26 ms·

Scientists uncover how the brain washes itself during sleep

341 points by pseudolus 2y ago

snsr 2y ago
Notably, the drug Ambien disrupts the norepinephrine oscillation that is part of this process.
- hypeatei 2y ago
  Ambien, to me, is an extremely scary drug. People in my life have become extremely reliant on it to sleep and it has strange side effects. Sleepwalking with no recollection is one of them, not going to the kitchen, but getting in the car types of sleepwalking.
  - WarOnPrivacy 2y ago
    > Ambien, to me, is an extremely scary drug. Meanwhile, older drugs that are less distressing aren't used any more because "We don't use it any more". -Dr: If I ask about Librium.
    - diggan 2y ago
      You're talking about "older drugs" like Chlordiazepoxide like they don't have any drawbacks or the drawbacks are less heavy compared to other more modern drugs. I'll give you that everyone is different, and doctors should evaluate what works for each patient, but I don't think it's ever as simple as "older drugs == better, newer drugs == worse".
      - WarOnPrivacy 2y ago
        > but I don't think it's ever as simple as "older drugs == better, newer drugs == worse". I don't think anyone here was making that assertion. As far as there is a broad, common experience, it is Dr's who won't consider older meds, even if they come with less baggage than their newer counterparts.
  - tartoran 2y ago
    I agree, Ambien is a scary drug to rely on as it can create dependency and also masks underlying issues that are causing not inability to sleep. In emergencies when one needs to get some form of sleep it could be useful to break the cycle of not being able to sleep and restore sleep hygiene. I had some sleep issues back in my 20s (luckily they haven't come back) and found that sometimes being too tired made falling and staying asleep quite hard. One thing that helped me is to forcefully yawn before going to sleep, doing it for a couple of minutes.
    - diggan 2y ago
      > Ambien is a scary drug to rely on as it can create dependency and also masks underlying issues that are causing not inability to sleep. That just sounds like you think every sleeping-pill is scary, as that's true for literally all of them. Sleeping pills are mostly effective together with other types of therapy to address the underlying causes, just like most "temporary solutions". They're supposed to be used as "We'll try to figure out what's wrong, but in the meantime, so you can feel relatively human, here is a temporary crutch", not as a long-term solution.
      - tootie 2y ago
        Intractable sleep conditions exist. I have narcolepsy which is incurable. I'm on sodium oxybate which is basically just GHB. It's a "scary" drug to be taking every night, but it's very effective and usually very safe in controlled dosage.
        lilyball 2y ago
        That drug is not a drug designed to put you to sleep though (I mean it kinda does, but that's not its purpose). The purpose of that drug is to change your sleep architecture during the night. I'm on the newer form of that drug (because of idiopathic hypersomnia) and most nights I still take 1–2 hours to fall asleep.
        tootie 2y ago
  - toastau 2y ago
    I use 5mg a few nights a week to get a full night’s rest. I’ve worked hard over the years on good sleep hygiene—no screens, wearing a sleep mask, and avoiding food (especially carbs or alcohol) before bed. No direct link has been found to this, but eating carbs has always given me deeply vivid (and often exciting) dreams since I was little. Unfortunately, from these I wake up exhausted, which isn’t great for the day. I’ll continue being careful, and especially stay mindful when life stress—like love or money—picks up. It’s good to be aware if anything is being masked or overlooked in the process.
    - AnthonBerg 2y ago
      Carbohydrates have been a big part of what I’ve needed to figure out in order to reach sleep again after an unusually tough period. Carbohydrate metabolism has histamine intimately involved in it; Histamine – as per its inflammatory role – is basically used by the body to open tissue to receive blood glucose. As it happens, histamine is also a neurotransmitter! An excitatory alertness neurotransmitter! Both these aspects have been extant as scientific knowledge on record for some significant time, but are only really becoming known-known as of recent. I have ADHD. I take lisdexamfetamine. Upon starting medication at 39.5 years of age, I quickly noticed that I had to be really careful with coffee, and especially to not at all touch any sweet foods or desserts around evening or so. Or I would wake up at 5:30 AM. (Exactly and precisely 5:30. Reliably. It’s sort of fascinating.) As it turns out, amphetamine releases histamine! And! Caffeine inhibits the enzymatic breakdown of histamine! And sugar causes histamine to be released.
      - LargoLasskhyfv 2y ago
        5:30 AM in the same place, or different places? If same place, I'd assume some environmental/technical reason. Some machine somewhere near starting up, producing infra- or ultrasonics, a manifest freight train rumbling by far away, doing the same, some other thing (electro-/static/magnetic fields changing), and so on. 'Technical' because nature would vary that with the seasons because of https://en.wikipedia.org/wiki/Solar_time https://en.wikipedia.org/wiki/Solar_time
  - jamal-kumar 2y ago
    It's bad enough that there's a whole subreddit dedicated to the shit people get up to on it [1]. Telling thing: the description for it starts off with CHOP OFF ALL YOUR HAIR, probably a reference to a toothpaste for dinner comic about "the ambien walrus" which is a popular meme in the uhhh ambien community [1] https://www.reddit.com/r/ambien/top/?t=all https://www.reddit.com/r/ambien/top/?t=all
  - 93po 2y ago
