Scientists discover cure for sleepiness

[CaptainChewbacca]

In what sounds like a dream for millions of tired coffee drinkers, Darpa-funded scientists might have found a drug that will eliminate sleepiness.

A nasal spray containing a naturally occurring brain hormone called orexin A reversed the effects of sleep deprivation in monkeys, allowing them to perform like well-rested monkeys on cognitive tests. The discovery's first application will probably be in treatment of the severe sleep disorder narcolepsy.

The treatment is "a totally new route for increasing arousal, and the new study shows it to be relatively benign," said Jerome Siegel, a professor of psychiatry at UCLA and a co-author of the paper. "It reduces sleepiness without causing edginess."

Orexin A is a promising candidate to become a "sleep replacement" drug. For decades, stimulants have been used to combat sleepiness, but they can be addictive and often have side effects, including raising blood pressure or causing mood swings. The military, for example, administers amphetamines to pilots flying long distances, and has funded research into new drugs like the stimulant modafinil (.pdf) and orexin A in an effort to help troops stay awake with the fewest side effects.

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.

Such a product could be widely desired by the more than 70 percent of Americans who the National Sleep Foundation estimates get less than the generally recommended eight hours of sleep per night (.pdf).

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."
Dr. Michael Twery, director of the National Center on Sleep Disorders Research, said that while research into drugs for sleepiness is "very interesting," he cautioned that the long-term consequences of not sleeping were not well-known.

Both Twery and Siegel noted that it is unclear whether or not treating the brain chemistry behind sleepiness would alleviate the other problems associated with sleep deprivation.

"New research indicates that not getting enough sleep is associated with increased risk of cardiovascular disease and metabolic disorders," said Twery.

Still, Siegel said that Americans already recognize that sleepiness is a problem and have long treated it with a variety of stimulants.
"We have to realize that we are already living in a society where we are already self-medicating with caffeine," he said.

He also said that modafinil, which is marketed as Provigil by Cephalon and Alertec in Canada, has become widely used by healthy individuals for managing sleepiness.

"We have these other precedents, and it's not clear that you can't use orexin A temporarily to reduce sleep," said Siegel. "On the other hand, you'd have to be a fool to advocate taking this and reducing sleep as much as possible."

Sleep advocates probably won't have to worry about orexin A reaching drugstore shelves for many years. Any commercial treatment using the substance would need approval from the Food and Drug Administration, which can take more than a decade.

Link

This sounds awesome and kinda unsettling at the same time. Could you go INDEFINITELY without sleep? Or, would sleep be something people only did on the weekends? Could soldiers take it and then go on four-day patrols, I wonder?

[Oni Koneko Damien]

While sleepiness is just your body's attempts to tell you that you need to get to sleep, doesn't the reason people sleep have something to do with mental stability? The brain needs rest of a sort to sort and file all sensory imput from that day, the side-effects of that being your dreams?

It seems that even if you gave something that eliminated the effects of sleepiness, wouldn't the stress of not having that mental-rest period add up to severe psychological problems down the line?

[Boyish-Tigerlilly]

Yes, you are correct. You need sleep for mental health and physical health. Your body will still wear down, even if you don't immediately feel the effects of being tired.

Unless they someone eliminate the the physical effects of not sleeping, but this seems cosmetic (as in focusing on symptoms such as tiredness). If you go without sleep for long enough, you will crash and burn, even if you aren't tired.

When you rest, your brain is still active obviously, but it's a necessary part of the cycle.

[Boyish-Tigerlilly]

Edit: crap, forget part of what I wrote. For some reason, only half the article showed up, but now it appeared. It seems that it actually reverses all the effects and actually restores their cognitive abilities to normal.

It is interesting. I would like to see more information on it over time to see how it pans out in testing further.

I am a bit skeptical that it could totally replace sleep, given the pounding I have been given in how important it is for mental health. But maybe I was wrong.

[Lord of the Abyss]

This sounds awesome and kinda unsettling at the same time. Could you go INDEFINITELY without sleep?

I doubt it; people who lose the ability to sleep die. Thus the word "fatal" in "Fatal Familial Insomnia".

