If this means I don't have to take Methylphenidate to function 100% all the time and as a result feel tremendously anxious 100% all the time. SIGN ME UP.
Adding guanfacine (Intuniv) to my methylphenidate took the weird anxious-angry edge off. Would be nice to not have to take one med to fix the side effects of the other, though.
It’s also a blood pressure med, so I went from borderline prehypertensive to perfect 105/70. You can’t go on and off it at will though, since you’ll get rebound high BP if you don’t taper.
FWIW, I was on MP for years and never really liked it. Tried all possible dosages and delivery methods. I switched to lisdexamfetamine a couple of years ago and never looked back. 0 side effects apart from my mouth.
The second I read the print in Nature a bit ago I knew some version would show up here. I swear I’ve met deployed Marines less obsessed with staying awake through chemistry than some people here.
Vegetable diarrhea, hypothyroidism medication defect causes hyperthyroidism, overseas underground labs are preparing for US govt promoted SARM goblin hordes, and the US Armed Services want to measure the gonads of 17yo recruits. Imma sit this one out.
> IMO the much more likely explanation is that the brain uses contrastive learning somewhere. [...] 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.
I reckon I'll buy some landscaping machinery and a truck before I ever sign up for that distopian nightmare. At least sound ordinance would prevent 24/7 operation.
on the recreational level, maybe, but from a therapeutic perspective for people who actually benefit from its prescribed use its absolutely game-changing to live a life without (or with mitigated) executive dysfunction.
A lot of people with ADHD that have success with medication can tell you that it's not just about work.
It also helps with non-work stuff that's just not fun to do, such as chores or filing your taxes. It even helps you stick with hobbies you actually enjoy but your brain gets bored of.
To some extent ADHD drugs are abused but to us neurodivergent people those stimulants (or in other cases just alpha 2 agonists) just help us do normal things that normal people can do without drugs, like laundry. Or reading a book, or be able to focus on literally anything that isn’t giving us a high level dopamine response.
The meds (both stimulant and non stimulant) help people with ADHD choose where to hyperfocus, but hyperfocus is an internal trait of the ADHD neurotype, so it isn’t just attributable to the drugs or something.
I.e. normal people use stimulants to go fast, while ND people with ADHD use them to go slow or have their brain actually be able to slow down.
I don't doubt that. For me, however, drugs like concerta changed my life from near catatonia to almost-regular function. If you see me behaving "normally", that is because I have taken my prescription. Otherwise, you will not see me because I will be sleeping, or worse, you will see me.
I know you're joking but I saw a company that had similar policies like fasting and stuff like that to improve productivity. They seemed to take it pretty seriously...
It sounds like is a genuine treatment for those who suffer from narcolepsy, and everything else is merely speculative and has seem pretty bad side-effects.
There is evidence that some forms of ADHD are effectively just the brain falling asleep rapidly and then waking up. This form cam be attenuated with norepinephrine reuptake inhibitor alone. Presents with ADHD like symptoms. But it’s a new thing most likely. Called “Cognitive Disengagement Syndrome”.
For the record, since I am on a mix of concerta and effexor, effexor alone does nothing to alleviate my symptoms (at the 150mg dosage). Although for me the adhd medication is no problem. It is actually effexor that torments me, because I have extreme withdrawal symptoms if I go even one day without it.
Or maybe venlafaxine is to counteract any anxiety that the upper may cause. Well that's the theory my doctor had anyway. (I took venlafaxine with ADHD meds because of this)
Effector is for dépression not ADHD. Do you get brain zap when you miss a dose ? Other medications don't have this problem, at least for many of not most people
Everyone involved in a stock market agrees it's quite useful to have a separation between days, although you could have a 23.5/7 stock market with only half hour day-ends. That's when things like index rebalancing, addition, removal, stock splits occur. You say whoever holds stock X at end of a certain day holds stock Y+Z at the start of the next day (due to a company splitting up) and there's no need to argue about which millisecond a trade occurred. (It's your own damn fault if you were trying to buy the stock in the milliseconds before closing, but some exchanges run a special closing auction with a different algorithm to prevent races)
I think you can have a separation between days while still allowing 24/7 trading. Just schedule automatic operations like stock splits at midnight, and with a proper staging environment you can deploy software in the middle of the day, too (just give a heads-up first).
