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Adenosine on the common path of rapid antidepressant action: The coffee paradox

submitted by PaulHo+(OP) on 2025-12-05 22:10:50 | 193 points 148 comments
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8. exmads+kl[view] [source] 2025-12-06 00:46:19
>>PaulHo+(OP)
This appears to be some kind of AI-slop rapid response to a piece of actual research (over at https://www.nature.com/articles/s41586-025-09755-9 ). I don't mind discussing that, but this piece should never have been published. Just look at Figure 2 if you don't believe me, or the publication timeline.
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19. pentap+0p[view] [source] [discussion] 2025-12-06 01:21:43
>>boothb+Wj
I've always associated this sort of life satisfaction & ritual spectrum with Zen "no-mind" [^1]

Whether it's coffee ritual, or doing dishes there's something pretty magical about the quiet flow state of engaging with the moment

[^1]: https://en.wikipedia.org/wiki/No-mind

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39. gsf_em+WC[view] [source] [discussion] 2025-12-06 03:44:01
>>k1musa+Vi
How about a reason to cycle your coffee :)

https://rouvy.com/blog/caffeine-in-cycling

Caffeine periodization in cycling: the science behind performance (2025)

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53. superk+cP[view] [source] [discussion] 2025-12-06 06:38:23
>>tayo42+FD
That's called chemical dependence and it's the point I'm trying to make. Dependence is not addiction. Addiction means wanting is hijacked, not that stopping is aversive.

Addiction and dependence have real medical meanings and in the context of this discussion and we shouldn't mix them up. See this very short and to the point lancet medical journal summary, https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0...

>Addiction (synonymous with substance use disorder), as defined by the DSM-5, entails compulsive use, craving, and impaired control over drug taking in addition to physical dependence. The vast majority of patients taking medications such as opioids and benzodiazepines are doing so as prescribed by clinicians, with only 1·5% of people taking benzodiazepine being addicted, for example. Physical dependence is much more common than addiction. Importantly, withdrawal effects occur irrespective of whether these drugs are taken as prescribed or misused.

>Failure to distinguish between addiction and physical dependence can have real-life consequences. People who have difficulty stopping their medications because of withdrawal effects can be accused of addiction or misuse. Misdiagnosis of physical dependence as addiction can also lead to inappropriate management, including referral to 12-step addiction-based detoxification and rehabilitation centres, focusing on psychological aspects of harmful use rather than the physiology of withdrawal.

>It should be made clear that dependence is not the same as addiction. The problems with prescribed drug dependence are not restricted to the small minority who are misusing or addicted to these drugs, but to the wider population who are physically dependent on and might not be able easily to stop their medications because of withdrawal effects. Antidepressants (superkuh note: and caffeine) should be categorised with other drugs that cause withdrawal syndromes as dependence-forming medications, while noting that they do not cause addiction.

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54. superk+NP[view] [source] [discussion] 2025-12-06 06:47:21
>>ses198+qE
"Addiction and physical dependence are not the same thing" https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0...
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63. dist-e+mV[view] [source] [discussion] 2025-12-06 08:23:08
>>Univer+jS
Caffeine, unlike some drugs and alcohol, doesn't cause severe withdrawal symptoms. Because of that, experts don't label regular caffeine use as an addiction.

https://www.webmd.com/diet/caffeine-myths-and-facts

72. gavinr+WY[view] [source] 2025-12-06 09:11:25
>>PaulHo+(OP)
To add something constructive:

I've used a novel nootropic which is an adenosine antagonist (KW-6356) for long-lasting energy without dopaminergic stimulation. Something I found and which is commonly reported by other users is mood-enhancing properties:

https://en.wikipedia.org/wiki/Sipagladenant

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76. zrm+y21[view] [source] [discussion] 2025-12-06 09:59:50
>>dotanc+8X
Ritalin is a chemical relative of amphetamine. In prescribed amounts it's often an effective treatment. In recreational amounts, ask your doctor about ΔFosB:

https://en.wikipedia.org/wiki/FOSB#DeltaFosB

90. shevy-+Ui1[view] [source] 2025-12-06 13:10:32
>>PaulHo+(OP)
> applied GRABAdo1.0, a GPCR-based sensor for adenosine

