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 dynamics occurring here too.
This ends my erowid/hive style “trip/nootropic” report ;)
Great book.
People who drink caffeine at night may claim to be able to sleep still, but they will find that deep sleep stages are shorter, which is significant because it may be the most important type of sleep.
I did this for a while working nights until I caught on. The nights I didn't have a can were much better.
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.
In your example, a 200 mg caffeine intake in the morning, least to 100mg at noon, 50mg at 5PM, 25mg at 10PM. Yes that means you still have 25mg of caffeine. But it's unlikely to have an outcome you can measure since it's below a minimum threshold.
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.
The literature for AASM protocols suggests 41 hours without caffeine is enough to safely control for those potential effects
In the new model, it's still smooth decay, but it's a compound exponential decay which is spread out over a longer time period, and close to linear for a while after that, before going on a longer exponential decline.
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.
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 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.
Billions all over the world managed to acquire it just fine.
If that's an acquired taste, I doubt 99% of drinks that aren't an acquired taste would do much better, assuming there's anything doing better than coffee to begin with.
Not even Cola and tea come close.
(And even if that source were true, that wouldn't make the genetic effect an absolute; it would depend on individual genetics and the variable expression of those genes. And probably on the individual's experience, either as a child or as an adult.)
I wouldn't be surprised if all tastes are essentially "acquired".
I agree with your main point, though. I hated coffee most of my life. Even the smell made me feel ill. At some point, I flipped. I've always liked tea, fwiw.
I guess I don't hate beer as much as I used to. Still don't like it, though. Maybe another few decades?
I don’t know where you live, but in Italy it’s extremely difficult to find a good espresso; you must go in "specialty coffee" places to taste real coffee, as all the bars use cheap coffee that tastes burnt. Ironically, it’s a country that takes pride in its coffee "tradition" but doesn’t know what coffee tastes like. The experience is the same in France, without the "tradition" thing.
I found the need I really needed satisfied was a warm cup of something to curl my hands around in the morning, and they all worked after I let them. ymmv.
Is that a warning or an endorsement?
I'm not a biologist, but I'm under the impression that your body uses the heuristic of "the more acutely a neurotransmitter is suddenly flooded into our system, the more of a homeostatic counter-response we're going to launch in the form of things like dopamine downregulation (etc, depending upon what neurutransmitter we're talking about)".
I'm not entirely sure this is true, but it seems to be corroborated by other researchers (e.g. Anna Lembke in her book Dopamine Nation, which isn't about caffeine though).
This is why substances like theacrine claim to offer even less tolerance than paraxanthine: it has a super gradual adenosine-blocking curve, with super long half-life (like 12-16 hours, IIRC). So when you take one theacrine, you won't notice it for hours, but its effects will last longer than one day (though I forget what its interaction with sleep is supposed to be?).
You have to consider pharmacodynamics: where is the site of action located, where are the receptors located. And how well do caffein and paraxanthine distribute to this compartment.
Soiler: Most metabolites are more hydrophilic than respective parent compounds (biological sense of metabolism: to increase renal clearance of xenobiotics). Therefore, receptor affinity alone tells you little about the relative contribution of any metabolite for the pharmacological effect observed.
And to complicate things even more: Long-half life metabolites are only ONE potential reason for prolonged biological effects.
Biochemistry is rarely a one-and-done event it would seem.
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!
~5 years ago I stopped drinking the afternoon coffee, and have subjectively noticed improvements in my sleep -- less wakeful in the night. It also fits better with my sleep habits, where when I was younger I commonly worked past midnight whereas now I'm asleep by 10 pm and wake up early.
I still drink the morning coffee and I wouldn't switch to another stimulant because the main reason I drink coffee is because I enjoy drinking coffee :)
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...
Harry Potter and the Methods of Rationality is worth a read.
Or a listen: https://hpmorpodcast.com/?page_id=56
And like, I'm not a writing snob. I read fanfic by amateur authors. But HPMOR just doesn't do much of anything interesting.
What does that mean?
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
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.
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.
Imagine dressing Pascal's Wager up in blinking lights and considering yourself a rationalist.
Yudkowsky banned discussion of it for 5 years because he considered it a threat
Aha: "identity". You nailed the misgivings I couldn't articulate. Thank you.
It also has neuro-protective effects if you're an older gentleman.
Years later, I replaced my ADHD medication with low-strength nicotine patches and I find it as effective, cheaper, longer-lasting and with less addictive potential than dexamphetamine. The side effects when I forget a patch are much less than not having my morning cup of coffee — just extremely distractable and lower energy.
Smoking is terrible, but I wish people learned that the effects of smoking are much more intense from the effects of pure nicotine.
That very much depends on the medium. It's virtually impossible for a nicotine naive individual to get addicted to losenges or gum.
It's all a matter of how long it takes to reach peak concentration in your blood stream. Smoking takes seconds, lozenges take minutes, a patch takes 2 to 3 hours.
If I'm on vacation I don't even think about having a gum. It's only when I'm working, notice I'm dragging, and remember the option.
