Today in the War on Sleep

Orexin A is a promising candidate to become a "sleep replacement" drug.

The monkeys were deprived of sleep for 30 to 36 hours and then given either orexin A or a saline placebo before taking standard cognitive tests. The monkeys given orexin A in a nasal spray scored about the same as alert monkeys, while the saline-control group was severely impaired.

The study, published in the Dec. 26 edition of The Journal of Neuroscience, found orexin A not only restored monkeys' cognitive abilities but made their brains look "awake" in PET scans.

Siegel said that orexin A is unique in that it only had an impact on sleepy monkeys, not alert ones, and that it is "specific in reversing the effects of sleepiness" without other impacts on the brain.

The research follows the discovery by Siegel that the absence of orexin A appears to cause narcolepsy. That finding pointed to a major role for the peptide's absence in causing sleepiness. It stood to reason that if the deficit of orexin A makes people sleepy, adding it back into the brain would reduce the effects, said Siegel.

"What we've been doing so far is increasing arousal without dealing with the underlying problem," he said. "If the underlying deficit is a loss of orexin, and it clearly is, then the best treatment would be orexin."


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40 Responses:

  1. recursive says:


    Except, then everyone is doing it, and society starts to expect everyone to work 80 hour weeks. :)

    • strathmeyer says:

      Yeah, but it's worth the three day weekend.

    • jwz says:

      80 wouldn't be fair, but 60 would be. If percentage of wakeful hours spent working stays constant, then eliminating sleep is the same as increasing lifespan by 1/3. Even if you ended up spending a larger (but not total) portion of that extra lifespan at work, it'd still be a good trade.

      • Even being more alert doesn't change the fact that the body still needs a set amount of sleep on a daily basis in order to maintain proper working order. I can force myself to be alert via use of various stimulents (that I won't list here, for hopefully obvious reasons, lol) for days at a time. Eventually though (about after 3 days, typically) I just crash and need a few days to recover. I don't see how this stuff would reduce the need for sleep in this way, but it will be neat to see what the research turns up.

        • jwz says:

          Well, for one thing, it works by a completely different principle than stimulants do.

          Maybe sleep is necessary, but we don't actually know that: we know that "stimulants don't work long-term".

          • zwol says:

            I doubt this molecule will fix the mysterious immune collapse and subsequent death by fulminant bacterial infection that happens if you force rats to remain awake for about two weeks. There may well be another molecule that fixes that -- but it won't be this one.

            • lafinjack says:

              But this molecule might be a step towards that next molecule.

            • Why not?

              I mean, I think you're probably right- but I wonder what your reasoning is.

              (FWIW, experiments show that humans also die after a couple weeks without sleep.)

              • zwol says:

                This molecule is being researched on the hypothesis that narcoleptics are deficient in it and that's why they can't stay awake. Narcoleptics in general don't have immune problems. Therefore, I am betting that this molecule doesn't affect the immune system at all.

            • strspn says:

              French soldiers taking Modafinil stayed up for two months without any health problems, but if I remember right they were taking short, periodic naps before each dose, totaling something like 2 hours per day.

          • I've read about cases of people being rendered incapable of sleep living long lives and not suffering from it. Wikipedia has a small writeup that mentions a Vientamese farmer, I also remember reading about a Russian WWII veteran losing ability to sleep after a contusion.

          • editer says:

            There's general agreement, from what I can tell, that sleep is important for muscle growth and repair; the lowered cortisol and elevated growth hormone levels are key to the process. Messing with the brain chemistry won't help in this regard.

            Wage slaves are already exposed to plenty of health hazards on the job; this would add another one.

  2. pathwalker says:

    From the journal article it looks like the effective dose was 10 micrograms per kilogram of body weight.

    There are a few labs selling orexin A for lab use right now - current prices are around $175 for 0.1 mg. I wonder how much demand will drive up the price over the next month or so.

  3. vees says:

    Great, now I'll have to compete with cowboy programmers who code ten times faster than me for 3 times as many hours. That's a lot of refactoring to fix everything they break.

  4. injector says:

    I wonder if the "loss of orexin" isn't a problem, but the body's solution to staying awake all the time.

    Though, as a treatment for people who burn off their orexin too quickly (e.g. narcoleptics) this finding could be worthwhile.

  5. pdkl95 says:

    As you noted above, all we have proven for certain is "stimulants don't work long term" in terms of eliminating sleep, but... I wonder about a few other things. The idea of simply supplementing your brain/body with what you are regenerating when you sleep is at lest a decent (and interesting) theory.

