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.
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.
Your entire argument rests on this statement, yet I don't see any further talk about it or anything to back it up. Perhaps sleep is the very best way to optimise cleaning, outweighing the disadvantages?
I think you overestimate the disadvantages of sleep. It's very species dependent, for some it might be a disadvantage because you're more vulnerable to predators, for others it's an advantage because you spend less energy. If you're safe you really only need enough wake time to eat and reproduce.
Obviously sleep is necessary. I'm saying that there isn't always a large pressure to minimize sleep. Long sleep can be beneficial just to preserve energy.
Right, but my argument is "high pressure never managed to push past this barrier, therefore it's a strong barrier." The existence of other, lower pressure circumstances doesn't have any bearing on the conclusion -- unless you want to argue that the low pressure circumstance is so universal that the high pressure circumstance doesn't exist, that no animal anywhere is inconvenienced by the need to sleep. But I don't think that is what you were going for.
I think it's often a bit of a mistake to assign one function to a given feature of a biological system. Biology tends to be messy and tangled and so something can quite easily have multiple functions.
If that were true, wouldn't you expect 50 year olds (who have mostly learned how to navigate life) to need little or no sleep? Seniors sleep only a little less than young adults, still 6-8 hours a night.
There are other known mechanisms in sleep, for example copying/condensing short-term to long-term memory by replaying it. Translating increased compression into better fundamental performance seems like a steep task and 50 year olds have already reproduced or not, so shrug
I think we made a big mistake by using biological terms for computer processes and now we have people like you coming to the """natural""" conclusion of going full circle and applying computer terms back to biological processes.
There is virtually no parrelel between both worlds besides the naming and no one has any idea about what's going on for real.
I don't see a need to be dismissive. There is a lot of evidence that there is a relationship betwwen sleep and learning. The hypothesis advanced by the OP is worth evaluating on its merits rather than being dismissed as a fale equivalence.
This smells a bit like a statement of faith. Digital neurons and neural networks are not the same as their biological counterparts, sure. But it is not an unreasonable proposition that their functions are isomorphic.
It's not zero clue. Neurologists have got a lot of observations on how the brain works and there are multiple plausible proposed mechanisms for how the brain might do something like backpropagation, it's just that the details are really messy so there's not a single clear picture that has emerged.
(Similarly, there is decent evidence that the brain uses higher-dimensional vector representations of concepts in a similar way to neural nets, at least in some parts of it, but again the details are messy and there's not a clear idea of how these representations emerge or how to decode them reliably)
I keep hearing that. At the same time people makes comments like the one you just answered to, using that analogy heavily. Could someone who understands both say where the analogy breaks down in this case?
While there is much to suggest that sleep is important for learning, why contrastive learning in particular? It seems to me that the "deactive IO" argument could apply to any learning technique. Similar to how railroad maintenance is carried out at night because it is too unsafe to do during the day when trains are whizzing by.
Contrastive learning provides an unusually strong push towards an offline solution, even though the offline solution is expensive.
Road maintenance isn't a good analogy; it _can_ be done "online" (with traffic, during the day) and in fact _is_ often done online, despite the pressure to do it online being less than "road workers will be eaten by monsters if they venture out between 8pm and 6am." This is the opposite circumstance we see with sleep. Animals always sleep despite the steep cost. If we want to fix the analogy, we could imagine a world in which all roadwork was done between 8pm and 6am despite workers regularly getting eaten by black-furred creatures of the night. Wouldn't that beg the question "why not do it during the day?" If you learned that every city and state and country did the same crazy overnight work schedules despite losing workers to them, wouldn't you suspect that there was a strong hidden reason?
Why would neurons be exempt from training just because they weren't clustered into a brain? By comparison, transport-related phenomena are almost completely trivialized in the simple creatures. The existence of sleep in simple critters seems strong evidence in favor of contrastive learning over cleaning explanations.
Could you make the case for metabolic explanations? Are there a bunch of coupled mechanisms that all require downtime and couldn't possibly be phased?
> 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.
I’ve used both Belsomra (suvorexant) and Quviviq (daridorexant) and compared to the litany of other sleeping aids, Quviviq in particular is great for me in terms of not being groggy, not knocking me out standing up in case I somehow don’t sleep or need to do something. No rebound on days I run out or if I stop. Feels quite natural—I imagine it feels like what most normal sleepers feel like every evening. It’s nearly impossible for many to get them, tho…
Edit: To add some academic merit — there’s been research for its use for cognitive decline [0]
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
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.