    i used it daily for a couple years and had no idea the impact it was having on me. i was an angry, irritable, grumpy person, and i completely changed when i finally stopped taking it. i had an addiction but didnt abuse it. it got to the point that i craved ambien during the day for reasons i can't even explain. i just inexplicably wanted to take it. i wasnt even taking full pills of the usual dose, i usually cut them in half. it took me a long time to learn to put my phone away before taking it. i would text people i was causally dating overly romantic and loving things and have zero memory of it. thankfully whenever it happened the people involved always just thought it was funny, and i did have the awareness to preface those texts with "maybe its just bc i took some ambien". After a few dates with someone i warned them i take ambien and might text them something stupid but loving, so they were well prepared
  - outworlder 2y ago
    I personally know of one ambien addict and it's scary. He just went through a divorce and lost his job. His barely coherent (and angry) voice messages while off the drug don't seem too different from addicts of illegal substances.
  - appstorelottery 2y ago
    I completely agree. I once took Ambien on a flight from San Fran -> London, but I didn't sleep. I suffered from crazy short term amnesia by the time I got to the other end, walking towards the Hilton just outside the airport in that long tunnel... I kept forgetting where I was and why I was there and then I'd snap back to reality. To the alarm of a friend that was supposed to be picking me up, I simply checked into the Hilton. What happened on the flight was another story altogether. I think I was repeatedly telling the attendants that I'd taken Ambien, they ended up shifting me to first class. Looking back, it was fun for reasons I won't talk about here - but belongs strongly in the recreational category. Sitter required.
  - desmosxxx 2y ago
    I took Ambien for one of my sleep studies and I had sleep paralysis and nightmares (bordering on hallucinations because I swear I was awake or at least in a lucid state). That was my first and last time doing Ambien.
  - FuriouslyAdrift 2y ago
    They gave us Ambien (no go pills) and Provigil (go pills) in the miltary during long ready states. After a while, I became dependent on Ambien and would sleep walk (among other things). My roomates would zip me up in my sleeping bag to deal with it. Took me about 2 years after the military to get back to "normal" I do miss the Provigil, though... that stuff made able to focus so well.
- AnthonBerg 2y ago
  Once upon a time I had severe difficulty sleeping due to high and sustained levels of stress. I had gotten prescribed some Zopiclone which is similar to Zolpidem as found in Ambien. Zopiclone makes me feel like I have a brain injury the day after. Sometimes after the first night, always after the second night if I find I need to take it two nights in a row. It’s frightening. I came across a paper: ”Pharmacokinetic and Pharmacodynamic Interactions Between Zolpidem and Caffeine” https://www.researchgate.net/profile/Roberta-Cysneiros/publication/6385851_Pharmacokinetic_and_Pharmacodynamic_Interactions_Between_Zolpidem_and_Caffeine/links/58a57d9da6fdcc0e07660197/Pharmacokinetic-and-Pharmacodynamic-Interactions-Between-Zolpidem-and-Caffeine.pdf https://www.researchgate.net/profile/Roberta-Cysneiros/publi... Based on my understanding of the results that a significant dose of caffeine counteracts “some but not all” of Zolpidem’s effects on cognition—and the two Z-drugs being similar—I tried drinking a tiny little bit of coffee with the tiny little bit of Zopiclone. (I take 2-3mg; a whole tablet is 7.5mg.) The result is that I am able to sleep and do not feel brain-damaged the day after, and the effect also seems to be that the failure rhythm of stress-related waking up at precisely 5:30 is broken. In other words, the combination seems to fix the problem. I suspect that part of the reason might be that the caffeine counteracts the disruption of the norepinephrine oscillation you mention. (Thanks!!)
  - akvadrako 2y ago
    That's quite interesting. I take half a Zolpidem once a week or so and I'll try taking it with caffeine. I've tried Zolpiclone but found it affects my sleep much more. Zolpidem is faster acting and gets out of your system quicker, while Zolpiclone continues working during the night. So if your issue is getting to sleep and not staying asleep I would recommend you try the original.
    - AnthonBerg 2y ago
      I know and trust that the implicit disclaimers are clear, that this comes with absolutely no guarantees of not being terrible for anyone else :) —I would indeed prefer the shorter duration of Zolpidem! Zopiclone was the only Z-drug option the doctor was willing to use. Fortunately, the caffeine seems to kind of mitigate the longish duration of Zopiclone. And Zolpidem has somewhat dangerously recreational effects on me :sweat_smile: … and is slightly addictive to me as well. I’d very much like to be able to try Zaleplon instead. It’s more recent than the two other Z-drugs and the shortest-acting; Not available in my country. https://en.wikipedia.org/wiki/Zaleplon https://en.wikipedia.org/wiki/Zaleplon
- breadwinner 2y ago
  If you have sleep issues try magnesium. https://hn.algolia.com/?query=magnesium%20sleep&type=comment https://hn.algolia.com/?query=magnesium%20sleep&type=comment
  - outworlder 2y ago
    What if blood magnesium levels tested normal?
    - breadwinner 2y ago
      My understanding is that magnesium blood tests are not reliable. Since magnesium is a natural element found in foods such as spinach, nuts, seeds, and whole grains, you know it is safe. Try a supplement and if it helps with muscle stiffness or sleep then you have a magnesium deficiency.
lapcat 2y ago
In mouse brains
- InDubioProRubio 2y ago
  So? What part of the washing chemistry is different?
  - kzrdude 2y ago
    The interesting thing is that everything with a brain sleeps. We really need to get to the bottom of understanding it.
  - bityard 2y ago
    That's exactly what we don't know yet.
  - deleted 2y ago
    [deleted]
- Ensorceled 2y ago
  This is a fundamental physiological process ... not a drug interaction.
- bux93 2y ago
  or, as the late great @justsaysinmice used to point out "IN MICE"
highfrequency 2y ago
> Some researchers have challenged parts of this picture, however; a 2024 study, for example, suggested waste clearance is actually faster during waking than during sleep. That’s a pretty big ambiguity in the story!
- beezlebroxxxxxx 2y ago