On the other hand, people have a broad range in how much sleep they need to function well. It's an interesting question if this or something similar can push everyone more towards the "needs less sleep" end of the spectrum, or if all that it will do is let you not feel it when you stay awake longer than is healthy for you.

[wautd]

Damn, still at least a decade. I sure as hell could use it right now

[CmdrWilkens]

I think what will end up being the roadblock will be the problem they already pointed out; cardiovascular health. Sleep is usually tied in to just resting the brain and letting it gear up for a new day but you also need to rest and recuperate the whole body so if prolonged, if mentally alert, periods of being awake shows signs of deteriorating cardivascular health then I think we have the likely drawback. That said there are plenty animals which don't slepp or at least don't sleep to the degree that we need (almost 1/3 or a day) so I don't think there is any paticular reason why we shouldn't be able to be awake and alert.

[Mr Bean]

Oy everyone, this is not for general use, this is for pilots or perhaps emergency use only. I can see truckers might abuse it, but it would be helluva lot useful for number of professions.

[TheMuffinKing]

We might be able to tailor this to rest half the brain at any given time. One step closer to making space marines every day...

[Molyneux]

We might be able to tailor this to rest half the brain at any given time. One step closer to making space marines every day...

The body itself still needs the rest-and-repair time. Otherwise you start to fall apart, no matter how rested your brain is.

[Admiral Valdemar]

There are drugs on the market now whose names escape me, that are capable of giving you 48 hours of perfectly natural alertness and which also don't suffer the catch up problem i.e. you have to sleep a good 48 hours to recover.

They were developed for such jobs as pilots, paramedics and soldiers under stress, but given we don't really understand what sleep is for, I doubt this is a miracle "cure" for sleep just yet. I'd still want to see long term studies, given the idea of a nasal spray making you perpetually awake is a tad far fetched.

EDIT: Modafinil. Damn article mentions the drug. Duh.

[General Trelane (Retired)]

"We have these other precedents, and it's not clear that you can't use orexin A temporarily to reduce sleep," said Siegel. "On the other hand, you'd have to be a fool to advocate taking this and reducing sleep as much as possible."

Somehow, I don't think there will be a shortage of fools.

[Gullible Jones]

Since REM sleep is apparently used for various memory-related tasks, excessive use of antisleep drugs could be an extraordinarly bad idea...

[Rekkon]

I doubt it; people who lose the ability to sleep die. Thus the word "fatal" in "Fatal Familial Insomnia".

Though we have this guy.

[CmdrWilkens]

Oy everyone, this is not for general use, this is for pilots or perhaps emergency use only. I can see truckers might abuse it, but it would be helluva lot useful for number of professions.

Actually pretty much every combat related military profession and quite a few combat service support professions would have great use for this. If one wants to wonder what the biggest problem gets to be with logistics you only have to consider that its still people doing the driving and there comes a point that you just can't push your truck drivers any further. For a 100mi advance that means the support personnel have to bring supplies to the front, return to the rear then forward again after more advances are made while yet other drivers have to keep pushing the restocking bases further and further forward. There is only so much and so far you can push those drivers and even with switching off the offensive into Iraq was seeing consistent 20 driving hour days for the forward resupply units, that's 20 hours behind the wheel so if you count in the added camp making details athese guys were getting less than 4 hours consistently for a few weeks. Suffice to say something like this would be highly useful in avoiding accidents and time loss due to bad route follwoing decisions, etc.

[FSTargetDrone]

What, no one saw the X-Files' "Sleepless" episode?

Sleep and the X-Files

From Apply Now, Your Guide to Sleep Disorders.

About.com Health's Disease and Condition content is reviewed by our Medical Review Board

"Sleepless"

Believe it or not, I do have a life beyond sleep disorders, and one of my interests is in the paranormal. I've been watching the reruns of the X-Files, and many of the stories remain in my mind well after the show ends.

The episode I watched last night, however, made such a strong impression on me and is so closely related to my Sleep Disorders work that I opted to write an extra article this week.