I remember the NASA doing extensive sleep studies, determining that the optimal pattern would consist of basically "naps only"?
I've been sleeping my adult life in usually 2x3-4h "shifts", which I also remember reading is a historically often used pattern. I do not see any negative effects.
Tiredness is a signal that the body/brain needs rest so the glymphatic system can go to work. You can lose the signal but still need rest. If your brain doesn't flush metabolic waste periodically you develop brain fog, bad memory, and increased risk of Alzheimer's, and you'll eventually die, as sleep deprivation studies have found.
Caffeine doesn't actually do any of the things sleep does to your brain. If you drink coffee during a late night, you won't feel as tired, but your brain performs worse, your reflexes are slower, you're less likely to remember things, etc. It's like painting over a rusted car instead of properly maintaining it, basically.
I think GP was just making a point about the fact that “tired” is a subjective experience, like pain. Arguably, if you’re on pain medication, you’re not in pain, even if your body is sending pain signals that your brain just isn’t receiving or paying attention to.
You have the ability to mentally push through a lot of stuff, but there are a host of signals your body will use to warn you such as: cognitive performance (although this is hard for yourself to actually admit its happening), behavioral indicators like yawning, head bobbing, frequent posture changes, and slowed speech are just a few indicators. Irritability is another big red flag.
I've only had two instances where I ignored all the signs and continue to push on until my body literally shut down on me. Finals week in college as an architecture student trying to finish a final studio project, and study for four finals. 5 days, 3 hours of sleep. That was one of them.
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.
oh perhaps you're right. i thought they were clones, not alternative domains. i had that captcha issue as well, it disappeared through no action of my own. hope the same for you.
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?
Reminds me of a discussion about how cyber implants would bring upon cyberpunk - a person who needs an implant asks themselves: What if I use my implant this way…
It gets abused by people who just want to stay awake, but not in the sense of being a party drug. For example, by students, drivers, security officers, and politicians.
Coffee isn't a Schedule IV controlled substance in the US. I'm using a pretty strict definition of abuse, which is just using medication outside of its indications, or when it isn't prescribed to you.
Are you saying people are using Adderall AND Modafinil at the same time?
That'd be either exceedingly rare or borderline unwise.
I'd love to see some actual forums or papers about that because this seems very unusual given the partly overlapping effect but significantly different paths.
"People who use adderall for work" is a generalization, for example stock traders at Wall Street are famous for doing cocaine, taking amphetamines for work and possibly every smart drug, including modafinil.
But they won't take them all at the same time because then they get too high to work.
Eh, you don't get "high" on modafinil. Adderall or other amphetamines used in therapeutic doses (or even above that) don't make user "get high".
Modafinil is extremely easy and cheap to get for anyone with one eye and one working finger, Adderall a tiny bit harder but easy for a "trader".
"Possibly every smart drug, including modafinil" is just many guesses mixed up, nothing to actually discuss with. I'll stop wasting electrons here, you do you.
I remember there being kind of a burst of articles about it on HN about ten or fifteen years ago, with a lot of commenters talking about their use of it.
> The Prolific advert stated that participants were being sought for an anonymous survey on their views on the use of modafinil as a cognitive enhancer by UK university students.
Textbook case of "how do we select the most number of people who would say yes" ism. People who are taking modafinil and have a strong opinion about it.
If I'm a student I would never click on that ad in the first place if I have never heard of modafinil (like most people haven't), because the survey is about something I don't know. And if I vaguely heard of it and click, there's a friendly awareness page and quiz right at the start about the thing and its side effects that says I won't get paid if I don't answer correctly, what are the chances I'll continue wasting my time?
"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.
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.
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
> 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).
> that last one is the most important for long term results
Empirically untrue. GLP-1s outperform diet and exercise alone.
> it's not like you couldn't combine a GLP-1 drug with great diet and exercise
This is how it's recommended to be taken. I personally know folks who were able to start regularly exercising and eating healthily because of the head start GLP-1s gave them. (They're mostly off them now, and they're all materially lighter and healthier than they were before.)