And of course, overnight trading is available on some stock exchanges now. (I’m not sure whether this is a new thing or has existed for a while, but I’ve only noticed it on TradingView for some papers about a year ago I think.)
Despite the stigma surrounding semaglutide, its impact across various health conditions has been remarkable. Bringing that same level of innovation to cognitive disorders could be truly transformative for society
There's a crust of "but that's cheating" folks who have opinions on "taking drugs to lose weight". They're ignorant, of course, but that never stopped anyone from being loud.
1) don’t need to sleep, be able to sleep: the coolest thing in the universe.
2) don’t need to sleep, be unable to sleep: you would likely cope. Also, be an irreplaceable shift worker.
3) need to sleep, be able to sleep: this is where most of us are now, nothing to write home about.
4) need to sleep, be unable to sleep: the rest of your life is short and full of exponentially growing suffering.
By „don’t need to sleep” I mean that the body refreshes itself by different means and you still reap the benefits.
I can’t really imagine how it would feel, much like I can’t imagine being immortal. Most fiction describing those phenomena as „nightmare” usually is about a character who gains the ability but none of the protective mechanisms.
My partner has had idiopathic hypersomnia (sleeps 12 hours most days, as much as 18 hours some days) for a few years now, and so far nothing we’ve tried has worked without awful side effects (e.g. constant heart palpitations and panic attacks.)
I had been looking into orexin agonists (along with other things like H3 autoreceptor antagonists) back when they were just a concept. It’s good to see them finally reaching commercialization. Although they’re not approved by our own (Canadian) regulatory body quite yet.
Now that they’re approved in the US, though, I’m looking very much forward to seeing how these drugs perform in off-label-ish treatment of the various other sleep disorders that I’m sure clinicians will now begin throwing them at.
Have they tried GHB? I know it's used in narcolepsy patients with great success. If you "microdose" it, it's also one of the best drugs on the planet. Slippery slope, though.
I am calm. GHB has wreaked havoc in The Netherlands, it is something tweakers consume. Recommending microdosing GHB in my eyes is like recommending microdosing heroin.
> GHB is difficult to dose. The difference between a dose with pleasant effects and the dose at which someone becomes overwhelmed by sleep and becomes unconscious is very small. People quickly take too much GHB. The combination with alcohol enhances the effects of GHB. This means that people can become unconscious even with a small dose of GHB.
To nitpick, I would point out that a "microdose", by definition, would be far below "a dose with pleasant effects", and so wouldn't be too hard to dose at all.
The reason GHB has a narrow tolerance window (which, note, is not exactly the same thing as a therapeutic index, as the upper bound here isn't where the drug becomes toxic; it's just where the drug stops being recreationally "fun" and becomes a potent sleep drug instead) is because you actually require a decently high amount of the drug to get the recreational effect; and then only a little more of it will put you to sleep. But a "microdose" would imply that you're not going anywhere near the dose that gives you the recreational effect in the first place.
The term "microdose" is usually employed in conversations like this to specifically mean "a dose of a normally-conceptualized-as-recreational drug, too small to experience recreational effects" — although it can technically also mean "a dose of a prescription medicine too small to see the regular clinical effect."
People talk about microdoses of e.g. LSD, MDMA, or ketamine, as potential treatments for various mood disorders. In none of these cases is there an expectation that you'd "feel" the drug. It's a microdose, not a dose.
Everything is addictive to the right/wrong person. GHB is no more addictive than alcohol [IMO] , just much more dangerous at high doses. Although safer at low doses.
Alcohol is extremely addictive so I don't understand the point you're trying to make. You shouldn't microdose alcohol either. Millions of people are addicted to alcohol and many more (ab)use it in the form of a bad habit.
GHB’s sodium salt (sodium oxybate, Xyrem/etc) is a legal prescription drug in several countries, used for treating narcolepsy, alcoholism, and also as an anaesthetic.
