If you value your time more, you’d be working less. If you value your time less, you’d be working more. Since you clearly spend exactly as much time working as you do, you value your free time that much.

It’s a very complicated problem. Many people cannot work more/​less than they do and yet retain their current job. And working to find a ‘more optimal’ job can be extremely costly. Also, as you note, different time might be valued differently. I can clip coupons while I’m tired from working all day, but I can’t do more programming or research as effectively.

If it was more on-topic, I might expand this into a post...

[mattnewport]

I imagine many people here will not be in the kind of job where you are actually paid by the hour and can easily adjust your income by adjusting the number of hours you work. I certainly haven’t been in a job like that since graduating from university.

[DanielLC]

Even so, it seems unlikely that people will consistently be hired to work less than the ideal amount.

The amount of time you spend working tends to be about the same regardless of your job. It’s not inherent in the job. It’s the jobs being geared towards how much people will work.

[mattnewport]

Even so, it seems unlikely that people will consistently be hired to work less than the ideal amount.

Ideal by what criteria? Personally I would prefer to work fewer hours at the same hourly wage (e.g. work 80% as much as I do for 80% of the salary) but many jobs are not very flexible regarding such arrangements. In my experience (game developer) companies are much more willing to negotiate higher salary than they are to negotiate on vacation time or on a standard 5 day /​ 40 hour working week.

The amount of time people spend working is culturally determined to a large extent. In North America for many people this means roughly 40 hours, 9 to 5, 5 days a week with 10 days annual vacation. In Europe it’s more like 35 hours with 25 days+ vacation. Many highly paid professional jobs where employees are not on an hourly wage will frequently require more than 40 hours per week. Some jobs make it relatively easy for individuals to strike their own balance between hours worked and income received but many people are more or less stuck with the cultural norm even if they would prefer a different balance.

[DanielLC]

Ideal in that you’d prefer to work that long.

You work more than your ideal amount. Equivalently, you value your free time at higher than what you get payed. Presumably, people like you mixed in with people who want to work longer averages out to free time being worth the same as what one gets payed.

I’m not sure if you’re agreeing with me, disagreeing, or going off on a tangent. If your agreeing, then I guess what I’m about to say is pointless.

The amount of time people spend working is culturally determined to a large extent.

This illustrates my point. In Europe, people value free time more or they get payed less (possibly due to taxes) or some combination of above. Due to this, their average time at work changes.

It’s possible that I significantly underestimated the decrease in marginal production as you work longer. Perhaps after eight hours, each additional hour people work is only worth minimum wage. On the other hand, it tends to be better to have fewer people on a project, so it seems like having fewer people spend more time working would be more efficient.

[mattnewport]

You work more than your ideal amount. Equivalently, you value your free time at higher than what you get payed. Presumably, people like you mixed in with people who want to work longer averages out to free time being worth the same as what one gets payed.

The marginal utility of an extra hour of free time outweighs my nominal hourly wage. My point is that most skilled jobs offer limited flexibility in the marginal substitution of additional free time for income. One reason for this is that most skilled jobs have an annual salary, not an hourly wage. I would prefer to work 10% or 20% less for 10% or 20% less income (which given progressive income taxes would actually amount to a cost saving of more than 10% or 20% to my employer) but there is limited flexibility to negotiate this in many jobs. Believe me, I’ve tried.

It’s possible that I significantly underestimated the decrease in marginal production as you work longer. Perhaps after eight hours, each additional hour people work is only worth minimum wage.

In my industry (software development) numerous studies have found that productivity flattens off beyond 40 hours a week and actually declines beyond about 60 hours a week (more mistakes are made and morale is impacted). Unfortunately management doesn’t always appreciate this fact. And again, reiterating that many skilled jobs are not paid on an hourly wage and do not pay overtime, there is no direct trade off between hours worked and income for many skilled employees.

[pdf23ds]

There are many exceptions to the general rule. Gaming industry programming jobs (especially EA), and teaching jobs in public schools, among others, are notorious for eating up huge amounts of employee’s time.

OTOH, you’re right in that few jobs have less work than employees find ideal.

[Morendil]

I have one of these jobs.

[Peter_de_Blanc]

I’m confused on why the value of an hour isn’t just your hourly wage

Even if you did nothing but work all day, that wouldn’t be true. There’s also the value you get from doing the work.

[gwern]

I’m confused on why the value of an hour isn’t just your hourly wage. If you value your time more, you’d be working less. If you value your time less, you’d be working more. Since you clearly spend exactly as much time working as you do, you value your free time that much.

Here’s a secondary justification beyond the economics substitution arguments of the others.

Assuming you have a job at all which could have an hourly wage, the wage must be equal or greater than the minimum wage. The more your hour is worth, the more valuable melatonin use is. The most pessimistic or conservative assumption is assume the hour is worth as little as possible, and the minimum wage is the least it’s worth.

Hence, using the minimum wage and not one’s actual hourly wage is the most pessimistic assumption—but the analysis still says the benefits are positive.