Yup, and even the title alone gives it away.

It's in the article no?

> Orexin antagonists (which block the molecules’ actions rather than mimicking it, and thus promote sleep), have been available since 2014 as treatments for insomnia. They work differently from conventional sleeping pills, which enhance GABA, one of the brain’s main inhibitory neurotransmitters. Birgitte Kornum, an expert on orexins at the University of Copenhagen, says such pills induce sedation rather than natural sleep and often lose effectiveness with continued use. Orexin antagonists instead turn down the brain’s wakefulness signal, letting its sleep-promoting systems take over. Evidence suggests this produces better sleep, with less risk of dependence and fewer long-term problems.

Sleep isn't about cleaning. It might include cleaning, but I don't believe for a second that cleaning is the main function.

Why? Cleaning is easy to optimize yet sleep is evidently hard to optimize. Going unconscious for a big chunk of the day in a world where everything wants to eat you is a crazy price to pay, yet sleep is highly conserved across species under this extreme selective pressure. Even the animals famous for avoiding sleep don't really avoid sleep so much as bend the rules! Seals partially wake up to breathe, migrating birds sleep a hemisphere of their brain at a time, but they all sleep. This didn't happen because "pumps are slow" or "filtering is hard." Biology is excellent at copy-paste-reinventing that stuff. Optimizing the pumps and filters is not something evolution would have struggled to do if it could have meant not going unconscious for a third of the day. Especially for organisms with small brains where the transport logistics are trivial.

IMO the much more likely explanation is that the brain uses contrastive learning somewhere. We know animal brains don't use backpropagation to train and contrastive learning is one of the biggest competing family of techniques. Instead of using calculus and outer products to calculate derivatives, you feed real data and false data forward through the network and each neuron tracks and trains on the difference. This can be batched -- many CL techniques could handle 16 hours of real data followed by 8 hours of false data -- but the false data can't be put off forever, or the contrast signal goes away. Also, you probably want to inactivate I/O while the false data is flowing through. In other words: sleep emerges from first-principles on the category of neural network learning techniques that the brain probably uses.

I don't think anyone was seriously about to shoot up with sleep-replacement peptides, but also: don't. Let someone else figure this out the hard way.

If you want something that displaces adenosine from your neurons you are in luck, because it already exists and is very easy to get; It's called methamphetamine

This would be incredible.

The closest thing now is amphetamine but it turns people into maniacs - presumably the action here is not actually the brain cleaning function of sleep, rather just preventing reuptake of neurotransmitting chemicals that would cause it, if allowed.

Would be nice to truly provide the mechanism in a synthetic form - I wonder what it would feel like to have the brain “slept” while awake.

By mimic do you mean it does the cleaning process or just that you feel like it did? If it was the former, that would be very interesting.

What if we just normalized taking naps more often?

general question: is there an alternative to archive.is ? it seems to be blocked in my country.

> Orexins are only produced by a small cluster of neurons in the hypothalamus, a brain region located roughly behind the eyes and between the ears.

https://sleep.hms.harvard.edu/education-training/public-educ...

> didn’t know that “neurons” themselves could make peptides

Neurons synthesize proteins [1]. (I think glia do the heavy lifting.)

[1] https://brain.mpg.de/164308/protein-supply-in-long-nerves-ho...

According to Wikipedia its accurate. Learn something new everyday

It doesn't matter what it is, people somewhere will abuse it. Maybe doesn't need to be anywhere near the subject.

Modafinil is available for ages, acts close to this (it's mentioned in the article), and I don't hear of people abusing it.

looks like potential for abuse is low - people with normal orexin activity could even experience diminished capacity by these drugs

Isn't it technically off label for ADHD ?

https://old.reddit.com/r/ExtraFabulousComics/comments/1iqsqd...

It's probably the default clickbait title for any article about a new drug.

I like my brain fatty /s

Don't forget the flowers.

Literally everything except the media writing non-sensationalist headlines about science.

"Hunger and sleep, argues Dan Skovronsky, the firm’s chief scientific officer, are both 'master homeostasis mechanisms'—systems that keep the body in balance. When they misbehave, illness follows. That, he says, helps explain why incretins, the hormone family behind GLP-1, proved so broadly useful. Hence why orexins could be just as important."

Also, orexins are peptides, like semaglutide (Ozempic), although in a different family.

Ozempic == GLP-1 which the first visible paragraph is discussing.

Ozempic is the poster boy for peptides.

Your brain is gonna lose so much weight!

Is "Lindy" a typo or have I missed another linguistic innovation?

Aging and cancer are also Lindy.

Two things you'll always find someone to defend with vigor are sleep and death. A lot of humans seem to despise living in general. It's fascinating to see.

> I think the real question with Ozempic is.....why are so many bodies not producing enough natural GLP-1 in the first place?

That's pretty easy: The last centuries (or decades, mostly) have provided an asymmetry in nutrition systems. Modern food engineering has optimized most of what people eat to have them crave more instead of being mainly filling. There is little to counter that, and GLP-1 is a way to do that. Another way is will power. Yet another is fixing what and how you eat (and how you exercise, but that'a a different topic).

> the real question with Ozempic is.....why are so many bodies not producing enough natural GLP-1 in the first place?

Why can’t we synthesize vitamin C?

The root-cause solution to vitamin C deficiency is supplementation (through food or otherwise). If our bodies couldn’t figure something like this out, something the rest of the animal kingdom (apart from guinea pigs) did, it strikes me as conceivable is badly optimized in other cases, too.

Our "natural" impulse is to eat everything tasty within reach until we're full. That's not so healthy when the tasty stuff regularly includes foods like liter soft drinks, ice cream sandwiches, French fries, and so on. Our bodies didn't evolve with calorie-bombs constantly just a drive-thru trip away.

Millions of years of evolution and selection ending up at humans needing one food supply and lifestyle while modern life is basically the opposite. Endless calories. Sugar and meat everywhere. Our bodies are did not evolve for modern life. That's why.

Because on an evolutionary time scale, we never had a consistent surplus of calories over a long period of time.

Imagine Grog and gang kill a mammoth but Grog only eats 500 calories before feeling so full he's going to throw up.