Snorting a Brain Chemical Could Replace Sleep

[zera]

Cool, seems to work pretty differently than standard stimulants. I did a search online and saw a site that was selling it. Obviously it is way too early for it to be scheduled. Could be interesting to try, but its certainly not cheap. Still an extra 40 hours a week definitely might be worth it. I like how one branch of the government is trying to shut down research chemicals, but other branches are giving us new ones. Story below


Snorting a Brain Chemical Could Replace Sleep
By Alexis Madrigal 12.28.07 | 12:00 AM


A nasal spray of a key brain hormone cures sleepiness in sleep-deprived monkeys. With no apparent side effects, the hormone might be a promising sleep-replacement drug.
Photo: Flickr/Mayr
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.

http://www.wired.com/science/discove...ep_deprivation

Reputation Comments on this post:

	although I don't agree, good find!
	good article
	Thanks for sharing.
	Great post.

[bloot]

This is definitely cool. I think this could be great for a lot of Americans wanting to put in extra hours, or stuff like that. But the way I think about it is if we have those extra seven hours everyday there really will be no rest. While the mind may be stimulated I doubt that the body could handle non stop movement etc. There are many things that could stem from this. Hell if you are an environmentalist you could go against how this would give an extra seven hours for SUV driving Americans to pollute our country and lead to what Americans should fear most, o-zone depletion.. global warming.. Having extra hours and no sleep could also lead to a shorter avg. lifetime. Certain elements in life in excess could cause extra stress which can cause so many things. I think this would be maybe a good pick me up for a studying college student. But I really don't think this should be something of daily use.. I see it causing more harm than good.

[Lethargy]

Ever read the book Beggars in Spain by Nancy Kress? It revolves around a development of a genetically superior 'sleepless' modification of the genome... this gives some shades of that... fascinating though.

[hh339]

Found some of this on the web too, but the price is sky high for a milligram.. How much is needed for effects?

[Zaprenz]

Originally Posted by hh339

Found some of this on the web too, but the price is sky high for a milligram.. How much is needed for effects?

It would be hard to say, it is a large peptide so absorption is probably going to be greatly affected by the vehicle it is delivered in via the nasal spray.

Snorting unmodified orexinA MIGHT just be a very efficient way to metabolise and get rid of a very expensive compound. (or risk dosing too high)


Also if the nasal spray gets through clinical trials ok it's probably just going to be a potentially safer(?not proven yet), more convenient(?not proven yet) modafinil type compound. Sure such compounds might become very useful/popular but until the nasal spray comes out (+demonstrates safety & efficacy) probably not going to be worth paying large sums of money to try and simulate it.

[bloot]

Doses are in the μg

[zera]

Here's the abstract:

Hypocretin-1 (orexin-A) was administered to sleep-deprived (30–36 h) rhesus monkeys immediately preceding testing on a multi-image delayed match-to-sample (DMS) short-term memory task. The DMS task used multiple delays and stimulus images and effectively measures cognitive defects produced by sleep deprivation (Porrino et al., 2005). Two methods of administration of orexin-A were tested, intravenous injections (2.5–10.0 µg/kg, i.v.) and a novel method developed for nasal delivery via an atomizer spray mist to the nostrils (dose estimated 1.0 µg/kg). Results showed that orexin-A delivered via the intravenous and nasal routes significantly improved performance in sleep-deprived monkeys; however, the nasal delivery method was significantly more effective than the highest dose (10 µg/kg) of intravenous orexin-A tested. The improvement in performance by orexin-A was specific to trials classified as high versus low cognitive load as determined by performance difficulty under normal testing conditions. Except for the maximum intravenous dose (10 µg/kg), neither delivery method affected task performance in alert non-sleep-deprived animals. The improved performance in sleep-deprived animals was accompanied by orexin-A related alterations in local cerebral glucose metabolism (CMRglc) in specific brain regions shown previously to be engaged by the task and impaired by sleep deprivation (Porrino et al., 2005). Consistent with the differential effects on performance, nasal delivered orexin-A produced a more pronounced reversal of sleep deprivation induced changes in brain metabolic activity (CMRglc) than intravenous orexin-A. These findings provide strong evidence for the effectiveness of intranasal orexin-A in alleviating cognitive deficits produced by loss of sleep

http://www.jneurosci.org/cgi/content...ct/27/52/14239

The monkeys were 1 microgram/kg. So for a 60 kg human, you're talking about 17 intranasal doses per milligram. Not sure how long it lasts though.

[Zaprenz]

^That has no information on the formulation of the nasal spray. (The pharm company are probably not going to reveal this information either)

It's a BIG peptide => so it will probably need help getting across nasal mucosa (penetration enhancers, buffer solutions etc etc at a guess)

a novel method developed for nasal delivery via an atomizer spray

Interesting article though btw, good read.

[Lettish]

That's interesting. Be good if this takes off and becomes the norm in a decade or so lol.

[Purest]

Dinosaur could really go for something like that, of course he wonders would people abuse the drug to keep partying or to drive late at night. If it comes on the market, he may have to try it.