The X-Files story was entitled "Sleepless" and involved the results of severe sleep deprivation on a group of soldiers fighting in Vietnam. In the story, an operation on the brain removed the need and the ability to sleep. The purpose was to produce soldiers who were more aggressive and fearless. Also, as they didn't sleep, they were available for duty twenty-four hours a day.

The experiment worked well beyond its planned perimeters. The soldiers became killing machines, aggressive, irritable and unstoppable. The entire squad went AWOL and wiped out a whole Vietnamese village - men, women and children.

The story is mostly about the remaining participants, men who have been without sleep, not twenty-four hours, but twenty-four years. Of course, as X-File episodes will, it continued into the realm of the paranormal with mind control and other supernatural elements.

But, the part that interested me, the part that should be of interest to all who suffer from the sleep disorders, was the effects of sleep deprivation. Although a bit exaggerated for the X-Files, this is indeed what happens to those deprived of sleep. They become irritable, aggressive, thought patterns are disrupted and they are apt to do things they wouldn't do if they were not suffering from sleep deprivation.

Everybody needs sufficient sleep each day to revive brain cells and keep bodily systems functioning effectively. Without sufficient sleep, there is a gradual breakdown, not only of mental abilities, but also of health in general.

If a person is sleep deprived, he or she is more susceptible to illnesses and the invasion of germs and viruses. Because the mind is not functioning at full power, there is a risk of making mistakes and of causing accidents. Getting less than 6 hours a night can affect coordination, reaction time and judgment. A recent survey revealed that one-half of all American adults admit to driving drowsy, and one in five actually fell asleep behind the wheel.

Sleep is as important in sustaining life as food and water and almost as important as the air we breathe. If you're not getting the sleep your mind and body requires, it's time you did something to remedy the situation

Updated: December 22, 2004

[ANGELUS]

What, no one saw the X-Files' "Sleepless" episode?

Or the Fairy Odd Parents' episode when Timmy wishes for no one to sleep anymore???

[Broomstick]

That said there are plenty animals which don't slepp or at least don't sleep to the degree that we need (almost 1/3 or a day) so I don't think there is any paticular reason why we shouldn't be able to be awake and alert.

I'd like you to name these animals that don't sleep. As far as I know every single mammal sleeps (although whales can sleep with half their brain at a time), every bird sleeps, reptiles sleep, amphibians sleep, fish sleep.... it seems everything with a brain has a need for sleep.

[FSTargetDrone]

I'd like you to name these animals that don't sleep. As far as I know every single mammal sleeps (although whales can sleep with half their brain at a time), every bird sleeps, reptiles sleep, amphibians sleep, fish sleep.... it seems everything with a brain has a need for sleep.

Interesting article on non-human animal sleep:

Different Animals, Different Patterns of Sleep

The phenomenon of sleep is amazingly widespread, occurring in almost all animals. Sleep durations range from 4 hours in giraffes and elephants to 18 hours in bats and opossums, and seem to display a general trend for smaller animals to sleep more (see figure 2). Another widely varying characteristic is the amount of REM sleep as a percentage of total sleep, which varies from 10% in guinea pigs and baboons to 25% in opossums, hedgehogs, dogs, and giraffes. This does not seem to have any obvious correlation to anything, as can be seen by the fact that two animals (giraffes and opossums) which were on opposite ends of the spectrum for total amount of sleep are now both on one end of the spectrum for percentage REM sleep.


Figure 2. Sleep duration in different animals
(source: http://faculty.washington.edu/chudler/chasleep.html)

One thing to keep in mind when considering sleep in animals is that we are not necessarily talking about the same sort of thing as with humans. Some animal sleep behavior can seem downright bizarre. For instance, marine mammals (dolphins and whales) actually only sleep with half their brain at any given time. Doing an EEG on a dolphin can yield the result that one half of the brain is displaying some stage of sleep, while the other half is fully awake, controlling movement and searching for danger. This ability implies that the brain of a dolphin must be set up quite differently from that of a human. If a human were able to put one hemisphere to sleep, he or she would cease to be aware of half of the visual field (hardly ideal for avoiding danger). Additionally, the problem of how motor inhibition during REM sleep would function without affecting the waking hemisphere would require a completely different approach. While there is a lot to be learned about human sleep through the study of animals, it is vital to remember that this approach can also easily lead to false conclusions.