Diet and exercise guidance is the standard of care for prescribing GLP1s.
But prescribing diet and exercise alone has long had mixed results, because it does nothing to address appetite, and it is even quite common for exercise to increase it.
> 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 bodies did figure it out(our common ancestor with the wet nosed primates could synthesize vitamin C).
But our bodies also figured out that for an extended period of time this ability was useless since vitamin C was so readily available in all our food sources in most circumstances.
> our bodies also figured out that for an extended period of time this ability was useless since vitamin C was so readily available in all our food sources in most circumstances
But none of the other animals in our biomes similarly optimized? Including none of the other apes?
The less Panglossian interpretation is a gene got fucked up, it didn't wipe us out, and the fuck-up got conserved because it doesn't kill us before reproduction, it just makes us sicker from time to time.
> All apes cannot produce vitamin C. In fact no dry nosed primates can
You're right! Sorry. And super cool!
I'll weaken my hypothesis. There may be a survival advantage in not having to metabolise a vitamin readily available through diet. Altogether, a neutral adaptation/mutation [1]. It's still a good case of nature optimising for leanness like a private-equity boss. And a good example of why something like GLP-1 may have similarly been optimized down for a world no longer relevant.
Fascinatingly, we could biohack our way into having the human liver produce vitamin c, like we have the science to do that. It's just an insane amount of risk compared to just eating an orange once in a while.
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.
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.
it seems however some things that are not excluded are just one step removed from biological entities, hence
>comedians do not have a fixed amount of comedic material to spread over TV appearances, but rather, the more appearances they make, the more future appearances they are predicted to make
sure, but earlier it says that it does not apply to humans because the Lindy effect would imply that a 100 year old would have more life left than an 11 year old, which is counterintuitive, but the example given above would imply George Burns had more television appearances left to do at the age of 99 than Macaulay Culkin at the age of 9, which is just a layer of abstraction laid over the biological age property.
It’s some shit a guy called Taleb came up with. It’s a useful indicator because someone quoting Taleb unironically is someone who can’t tell that Taleb is a midwit.
I get the vibe, but I wouldn't say shocked, merely disappointed. The Black Swan's point would fit on the book's cover even if printed in the font used for the author's name, the work felt to me like 99% was just garrulous "look at me aren't I smart" padding.
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.
Well... Sleep and death are natural. I'm not convinced you see people "defend" death so much as (rightly) acknowledging the inevitability of it.
The latter half of your comment is rather smug, but I wouldn't look down on people who have peacefully accepted reality. Time is fleeting and we are but flowers in a field—briefly brightly bloomed and then withered.
> I wouldn't look down on people who have peacefully accepted reality
Throughout human history, all progress was achieved by people who refused to "peacefully accept reality". But I hope you also get to reap the benefits and correct your depressing mindset some day.
I'm filled with joy and it has nothing to do with my "mindset", I appreciate your concern though!
While it is tempting view all of human progress as some heroic feat of raging against the machine, it seems much more likely to me that progress came from accepting reality, and then working within the bounds of physics.
Sleep is less surprising for me to see people defend than death, to the extent that I'm not sure if I myself have or not done so.
I mean, I can directly feel the benefit of a good sleep that refreshes me in the morning, whereas there's those who have passed on whom I miss.
If I didn't need sleep, really didn't, I wouldn't seek to re-invent it; but of the two it is old age that I'd actively pay money to hold back, if treatments for both existed at the same cost per extra hour of consciousness in my lifetime.
Obviously, every single one of us needs sleep to survive. But it's a biological chore, not some sacred ritual to be celebrated. Reducing the amount of sleep that we need is worth researching. What is surprising to me is the knee-jerk reaction I see whenever the idea of looking into this is brought up.
> likely result would be employers forcing people to take the drug
How so? You can just... refuse? And do you prefer sleeping to working? Doing a job that you hate for 8h and sleeping for 8h is much worse than doing a job that you love for 16h. Something to think about.
In addition to what Qem said, some people don't have much control over their job opportunities, take whatever they can get, and in those roles do whatever they're ordered to do.
Amazon piss bottles come to mind.
Even without malice or orders, sometimes every actor in the economy can be locally motivated in a way that ends up the same. Boss gives you 40 hours, but rent is too high for a 40-hour week? Guess you're taking two jobs now.
