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Science

Provigil Extends Your Day? 660

John Mearns writes "It looks like before long all caffeine junkies will be able to ditch the bottle of Mountain Dew or cup of coffee in favor of pill. Its not a true stimulant so you don't get the "caffeine crash," just countless hours of alert attentiveness. " It's also still in testing so it'll probably make you grow horns or something, and is supposed to only be used for people who are sleepy during the day, but it raises several interesting ethical questions.
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Provigil Extends Your Day?

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  • I've used it. (Score:5, Informative)

    by dietz ( 553239 ) on Wednesday April 17, 2002 @05:31PM (#3361497)
    I've used it. The longest I've ever stayed up is 40 hours or so. The only noticible side effect was a slight headache, but that could've been caused by any number of things (I get headaches a fair amount because I don't eat very well :/). Headaches are the most common reported side-effect [provigil.com] by far.

    Even after 40 hours of being awake, I was still at nearly full mental capactity and able to work, etc. I did not feel the normal symptoms of sleep deprevation at all (I've stayed awake too long many times, and I'm familiar with how it makes you feel). I did not feel high, either. I was just... awake. I also didn't feel many physical problems (sore back, sore legs, etc) like I expected to, but YMMV, of course.

    Afterwards I slept about 9 hours and had a normal next day. By my calculations (figuring you normally sleep .5 hours for each hour of wakefulness), that means I gained 22 hours of wakefulness.

    You can find them on the internet if you look around enough. I am hesitant to mention sites, but there are two in the UK that sell 100mg pills. I have been unable to find the 200mg pills. They sell for about $145 + shipping ($15 or so) for 30 pills. That's $5.33 a pill. During my 40 hours awake, I took four, which works out to about $1 per hour.

    Many people I tell this to think it would be a good idea to take them during finals. I must warn you that it's probably not a good idea because there is a very good chance your sleep schedule will get completely fucked up. For example, you may stay up for 32 hours, decide it's time for sleep, and then sleep through a final. In other words, I would take it a few times beforehand to get used to it before you decide to jump in and potentially fuck up something important.
  • by Nilatir ( 179045 ) on Wednesday April 17, 2002 @05:36PM (#3361537) Homepage
    Hate to break it to you but if you check out www.rxlist.com [rxlist.com] you'll find that doctors and scientists don't really know how a lot of drugs work.
  • by Anonymous Coward on Wednesday April 17, 2002 @05:36PM (#3361540)
    I currently take this drug, and I was prescribed this drug for a specific purpose. The fact that it appears on slashdot as "the new caffeine" is disturbing, to say the least.

    Thank you, slashdot, for telling the masses about medications they should ask their doctors for. While your at it, start running ads for Viagra, Prozac, Paxil, Claratin, and Ritalin.
  • by jjn1056 ( 85209 ) <jjn1056&yahoo,com> on Wednesday April 17, 2002 @05:43PM (#3361579) Homepage Journal
    I was prescribed the drug by my doctor because a different medication I was on made me very sleepy in the morning. I was so tired it was affecting my ability to get up and go to work. When I was on Provigal I did notice some minor improvements; more alertness in the morning being the #1 effect. The effect was very minor, almost indetectable. I didn't feel wired or anything like what you get from coffee, and there was no 'crash' later in the day.

    I stopped taking it because I thought it was causing me to feel very sick to my stomach, but of course that might have just been because I live in downtown NYC and this was in October.

    Generally this is a drug taken by people with serious sleeping problems, like people that fall asleep while driving all the time, etc. It is also thought to have some affect on depression, although the mechanism by which it accomplishes that is unknown. It might just be that getting a good start on the day helps depressed people!

    Since this drug is not a traditional stimulant, such as caffeine, or cocaine, it can affect people in very different ways. It's more like Prozac, which seemed to help some people a lot, while others were not helped at all.
  • by Quixote ( 154172 ) on Wednesday April 17, 2002 @05:48PM (#3361627) Homepage Journal
    I saw a news magazine program once which monitored a guy doing this for weeks. They had a camera setup in the bedroom, and this dude was supposed to perform mental tasks (puzzles, memorization, etc.) at periodic intervals.

    He seemed to be getting along just fine, until about day 62 or so, and then he crashed, and crashed hard!

