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gwern comments on Open Thread for January 17 - 23 2014 - Less Wrong
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Why do you care about the half-life?
Seems relevant for not interfering with sleep. For example, I can't use modafinil after 11AM because it interferes with my sleep that night if taken later; if I take modafinil or armodafinil at 5PM I might as well just skip the night's sleep. On the other hand, I can use caffeine up to 7/8PM without issue, and nicotine up to 10/11PM. (This is unfortunate because I am a bit of an owl and the evening is precisely when I'd like to be able to use a stimulant.)
If that's the goal why don't ask for it directly?
Ask for what directly? If he asked for stimulants that didn't interfere with sleep, he'd get replies suggesting... he look for ones with short half-lives like nicotine and avoid long-acting ones like modafinil. Short half-lives is the governing criterion, so he simply asked for it.
I think there are plenty of people that have tested various stimulants and know the effects those substances have on them, but who don't know the exact half-life of the substances.
I'm not even sure whether the real half life of caffeine is the thing that matters. When it comes to designing drugs there are quite a few things that are done in the delivery mechanism of the drug that can effect half-life.
Pharmacokinetics (half-life and other variables) of drugs and their different delivery methods are public knowledge, there are individual differences in metabolism of course.
For most drugs the elimination half-life is so long that a faster route of administration makes minor difference. For caffeine for example it's about 4.5 hours. You can shorten the absorption from < 1 hour to seconds but that probably won't matter much in this case.
You can make the absorption slower in a way that makes a difference however, for example there are several timed release versions of methylphenidate.
There are number that are public knowledge. Those numbers do have meaning. On the other hand individual differences are also important.
A lot of pseudoscience comes from people having a rough theory about isolated facts and personal observations. I think it's often very valuable to stay with personal observations instead of trying to fit them into a simple theory you made up that seems to fit and that corresponds to isolated facts you find in books.
You lose relevant information when you ask for half-life data instead of asking about what stimulants other people found useful for being stimulated at events closer to bed time without adverse effects on sleep.
Take Vitamin D. A lot of the published research on it is misguided because it presumes that blood level of Vitamin D is the central variable that matters. Whether you take Vitamin D in the morning or evening doesn't have much effect on long term Vitamin D blood levels. It therefore isn't subject to study in academia. Making too much assumption when you don't need to do so often hurts understanding.
So, are you claiming that the blood level of vitamin D is NOT the central variable that matters? And that whether you take it in the mornings or in the evenings is important?
Links, evidence?
A bunch of QS people have observed that the timing of vitamin D supplements matters a great deal. Seth Robert wrote a lot about it (http://blog.sethroberts.net/2012/11/01/vitamin-d3-in-morning-improves-sleep-after-all-story-26/ for example).
As far as people you might trust, Gwern replicated the finding: http://www.gwern.net/Zeo#vitamin-d . Taking the supplement at night damaged his sleep.
I don't want to claim that blood level of vitamin doesn't matter at all, but I do claim that it's very unfortunate that there aren't more studies tracking the timing of vitamin D ingestion. I'm also thinking that getting the timing wrong is a good explantion for the studies that are out there that don't show improvement given vitamin D supplemention. Those studies are also the reason why the RDA of vitamin D is at 600 UI while QS folk generally recommend 2000 UI+ (again I think Gwern takes something like 5000 UI).
There a long term study called the VITAL study by Harvard Medical School in progress that tests the effects of 2000 UI vitamin D supplements on mortality rates. Unfortunately it doesn't track the intake of the timing so the resulting data might be worthless.
From the studies that showed effects for vitamin D you could deduce that the supplements can bring 2 additional years of lifespan. If the studies that say vitamin D does nothing come to that conclusion because of bad timing, that's a serious issue. As far as references go I remember the number of 3 years of lifespan for curing cancer.
I don't claim that I know with 100% certainity that it's in the timing and not in the average blood level. I do claim that the medical establishment is stupid for assuming that it's in the blood level. That's not even a real outsider opinion. That more or less the opinion I was thought by my bioinformatics professors. People in medicine make a lot of stupid assumptions that aren't based on evidence.
Now when I do QS I do make a bunch of assumptions that wouldn't pass in the academic context of bioinformatics. On of the great things about QS is that you aren't blind. You know reasonably well when you take your supplements while the doctors who administer clinical trials don't have any information in their data by default about when their subjects take the supplements.
As a result it's good practice to stay near empiricial data and not make assumption unless they will help you.
Model the problem as seeking of being tired as seeking an efficient stimuluant is a choice. When I instead propose that he should focus on getting better at relaxing than I'm pushing a different model for the situation.
It's not that my model is inherently based on the truth. It is in some sense "science inspired" when I use the mental model of the body downregulating itself via a cybernetic process. Thinking in terms of cybernetics (the word doesn't get used much these days) is one of the model I learned at university. That doesn't make it right but it's an available model to explore for the problem.
Now I have different kind of evidence that over a handful of different trance states that I learned about in different contexts help people to sleep better afterwards. Hypnotherapists do have a body of theory that predicts that's a usual effect side effect of hypnosis. One of my hypnosis teachers for example told a story about how a person who didn't even spoke his language and who was escorting a patient got into trance while watching the session and afterwards resolved her problem of not being able to sleep well. It's an effect that can happen as "correlateral damage".
I don't know the exact kind of relaxation protocol that best for btrettel. I didn't even try to push my favorite relaxation protocol that gave me QS validated benefits for another medical issue because he wouldn't find a practioner for it in Texas anyway.
Comparing different relaxation protocols against each other isn't something that well done by the academic establishment because it not really in the model of how to go about treating a patient. No patents that pay for expansive clinical trials. Exactly the area where it's good to do your your empirics.
Matters for what?
Your links say that the timing of vitamin D intake affects sleep. Fine, but that's not really what most people take vitamin D for. There is a variety of claims for vitamin D supplements which generally have to do with bone health, viral infections, CVD, etc. I don't want to get into evidence for and against these claims, but are you saying that the timing of vitamin D affects these outcomes?
Looking at it in the most general fashion, the overall claim is that taking vitamin D supplements affect mortality. Crudely, you live longer. That may or may not be so, but do you think that timing of vitamin D ingestion would affect that? What evidence do you have? Sleep disturbance is a time-local short-term effect, it isn't obvious to me that it indicates problems with long-term consequences.
Why? "Stupid" is a strong word. If your hypothesis is that timing matters but the blood level doesn't matter, what's the underlying biochemical mechanism? Is there any evidence that the right time in the circadian cycle is crucial?
Also, if you are taking vitamin D supplements wouldn't you be interested in your blood level? How would you know how much of vitamin D do you need?
Search on vitamin D at blog.sethroberts.net -- you'll get a bunch from the self-tracking perspective.
Have you tried any drugs to fall asleep faster when using stimulants in the evening?
I don't usually look at interactions, because it's more important to establish an effect exists in the first place. Right now, I know that melatonin helps in getting to sleep, vitamin D impedes getting to sleep, high doses of magnesium citrate have ambiguous effects on sleep, alcohol usage seems to correlate with early bedtime (I forget about getting to sleep), and I speculate that Redshift/f.lux and masturbation help in getting to sleep but I haven't analyzed that experiment yet. I haven't looked at any interactions with nicotine or modafinil or anything, since I'd expect them to just independently make it harder to get to sleep.