It would be like doping in some elite sports, say road race cycling in Lance Armstrong era. Nobody would be coerced by force, but some people would start taking it, making less sleep time the new normal. With time business would adjust to expect and require it, and other people would be forced to take the drug just to not become unemployable in a market with a upshifted baseline. I think this is already happening in education, with ADHD medications. Children are likely being overdiagnosed, because in a environment with many medicated children, just displaying normal child behaviour starts looking odd, pathology-like.
> Doing a job that you hate for 8h and sleeping for 8h is much worse than doing a job that you love for 16h.
Some jobs just suck but somebody still has to do them.
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.
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.
"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.
https://archive.is/WoHuY
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?
FTA Modafinil et al work at a different level than these peptides do.
FTA Modafinil
Free Trade Agreement Modafinil?
From The Article
Yup, and even the title alone gives it away.
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.
> Cleaning is easy to optimize
Your entire argument rests on this statement, yet I don't see any further talk about it or anything to back it up. Perhaps sleep is the very best way to optimise cleaning, outweighing the disadvantages?
I think you overestimate the disadvantages of sleep. It's very species dependent, for some it might be a disadvantage because you're more vulnerable to predators, for others it's an advantage because you spend less energy. If you're safe you really only need enough wake time to eat and reproduce.
If you're safe.
You definitely see a bit of this in other primates. They sleep on trees (much safer) and for a lot more hours than humans.
That's great for primates, but what about nematodes? Everything with a nervous system sleeps, even when the cost is high.
Obviously sleep is necessary. I'm saying that there isn't always a large pressure to minimize sleep. Long sleep can be beneficial just to preserve energy.
Right, but my argument is "high pressure never managed to push past this barrier, therefore it's a strong barrier." The existence of other, lower pressure circumstances doesn't have any bearing on the conclusion -- unless you want to argue that the low pressure circumstance is so universal that the high pressure circumstance doesn't exist, that no animal anywhere is inconvenienced by the need to sleep. But I don't think that is what you were going for.
I think it's often a bit of a mistake to assign one function to a given feature of a biological system. Biology tends to be messy and tangled and so something can quite easily have multiple functions.
If that were true, wouldn't you expect 50 year olds (who have mostly learned how to navigate life) to need little or no sleep? Seniors sleep only a little less than young adults, still 6-8 hours a night.
There are other known mechanisms in sleep, for example copying/condensing short-term to long-term memory by replaying it. Translating increased compression into better fundamental performance seems like a steep task and 50 year olds have already reproduced or not, so shrug
I think we made a big mistake by using biological terms for computer processes and now we have people like you coming to the """natural""" conclusion of going full circle and applying computer terms back to biological processes.
There is virtually no parrelel between both worlds besides the naming and no one has any idea about what's going on for real.
I don't see a need to be dismissive. There is a lot of evidence that there is a relationship betwwen sleep and learning. The hypothesis advanced by the OP is worth evaluating on its merits rather than being dismissed as a fale equivalence.
This smells a bit like a statement of faith. Digital neurons and neural networks are not the same as their biological counterparts, sure. But it is not an unreasonable proposition that their functions are isomorphic.
It is unreasonable, because a neuron is categorical different from a so called "neuron" used by AI.
Same is true when you compare an actual brain and an AI model.
> not an unreasonable
Yet we have absolutely 0 clue nor proof besides "it feels about right", that's not how the scientific method works.
It's not zero clue. Neurologists have got a lot of observations on how the brain works and there are multiple plausible proposed mechanisms for how the brain might do something like backpropagation, it's just that the details are really messy so there's not a single clear picture that has emerged.
(Similarly, there is decent evidence that the brain uses higher-dimensional vector representations of concepts in a similar way to neural nets, at least in some parts of it, but again the details are messy and there's not a clear idea of how these representations emerge or how to decode them reliably)
I keep hearing that. At the same time people makes comments like the one you just answered to, using that analogy heavily. Could someone who understands both say where the analogy breaks down in this case?
The brain is...
~a machine~
~a steam engine~
~a computer~
an LLM
Analogies help understand the brain but OP is taking the analogy and then going back and applying principles from the analog to the brain.
The brain is the brain, it isn't any of those other things.