  • by Anonymous Coward on Wednesday April 17, 2002 @05:59PM (#3361689)
    Uh... but a brain needs to sleep to store enough energy for the next day. NEEDS TO. That's why every animal has to sleep, otherwise there would be a predator or prey with the great advantage of not sleeping. (yes, a shark sleeps also)

    Brains use more chemical energy than the bloodstream can deliver. They store energy in the support cells around the neurons during sleep. While awake the brain uses energy from the bloodstream and the stored energy.

    When there is not enough energy available things start failing. Like optic processing -- look up the symptoms of lack of sleep: flickers of movement at the edge of the field of vision (ie, spiders hiding).
  • by Guppy06 ( 410832 ) on Wednesday April 17, 2002 @06:07PM (#3361743)
    As I've learned the hard way in recent years, you NEED several hours of REM sleep a day. It's not just a matter of feeling "refreshed" in the morning, it's a big factor in mental health.
  • by Walter Wart ( 181556 ) on Wednesday April 17, 2002 @06:19PM (#3361825) Homepage
    Several people have already pointed out that "natural" doesn't mean "good for you". Perhaps a little more emphasis is in order.

    Back when I did more botany I discovered that plants produce chemicals that do two basic sorts of things:

    1)Produce more plant tissue by making food, growing, reproducing, or something of the sort

    2)Bug killer. Stuff that makes them poisonous or unpalatable to things that eat them at the macroscopic or microscopic level.

    Our favorite alkaloid - caffeine - is the second sort of chemical. We just happen to find the effects useful or pleasurable. Think about it, a bug that has its appetite suppressed and is jittery is going to eat less of you and eat that less efficiently.

    Other perfectly natural substances like oil of wormwood will eat holes in your brain because that is what makes it worth the metabolic cost to the plant to produce them. Dead bugs don't eat you if you are a plant.
  • by machinegestalt ( 452055 ) on Wednesday April 17, 2002 @07:47PM (#3362297)
    There is another which has similar effects, called 4-methylaminorex (dl-cis-2-amino-4-methyl-5-phenyl-2-oxazoline) which effects most specifically the the norepinephrine and acetylcholine receptors in the brain, with comparitively minimal/nonexistant effect at the dopamine receptors unlike most standard stimulants.

    Unfortunately this chemical has a rather long active duration when taken by oral administration (which, besides it's potential for abuse, is probably the main reason this chemical has not seen commercial use), however it VERY effective at reducing the effects of sleep deprivation without the anxiety and psychotic effects usually attributed to methamphetamines and other stimulants which are highly active on the dopamine system.

    As for the previously mentioned Uberman sleep schedule, I can see it being effective at producing mental altertness with a minimum of sleep, however I would suspect that it would have an effect on the recuperative capabilities of your body in addition to reducing the immune system. As a weightlifter I've found that additional sleep beyond the eight hours I usually require is very helpful in speeding recovery.

    Machine Gestalt
  • by darkstar2a ( 546635 ) on Wednesday April 17, 2002 @08:02PM (#3362378) Homepage
    Other than headaches (50%) and Nausea (13%), there are some issues here.

    Provigal affects Birth Control!

    Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy. Patients should be cautioned regarding the potential increased risk of pregnancy when using steroidal contraceptives (including depot or implantable contraceptives) with PROVIGIL tablets and for one month after discontinuation of therapy
    I found a few references to possible birth defects as well, however not seriously sightable statements. Even the official website [provigil.com] states that dosage during pregnancy should seriously consider the benefits to outweigh the risks.

    The strangest issue is that for a drug that has been around since the 70's there is very little data about interaction with other drugs and they just recommend you don't use alot of different types. Brings up something I remember hearing about a company in the past that found negative results and decided that they just "hadn't performed those tests". Who knows.

    Buyer Beware.

    I'm male though, so where do I order my emergency supply! :)

    Garth/Darkstar

  • by Wonko42 ( 29194 ) <.ryan+slashdot. .at. .wonko.com.> on Wednesday April 17, 2002 @08:04PM (#3362398) Homepage
    With Uberman's cycle, you end up getting more REM sleep every day than you would with 8 hours of consecutive sleep. Your brain learns to drop into REM sleep immediately, so each 20-30 minute nap is entirely REM, which adds up to between 2 and 3 hours of purely REM sleep per day, which is more than enough.
  • by t ( 8386 ) on Wednesday April 17, 2002 @08:29PM (#3362504) Homepage
    And what the reply was trying to say is that it would be like adding salt to the water. You would clearly notice the taste since caffiene is quite bitter.
  • Re:Seriously (Score:3, Informative)

    by curunir ( 98273 ) on Wednesday April 17, 2002 @08:38PM (#3362540) Homepage Journal
    Exstacy can make you depressed

    While it's true that Ecstacy can make you depressed, it's a bit unfair to say that depression is a side effect of the drug since there are steps one can take to prevent it.