    Unfortunately, as someone who has also desired to eliminate the need for sleep, there's one problem I still haven't heard a theory on how to fix. It has to do with the theory I heard about the rate the brain uses resources. Basically - the already high blood-flow to the brain is insufficient to maintain normal function. The brain simply uses resources too quickly. So one theory on sleep was that it was necessary to run the brain in a "reduced power" mode for a while, so it can re-stockpile various things.

    The source I remember reading for all of this suggested that the myelin sheath was able to act as a buffer or storage area, and not just the electrical insulation they are known to provide. While this new drug may replace one important resource, I seem to remember the buffering also included basic things like sugars, that wouldn't work in a simple nasal spray. Sigh.

    This is from memory, though, so I'd love to be shown where this is in error. Any prospect to get that 1/3 extra life would be great...

    Also, there seems to be a growing controversy about using such benefits. More people fighting "better living through chemistry" in somewhat unexpected places...

    • jwz says:

      Sure, all that, but... I like to think of "reduced power mode" as the state I refer to as "watching TV".

  6. veritatem says:

    i really enjoy sleeping though. they better not take that away from me or i'll have to beat ass.

  7. killbox says:

    Question is can it cheaply and easily be synthesized? I would gladly do it once a week if it ment i could go out to the club without being amazingly drag-ass tired the next day.

    • pathwalker says:

      With the prices I've seen in a few minutes of poking around, and the dosage info from the abstract for the paper, for a 200 pound person, the effective dose would cost about $1,587.

      Additionally, the fact that (at least from the suppliers I checked) this comes from a mixture of animal sources, including rat and mouse, just screams "DO NOT PUT IN FACE" to me.

      • jwz says:


      • webmaven says:

        Assuming it is as useful/popular as HGH or Insulin (not unreasonable), a cost-effective source will be devised: Either a synthetic version, or (more likely) a bacterium will be hacked to produce it in industrial quantities.

      • scullin says:

        The last I checked, a microgram (µg) was 1/1000th of a milligram (mg). That seems to put the cost/dose closer to $1.

        Edit: Redoing math: Effective inhaled dose 1µg/kg * 200lb ~ 90kg = 90µg dose for human. Cost appears to be $195/mg, or $195 * .09 = $17.55/dose. But perhaps I'm missing something.

  8. divergio says:

    I, for one, welcome our new perpetually alert monkey overlords.

  9. mobiletash says:

    Hi, I added you, is that ok?
    Would you like to add me back?

    • You must be new 'round here.

    • xenogram says:

      jwz is a internet celebrity. He did some important stuff with computers, made a bunch of money, bought a nightclub in San Francisco, and posts interesting and funny stuff in his journal, for certain values of interesting and funny.

      Anyway, he has many more "friends" than people he genuinely wants to be "friends" with. That's not because he's a mean person or anything (actually I have no idea of what he's like in person, maybe he is), it's just that you can only be interested in so many people. So, don't take it personally if he doesn't friend you back, if he friended everyone his friends list wouldn't be much good for reading.

      Apologies if any of this is obvious and patronising, it's easy to be a dick on the internet. You should check out fantasygoat as well.

  10. Without sleep, I already score about as well as an alert monkey.

  11. roninspoon says:

    Potential side effects may include; drowsiness, high fever, headaches, stomach cramps, loss of appetite, anal leakage, increased blood pressure, cotton mouth, explosive tentacle growth, blurred vision, persistent skin irritation, neo-conservatism, hallucinations, hair loss, shortness of breath, and in some rare cases, zombieitis.

    • editer says:

      Agitation, palpitations,
      Excessive salivation,
      Constipation, male lactation,
      Rust-colored urination,
      Hallucinations, bad vibrations,
      Mild electric shock sensations,
      But it's worth it for the drugs I need.

      Deprivation, humiliation,
      Debtor's prison and deportation,
      Dark depictions, dire predictions,
      Life as seen in Dickens fiction,
      Empty pockets, court dockets,
      May cause eyes to pop from sockets,
      But it's worth it for the drugs I need.

      *May cause drowsiness or restlessness in lab animals. Any unauthorized use of your own judgment in the application of orexin A is strictly prohibited. Do not resume sexual activity while operating heavy machinery without a doctor's permission. Offer void in Wisconsin.

    • lionsphil says:

      I bet that some people would want to take it if there was a chance of "explosive tentacle growth".

  12. baconmonkey says:

    so now those monkeys who shout during sex can stay up longer having crazy, wild monkeysex.

    also, this will become extremely unpopular among male humans when it is discovered that they cannot just roll over and fall asleep after sex, but will instead have to stay up, cuddle and talk about feelings.