Sleep is literally cleaning. It is flushing out the brain.
dreams are false data
*synthetic training data
exactly!
While there is much to suggest that sleep is important for learning, why contrastive learning in particular? It seems to me that the "deactive IO" argument could apply to any learning technique. Similar to how railroad maintenance is carried out at night because it is too unsafe to do during the day when trains are whizzing by.
Contrastive learning provides an unusually strong push towards an offline solution, even though the offline solution is expensive.
Road maintenance isn't a good analogy; it _can_ be done "online" (with traffic, during the day) and in fact _is_ often done online, despite the pressure to do it online being less than "road workers will be eaten by monsters if they venture out between 8pm and 6am." This is the opposite circumstance we see with sleep. Animals always sleep despite the steep cost. If we want to fix the analogy, we could imagine a world in which all roadwork was done between 8pm and 6am despite workers regularly getting eaten by black-furred creatures of the night. Wouldn't that beg the question "why not do it during the day?" If you learned that every city and state and country did the same crazy overnight work schedules despite losing workers to them, wouldn't you suspect that there was a strong hidden reason?
Ok, but this has nothing to do with contrastive learning. Your argument applies to all kinds of self-supervised learning methods.
> the much more likely explanation is that the brain uses contrastive learning somewhere
This doesn’t explain sleep in virtually brainless creatures. A metabolic root cause seems more likely.
Why would neurons be exempt from training just because they weren't clustered into a brain? By comparison, transport-related phenomena are almost completely trivialized in the simple creatures. The existence of sleep in simple critters seems strong evidence in favor of contrastive learning over cleaning explanations.
Could you make the case for metabolic explanations? Are there a bunch of coupled mechanisms that all require downtime and couldn't possibly be phased?
> Could you make the case for metabolic explanations?
Animals without nervous systems exhibit sleep-like states [1]. Potentially even animals without neurons [2].
[1] https://pubmed.ncbi.nlm.nih.gov/28943083/
[2] https://www.science.org/content/article/if-alive-sleeps-brai...
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.
I’ve used both Belsomra (suvorexant) and Quviviq (daridorexant) and compared to the litany of other sleeping aids, Quviviq in particular is great for me in terms of not being groggy, not knocking me out standing up in case I somehow don’t sleep or need to do something. No rebound on days I run out or if I stop. Feels quite natural—I imagine it feels like what most normal sleepers feel like every evening. It’s nearly impossible for many to get them, tho…
Edit: To add some academic merit — there’s been research for its use for cognitive decline [0]
[0] https://www.nature.com/articles/s44323-025-00025-5
That's just a sleep med, right? I mean something to let you get the repair and cleaning faster, not just induce sleep.
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
Excellent, but now I have a new problem: An addiction to meth.
Is that worse than an addiction to sleep?
Do not, my friends, become addicted to sleep. It will take hold of you, and you will resent its absence!
Beware! If you start on a sleep addiction, one day you'll take a nap and never wake up!
Honestly that doesn't sound so bad.
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.
Sounds like the plot to a horror movie.
Why just fiction? Nazi soldiers popped amphetamine pills to perform better.
As do the Zionist soldiers today
This will likely turn them into a different flavour of maniac.
Just go to bed.
What if we just normalized taking naps more often?
I feel like people insist that if you get 8 hours of good sleep you shouldn't need a nap
Not everyone can nap. Besides, the need to nap is an indicator of poor sleep. Why not just normalize sleeping properly (nb: rhetorical question)?
> the need to nap is an indicator of poor sleep.
Is it? Where do you get that from?
I remember the NASA doing extensive sleep studies, determining that the optimal pattern would consist of basically "naps only"?
I've been sleeping my adult life in usually 2x3-4h "shifts", which I also remember reading is a historically often used pattern. I do not see any negative effects.
Wild to read this about your sleep pattern. Please explain more. I find myself needing to sleep like 12+ hours every day.
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.
The latter is how caffeine works. Blocks adenosine receptors so you don't feel tired even though you are.
If you don't feel tired, are you really? I'm curious what are the objective metrics to determine someone is tired
Tiredness is a signal that the body/brain needs rest so the glymphatic system can go to work. You can lose the signal but still need rest. If your brain doesn't flush metabolic waste periodically you develop brain fog, bad memory, and increased risk of Alzheimer's, and you'll eventually die, as sleep deprivation studies have found.