    At one point, I considered no longer using the drug because of this very fact. However, I did some research into how the drug works and why it causes depression. Basically, you get depressed because you either have too little seratonin in your brain for it to function normally or you've damaged the seratonin receptors in your brain to the point where you no longer have a sufficient number to support normal serotonin levels.

    So, the goal is to counteract those affects in some way. In order to boost low seratonin levels, my friends and I take 5-HTP (the body's natural precursor to serotonin). This won't ensure high serotonin levels in all cases, but usually does. It's also important to maintain high levels of MAOs (monoamine oxidases IIRC...anti-oxidants...vitamin C, for example). The MAOs help your brain metabolize serotonin that is not recaptured by the receptors. If that serotonin isn't matoblized, it can cause brain damage. This is also why people taking MAOIs (the I is for inhibitors) should never take e.

    So basically, if you're going to be using e anywhere close to regularly, go down to the local pharmacy/GNC and pick up some 5-HTP and some multi-vitamins (or however you feel like loading up on anti-oxidants). I can't offer any scientific evidence that this works, but within my circle of friends (about 30-45...all of whom follow this advice), not one person has complained about depression as a side effect of e.

    Bottom line is: if you're going to do any drug, be educated about it. Read as much as you can about how it affects your body. There is a lot of misinformation on both sides of the issue, so think about the source of the information you read (i.e. trust the government about as much as the buy passed out on the floor with his face in a pool of drool).
  • Re:I've used it. (Score:3, Informative)

    by 3ryon ( 415000 ) on Wednesday April 17, 2002 @08:56PM (#3362619)
    I never grokked why this stay-up-for-hours mentality became such a powerful meme with college students. I *always* did better by getting a reasonable amount of sleep than by staying up to cram. Give yourself a few extra days lead time for in-depth studying. Get proper sleep sleep for the period just before and during exams. Watch your performance soar.


    There have been several important studies [dohealthnet.com] which show [wisc.edu] the importance [ucla.edu] of sleep on learning [harvard.edu]. If you want to do better on tests, get enough sleep.

  • I have too. (Score:3, Informative)

    by onjay ( 27282 ) on Wednesday April 17, 2002 @09:11PM (#3362678)
    As someone who literally can fall asleep in two minutes and someone who has to pull 24-28 hour shifts requiring intense attention on a monthly basis (and still make it home), I did reach beyond the caffeine to the antinarcoleptic Provigil. I am not impressed, and will stick to coffee. YMMV, and FWIW I do keep one tab on me in case I absolutely absolutely had to stay awake into the 40-50 hour range for a road trip.

    My test drive opinions, negatives first:

    - headaches - Very distracting and not fixed with OTC remedies. I consider this a killer side effect. I saw this at both 100mg and 200mg.

    - da jitters - well, if you are going all Cornholio, it is going to cut into your productivity. I went from juggling 5 different things at once to dropping three and fucking up one of the remaining two. Maybe you can train yourself to keep it all together.

    - elevated blood pressure - This may have something to do with the headaches, but that feeling of impending aneurysm does not rock.

    - dehydration - I fly through the water, and all of my piss smells really rank and chemical-like. There is a productivity hit to this I suppose, and it seems like more than that imposed by chugging coffee.

    - rebound - the crash can be hard, and the duration of sleep is not really predictable. I tended to be irritable the day after, as well.

    positive: you are slightly more alert. 100mg and I can still sleep no problem. in my chair. . .not good. 200mg and you are are awake, but more side effect manifestation.

    DO NOT take 4 per shift like the guy up there. You are going to get prescription info from Slashdot?

    Don't be a dumbass: check out the info on ANY drug before you take it. Know the maximum dose. Know the interactions. Know the side effects. Know if it is excreted by the liver or kidney if you have problems with one of them. If you are going to take the doctor out of the loop, who is going to look out for your sorry ass?