At first the intro was:

> Using genetically encoded adenosine sensors

And I did not know what was meant with that. Lateron this became more clear - GPCR is a common motif for membrane-based receptor systems. https://en.wikipedia.org/wiki/G_protein-coupled_receptor

So, saying it is "genetically encoded" xyz, means absolutely NOTHING at all, because all the other receptors based on GPCR (see the wikipedia article) are ALSO "genetically encoded". After all some stretch of DNA yields mRNA which in turn is translated into the corresponding aminoacid sequence (= protein), if we ignore splicing and so forth to simplify this (and then transport into the membrane). This is supposed to be a scientific article though - why do they use such a strange terminology e. g. "genetically encoded"? I mean, this follows by simple logic unless it was made completely artificially. Lateron in the article it is more clear, but it is strange that they use those words in the summary-intro part. It almost seems to me as if they wanted to integrate certain keywords as buzzwords or to rank an article higher. I don't quite like that.

Contrast this to Watson and Crick from 1953:

"It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material."

It is probably one of the most famous intro lines, e. g. the "It has not escaped our notice" since it was so casual. (And they built their insights on data of others, so it wasn't just Watson and Crick to have made the discovery; not even only Franklin etc.. but several more that should have been credited with it. Watson and Crick's main achivement here was more that they built it together into a simple, cohesive overview and explanation model. If I recall correctly, Linus Pauling also came close but proposed three helices.)

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101. ryukop+Wo1[view] [source] [discussion] 2025-12-06 14:03:51
>>candid+fk1
The manufacturer doesn't make it clear why they axed it, but from my experience in med-tech I think this translates to "the FDA is going to balk at it"

https://www.kyowakirin.com/media_center/news_releases/2022/p...

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102. reacto+3p1[view] [source] [discussion] 2025-12-06 14:05:04
>>dist-e+mV
There’s so many layers to this. First, there’s history: Coka-cola (originally made from a Kola nut and cocaine) was told they couldn’t put cocaine in their “medicine” anymore so they just sold it as a “soft-drink” without the cocaine.

Then there’s the beverage industry who pointed out there’s caffeine in tea leaves and other plant material and that it’s not a threat: (1) US vs 40 barrels and 20 kegs of Coka-cola. Ultimately reducing the amount of caffeine in soft-drinks.

Round and round we go allowing companies to use chemicals to keep us buying their consumables.

(1) https://en.wikipedia.org/wiki/United_States_v._Forty_Barrels...

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107. bonsai+7s1[view] [source] [discussion] 2025-12-06 14:32:55
>>shevy-+Ui1
> This is supposed to be a scientific article

The 'article'[1] is completely written by an LLM.

1. https://genomicpress.kglmeridian.com/view/journals/brainmed/... currently, hopefully it is changed to the actual research link which is https://www.nature.com/articles/s41586-025-09755-9

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112. ameliu+au1[view] [source] [discussion] 2025-12-06 14:53:59
>>boothb+Wj
Coffee in the morning is especially good because it induces bowel movements.

https://www.nytimes.com/2021/11/30/well/eat/why-does-coffee-...

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119. cubefo+CD1[view] [source] [discussion] 2025-12-06 16:06:33
>>morkal+Pr1
Not really. There a things like the square-cube law and Kleiber's law which indicate that drugs don't scale with weight. See

http://clymer.altervista.org/minor/allometry.html

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133. erikro+Pb2[view] [source] [discussion] 2025-12-06 20:47:51
>>idkwha+4y1
I went to the US recently and was fully prepared to drink caffeine on the trip because of all the cool coffee shops and roasters. But I was amazed that decaf was basically a first-class citizen there. The hotel breakfast had one giant brewer for regular and the same giant brewer for decaf. It was amazing.

And it’s pretty important to realize that well-made decaf doesn’t have to taste worse than regular coffee. James Hoffmanns decaf project proved this for me, and his video about decaf sold me on the idea: decaf drinkers are the OG coffee drinker, drinking it purely for the taste, even without the drug-induced high that caffeine gives you.

https://youtu.be/yYTSdlOdkn0?si=V0xKFGCZR1-YgGmO

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