Caffeine doesn't actually do any of the things sleep does to your brain. If you drink coffee during a late night, you won't feel as tired, but your brain performs worse, your reflexes are slower, you're less likely to remember things, etc. It's like painting over a rusted car instead of properly maintaining it, basically.
I think GP was just making a point about the fact that “tired” is a subjective experience, like pain. Arguably, if you’re on pain medication, you’re not in pain, even if your body is sending pain signals that your brain just isn’t receiving or paying attention to.
Indeed. Pain is also interesting because chronic pain, AFAIK is sometimes a misfiring of pain signals even when nothing is physically wrong.
Turning off that misfiring with drugs would be dangerous (pain is an alert) but also improve the quality of life of so many people!
Isn't the answer yes if people still die from overwork despite being caffeined up?
If I’m on morphine is my leg even still broken?
You have the ability to mentally push through a lot of stuff, but there are a host of signals your body will use to warn you such as: cognitive performance (although this is hard for yourself to actually admit its happening), behavioral indicators like yawning, head bobbing, frequent posture changes, and slowed speech are just a few indicators. Irritability is another big red flag.
I've only had two instances where I ignored all the signs and continue to push on until my body literally shut down on me. Finals week in college as an architecture student trying to finish a final studio project, and study for four finals. 5 days, 3 hours of sleep. That was one of them.
Michael Jackson is the ultimate case study for this.
so the former then
sorry I'm dumb and read it wrong
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
https://archive.is/WoHuY
general question: is there an alternative to archive.is ? it seems to be blocked in my country.
http://archiveiya74codqgiixo33q62qlrqtkgmcitqx5u2oeqnmn5bpcb... via tor browser
there are variations but some are shady... archive.ph, archive.today, etc. there's probably a central list somewhere.
I thought they were alternative domains for the same service...
Regardless, I'm stuck in captcha hell whenever I try to reach them (I've tried switching browsers and DNS servers, no luck).
oh perhaps you're right. i thought they were clones, not alternative domains. i had that captcha issue as well, it disappeared through no action of my own. hope the same for you.
archive.today and archive.fo is literally the same service.
check URL list on its wikipedia page.
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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.
Reminds me of a discussion about how cyber implants would bring upon cyberpunk - a person who needs an implant asks themselves: What if I use my implant this way…
Modafinil is available for ages, acts close to this (it's mentioned in the article), and I don't hear of people abusing it.
It gets abused by people who just want to stay awake, but not in the sense of being a party drug. For example, by students, drivers, security officers, and politicians.
It promotes wakefulness and (allegedly) concentration. It's not a magic or amphetamines, not sure how is that an "abuse"?
Do people drinking coffee in the morning *abuse* it?
Coffee isn't a Schedule IV controlled substance in the US. I'm using a pretty strict definition of abuse, which is just using medication outside of its indications, or when it isn't prescribed to you.
Modafinil is abused as a smart drug by students, entrepreneurs, stock market traders etc
Same people who use adderall for work.
Are you saying people are using Adderall AND Modafinil at the same time?
That'd be either exceedingly rare or borderline unwise.
I'd love to see some actual forums or papers about that because this seems very unusual given the partly overlapping effect but significantly different paths.
It's an OR not an AND
Whatever is available currently.
"People who use adderall for work" is a generalization, for example stock traders at Wall Street are famous for doing cocaine, taking amphetamines for work and possibly every smart drug, including modafinil.
But they won't take them all at the same time because then they get too high to work.
Eh, you don't get "high" on modafinil. Adderall or other amphetamines used in therapeutic doses (or even above that) don't make user "get high".
Modafinil is extremely easy and cheap to get for anyone with one eye and one working finger, Adderall a tiny bit harder but easy for a "trader".
"Possibly every smart drug, including modafinil" is just many guesses mixed up, nothing to actually discuss with. I'll stop wasting electrons here, you do you.
Stop wasting electrons with replying then? If my answer is pointless your is even more.
I don't know of anyone using it in the first place...
Apparently it's used by about 10% of UK university students, according to a survey:
https://link.springer.com/article/10.1007/s40979-024-00174-3
I remember there being kind of a burst of articles about it on HN about ten or fifteen years ago, with a lot of commenters talking about their use of it.