I don’t see what’s the problem with someone taking any drug legally prescribed to them by their doctor. Lots of prescription drugs are potentially addictive, but that’s a risk to be weighed against the potential benefits.
Controlled medicinal use of sodium oxybate under the supervision of a medical professional differs greatly from microdosing/self-medicating cleaning agents turned into GHB by yourself or your local dealer
Yes, I agree that taking drugs manufactured by unregulated black market operators is dangerous and not to be recommended.
But "microdosing" per se isn't the issue.
I once stumbled upon a psychiatry case report about a man with a psychotic illness, who found out by experimentation that taking significantly less of his antipsychotics than prescribed, along with up-titration when he began to notice the prodromal signs of relapse, helped him avoid relapse while also avoiding most of the unpleasant side effects. He did this on his own, only later confided in his psychiatrist he was doing it. Some psychiatrists would have reacted rather negatively, but his (being somewhat influenced by R. D. Laing & friends) actually thought it was smart, and wrote it up.
I’m not about to stifle research into genuinely useful therapies just because some aspects of society will abuse the absolute shit out of them, and these therapies seem profoundly useful to those who suffer from the mentioned ailments.
Here’s the thing: what a lot of these drugs are doing are basically acting as equivalents to the store-bought neurotransmitters you’d find in things like SSRIs or -phetamines/stimulants. To people lacking in these substances, they’re game changers.
The problem right now is a mismatch between regulation, availability, and testing regimes. Regulations are meant to prevent dystopian shit like employers mandating (or encouraging) a drug regimen for employment through threat of punitive fines or prosecution, while the private insurance markets promote unaffordability domestically (as North America is where over half of pharma revenues come from) and testing regimes fail to identify who is best suited for a given drug. All three of these prongs will shake out in time, but cause new problems as a result.
Where we’re at right now is less of a click-baity headline from The Economist, and more at the start of a new frontier in medicine that capitalizes on decades of research. We’ve maximized the benefits of “low-hanging” chemical-based drugs, and have moved into more complex, nuanced, or targeted drugs developed through modern compute rather than traditional drug trials alone. Things will change very quickly, and then stagnate again when we’ve picked clean the easy fruits from these new branches.
84 comments
[ 0.28 ms ] story [ 8.5 ms ] thread2. Unhealthy desire to get rich (or work on interesting projects, which would be the better option).
> IMO the much more likely explanation is that the brain uses contrastive learning somewhere. [...] 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.
- when learning on the real examples, just propagate forward
- when learning on the fake examples, first generate them by propagating white noise backward
We have our NeuroLinkBrain Implant plugin to AI agent , so that you can vibe code 24/7 . To maximize shareholder value.
It also helps with non-work stuff that's just not fun to do, such as chores or filing your taxes. It even helps you stick with hobbies you actually enjoy but your brain gets bored of.
The meds (both stimulant and non stimulant) help people with ADHD choose where to hyperfocus, but hyperfocus is an internal trait of the ADHD neurotype, so it isn’t just attributable to the drugs or something.
I.e. normal people use stimulants to go fast, while ND people with ADHD use them to go slow or have their brain actually be able to slow down.
Probs already there…
Nothing like losing 100 pounds to show you how profoundly lookist society is. It's been great.
Everyone involved in a stock market agrees it's quite useful to have a separation between days, although you could have a 23.5/7 stock market with only half hour day-ends. That's when things like index rebalancing, addition, removal, stock splits occur. You say whoever holds stock X at end of a certain day holds stock Y+Z at the start of the next day (due to a company splitting up) and there's no need to argue about which millisecond a trade occurred. (It's your own damn fault if you were trying to buy the stock in the milliseconds before closing, but some exchanges run a special closing auction with a different algorithm to prevent races)
And of course, overnight trading is available on some stock exchanges now. (I’m not sure whether this is a new thing or has existed for a while, but I’ve only noticed it on TradingView for some papers about a year ago I think.)
Is it from these Valley Bros I read about experimenting with designer semaglutide on themselves? Or is there another stigma?
1) don’t need to sleep, be able to sleep: the coolest thing in the universe.
2) don’t need to sleep, be unable to sleep: you would likely cope. Also, be an irreplaceable shift worker.