  When you talk to neuroscientists and researchers in private you often find that they are far less confident than public personas, PR, articles, or science reporting, make them sound. A lot of their findings are really more like "huh, that's weird. We should look at this more." What seems like a ton of consensus at cruising altitude is actually much more divisive as you approach ground level. The more recent emergence of the idea that neuroscientists are a kind of "super scientist" of human behavior (all self-help books are now "neuroscience"-based now, for example) has also made them seem much more certain about certain things than they actually are.
  - smokedetector1 2y ago
    [flagged]
    - krapp 2y ago
      >It's not just optimistic - its qualitatively unjustified to think that neuroscience (in its current form, at least) is inevitably capable of cracking consciousness. The fact that you had to add the parenthetical here to hedge your bet demonstrates that you don't even entirely believe your own claims.
      - smokedetector1 2y ago
        [flagged]
        smallmancontrov 2y ago
        God of the Gaps is not intellectual honesty. Neither is running from an argument.
debacle 2y ago
A little over a year ago I was having awful sleep hygiene. From time to time, I still wake up at ~2am and just can't find restfulness again. I picked up a simple smart watch that tracks sleep (one of the Garmins, as they are one of the few that protect privacy and don't need to connect to the Internet). I slowly and methodically improved my sleep, and I feel like a different person. I have noticed that if I turn my blue light filter on my screens off, that has a huge impact. Working long days has a huge impact. I take a hell of a lot of magnesium. I need ~20 minutes of outdoor walking a day and I need to eat dinner before 4pm. Lots of other small things that have an impact that I'm probably forgetting. How many of us are just chronically tired?
- kzrdude 2y ago
  I've had some periods of "intense work on sleep schedule". A big one was discovering that I was on the higher end of caffeine sensitivity (but I can still sleep if I only drink coffee in the morning). I have thought that the blue light filter doesn't do so much, with a caveat. The laptop screen is much less bright, so it doesn't bother me. It seems like the blue light of a desk screen has a bigger effect. But I also think it is the brain activity of stimulus seeking on the screen itself that has a big effect on sleep. It's better to turn of screens entirely to wind down, or do something that actually helps you wind down for sleep.
  - TeMPOraL 2y ago
    For me, the light doesn't seem to have much effect - but what I do on the computer matters. For example, as much as I liked to watch something in the evening, I now find that if I watch an interesting movie or TV show too late, my mind is still wound up in it when I lie down, and I find it much harder to fall asleep.
    - kzrdude 2y ago
      Yes. I think that should be the commonly spread advice instead of the blue/red light thing
    - mattgreenrocks 2y ago
jerbearito 2y ago
Just to clarify -- we already knew about the washing, right? But this refers to the specific mechanism where the blood vessels contract to cause the washing?
- iandanforth 2y ago
  And more specifically that norepinephrine waves are highly correlated with and perhaps causative of that pumping.
- bityard 2y ago
  Yes. And to further qualify the conclusion, the research was done in mice so it's premature to say whether or not human brains operate identically. (Mammalian anatomy between species is often similar, but just as often is found to be different in unexpected ways.)
  - adsteel_ 2y ago
    I'd like to learn more about the washing. Do you have a link or word/phrase to Google?
    - FuriouslyAdrift 2y ago
      The glymphatic system https://en.wikipedia.org/wiki/Glymphatic_system https://en.wikipedia.org/wiki/Glymphatic_system
abeppu 2y ago
... so, perhaps a fool-hardy idea, but could we use an external device to create or amplify the same effect? - if you rhythmically give mice norepinephrine while they're awake, can you create the same movement in cerebrospinal fluid? Would mice go to sleep later following such an intervention? - could you directly just pump cerebrospinal fluid faster? If you were willing to have a mechanical device surgically installed, could you have a rapid, extra-refreshing sleep at the press of a button? - if the efficacy of washing is partly due to the contents of cerebrospinal fluid, could you look at what's being "washed out" and add stuff to the cerebrospinal fluid that makes those things more soluble?
- bityard 2y ago
  As much as I applaud the biohacking curiosity, we've known for a while that sleep does lots of things to rest and repair the whole body. "Cleaning" the brain is only one of them. Finding an easy button to hack around the need for sleep is probably as unlikely as finding an immortality pill.
  - abeppu 2y ago
    I guess on the animal model research side, the gap in various metrics between artificially "cleaning" the brains of sleep-deprived mice vs mice that get to sleep would be one way of measuring some of the non-cleaning functions of sleep (e.g. memory consolidation). In some far hypothetical future human device, I think even if amplifying a "washing" function doesn't replace sleep it could still be helpful ... but outweighing the risks involved in the intervention (attaching a person to a pump?) would be a high bar. But if decades from now you were already going to put in a neuralink v20, perhaps it would seem reasonable.
lawlessone 2y ago
I wonder how nicotine affects this? since it can affect norepinephrine
- napoleongl 2y ago
  Falling asleep with nicotine patches on results in wild dreams so it clearly screws up something in the brain!
vladslav 2y ago
Perhaps it seems odd, but could experiencing nightmares actually aid in the cleansing process?
segfaultbuserr 2y ago
The brain truly is a system with terrible service availability. On average, after running for just 16 hours, it must be offlined for 8 hours to run maintenance tasks such as "scrub", "garbage collect", "trim", and "fsck".
- baxtr 2y ago
  SLAs are terrible. I agree. But at least there’s (usually) some exciting shows on while you are waiting!