> The Prolific advert stated that participants were being sought for an anonymous survey on their views on the use of modafinil as a cognitive enhancer by UK university students.
Textbook case of "how do we select the most number of people who would say yes" ism. People who are taking modafinil and have a strong opinion about it.
If I'm a student I would never click on that ad in the first place if I have never heard of modafinil (like most people haven't), because the survey is about something I don't know. And if I vaguely heard of it and click, there's a friendly awareness page and quiz right at the start about the thing and its side effects that says I won't get paid if I don't answer correctly, what are the chances I'll continue wasting my time?
That's okay, they're elsewhere.
I'm sure all 12 of them are.
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 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
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.
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
> 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).
Exactly. And that last one is the most important for long term results.
Plus it's not like you couldn't combine a GLP-1 drug with great diet and exercise
> that last one is the most important for long term results
Empirically untrue. GLP-1s outperform diet and exercise alone.
> it's not like you couldn't combine a GLP-1 drug with great diet and exercise
This is how it's recommended to be taken. I personally know folks who were able to start regularly exercising and eating healthily because of the head start GLP-1s gave them. (They're mostly off them now, and they're all materially lighter and healthier than they were before.)
Diet and exercise guidance is the standard of care for prescribing GLP1s.
But prescribing diet and exercise alone has long had mixed results, because it does nothing to address appetite, and it is even quite common for exercise to increase it.
> 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 bodies did figure it out(our common ancestor with the wet nosed primates could synthesize vitamin C).
But our bodies also figured out that for an extended period of time this ability was useless since vitamin C was so readily available in all our food sources in most circumstances.
> our bodies also figured out that for an extended period of time this ability was useless since vitamin C was so readily available in all our food sources in most circumstances
But none of the other animals in our biomes similarly optimized? Including none of the other apes?
The less Panglossian interpretation is a gene got fucked up, it didn't wipe us out, and the fuck-up got conserved because it doesn't kill us before reproduction, it just makes us sicker from time to time.
All apes cannot produce vitamin C. In fact no dry nosed primates can. Also fruit bats generally can't, as well as some passerines, and some bony fish.
> All apes cannot produce vitamin C. In fact no dry nosed primates can
You're right! Sorry. And super cool!
I'll weaken my hypothesis. There may be a survival advantage in not having to metabolise a vitamin readily available through diet. Altogether, a neutral adaptation/mutation [1]. It's still a good case of nature optimising for leanness like a private-equity boss. And a good example of why something like GLP-1 may have similarly been optimized down for a world no longer relevant.
[1] https://pmc.ncbi.nlm.nih.gov/articles/PMC3145266/
Fascinatingly, we could biohack our way into having the human liver produce vitamin c, like we have the science to do that. It's just an insane amount of risk compared to just eating an orange once in a while.
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.
Meat? Errrr, did you mean to write refined white carbs? Those obsidian spear points were not for shucking corn…
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.
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.
Is "Lindy" a typo or have I missed another linguistic innovation?
Another linguistic innovation[0] -- the idea that things that have been around for a long time are more likely to persist for another long time.
[0]: https://en.wikipedia.org/wiki/Lindy_effect
This feels like a stupid heuristic to use if applied to biological forces.
In the definition of it, living things are specifically excluded.
it seems however some things that are not excluded are just one step removed from biological entities, hence
>comedians do not have a fixed amount of comedic material to spread over TV appearances, but rather, the more appearances they make, the more future appearances they are predicted to make
sure, but earlier it says that it does not apply to humans because the Lindy effect would imply that a 100 year old would have more life left than an 11 year old, which is counterintuitive, but the example given above would imply George Burns had more television appearances left to do at the age of 99 than Macaulay Culkin at the age of 9, which is just a layer of abstraction laid over the biological age property.
It’s some shit a guy called Taleb came up with. It’s a useful indicator because someone quoting Taleb unironically is someone who can’t tell that Taleb is a midwit.
I was kind of shocked how bad some of his writing and "logic" were after hearing people rave about his books for years.
I get the vibe, but I wouldn't say shocked, merely disappointed. The Black Swan's point would fit on the book's cover even if printed in the font used for the author's name, the work felt to me like 99% was just garrulous "look at me aren't I smart" padding.
