I take pentoxyfylline (a synthetic substituted xanthine, caffeine is a natural substituted xanthine) occasionally as a nootropic and supplement for vascular health and anecdotally for me it has several nice caffeine like properties without the jitters/ long tail, sleep effects etc.
I find the listed side effects don’t happen for me besides occasional flush/blush. Which at my age is more like youthful vigor.
Caffeine is is 1,3,7-trimethylxanthine, pentoxyfylline is
3,7-dimethyl-1-(5-oxohexyl)xanthine.
Good effects are: sustained mental clarity, focus and energy with a smoother more stable baseline than caffeine’s bursty performance; good sleep, but strangely you can also stay up, if you prefer; feeling similar to “after exercise”. Half life is listed as under 1 hour, but beneficial effects can be felt for half a day after 400mg (a standard dose). So maybe there’s something like metabolite dynamic occurring here too.
This ends my erowid/hive style “trip/nootropic” report ;)
I think it is already pretty widely recognized that caffeine can disrupt sleep taken even as early as 6 or 7 hours before bed. I usually don't drink coffee or caffeinated tea after 12 for this reason. Caffeine also has many other known benefits, possible beneficial effects on all-cause mortality, etc, and I'm not sure if we have any research showing the same benefits coming from paraxanthine. Seems like potentially a bit of a waste just to be able to get the stimulant effect a couple of hours closer to sleep time.
This is a distinct claim. Caffeine can disrupt sleep even 48 hours later, a little bit; It is traditionally modelled with an elimination half-life of 5 hours, meaning 1/2 effect at 5 hours, 1/4 effect at 10 hours, 1/8 effect at 15 hours, an exponential decay curve.
The claim being made is that due to cascading decay of a secondary metabolite that does a lot of the work producing the clinical effect, caffeine elimination is a much more linear, slow process that only reaches half effect at around 10 hours and 1/4 effect at 17 hours, 1/8 effect at 23 hours.
I went decaf drinks only back in 2024. I was fine and thinking “what’s the big deal” until day three. I will never forget that day. So horrible.
Still decaf only. Has been a pretty positive change for me. Kicked the soda habit completely. Sleep is better. I find I’m even all day. I generally only get tired when I’m bored.
This article makes the case for paraxanthine supplements; 80% of caffeine is metabolized into paraxanthine anyway, and it turns out paraxanthine behaves a bit more like we (apparently wrongly) assume caffeine works.
But the real question is: does it taste as good as espresso?
Coffee is an acquired taste, I think. People conditions themselves to like the bitter taste of coffee over time. I remember hating the taste of coffee (or beer, for example) in childhood.
Weirdly enough, I loved coffee from the first time I tried it, at maybe 13. Even though, looking back, it must have been terrible coffee, it was at something vaguely model UN like thing our entire class went to in an overnight trip. Obviously not enough sleep was had. A vending machine (in the late 90s) provided coffee...
Yes, I also tried coffee first time when in England when 13, and it was like a revelation. I understand that beer and cigarettes are an acquired taste, they tasted terrible, but coffee was a love at first sip.
Douglas Adams nailed the quality of tea from a vending machine, "almost, but not quite, entirely unlike tea", and that era of coffee machines weren't much better at coffee.
I’ve heard that bitterness affects children more intensely. So I wonder how much of it is an acquired taste vs bitterness just becoming “milder” over time.
My three year old loves the taste of matcha. Even when I don't prepare it quite right and it turns out very bitter. He's pretty picky about near everything else. I think it's acquisition through mimicry.
Matcha is one of the more concentrated amino acids drinks you can make; given how hungry I remember being as a kid, I bet it tastes like liquid gold. And if you’re in a climate that tolerates rhododendrons you can plant a camellia sinensis bush for it straight from the vine as a bridge from matcha to steeped tea, steaming and roasting, etc.
Regular coffee, too, can be very delicate, minimally bitter, giving herbal or strong tea-like notes, among other things.
I've not gotten that kind of profile out of anything but fairly-expensive beans roasted within the last couple of weeks, though. I've never seen it out of even mid-priced beans, nor anything nationally distributed. It's practically a totally different drink from what you get if you ask for a coffee in most contexts.
Iced coffee and cold brew are also fairly different. I find middling beans can make a much milder and more pleasant cold brew coffee than hot. Tiny (like, a teaspoon) splash of cream or milk and it takes the bitter edge all but completely off, to my taste anyway.
> I've not gotten that kind of profile out of anything but fairly-expensive beans roasted within the last couple of weeks, though.