[FSTargetDrone]

Sorry, I meant to add that in other animals, sleep may have different outward manifestations, as the article mentions.

It even appears that insects sleep (excerpt):

To date, sleep studies have predominately focused on mammals. The first scientifically valid investigation of sleeping habits of invertebrates was conducted only twenty years ago. This study looked at the effects of sleep deprivation in cockroaches. There are only one million known invertebrate species out of an estimated existing ten to fifty million, therefore no simple generalization on the basis of a few observations can account for the considerable diversity that must exist. Some insects, especially aquatic ones and those that live near the poles, may have different daily cycles, or even maintain round-the-clock activity. For this reason, the term 'torpor' seems to provide a more inclusive and accurate term for describing sleep activity in insects. An insect in torpor exhibits immobility and distinctly reduced response to stimuli, although it can rouse from torpor in a matter of seconds given a strong enough stimulus. Even among insects that do exhibit torpor, the degree and nature of its expression are somewhat variable.

One of the more dramatic forms of torpor is seen in some bees (chiefly in the family Apidae), which firmly clamp onto a plant with their jaws in the evening. They then fold up their legs and maintain this odd, dangling pose all night long, until they rouse the following morning. The species that observe this ritual use the same spot every evening, presumably marking it with some chemical that they can detect from a distance. This very specific behavior is regarded by many researchers as the closest thing any insect has to conventional sleep.

Instead of gauging the degree to which insects sleep using the behavioral criteria checklist, scientists have devised clever ways of establishing an experimental checklist to test for sleep in insects. Since many insects are too small to have their brainwaves measured, scientists have implemented metabolic and genetic tests for sleep. For invertebrates, elements such as body position, arousal threshold, muscle activity, and heart rate have been identified, which allow researchers to differentiate rest from sleep.

The most celebrated results from insect sleep studies have stemmed from Drosophila experimentation. In Drosophila, researchers tested for sleep by videotaping the flies during rest periods to document the insects behavior. Each night, the flies crawled off to resting places and settled into what the researchers defined as a sleep pose, slumped 'face down'. For about seven hours every night, the flies stayed still except for occasional twitches of the legs and proboscis. As the evening progressed, louder and louder taps on the cages were needed to rouse the insects. In some sessions, scientists tapped on the containers to keep the flies from resting. The sleep-deprived insects compensated by increasing the amount that they slept over the next few days, as sleep-deprived people do.

So it would appear that all animals, even insects, do indeed sleep to some degree.

[Oskuro]

Would that wonderdrug wake me up when I fall asleep on my keyboard at fucking 9 a.m. after a full night's sleep and a couple cofee cups?!


Preventing actuall sleep, bad.

Waking up when, by whatever reason, your body decides it's sleepy time while your boss is making an important presentation, AWESOME.

[Molyneux]

Would that wonderdrug wake me up when I fall asleep on my keyboard at fucking 9 a.m. after a full night's sleep and a couple cofee cups?!


Preventing actuall sleep, bad.

Waking up when, by whatever reason, your body decides it's sleepy time while your boss is making an important presentation, AWESOME.

Agreed. I could definitely make some use of that...caffeine only has limited effect on me, and I tend to crash when it wears off. Something like this could be a godsend for when my body's sleep clock gets out of whack.

[Wyrm]

I doubt it; people who lose the ability to sleep die. Thus the word "fatal" in "Fatal Familial Insomnia".

Though we have this guy.

FFI is a prion disease that fucks up the thalamus, an important area of the brain responsible for far more than sleep. Insomnia is one of the symptoms, not the ultimate cause of death.

As to Mr. No Sleep In 30 years, I wonder if he spends half an hour hallucinating every day. (I read in some book that there exists other sleepless people who are perfectly healthy, but they spend ~30 min each day hallucinating, like a replacement for REM sleep — there's your half-reemmbered factoid of the day. )