  • by lukesl ( 555535 ) on Thursday April 18, 2002 @02:11AM (#3363689)
    The Uberman sleep cycle thing is complete bullshit. There have been numerous REM deprivation studies done in animals, and what your brain and body really need is stage 4 sleep, not REM. REM is the lightest part of sleep, and stage 4 is the deepest. I'm a narcoleptic MD/PhD student studying neurophysiology, so I know a little about this stuff. If you want to be more efficient with your sleep, don't sleep more than four hours at a time. EEG studies have shown that four hours is about the optimum length of time for sleep, and it becomes much less efficient after that. So if you can sleep for two four-hour periods per day, you are in very good shape. There are multiple lines of evidence supporting the fact that Homo sapiens in "nature" slept twice a day, including a periodic body temperature changes with a 12 hour period (you're always sleepier when your body temp. is just past its peak, IIRC). Most people get very tired after lunch--this is not a coincidence. Note that in many cultures, this is the sleeping pattern people have (e.g. the Siesta).

    No one really knows for sure why all animals sleep (down to fruit flies and earthworms), especially since one would think it would be strongly selected against, evolutionarily speaking. The fact that we spend 1/3 of our day defenseless shows just how important sleep is (that and the fact that sleep deprivation is fatal in all organisms from humans down to fruit flies). Interestingly, even birds that fly for days on end or whales that have to swim to the surface to breathe still sleep. However, their brains are capable of sleeping one hemisphere at a time! Another interesting/random fact is that hibernation is different than sleep because at least some animals that hibernate wake up out of their hibernation periodically and sleep for a day, then wake up again and hibernate some more. Apparently the hibernation and sleep are distinguishable by EEG (recording "brain waves" by scalp electrode). Most evidence points towards sleep's most important role being in consolidation of memory in cortex (and probably general homeostasis of neurons). People used to think this occurred during REM, but now it sounds more like this is occurring during different stages of sleep, while REM is more like a waking state where information is filtered and organized and prepared for consolidation in deeper stages of sleep. Your conscious perception of these processes occurring is called "dreams," BTW, and contrary to common belief, they do not happen exclusively during REM sleep. The reason why we need "sleep," a period of inactivity, is apparently because there simply isn't a way to perform certain tasks of homestasis, synaptic strength updating, etc. while the network is functional. This makes sense if you think about it, and apparently there's some interesting data supporting. Destexhe and Sejnowski have a book about some of this stuff, and I think they argue that pyramidal cells in cortex receive synchronous excitatory and inhibitory inputs from the intralaminar nuclei and reticular nucleus, respectively. Both of those are parts of the thalamus, a structure in the middle of the brain that sends some projections out to the cortex, or the layers of cells on the surface. Anyway, the excitatory input activates NMDA receptors and voltage-gated calcium channels in the dendrites, while the inhibitory input shunts the depolarization, preventing firing of action potentials. The dendrite therefore fills with calcium, activating various pathways involved in synaptic plasticity, etc.

    But I digress. The point is, sleep is important, and just because there is a drug out there that can fool your brain into thinking it doesn't need sleep, it still does. Forced sleep deprivation, in time, has been shown to cause permanent brain damage and eventually death. Taking a drug like provigil will most likely not prevent these things from happening--it will only prevent you from knowing that these things are happening. Another thing is that some people will say that scientists don't know how provigil works. This is partly true. There was a paper in Cell (I think) a couple years ago demonstrating that provigil (also called modafinil) increases firing in cells expressing a certain receptor for hypocretin/orexin, this short peptide neurotransmitter that regulates various aspects of wakefulness and hunger. The neurons that make that stuff were recently shown to be the ones that mysteriously die in narcoleptic patients. However, we don't know the exact mechanism by which the provigil affects these cells. IIRC, the provigil doesn't interact directly with the receptor, but nonspecifically intercalates into the membranes and does who-knows-what, with one end result being increased firing rate in cells expressing the proper receptors. However, this drug is not some sort of high-specificity compound that was rationally designed or found by interaction with a known target like most of the new drugs coming out on the market. It may have many side effects that are not documented. I took it for several months, and it made me extremely stupid. I became severely depressed and was driven almost to suicide. I would just sit on the floor and cry, babbling that I used to be smart and I didn't know what was happening to me. The disturbing thing was that I somehow didn't realize that it was the drug doing it to me. Once my girlfriend figured this out and got me to stop taking it, I was fine. When I looked into it a little more, I found that there were a few people in narcolepsy support groups who had similar side effects, despite the fact that these were not reported during clinical trials (and therefore, my doctors had a hard time believing that they were real). In summary, stay away from provigil unless you need it. For the people it works for, it's a miracle drug, but it is a very serious drug, not just a caffeine pill.

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