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ChristianKl comments on Open Thread for January 17 - 23 2014 - Less Wrong
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Which stimulants/eugeroics have a short (< 3 hours) half-life? I did some research into this. Nicotine and selegiline (~1.5 hours) are the shortest I could find. Methylphenidate comes in next (~3.5 hours), but that's longer than I'd like. I don't particularly like any of these choices for various reasons and am interested in learning about others. Alternatively, if there's a way to significantly reduce the half-life of modafinil, I'd like to hear about that.
I've considered amphetamine, armodafinil, atomoxetine, caffeine, ephedrine, methylphenidate, modafinil, nicotine, pseudoephedrine, and selegiline.
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.
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.
gwern is partly right about my motivations.
I have some sort of sleep disorder (perhaps narcolepsy; the sleep study I had was inconclusive on that, though it did rule out sleep apnea) where the treatment might involve taking stimulants. My sleep quality at night might be particularly bad in general, and taking a stimulant could make it worse. Modafinil's half-life is about 15 hours, which is quite long. Even if I took it in the morning, it still might impact my sleep at night.
Also, the stimulants I have had generally do not agree well with me. Often they make me nervous, even in low doses.
If I were to take a stimulant regularly, I'd rather take a short-acting one, and only take it when absolutely necessary.
I have some armodafinil now and am going to do a study on myself. My sleep doctor suggests testing my concerns as they may not pan out in reality.
I don't think he's right. You don't intend to have a stimulus for an activity right before bed time.
If you don't want to take a stimulant regularly you probably care more about side effects than about half-life.
One of the issues with caffeine is that it causes the body to produce more A1 receptors which you probably don't want given that your sleep is already screwed up.
Given what you wrote I would also look into non drug treatments. Especially something to reach a deep state of trance, be it meditation, hypnosis or a flotation tank.
Thanks for the advice. I think I see what you mean in this post about asking a more general question. Perhaps I'll post a discussion item about advice for rationalists with hypersomnia disorders, or post something to the next open thread. Most of the advice I've seen about sleep on here seems to apply only to normal people, or even just a subset of normal folks.
Yes, I'm not very interested in stimulants largely because of the side effects (on my mood, or sleep, or cardiovascular system, etc.), but they are the first line of treatment for whatever it is that I have. My sleep doctor offered to prescribe me modafinil, but I declined, citing tolerance, its long half-life, and the side effects, so instead he gave me some free samples of armodafinil and said to try it and see, which is reasonable. (Perhaps this makes me a bad rationalist. Given all of the discussion of modafinil here, I'm sure some people would see declining legal modafinil paid for by my insurance company as a great folly.)
Non-drug treatments interest me greatly. Unfortunately, there is little research interest into them, but I have read two detailed reviews of behavioral treatment of narcolepsy and other hypersomnia disorders. My sleep hygiene is excellent, and could hardly be improved. Right now I'm working two naps a day into my schedule. Naps are one of the few behavioral changes I've found to help. There are some difficulties in terms of logistics, but once that is settled I should see a marked improvement in my functioning. I am also working in more exercise into my schedule, as exercise will wake me up (though not for as long as a nap, which seems supported by the literature I've read). I already get an adequate amount of exercise, but there seems to be a few things I can do to optimize my wakefulness and sleep quality via modifying my exercise routines.
I am curious. What would be the goal in getting into a deep state of trance? Would this serve to help me sleep more solidly?
I mentioned three ways: 1) Meditation. My general advice would find a local group course.
2) Hypnosis. There are basically two ways. The first is to get some audio file to play right before you go to bed.
The second would be to find a qualified local hypnotherapist. A straightforward hypnosis format for going into a deep trance in an efficient manner is the Elman induction.
3) The third is to go into a floating tank.
As far as hypnosis session I would think that you need a handful or less for the effect. The same goes for a floating tank.
I would think that meditation group sessions and bedtime hypnosis audio tapes take a bit longer, but they might also have fast effects.
My model would be that some process that normally is to be supposed to switch into relaxation mode when you sleep is constantly in active mode draining energy. I believe that's a common failure mode of the human system that can cause the kind of issue that you have and that isn't well treated with existing drugs.
Just going once through the experience of switching into into relaxation mode, might be enough for your brain to learn how to switch the process into relaxation mode.
As you mentioned solid research going into non-drug treatments is often scarce.
In general I think the idea of trying to upregulate a body through stimulus drugs that purposefully downregulates itself because it doesn't get enough real rest to be silly. Yes you might get a positive test result on a clinical trial but you are fighting the body. I think it's a lot more sensible to focus on getting better at relaxation. Poisoning the body with sleeping pills is also not getting better at relaxation.
Thanks. I had intended to try some meditation for other reasons. I'll investigate your other suggestions, as well. (Edit: Checking my notes, it seems I had considered some form of hypnosis before as well, but I forgot about it.)
Your idea of improving sleep quality at night to improve daytime functioning in hypersomnia disorders is not so unusual. The goal would be to increase deep sleep (most narcoleptics have far too little). One of the main treatments for narcolepsy takes exact approach via pharmaceuticals (Xyrem/GHB). Unfortunately, GHB is neurotoxic when used chronically, but there are other drugs (ritanserin, trazodone, etc.) that have the same effect. Ritanserin is particularly effective and has no real side effects best I can tell, but it's also unfortunately not available cheaply because narcolepsy is such a small market.
In my case, there's no objective evidence that my sleep quality is bad. My amount of deep sleep is not unusual, though it is a little low according to my sleep doctor. My sleep was not particularly fragmented, either. This does not explain why I don't feel particularly rested when waking after sleeping a normal (7 to 8 hours) duration. It is possible that my sleep study was misleading for any number of reasons (my sleep doctor suggested two weeks of data would be much more definitive), but until I set up my home EEG (I'll be using a modified NeuroSky Mindwave Mobile as Zeo went out of business), I can't check the accuracy of my sleep study. Whether my brain is actually doing what it should be when it's in deep sleep is another question. For the moment, I believe the sleep study was accurate, and my top hypothesis is that I'm a long sleeper who requires 10+ hours of sleep per night. This possibility has not been examined as rigorously as the others.
You should definitely test it. Many people find that modafinil does not interfere with sleep.
I'm under the impression that taking substances in intense spikes generally causes tolerance to occur more quickly than taking a slow build-up and slow come-down dose. The former profile is also superior for avoiding negative high/crash side effects resulting from rapid ramp-up / come-down.
However, the only actual sources I can find for which this is true relate to insulin, which could easily be a special case, and I'm not really sure where I got this impression. It's filed away in my mind's "conventional wisdom" drawer and I've never questioned it until today. Can anyone who actually knows confirm/deny this?
I've read that short half-life drugs in general build tolerance faster. No idea if it is true. I too would be interested in confirmation or denial of this line of thought and the others you mentioned.
With that being said, my sleep doctor doesn't think stimulants taken infrequently (a few times per week at most) would have significant tolerance effects. I don't mind a crash too much; might just take a nap because of it.
That wouldn't be too bad, but don't stimulant crashes involve more irritability / low affect / lack of focus than they do sleepiness?
In my case, I wouldn't know. I can't say I've ever experienced a crash any time I've taken stimulants.