Good beans will last more than 2 weeks, but yes—just as you wouldn't judge all sushi based on gas station sushi, we shouldn't judge coffee based on months-old pre-ground grocery store roasts.
I now like bitters and soda, and I didn’t like bitter as a kid, so I think there might also be shifts in favor of bitter unrelated to coffee. Perhaps the same thing that leads people to appreciate spicy or sour as experiences broaden.
That is entirely dependent on your diet as a child. I know children that love bitter or sour/fermented foods. Not to mention they dislike things that are overly sweet.
I wouldn't be surprised if all tastes are essentially "acquired".
I'd imagine it would not be hard to breed/engineer a coffee plant that produces more paraxanthine than caffeine. The plants take 5 years to mature so getting a crop to market would take a while though.
There are some fairly common genes that can drastically effect the strength and duration of caffeine so your experience may vary. For me the effect is very strong and one cup lasts all day, even as a habitual consumer.
That's an interesting takes. I found it quite suspicious at first, especially because it doesn't present well the myths that it's trying to debunk: are we talking abouy caffeine half life or its effects; and is that 5h half life related to the metabolism of caffeine, or related to its effects.
It looks like pharmacokinetics (ie how long caffeine stays in blood) is what's been studied mostly, and that's where the 5h timeline is coming from. I couldn't find papers on the timeline of pharmacodynamics of caffeine (how long it has effects).
That's an interesting gap this article is underlining!
Nicotine is also a nice alternative to coffee. I still drink coffee but past late morning I'll usually reach for nicotine because the effect is much shorter.
It also has neuro-protective effects if you're an older gentleman.
I generally avoid caffeine at all costs. I'm susceptible to SVT, and I want the Adenosine to work if I should need it. Caffeine blocks Adenosine receptors. But on the rare occasion I have a single can of caffeinated Diet Coke, I experience a crash 48 hours later so profound that I cannot get out of bed that day.
I feel it my due diligence to advise you that LessWrong is closely associated with the rationalists and all that comes with them. It is worth doing a tad of research into the rationalist community and Eliezer Yudkowsky before going too deep down the LessWrong rabbit hole. https://en.wikipedia.org/wiki/Rationalist_community
One can take many good ideas from less wrong, yudkowsky et al without adopting a rationalist identity. Sure, it attracted wackos and they made a cult or two. But that could happen to anyone!
It's a particular variety of "everyone else is wrong (and maybe a bit stupid)".
Like, sure, sometimes you get popular nonsense like recovered memories or accidental fires can't be as hot as intentional fires or shaken-baby syndrome or bite-mark analysis. But a lot of times, everyone isn't wrong and you've just overlooked something critical or misdefined the problem.
>Writing in Asterisk, a magazine related to effective altruism, Ozy Brennan criticized Gebru's and Torres's grouping of different philosophies as if they were a "monolithic" movement. Brennan argues Torres has misunderstood these different philosophies, and has taken philosophical thought experiments out of context.[21] Similarly, Oliver Habryka of LessWrong has criticized the concept, saying: "I've never in my life met a cosmist; apparently I'm great friends with them. Apparently, I'm like in cahoots [with them]."
The people that coined TESCREAL seem to not really be related to rationalists, and seem to have coined a term for "those vaguely related ideas from people that do some stuff we consider wrong and we consider bad". "Evil people from San Francisco" could work just as well I think.
And wait, shouldn't I beware arguments for utilitarianism rather than against? If that's what you meant yeah I agree, especially pushed to the extreme it leads you in very weird places.
I know nothing about the drama, but treating "utilitarianism" as if it is one thing or that a particular person or group's position is identical to utilitarianism seems ironic in the context. It is like claiming all pizza is bad because I went to dominoes and didn't like the experience.
I'm not sure what the parent meant by "beware arguments against utilitarianism" - there is nothing wrong with arguing for or against utilitarianism. It's a popular moral philosophy.
You should beware of bad utilitarian arguments though, which is where you often get the real "gotta break a few eggs to make an omelette" kind of arguments that justify all manners of atrocity in service of some narrow hypothetical future good.
Like when Marc Andreessen says we should consider anyone who would do something to slow down or regulate AI advancement murderers of future humans. Bad utilitarianism right there.
Proper utilitarians are concerned with the net difference between all positive and negative consequences of actions.