3) need to sleep, be able to sleep: this is where most of us are now, nothing to write home about.
4) need to sleep, be unable to sleep: the rest of your life is short and full of exponentially growing suffering.
By „don’t need to sleep” I mean that the body refreshes itself by different means and you still reap the benefits.
I can’t really imagine how it would feel, much like I can’t imagine being immortal. Most fiction describing those phenomena as „nightmare” usually is about a character who gains the ability but none of the protective mechanisms.
I had been looking into orexin agonists (along with other things like H3 autoreceptor antagonists) back when they were just a concept. It’s good to see them finally reaching commercialization. Although they’re not approved by our own (Canadian) regulatory body quite yet.
Now that they’re approved in the US, though, I’m looking very much forward to seeing how these drugs perform in off-label-ish treatment of the various other sleep disorders that I’m sure clinicians will now begin throwing them at.
https://www.jellinek.nl/en/alcohol-drugs-behavior/ghb/
> GHB is difficult to dose. The difference between a dose with pleasant effects and the dose at which someone becomes overwhelmed by sleep and becomes unconscious is very small. People quickly take too much GHB. The combination with alcohol enhances the effects of GHB. This means that people can become unconscious even with a small dose of GHB.
The reason GHB has a narrow tolerance window (which, note, is not exactly the same thing as a therapeutic index, as the upper bound here isn't where the drug becomes toxic; it's just where the drug stops being recreationally "fun" and becomes a potent sleep drug instead) is because you actually require a decently high amount of the drug to get the recreational effect; and then only a little more of it will put you to sleep. But a "microdose" would imply that you're not going anywhere near the dose that gives you the recreational effect in the first place.
The term "microdose" is usually employed in conversations like this to specifically mean "a dose of a normally-conceptualized-as-recreational drug, too small to experience recreational effects" — although it can technically also mean "a dose of a prescription medicine too small to see the regular clinical effect."
People talk about microdoses of e.g. LSD, MDMA, or ketamine, as potential treatments for various mood disorders. In none of these cases is there an expectation that you'd "feel" the drug. It's a microdose, not a dose.
I added the “pretending to be an adult” part because I knew someone was going to be a pedant about it.
I don’t see what’s the problem with someone taking any drug legally prescribed to them by their doctor. Lots of prescription drugs are potentially addictive, but that’s a risk to be weighed against the potential benefits.
https://en.wikipedia.org/wiki/Sodium_oxybate
But "microdosing" per se isn't the issue.
I once stumbled upon a psychiatry case report about a man with a psychotic illness, who found out by experimentation that taking significantly less of his antipsychotics than prescribed, along with up-titration when he began to notice the prodromal signs of relapse, helped him avoid relapse while also avoiding most of the unpleasant side effects. He did this on his own, only later confided in his psychiatrist he was doing it. Some psychiatrists would have reacted rather negatively, but his (being somewhat influenced by R. D. Laing & friends) actually thought it was smart, and wrote it up.
BHB is quite similar to GHB, but is a naturally produced ketone.
(I did try google)
Here’s the thing: what a lot of these drugs are doing are basically acting as equivalents to the store-bought neurotransmitters you’d find in things like SSRIs or -phetamines/stimulants. To people lacking in these substances, they’re game changers.
The problem right now is a mismatch between regulation, availability, and testing regimes. Regulations are meant to prevent dystopian shit like employers mandating (or encouraging) a drug regimen for employment through threat of punitive fines or prosecution, while the private insurance markets promote unaffordability domestically (as North America is where over half of pharma revenues come from) and testing regimes fail to identify who is best suited for a given drug. All three of these prongs will shake out in time, but cause new problems as a result.
Where we’re at right now is less of a click-baity headline from The Economist, and more at the start of a new frontier in medicine that capitalizes on decades of research. We’ve maximized the benefits of “low-hanging” chemical-based drugs, and have moved into more complex, nuanced, or targeted drugs developed through modern compute rather than traditional drug trials alone. Things will change very quickly, and then stagnate again when we’ve picked clean the easy fruits from these new branches.
The only way through will be anecdata. Science of one.
I await basic safety reports.