- tivert 2y ago
  > The brain truly is a system with terrible service availability. On average, after running for just 16 hours, it must be offlined for 8 hours to run maintenance tasks such as "scrub", "garbage collect", "trim", and "fsck". There's hope. If the carbon chauvinists can be prevented from messing things up, AI is on track to provide something with a better SLA, which will finally allow us to decommission and junk those troublesome legacy systems without disrupting the business.
- PaulDavisThe1st 2y ago
  You've got it all wrong, and LLMs have it all correct. True brains, after 16hrs of actual work, need to hallucinate strongly for 8 hours or so, in order to continue their high level contributions to society.
  - ifyoubuildit 2y ago
    Interesting. What if that is actually a beneficial part of our own development: comparing the nonsense in our dreams to waking life and building the ability to tell the difference?
    - euroderf 2y ago
      Get an LLM to dream, and to use the time effectively to purge those hallucinations, and reinforce the "valid and true" memories, and you might have something there ?
jokoon 2y ago
There was a MRI looking video showing this
deleted 2y ago
[deleted]
treprinum 2y ago
Didn't Chinese scientists recently show a crazy success rate (~90%) of treating advanced Alzheimer/dementia by performing a microsurgery of the neck, allowing brain to dispose accumulated waste?
- burkaman 2y ago
  They tried it on 6 people and found "slight improvements" after 5 weeks, with no control group to compare to and no longer term effects known yet. - https://gpsych.bmj.com/content/37/3/e101641 https://gpsych.bmj.com/content/37/3/e101641 Certainly seems worth investigating but I wouldn't call it a crazy success yet.
ongytenes 2y ago
One thing to look at is Alzheimer's. The current leading theory is that a build up of amyloid protein is the root cause of this disease. It would be wonderful if someone connected the dots to find the reason for the build up and they're able to develop a treatment to prevent the onset of the disease.
- mschuster91 2y ago
  > The current leading theory is that a build up of amyloid protein is the root cause of this disease That's ... controversial, a few years ago fraud allegations surfaced [1]. [1] https://www.alzheimers.org.uk/for-researchers/explaining-amyloid-research-study-controversy https://www.alzheimers.org.uk/for-researchers/explaining-amy...
  - criddell 2y ago
    Reading that link, it sounds like the build up of amyloid protein is still the current leading theory.
idlewords 2y ago
"In mice"
kcartlidge 2y ago
> To avoid this problem, the scientists surgically implanted mice with electrodes and fiber optic filaments. Although the rodents are tethered to a set of cables, they can fall asleep normally while researchers track blood volume, electrical activity, and chemical levels and use light transmitted through the fiber optic lines to activate certain groups of neurons. I detest this kind of medical research. It's horrific barbarity. If the output is important enough for this kind of activity to take place, then it's important enough for humans to volunteer to be the subjects. If nobody volunteers then it isn't that important after all. Leave other species out of it.
- bowsamic 2y ago
  What is the logic behind this? I genuinely don’t understand your moral argument
mrayycombi 2y ago
Am I reading this right as implying Ambien...promotes Alheimers....?
jakeogh 2y ago
Very interesting CSF talk: https://www.youtube.com/watch?v=WicKmA9lQTI https://www.youtube.com/watch?v=WicKmA9lQTI
croemer 2y ago
Ugh, this is multiple correlation/causation fallacies in one: > Studies from Nedergaard’s group and others suggest vigorous glymphatic clearance is beneficial: Circulation falters in Alzheimer’s disease and other neurodegenerative illnesses. That circulation falters in Alzheimer's does not suggest anything re the benefit of circulation. Science's science journalism is usually SOTA, this is not.
fuzzfactor 2y ago
I guess I've been brainwashed without knowing it, which seems about par for the course :\
MollyRealized 2y ago
it licks its paw and then runs it over its fur
interludead 2y ago
As someone who sometimes has trouble sleeping, I'm struck by how much sleep affects the brain
pedalpete 2y ago
The glymphatic system activity is greatest during slow-waves in N3 (deep) sleep. A slow-wave is the synchronous firing of neurons which is seen as the glymphatic system pumps CBF through the brain. For the past 5 years we've been developing phase-targeted auditory stimulation to increase slow-wave activity, which has been shown to have a positive response in amyloid response, as well as memory, and a bunch of other biomarkers. https://pubmed.ncbi.nlm.nih.gov/38163288/ https://pubmed.ncbi.nlm.nih.gov/38163288/ I link to more research on our website for anyone interested in the space - https://affectablesleep.com/research https://affectablesleep.com/research
robg 2y ago
Nedergaard (lab head here and main findings of this effect since 2012) is going to win the Nobel for this line of research. When I got my Ph.D. 20 years ago in cognitive neuroscience we knew three main deficits to a lack of sleep but couldn’t connect them mechanistically: 1) loss of daily performance metrics 2) increased risks of mental health concerns 3) increased risks of cognitive declines The glymphatic nervous system, like any great scientific theory, unites disparate findings under a common mechanism. Not getting enough sleep is akin to not running your dishwasher or washing machine long enough, the gunk accumulates. And for all the parents out there, pediatric recommendation is 10-12 hours a night for kids 6-12 years old and 8-10 hours a night for kids 13-18 years old.
- dogcomplex 2y ago
  Recommended hours not nearly hit enough when they have to finish the night's homework then catch the 7am school bus...
- adsteel_ 2y ago
  It makes me think of long COVID and CFS, where patients complain of a lack of "unrefreshing sleep" and "brain fog". A lack of perfusion resulting in waste not being sufficiently flushed out could possibly result in those symptoms.
waitasec 2y ago
i dunno, sounds like brainwashing