Like any group of humans, there are power structures and edge cases that can lead to horrific outcomes. Giving the person that posted the warning the benefit of the doubt, I think what they are saying is that "Rationalist does not necessarily mean positive for humanity, nor even no harm for humanity". This holds for all religions and religion-like movements, of which Rationalism, in this sense, is one.
I think this holds for basically all movements in which case, I don't really understand the need to flag that website over any website.
Edit: though I don't want to diminish that this specific group is a cult with classical cult techniques like sleep deprivation and with the disastrous consequences often associated with cults.
> They claim to practice unihemispheric sleep (UHS), a form of sleep deprivation intended to "jailbreak" the mind, which they believe can enhance their commitment to their cause.[
> I think this holds for basically all movements in which case, I don't really understand the need to flag that website over any website.
Because it uses the language and thinking patterns of the Rationalists, it serves as a strong indoctrination tool. The site itself isn't bad but, as someone who flirted with those communities as a result of the site, I think the warning is deserved.
sight correction....caffeine impacts two neuron groups not just one!
Dopamine and Noradrenaline
For dopamine its the competitive for the adenosine part of the dopamine heretodimer....meaning it prevents adenosine from binding and closing the dopamine receptor....
I use the effect on both dopamine and noradrenaline to assist in controlling my ADHD via more herb based means....
But author is yes correct that the metabolism of caffeine in how it breaks down does make the half life of its effects longer than 5 hours...I combine my dose with green tea ECGC which gives me a good focus boost of 12-16 hours...
I take pentoxyfylline (a synthetic substituted xanthine, caffeine is a natural substituted xanthine) occasionally as a nootropic and supplement for vascular health and anecdotally for me it has several nice caffeine like properties without the jitters/ long tail, sleep effects etc.
I find the listed side effects don’t happen for me besides occasional flush/blush. Which at my age is more like youthful vigor.
Caffeine is is 1,3,7-trimethylxanthine, pentoxyfylline is 3,7-dimethyl-1-(5-oxohexyl)xanthine.
Good effects are: sustained mental clarity, focus and energy with a smoother more stable baseline than caffeine’s bursty performance; good sleep, but strangely you can also stay up, if you prefer; feeling similar to “after exercise”. Half life is listed as under 1 hour, but beneficial effects can be felt for half a day after 400mg (a standard dose). So maybe there’s something like metabolite dynamic occurring here too.
This ends my erowid/hive style “trip/nootropic” report ;)
I think it is already pretty widely recognized that caffeine can disrupt sleep taken even as early as 6 or 7 hours before bed. I usually don't drink coffee or caffeinated tea after 12 for this reason. Caffeine also has many other known benefits, possible beneficial effects on all-cause mortality, etc, and I'm not sure if we have any research showing the same benefits coming from paraxanthine. Seems like potentially a bit of a waste just to be able to get the stimulant effect a couple of hours closer to sleep time.
This is a distinct claim. Caffeine can disrupt sleep even 48 hours later, a little bit; It is traditionally modelled with an elimination half-life of 5 hours, meaning 1/2 effect at 5 hours, 1/4 effect at 10 hours, 1/8 effect at 15 hours, an exponential decay curve.
The claim being made is that due to cascading decay of a secondary metabolite that does a lot of the work producing the clinical effect, caffeine elimination is a much more linear, slow process that only reaches half effect at around 10 hours and 1/4 effect at 17 hours, 1/8 effect at 23 hours.
This may explain why cold turkey effects for me take 24h to start
I went decaf drinks only back in 2024. I was fine and thinking “what’s the big deal” until day three. I will never forget that day. So horrible.
Still decaf only. Has been a pretty positive change for me. Kicked the soda habit completely. Sleep is better. I find I’m even all day. I generally only get tired when I’m bored.
This article makes the case for paraxanthine supplements; 80% of caffeine is metabolized into paraxanthine anyway, and it turns out paraxanthine behaves a bit more like we (apparently wrongly) assume caffeine works.
But the real question is: does it taste as good as espresso?
> does it taste as good as espresso?
Coffee is an acquired taste, I think. People conditions themselves to like the bitter taste of coffee over time. I remember hating the taste of coffee (or beer, for example) in childhood.
Weirdly enough, I loved coffee from the first time I tried it, at maybe 13. Even though, looking back, it must have been terrible coffee, it was at something vaguely model UN like thing our entire class went to in an overnight trip. Obviously not enough sleep was had. A vending machine (in the late 90s) provided coffee...
Yes, I also tried coffee first time when in England when 13, and it was like a revelation. I understand that beer and cigarettes are an acquired taste, they tasted terrible, but coffee was a love at first sip.
