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The article is about modulating orexins in the brain. Orexin receptor agonism was thought to be a mechanism of modafinil/armodafinil but this isn't mentioned anywhere in the article. Modafinil is mentioned as a mere stimulant. It sort of makes me want to dismiss the article as manufactured hype for a new class of modafinil successors.
>Orexin receptor agonism was thought to be a mechanism of modafinil/armodafinil.
The article seems to imply this is not the case. Do you have a source that says that Orexin agonism is the mechanism of action for modafinil?
Yup, and even the title alone gives it away.
FTA Modafinil et al work at a different level than these peptides do.
I feel like I'd want the opposite of this - something that mimics the cleaning process of sleep that you could use in the afternoon for a nap or etc.
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.
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.
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
What if we just normalized taking naps more often?
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.
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.
Not to take away from the broader point, but modafinil is lumped in with methylphenidate as a stimulant that "increase[s] the activity of neurotransmitters such as dopamine and norepinephrine". Modafinil does also stimulate the orexin system and is part of why it's so effective for wakefulness and not as a stimulant in the medium/long-term.
Consider: Beggars in Spain. https://www.goodreads.com/book/show/68333.Beggars_in_Spain
This is what I exactly thought
general question: is there an alternative to archive.is ? it seems to be blocked in my country.
It sounds to me like something that's quite dangerious. Maybe it helps people with narcolepsy but maybe it will be another thing people abuse like amphetamines?
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
"Ozempic moment" seems like a manufactured buzzword in this context. A new modafinil variant is nothing like Ozempic. The thing that was actually interesting about Ozempic wasn't its windfall profits, it was the fact that it is a new class of drugs, and the fact that it's able to rather directly target a habit without wreaking havoc on the body. Part of the article mentions there is hope it may be useful for depression, ADHD, and addiction, but whether any of this is actually actually effective is up in the air. Lots of things are in "pharmaceutical companies hope it can treat mental illness" status... but trying to cast an image of being on the verge of a breakthrough is big pharma's whole marketing.
> Orexins are made by a small number of neurons in the hypothalamus, a brain region tucked behind the eyes.
> 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
Why couldn't they, if they've got DNA and ribosomes?
Related:
- Ozempic For Sleep https://www.isaak.net/sleepless/ (November 2024)
It is the same author from https://news.ycombinator.com/item?id=41742432
He recently founded https://capable.com, also related
Previous post: https://news.ycombinator.com/item?id=49206165
Isn't the problem with lack of sleep (and what causes death with enough deprivation) oxydation that happens in the gut and spreads to the organs?
If I'm not mistaken there was an experiment using fruit flies where they fed them antioxidants and that made them not die from lack of sleep.
Title implies people will flock to a pill that makes them shed gray matter
It's probably the default clickbait title for any article about a new drug.
Yeah, I really dislike this “Thing is has its Other Thing Moment.”
For starters, I what the hell does this mean?
But it’s also a style of reporting that treats the attention cycle as the thing that must be covered rather than the thing itself.
I like my brain fatty /s
Imagine a cure for sleep, it would be a big productivity gain for society if people could work way more hours or spend more hours consuming every day and not even be tired.
I just want something that increases deep sleep -- I think just tricking the brain to control sleep is probably not enough -- it's likely a two way street.
Isn't that what the antagonists mentioned in the article are for?
As an aside, are there any habitual modafinil takers here? I had a period in college where I took it very rarely when I had to cram. Worked pretty well.
Modafinil has been a lifesaver for me for over a decade, but always great to have more options for medium ADHD.
Isn't it technically off label for ADHD ?
I think the real question with Ozempic is.....why are so many people's bodies not producing enough natural GLP-1 in the first place?
Ozempic is for sure a miracle for some who really need it but for many I think they would be better off by solving that problem at the source (likely gut bacteria based and consuming a better mix of prebiotic fibers). Increase your natural levels of GLP-1
Sleep is Lindy... obesity and constant wakefulness are not.
The sad fact is that people will be pressured into taking this.
E: Lindy was probably the wrong term. But still, it's like Chesterton's fence. We are far from fully understanding human biology... and deleting sleep will lead to unknown effects. All power to those who try, I guess.
For a minute I thought they'd found a cure for fatheads.
The brain may be about to have its Algernon moment
FTFY
Every conceivable thing 'may be about to' happen.
What has anything in this article to do with Ozempic? Is mentioned in the title once and never again. Engagement bait?