341 points by pseudolus 2y ago

snsr 2y ago

Notably, the drug Ambien disrupts the norepinephrine oscillation that is part of this process.

hypeatei 2y ago
Ambien, to me, is an extremely scary drug. People in my life have become extremely reliant on it to sleep and it has strange side effects. Sleepwalking with no recollection is one of them, not going to the kitchen, but getting in the car types of sleepwalking.
- WarOnPrivacy 2y ago
  > Ambien, to me, is an extremely scary drug. Meanwhile, older drugs that are less distressing aren't used any more because "We don't use it any more". -Dr: If I ask about Librium.
  - diggan 2y ago
    You're talking about "older drugs" like Chlordiazepoxide like they don't have any drawbacks or the drawbacks are less heavy compared to other more modern drugs. I'll give you that everyone is different, and doctors should evaluate what works for each patient, but I don't think it's ever as simple as "older drugs == better, newer drugs == worse".
    - WarOnPrivacy 2y ago
      > but I don't think it's ever as simple as "older drugs == better, newer drugs == worse". I don't think anyone here was making that assertion. As far as there is a broad, common experience, it is Dr's who won't consider older meds, even if they come with less baggage than their newer counterparts.
- tartoran 2y ago
  I agree, Ambien is a scary drug to rely on as it can create dependency and also masks underlying issues that are causing not inability to sleep. In emergencies when one needs to get some form of sleep it could be useful to break the cycle of not being able to sleep and restore sleep hygiene. I had some sleep issues back in my 20s (luckily they haven't come back) and found that sometimes being too tired made falling and staying asleep quite hard. One thing that helped me is to forcefully yawn before going to sleep, doing it for a couple of minutes.
  - diggan 2y ago
    > Ambien is a scary drug to rely on as it can create dependency and also masks underlying issues that are causing not inability to sleep. That just sounds like you think every sleeping-pill is scary, as that's true for literally all of them. Sleeping pills are mostly effective together with other types of therapy to address the underlying causes, just like most "temporary solutions". They're supposed to be used as "We'll try to figure out what's wrong, but in the meantime, so you can feel relatively human, here is a temporary crutch", not as a long-term solution.
    - tootie 2y ago
      Intractable sleep conditions exist. I have narcolepsy which is incurable. I'm on sodium oxybate which is basically just GHB. It's a "scary" drug to be taking every night, but it's very effective and usually very safe in controlled dosage.
      - lilyball 2y ago
        That drug is not a drug designed to put you to sleep though (I mean it kinda does, but that's not its purpose). The purpose of that drug is to change your sleep architecture during the night. I'm on the newer form of that drug (because of idiopathic hypersomnia) and most nights I still take 1–2 hours to fall asleep.
        tootie 2y ago
- toastau 2y ago
  I use 5mg a few nights a week to get a full night’s rest. I’ve worked hard over the years on good sleep hygiene—no screens, wearing a sleep mask, and avoiding food (especially carbs or alcohol) before bed. No direct link has been found to this, but eating carbs has always given me deeply vivid (and often exciting) dreams since I was little. Unfortunately, from these I wake up exhausted, which isn’t great for the day. I’ll continue being careful, and especially stay mindful when life stress—like love or money—picks up. It’s good to be aware if anything is being masked or overlooked in the process.
  - AnthonBerg 2y ago
    Carbohydrates have been a big part of what I’ve needed to figure out in order to reach sleep again after an unusually tough period. Carbohydrate metabolism has histamine intimately involved in it; Histamine – as per its inflammatory role – is basically used by the body to open tissue to receive blood glucose. As it happens, histamine is also a neurotransmitter! An excitatory alertness neurotransmitter! Both these aspects have been extant as scientific knowledge on record for some significant time, but are only really becoming known-known as of recent. I have ADHD. I take lisdexamfetamine. Upon starting medication at 39.5 years of age, I quickly noticed that I had to be really careful with coffee, and especially to not at all touch any sweet foods or desserts around evening or so. Or I would wake up at 5:30 AM. (Exactly and precisely 5:30. Reliably. It’s sort of fascinating.) As it turns out, amphetamine releases histamine! And! Caffeine inhibits the enzymatic breakdown of histamine! And sugar causes histamine to be released.
    - LargoLasskhyfv 2y ago
      5:30 AM in the same place, or different places? If same place, I'd assume some environmental/technical reason. Some machine somewhere near starting up, producing infra- or ultrasonics, a manifest freight train rumbling by far away, doing the same, some other thing (electro-/static/magnetic fields changing), and so on. 'Technical' because nature would vary that with the seasons because of https://en.wikipedia.org/wiki/Solar_time https://en.wikipedia.org/wiki/Solar_time
- jamal-kumar 2y ago
  It's bad enough that there's a whole subreddit dedicated to the shit people get up to on it [1]. Telling thing: the description for it starts off with CHOP OFF ALL YOUR HAIR, probably a reference to a toothpaste for dinner comic about "the ambien walrus" which is a popular meme in the uhhh ambien community [1] https://www.reddit.com/r/ambien/top/?t=all https://www.reddit.com/r/ambien/top/?t=all
- 93po 2y ago
