It'd be extraordinary compelling to genuinely have a unified mechanism to explain depression treatments, but I am not qualified to make heads or tails of the research. Wondering what the take of those with relevant experience is on this?
On chronic coffee consumption: "One meta-analysis found that RR coffee 0.757, RR caffeine 0.721 (12). Another one found RR 0.76, with an optimal protective effect at ∼400 mL/day (13). In comparison to many drug treatments that have an effect size in this range, this is not a small effect size. A risk reduction of 20 to 25% is quite impressive."
IMHO Coffee is way too strong for most of us. Sipping green tea gives a smooth subtle high all day. And you can sleep at night. And not be an angry/anxious bastard.
I tried it but coffee to me just tastes horribly bad. Chocolate on the other hand can be quite great (there is also a lot of horrible chocolate, but good chocolate has a better taste to me than coffee.)
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.
It seems that a session like 10×100 m sprints with <90 seconds of rest produces a metabolic pattern very similar to acute intermittent hypoxia, short intense bouts with incomplete recovery. Am I thinking about this right?
I never knew that “acute intermittent hypoxia” was a known treatment for depression, but I’ve found both freediving and Wim Hof breathing to be effective at treating my depression- however never the two at the same time as that is extremely dangerous.
Wholly anecdotal, but as a 52 year old nearly-lifelong caffeine (ab)user I quit this year and the withdrawal period was horrendous -- not for the headaches everyone knows about (they were bad but only lasted a couple of days) but for the somewhat extended depression/anhedonia which I had never really experienced before.
I was worried during that stretch of time that maybe the caffeine had been masking some underlying depression I already had, but a couple of weeks in it passed, so I think my brain just needed to rebalance itself to the new caffeine-free reality.
I'm glad I quit (less anxiety, better sleep, I'm finding it a lot easier to eat healthy while not buzzed on caffeine all the time, and the depressive episode was temporary) but going through that makes it pretty easy for me to believe caffeine can have rather powerful effects in this area.
I think a lot of the difficulty in quitting can be mitigated by slowly titrating down the dose over a month or two instead of quitting cold turkey.
But your experience mirrors mine in going cold turkey which I think demonstrates that caffeine can cause both physical chemical dependence, and psychological addiction.
Maybe this is normal for mice but the dose of ketamine used (5-20 mg/kg) seems high? I know mice metabolism is very different but that's in the range of a gram of ketamine for a normal sized human.
The mice may not have been depressed because it's hard to be depressed when you're in a k hole
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:
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.)
Here in Finland we have the world's highest coffee consumption per capita, and also long, dark winters. Is it a coincidence? I don't think so.
I've found combination of coffee and light therapy to be quite effective against seasonal affective disorder (the kind of temporary depression where lack of sunlight is a significant cause).
17 comments
[ 1.4 ms ] story [ 44.5 ms ] threadAs if I needed another reason to drink coffee.
I tried it but coffee to me just tastes horribly bad. Chocolate on the other hand can be quite great (there is also a lot of horrible chocolate, but good chocolate has a better taste to me than coffee.)
More evidence for Chris Palmer's 'Metabolic Theory of Mental Disorders'
I was worried during that stretch of time that maybe the caffeine had been masking some underlying depression I already had, but a couple of weeks in it passed, so I think my brain just needed to rebalance itself to the new caffeine-free reality.
I'm glad I quit (less anxiety, better sleep, I'm finding it a lot easier to eat healthy while not buzzed on caffeine all the time, and the depressive episode was temporary) but going through that makes it pretty easy for me to believe caffeine can have rather powerful effects in this area.
But your experience mirrors mine in going cold turkey which I think demonstrates that caffeine can cause both physical chemical dependence, and psychological addiction.
The mice may not have been depressed because it's hard to be depressed when you're in a k hole
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
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.)
I've found combination of coffee and light therapy to be quite effective against seasonal affective disorder (the kind of temporary depression where lack of sunlight is a significant cause).