So he used an LLM? /s
Checking out his Twitter feed first might have dampened some of that shock.
Seems like it predates him significantly:
https://en.wikipedia.org/wiki/Lindy_effect#History
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.
Well... Sleep and death are natural. I'm not convinced you see people "defend" death so much as (rightly) acknowledging the inevitability of it.
The latter half of your comment is rather smug, but I wouldn't look down on people who have peacefully accepted reality. Time is fleeting and we are but flowers in a field—briefly brightly bloomed and then withered.
> I wouldn't look down on people who have peacefully accepted reality
Throughout human history, all progress was achieved by people who refused to "peacefully accept reality". But I hope you also get to reap the benefits and correct your depressing mindset some day.
I'm filled with joy and it has nothing to do with my "mindset", I appreciate your concern though!
While it is tempting view all of human progress as some heroic feat of raging against the machine, it seems much more likely to me that progress came from accepting reality, and then working within the bounds of physics.
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Society would adapt without sleep, but ending death would mark the beginning of a nightmare humanity never wakes up from.
Like clockwork :)
Sleep is less surprising for me to see people defend than death, to the extent that I'm not sure if I myself have or not done so.
I mean, I can directly feel the benefit of a good sleep that refreshes me in the morning, whereas there's those who have passed on whom I miss.
If I didn't need sleep, really didn't, I wouldn't seek to re-invent it; but of the two it is old age that I'd actively pay money to hold back, if treatments for both existed at the same cost per extra hour of consciousness in my lifetime.
Obviously, every single one of us needs sleep to survive. But it's a biological chore, not some sacred ritual to be celebrated. Reducing the amount of sleep that we need is worth researching. What is surprising to me is the knee-jerk reaction I see whenever the idea of looking into this is brought up.
> What is surprising to me is the knee-jerk reaction I see whenever the idea of looking into this is brought up.
It's because if it were achieved, likely result would be employers forcing people to take the drug and increasing daily work hours back to 16+.
> likely result would be employers forcing people to take the drug
How so? You can just... refuse? And do you prefer sleeping to working? Doing a job that you hate for 8h and sleeping for 8h is much worse than doing a job that you love for 16h. Something to think about.
In addition to what Qem said, some people don't have much control over their job opportunities, take whatever they can get, and in those roles do whatever they're ordered to do.
Amazon piss bottles come to mind.
Even without malice or orders, sometimes every actor in the economy can be locally motivated in a way that ends up the same. Boss gives you 40 hours, but rent is too high for a 40-hour week? Guess you're taking two jobs now.
> How so? You can just... refuse?
It would be like doping in some elite sports, say road race cycling in Lance Armstrong era. Nobody would be coerced by force, but some people would start taking it, making less sleep time the new normal. With time business would adjust to expect and require it, and other people would be forced to take the drug just to not become unemployable in a market with a upshifted baseline. I think this is already happening in education, with ADHD medications. Children are likely being overdiagnosed, because in a environment with many medicated children, just displaying normal child behaviour starts looking odd, pathology-like.
> Doing a job that you hate for 8h and sleeping for 8h is much worse than doing a job that you love for 16h.
Some jobs just suck but somebody still has to do them.
Even if I never needed to sleep again I would kind of miss dreaming. Maybe we could take another drug to make us dream.
For a minute I thought they'd found a cure for fatheads.
The brain may be about to have its Algernon moment
FTFY
Don't forget the flowers.
Previous post: https://news.ycombinator.com/item?id=49206165
Title implies people will flock to a pill that makes them shed gray matter
https://old.reddit.com/r/ExtraFabulousComics/comments/1iqsqd...
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.
> For starters, I what the hell does this mean?
Well, there's a whole bunch of words after the title that help explain that.
It's probably the default clickbait title for any article about a new drug.
I like my brain fatty /s
You reminded me I need to buy more Omega 3
Dont forget Omega 7 and 9 !
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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?
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.
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Every conceivable thing 'may be about to' happen.
Literally everything except the media writing non-sensationalist headlines about science.
What has anything in this article to do with Ozempic? Is mentioned in the title once and never again. Engagement bait?
"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 is the poster boy for peptides.
Ozempic == GLP-1 which the first visible paragraph is discussing.
Your brain is gonna lose so much weight!
Neural minimalism, the newest health trend coming to a social network near you.