  i used it daily for a couple years and had no idea the impact it was having on me. i was an angry, irritable, grumpy person, and i completely changed when i finally stopped taking it. i had an addiction but didnt abuse it. it got to the point that i craved ambien during the day for reasons i can't even explain. i just inexplicably wanted to take it. i wasnt even taking full pills of the usual dose, i usually cut them in half. it took me a long time to learn to put my phone away before taking it. i would text people i was causally dating overly romantic and loving things and have zero memory of it. thankfully whenever it happened the people involved always just thought it was funny, and i did have the awareness to preface those texts with "maybe its just bc i took some ambien". After a few dates with someone i warned them i take ambien and might text them something stupid but loving, so they were well prepared
- outworlder 2y ago
  I personally know of one ambien addict and it's scary. He just went through a divorce and lost his job. His barely coherent (and angry) voice messages while off the drug don't seem too different from addicts of illegal substances.
- appstorelottery 2y ago
  I completely agree. I once took Ambien on a flight from San Fran -> London, but I didn't sleep. I suffered from crazy short term amnesia by the time I got to the other end, walking towards the Hilton just outside the airport in that long tunnel... I kept forgetting where I was and why I was there and then I'd snap back to reality. To the alarm of a friend that was supposed to be picking me up, I simply checked into the Hilton. What happened on the flight was another story altogether. I think I was repeatedly telling the attendants that I'd taken Ambien, they ended up shifting me to first class. Looking back, it was fun for reasons I won't talk about here - but belongs strongly in the recreational category. Sitter required.
- desmosxxx 2y ago
  I took Ambien for one of my sleep studies and I had sleep paralysis and nightmares (bordering on hallucinations because I swear I was awake or at least in a lucid state). That was my first and last time doing Ambien.
- FuriouslyAdrift 2y ago
  They gave us Ambien (no go pills) and Provigil (go pills) in the miltary during long ready states. After a while, I became dependent on Ambien and would sleep walk (among other things). My roomates would zip me up in my sleeping bag to deal with it. Took me about 2 years after the military to get back to "normal" I do miss the Provigil, though... that stuff made able to focus so well.
AnthonBerg 2y ago
Once upon a time I had severe difficulty sleeping due to high and sustained levels of stress. I had gotten prescribed some Zopiclone which is similar to Zolpidem as found in Ambien. Zopiclone makes me feel like I have a brain injury the day after. Sometimes after the first night, always after the second night if I find I need to take it two nights in a row. It’s frightening. I came across a paper: ”Pharmacokinetic and Pharmacodynamic Interactions Between Zolpidem and Caffeine” https://www.researchgate.net/profile/Roberta-Cysneiros/publication/6385851_Pharmacokinetic_and_Pharmacodynamic_Interactions_Between_Zolpidem_and_Caffeine/links/58a57d9da6fdcc0e07660197/Pharmacokinetic-and-Pharmacodynamic-Interactions-Between-Zolpidem-and-Caffeine.pdf https://www.researchgate.net/profile/Roberta-Cysneiros/publi... Based on my understanding of the results that a significant dose of caffeine counteracts “some but not all” of Zolpidem’s effects on cognition—and the two Z-drugs being similar—I tried drinking a tiny little bit of coffee with the tiny little bit of Zopiclone. (I take 2-3mg; a whole tablet is 7.5mg.) The result is that I am able to sleep and do not feel brain-damaged the day after, and the effect also seems to be that the failure rhythm of stress-related waking up at precisely 5:30 is broken. In other words, the combination seems to fix the problem. I suspect that part of the reason might be that the caffeine counteracts the disruption of the norepinephrine oscillation you mention. (Thanks!!)
- akvadrako 2y ago
  That's quite interesting. I take half a Zolpidem once a week or so and I'll try taking it with caffeine. I've tried Zolpiclone but found it affects my sleep much more. Zolpidem is faster acting and gets out of your system quicker, while Zolpiclone continues working during the night. So if your issue is getting to sleep and not staying asleep I would recommend you try the original.
  - AnthonBerg 2y ago
    I know and trust that the implicit disclaimers are clear, that this comes with absolutely no guarantees of not being terrible for anyone else :) —I would indeed prefer the shorter duration of Zolpidem! Zopiclone was the only Z-drug option the doctor was willing to use. Fortunately, the caffeine seems to kind of mitigate the longish duration of Zopiclone. And Zolpidem has somewhat dangerously recreational effects on me :sweat_smile: … and is slightly addictive to me as well. I’d very much like to be able to try Zaleplon instead. It’s more recent than the two other Z-drugs and the shortest-acting; Not available in my country. https://en.wikipedia.org/wiki/Zaleplon https://en.wikipedia.org/wiki/Zaleplon
breadwinner 2y ago
If you have sleep issues try magnesium. https://hn.algolia.com/?query=magnesium%20sleep&type=comment https://hn.algolia.com/?query=magnesium%20sleep&type=comment
- outworlder 2y ago
  What if blood magnesium levels tested normal?
  - breadwinner 2y ago
    My understanding is that magnesium blood tests are not reliable. Since magnesium is a natural element found in foods such as spinach, nuts, seeds, and whole grains, you know it is safe. Try a supplement and if it helps with muscle stiffness or sleep then you have a magnesium deficiency.