> it must have been terrible coffee
Douglas Adams nailed the quality of tea from a vending machine, "almost, but not quite, entirely unlike tea", and that era of coffee machines weren't much better at coffee.
I’ve heard that bitterness affects children more intensely. So I wonder how much of it is an acquired taste vs bitterness just becoming “milder” over time.
My three year old loves the taste of matcha. Even when I don't prepare it quite right and it turns out very bitter. He's pretty picky about near everything else. I think it's acquisition through mimicry.
Matcha is one of the more concentrated amino acids drinks you can make; given how hungry I remember being as a kid, I bet it tastes like liquid gold. And if you’re in a climate that tolerates rhododendrons you can plant a camellia sinensis bush for it straight from the vine as a bridge from matcha to steeped tea, steaming and roasting, etc.
It's definitely an acquired taste. But an espresso doesn't have to be overwhelmingly bitter! It can be almost sweet if it's extracted well.
Regular coffee, too, can be very delicate, minimally bitter, giving herbal or strong tea-like notes, among other things.
I've not gotten that kind of profile out of anything but fairly-expensive beans roasted within the last couple of weeks, though. I've never seen it out of even mid-priced beans, nor anything nationally distributed. It's practically a totally different drink from what you get if you ask for a coffee in most contexts.
Iced coffee and cold brew are also fairly different. I find middling beans can make a much milder and more pleasant cold brew coffee than hot. Tiny (like, a teaspoon) splash of cream or milk and it takes the bitter edge all but completely off, to my taste anyway.
> I've not gotten that kind of profile out of anything but fairly-expensive beans roasted within the last couple of weeks, though.
Good beans will last more than 2 weeks, but yes—just as you wouldn't judge all sushi based on gas station sushi, we shouldn't judge coffee based on months-old pre-ground grocery store roasts.
I now like bitters and soda, and I didn’t like bitter as a kid, so I think there might also be shifts in favor of bitter unrelated to coffee. Perhaps the same thing that leads people to appreciate spicy or sour as experiences broaden.
That is entirely dependent on your diet as a child. I know children that love bitter or sour/fermented foods. Not to mention they dislike things that are overly sweet.
I wouldn't be surprised if all tastes are essentially "acquired".
I'd imagine it would not be hard to breed/engineer a coffee plant that produces more paraxanthine than caffeine. The plants take 5 years to mature so getting a crop to market would take a while though.
I can understand espresso being drunk for many reasons, but none of them are "tasting good".
[delayed]
I actually envy you, because having my first truly good espresso was an experience I wish I could relive
There are some fairly common genes that can drastically effect the strength and duration of caffeine so your experience may vary. For me the effect is very strong and one cup lasts all day, even as a habitual consumer.
Great point. I'm a fast metabolizer, it's highly individualized.
That's an interesting takes. I found it quite suspicious at first, especially because it doesn't present well the myths that it's trying to debunk: are we talking abouy caffeine half life or its effects; and is that 5h half life related to the metabolism of caffeine, or related to its effects.
It looks like pharmacokinetics (ie how long caffeine stays in blood) is what's been studied mostly, and that's where the 5h timeline is coming from. I couldn't find papers on the timeline of pharmacodynamics of caffeine (how long it has effects).
That's an interesting gap this article is underlining!
Nicotine is also a nice alternative to coffee. I still drink coffee but past late morning I'll usually reach for nicotine because the effect is much shorter.
It also has neuro-protective effects if you're an older gentleman.
It's also cripplingly addictive. Ask me how I know.
Its like a 45 minute decay - Im not shaking the cup's shaking. I can quit anytime I want, I just dont want to.
forehead twitch
sips half cup
BASED
I generally avoid caffeine at all costs. I'm susceptible to SVT, and I want the Adenosine to work if I should need it. Caffeine blocks Adenosine receptors. But on the rare occasion I have a single can of caffeinated Diet Coke, I experience a crash 48 hours later so profound that I cannot get out of bed that day.
Why change what works? Especially if you enjoy it.
For me a coffee is more kind of a ritual addiction.
Making coffee is often the only part of my day that I have control over.
I haven’t come across lesswrong before! Great site and this caffeine article is great presentation of data.