lapcat 2y ago

In mouse brains

InDubioProRubio 2y ago
So? What part of the washing chemistry is different?
- kzrdude 2y ago
  The interesting thing is that everything with a brain sleeps. We really need to get to the bottom of understanding it.
- bityard 2y ago
  That's exactly what we don't know yet.
- deleted 2y ago
  [deleted]
Ensorceled 2y ago
This is a fundamental physiological process ... not a drug interaction.
bux93 2y ago
or, as the late great @justsaysinmice used to point out "IN MICE"

highfrequency 2y ago

> Some researchers have challenged parts of this picture, however; a 2024 study, for example, suggested waste clearance is actually faster during waking than during sleep. That’s a pretty big ambiguity in the story!

beezlebroxxxxxx 2y ago
When you talk to neuroscientists and researchers in private you often find that they are far less confident than public personas, PR, articles, or science reporting, make them sound. A lot of their findings are really more like "huh, that's weird. We should look at this more." What seems like a ton of consensus at cruising altitude is actually much more divisive as you approach ground level. The more recent emergence of the idea that neuroscientists are a kind of "super scientist" of human behavior (all self-help books are now "neuroscience"-based now, for example) has also made them seem much more certain about certain things than they actually are.
- smokedetector1 2y ago
  [flagged]
  - krapp 2y ago
    >It's not just optimistic - its qualitatively unjustified to think that neuroscience (in its current form, at least) is inevitably capable of cracking consciousness. The fact that you had to add the parenthetical here to hedge your bet demonstrates that you don't even entirely believe your own claims.
    - smokedetector1 2y ago
      [flagged]
      - smallmancontrov 2y ago
        God of the Gaps is not intellectual honesty. Neither is running from an argument.

debacle 2y ago

A little over a year ago I was having awful sleep hygiene. From time to time, I still wake up at ~2am and just can't find restfulness again. I picked up a simple smart watch that tracks sleep (one of the Garmins, as they are one of the few that protect privacy and don't need to connect to the Internet). I slowly and methodically improved my sleep, and I feel like a different person. I have noticed that if I turn my blue light filter on my screens off, that has a huge impact. Working long days has a huge impact. I take a hell of a lot of magnesium. I need ~20 minutes of outdoor walking a day and I need to eat dinner before 4pm. Lots of other small things that have an impact that I'm probably forgetting. How many of us are just chronically tired?

kzrdude 2y ago
I've had some periods of "intense work on sleep schedule". A big one was discovering that I was on the higher end of caffeine sensitivity (but I can still sleep if I only drink coffee in the morning). I have thought that the blue light filter doesn't do so much, with a caveat. The laptop screen is much less bright, so it doesn't bother me. It seems like the blue light of a desk screen has a bigger effect. But I also think it is the brain activity of stimulus seeking on the screen itself that has a big effect on sleep. It's better to turn of screens entirely to wind down, or do something that actually helps you wind down for sleep.
- TeMPOraL 2y ago
  For me, the light doesn't seem to have much effect - but what I do on the computer matters. For example, as much as I liked to watch something in the evening, I now find that if I watch an interesting movie or TV show too late, my mind is still wound up in it when I lie down, and I find it much harder to fall asleep.
  - kzrdude 2y ago
    Yes. I think that should be the commonly spread advice instead of the blue/red light thing
  - mattgreenrocks 2y ago

jerbearito 2y ago

Just to clarify -- we already knew about the washing, right? But this refers to the specific mechanism where the blood vessels contract to cause the washing?

iandanforth 2y ago
And more specifically that norepinephrine waves are highly correlated with and perhaps causative of that pumping.
bityard 2y ago
Yes. And to further qualify the conclusion, the research was done in mice so it's premature to say whether or not human brains operate identically. (Mammalian anatomy between species is often similar, but just as often is found to be different in unexpected ways.)
- adsteel_ 2y ago
  I'd like to learn more about the washing. Do you have a link or word/phrase to Google?
  - FuriouslyAdrift 2y ago
    The glymphatic system https://en.wikipedia.org/wiki/Glymphatic_system https://en.wikipedia.org/wiki/Glymphatic_system

abeppu 2y ago

... so, perhaps a fool-hardy idea, but could we use an external device to create or amplify the same effect? - if you rhythmically give mice norepinephrine while they're awake, can you create the same movement in cerebrospinal fluid? Would mice go to sleep later following such an intervention? - could you directly just pump cerebrospinal fluid faster? If you were willing to have a mechanical device surgically installed, could you have a rapid, extra-refreshing sleep at the press of a button? - if the efficacy of washing is partly due to the contents of cerebrospinal fluid, could you look at what's being "washed out" and add stuff to the cerebrospinal fluid that makes those things more soluble?

bityard 2y ago
As much as I applaud the biohacking curiosity, we've known for a while that sleep does lots of things to rest and repair the whole body. "Cleaning" the brain is only one of them. Finding an easy button to hack around the need for sleep is probably as unlikely as finding an immortality pill.
- abeppu 2y ago
  I guess on the animal model research side, the gap in various metrics between artificially "cleaning" the brains of sleep-deprived mice vs mice that get to sleep would be one way of measuring some of the non-cleaning functions of sleep (e.g. memory consolidation). In some far hypothetical future human device, I think even if amplifying a "washing" function doesn't replace sleep it could still be helpful ... but outweighing the risks involved in the intervention (attaching a person to a pump?) would be a high bar. But if decades from now you were already going to put in a neuralink v20, perhaps it would seem reasonable.

lawlessone 2y ago

I wonder how nicotine affects this? since it can affect norepinephrine

napoleongl 2y ago
Falling asleep with nicotine patches on results in wild dreams so it clearly screws up something in the brain!

vladslav 2y ago

Perhaps it seems odd, but could experiencing nightmares actually aid in the cleansing process?

segfaultbuserr 2y ago

The brain truly is a system with terrible service availability. On average, after running for just 16 hours, it must be offlined for 8 hours to run maintenance tasks such as "scrub", "garbage collect", "trim", and "fsck".