I feel it my due diligence to advise you that LessWrong is closely associated with the rationalists and all that comes with them. It is worth doing a tad of research into the rationalist community and Eliezer Yudkowsky before going too deep down the LessWrong rabbit hole. https://en.wikipedia.org/wiki/Rationalist_community
Regardless of the community,
Harry Potter and the Methods of Rationality is worth a read.
https://hpmor.com/chapter/1
Or a listen: https://hpmorpodcast.com/?page_id=56
One can take many good ideas from less wrong, yudkowsky et al without adopting a rationalist identity. Sure, it attracted wackos and they made a cult or two. But that could happen to anyone!
>the rationalists and all that comes with them.
What does that mean?
It's a particular variety of "everyone else is wrong (and maybe a bit stupid)".
Like, sure, sometimes you get popular nonsense like recovered memories or accidental fires can't be as hot as intentional fires or shaken-baby syndrome or bite-mark analysis. But a lot of times, everyone isn't wrong and you've just overlooked something critical or misdefined the problem.
Probably referring to https://en.wikipedia.org/wiki/TESCREAL
or, if you don't buy into the "they're all the same" arguments, at least beware of the arguments against utilitarianism https://en.wikipedia.org/wiki/Utilitarianism
Yeah but like:
>Writing in Asterisk, a magazine related to effective altruism, Ozy Brennan criticized Gebru's and Torres's grouping of different philosophies as if they were a "monolithic" movement. Brennan argues Torres has misunderstood these different philosophies, and has taken philosophical thought experiments out of context.[21] Similarly, Oliver Habryka of LessWrong has criticized the concept, saying: "I've never in my life met a cosmist; apparently I'm great friends with them. Apparently, I'm like in cahoots [with them]."
The people that coined TESCREAL seem to not really be related to rationalists, and seem to have coined a term for "those vaguely related ideas from people that do some stuff we consider wrong and we consider bad". "Evil people from San Francisco" could work just as well I think.
And wait, shouldn't I beware arguments for utilitarianism rather than against? If that's what you meant yeah I agree, especially pushed to the extreme it leads you in very weird places.
I know nothing about the drama, but treating "utilitarianism" as if it is one thing or that a particular person or group's position is identical to utilitarianism seems ironic in the context. It is like claiming all pizza is bad because I went to dominoes and didn't like the experience.
I'm not sure what the parent meant by "beware arguments against utilitarianism" - there is nothing wrong with arguing for or against utilitarianism. It's a popular moral philosophy.
You should beware of bad utilitarian arguments though, which is where you often get the real "gotta break a few eggs to make an omelette" kind of arguments that justify all manners of atrocity in service of some narrow hypothetical future good.
Like when Marc Andreessen says we should consider anyone who would do something to slow down or regulate AI advancement murderers of future humans. Bad utilitarianism right there.
Proper utilitarians are concerned with the net difference between all positive and negative consequences of actions.
Quick Wikipedia search: https://en.wikipedia.org/wiki/Zizians
Like any group of humans, there are power structures and edge cases that can lead to horrific outcomes. Giving the person that posted the warning the benefit of the doubt, I think what they are saying is that "Rationalist does not necessarily mean positive for humanity, nor even no harm for humanity". This holds for all religions and religion-like movements, of which Rationalism, in this sense, is one.
I think this holds for basically all movements in which case, I don't really understand the need to flag that website over any website.
Edit: though I don't want to diminish that this specific group is a cult with classical cult techniques like sleep deprivation and with the disastrous consequences often associated with cults.
> They claim to practice unihemispheric sleep (UHS), a form of sleep deprivation intended to "jailbreak" the mind, which they believe can enhance their commitment to their cause.[
> I think this holds for basically all movements in which case, I don't really understand the need to flag that website over any website.
Because it uses the language and thinking patterns of the Rationalists, it serves as a strong indoctrination tool. The site itself isn't bad but, as someone who flirted with those communities as a result of the site, I think the warning is deserved.
> Importantly, the primary metabolites also block adenosine receptors.
Biochemistry is rarely a one-and-done event it would seem.
This feels like a Gwern blog, or something he'd be interested in.
Gwern is active on LessWrong: https://www.lesswrong.com/users/gwern
sight correction....caffeine impacts two neuron groups not just one!
Dopamine and Noradrenaline
For dopamine its the competitive for the adenosine part of the dopamine heretodimer....meaning it prevents adenosine from binding and closing the dopamine receptor....
I use the effect on both dopamine and noradrenaline to assist in controlling my ADHD via more herb based means....
But author is yes correct that the metabolism of caffeine in how it breaks down does make the half life of its effects longer than 5 hours...I combine my dose with green tea ECGC which gives me a good focus boost of 12-16 hours...