baxtr 2y ago
SLAs are terrible. I agree. But at least there’s (usually) some exciting shows on while you are waiting!
tivert 2y ago
> The brain truly is a system with terrible service availability. On average, after running for just 16 hours, it must be offlined for 8 hours to run maintenance tasks such as "scrub", "garbage collect", "trim", and "fsck". There's hope. If the carbon chauvinists can be prevented from messing things up, AI is on track to provide something with a better SLA, which will finally allow us to decommission and junk those troublesome legacy systems without disrupting the business.
PaulDavisThe1st 2y ago
You've got it all wrong, and LLMs have it all correct. True brains, after 16hrs of actual work, need to hallucinate strongly for 8 hours or so, in order to continue their high level contributions to society.
- ifyoubuildit 2y ago
  Interesting. What if that is actually a beneficial part of our own development: comparing the nonsense in our dreams to waking life and building the ability to tell the difference?
  - euroderf 2y ago
    Get an LLM to dream, and to use the time effectively to purge those hallucinations, and reinforce the "valid and true" memories, and you might have something there ?

jokoon 2y ago

There was a MRI looking video showing this

deleted 2y ago

[deleted]

treprinum 2y ago

Didn't Chinese scientists recently show a crazy success rate (~90%) of treating advanced Alzheimer/dementia by performing a microsurgery of the neck, allowing brain to dispose accumulated waste?

burkaman 2y ago
They tried it on 6 people and found "slight improvements" after 5 weeks, with no control group to compare to and no longer term effects known yet. - https://gpsych.bmj.com/content/37/3/e101641 https://gpsych.bmj.com/content/37/3/e101641 Certainly seems worth investigating but I wouldn't call it a crazy success yet.

ongytenes 2y ago

One thing to look at is Alzheimer's. The current leading theory is that a build up of amyloid protein is the root cause of this disease. It would be wonderful if someone connected the dots to find the reason for the build up and they're able to develop a treatment to prevent the onset of the disease.

mschuster91 2y ago
> The current leading theory is that a build up of amyloid protein is the root cause of this disease That's ... controversial, a few years ago fraud allegations surfaced [1]. [1] https://www.alzheimers.org.uk/for-researchers/explaining-amyloid-research-study-controversy https://www.alzheimers.org.uk/for-researchers/explaining-amy...
- criddell 2y ago
  Reading that link, it sounds like the build up of amyloid protein is still the current leading theory.

idlewords 2y ago

"In mice"

kcartlidge 2y ago

> To avoid this problem, the scientists surgically implanted mice with electrodes and fiber optic filaments. Although the rodents are tethered to a set of cables, they can fall asleep normally while researchers track blood volume, electrical activity, and chemical levels and use light transmitted through the fiber optic lines to activate certain groups of neurons. I detest this kind of medical research. It's horrific barbarity. If the output is important enough for this kind of activity to take place, then it's important enough for humans to volunteer to be the subjects. If nobody volunteers then it isn't that important after all. Leave other species out of it.

bowsamic 2y ago
What is the logic behind this? I genuinely don’t understand your moral argument

mrayycombi 2y ago

Am I reading this right as implying Ambien...promotes Alheimers....?

jakeogh 2y ago

Very interesting CSF talk: https://www.youtube.com/watch?v=WicKmA9lQTI https://www.youtube.com/watch?v=WicKmA9lQTI

croemer 2y ago

Ugh, this is multiple correlation/causation fallacies in one: > Studies from Nedergaard’s group and others suggest vigorous glymphatic clearance is beneficial: Circulation falters in Alzheimer’s disease and other neurodegenerative illnesses. That circulation falters in Alzheimer's does not suggest anything re the benefit of circulation. Science's science journalism is usually SOTA, this is not.

fuzzfactor 2y ago

I guess I've been brainwashed without knowing it, which seems about par for the course :\

MollyRealized 2y ago

it licks its paw and then runs it over its fur

interludead 2y ago

As someone who sometimes has trouble sleeping, I'm struck by how much sleep affects the brain

pedalpete 2y ago

The glymphatic system activity is greatest during slow-waves in N3 (deep) sleep. A slow-wave is the synchronous firing of neurons which is seen as the glymphatic system pumps CBF through the brain. For the past 5 years we've been developing phase-targeted auditory stimulation to increase slow-wave activity, which has been shown to have a positive response in amyloid response, as well as memory, and a bunch of other biomarkers. https://pubmed.ncbi.nlm.nih.gov/38163288/ https://pubmed.ncbi.nlm.nih.gov/38163288/ I link to more research on our website for anyone interested in the space - https://affectablesleep.com/research https://affectablesleep.com/research

robg 2y ago

Nedergaard (lab head here and main findings of this effect since 2012) is going to win the Nobel for this line of research. When I got my Ph.D. 20 years ago in cognitive neuroscience we knew three main deficits to a lack of sleep but couldn’t connect them mechanistically: 1) loss of daily performance metrics 2) increased risks of mental health concerns 3) increased risks of cognitive declines The glymphatic nervous system, like any great scientific theory, unites disparate findings under a common mechanism. Not getting enough sleep is akin to not running your dishwasher or washing machine long enough, the gunk accumulates. And for all the parents out there, pediatric recommendation is 10-12 hours a night for kids 6-12 years old and 8-10 hours a night for kids 13-18 years old.

dogcomplex 2y ago
Recommended hours not nearly hit enough when they have to finish the night's homework then catch the 7am school bus...
adsteel_ 2y ago
It makes me think of long COVID and CFS, where patients complain of a lack of "unrefreshing sleep" and "brain fog". A lack of perfusion resulting in waste not being sufficiently flushed out could possibly result in those symptoms.

waitasec 2y ago

i dunno, sounds like brainwashing