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."
One thing you learn from reading depression papers is that there are a lot of things that supposedly have significant effects on depression according to some papers, but then fail to work when people try them or they’re tested in trials.
The linked paper is pretty obvious AI paper mill content, so I wouldn’t take anything it says as directly true without checking citations. The citation is a meta-analysis so you’d have to check the criteria and the studies.
The most common explanation for the “everything treats depression” result is inclusion of studies that have no control group. The placebo response rate in depression studies is very high as many patients revert to the mean of being not-super-depressed after they are so depressed that they enroll in a study for depression treatments. Paper writers seeking a positive result will abuse this to their benefit by omitting the control group. They’ll collect depressed patients, give them some treatment, and when the average improves they’ll publish a paper saying that the treatment has positive effects in depression. So after reading a lot of papers about depression, you start dismissing claims by default unless you can confirm they came from a properly powered, placebo-controlled, double-blind study.
But hey, if you’re already drinking coffee and enjoying it, continue to enjoy it!
One thing I've learned over the years is that specifically setting out to enjoy and appreciate something on a daily basis is beneficial to overall satisfaction with life. And for me, that's my morning cuppa before the rest of the house wakes up. Is it (just) the coffee or is it (also) the rituals surrounding coffee?
Well, that's a bit of an unfair projection; I'm fairly fastidious about keeping my consumption around 2-3 cups a day before 11am and taking occasional tolerance breaks without consequence. But if you feel like your coffee intake is a problem that you have trouble controlling, maybe cut back.
Addiction to any given substance is highly variable from person to person, and there's a lot of data to back that up.
I recall a friend describing their struggle to quit caffeine, which I mocked at first, until I realized it sounded exactly like my brutal struggle to quit nicotine. Yet, plenty of people quit cigarettes effortlessly. Nicotine is one of the most variable, but caffeine, alcohol and cocaine vary widely too. I imagine we'd find this is the case for most substances if we had the data. In a sane world, we'd give every kid their addiction predisposition profile when they turn 13.
I also enjoy my morning ritual of preparing the grinds and brewing a fresh pot. But I'll be honest, at the end of the day it doesn't really matter where I get it -- brunch at a nice restaurant, Starbucks, McDonalds, a cheap hotel buffet, lukewarm from a flight attendant ... as long as I get it. Sounds healthy, right?! ;)
It kinda makes sense if you consider depression to be a mechanism to get into winter hibernation. It's just we can't hibernate and even if we could, somebody has to pay them bills.
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.
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'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?
Not an expert, but the standout thing about ketamine in particular is that it targets an entirely different neurotransmitter pathway than almost all traditional anxiety and depression meds. Traditionally, people treating serious depression or anxiety rotate through a variety of drugs that all hit same small set of neurotransmitters and settle on the one that works the best/sucks the least.
This is why people get excited about ketamine and psychedelics as therapeutics. Otherwise, we're just sitting around waiting for the next round of "new" drugs that manipulate the same pathways as all the old drugs (and carry much of the same risks).
> sleep deprivation can temporarily boost mood in some depressed people, and research suggests this may involve a short-term surge in adenosine and other metabolic changes, similar to rapid antidepressants.
This is also true that sleep deprivation can act as shock therapy! But it seems to still indicate that depression can be caused by chronic adenosine dysfunction. So temporary sleep deprivation will put the adenosine system in a state it isn't usually in, and alleviate symptoms.
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?
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."
As if I needed another reason to drink coffee.
One thing you learn from reading depression papers is that there are a lot of things that supposedly have significant effects on depression according to some papers, but then fail to work when people try them or they’re tested in trials.
The linked paper is pretty obvious AI paper mill content, so I wouldn’t take anything it says as directly true without checking citations. The citation is a meta-analysis so you’d have to check the criteria and the studies.
The most common explanation for the “everything treats depression” result is inclusion of studies that have no control group. The placebo response rate in depression studies is very high as many patients revert to the mean of being not-super-depressed after they are so depressed that they enroll in a study for depression treatments. Paper writers seeking a positive result will abuse this to their benefit by omitting the control group. They’ll collect depressed patients, give them some treatment, and when the average improves they’ll publish a paper saying that the treatment has positive effects in depression. So after reading a lot of papers about depression, you start dismissing claims by default unless you can confirm they came from a properly powered, placebo-controlled, double-blind study.
But hey, if you’re already drinking coffee and enjoying it, continue to enjoy it!
One thing I've learned over the years is that specifically setting out to enjoy and appreciate something on a daily basis is beneficial to overall satisfaction with life. And for me, that's my morning cuppa before the rest of the house wakes up. Is it (just) the coffee or is it (also) the rituals surrounding coffee?
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
It’s 100% the addiction.
It’s ok, me too. At home I’m a 4-6 cup a day drinker. On the go 2-3 Starbucks. I have a serious problem.
People act like addiction is a word with an inherent negative connotation, but that's not the case, you can totally be addicted to healthy behaviours
That was me too. Turns out I was just self-medicating for adhd. I still skip the meds on the weekend so I can enjoy larger quantities of coffee.
I'm not gonna lie, double espresso with ritalin before work is pretty good too. It's the T+2 date which is uncool.
Well, that's a bit of an unfair projection; I'm fairly fastidious about keeping my consumption around 2-3 cups a day before 11am and taking occasional tolerance breaks without consequence. But if you feel like your coffee intake is a problem that you have trouble controlling, maybe cut back.
Addiction to any given substance is highly variable from person to person, and there's a lot of data to back that up.
I recall a friend describing their struggle to quit caffeine, which I mocked at first, until I realized it sounded exactly like my brutal struggle to quit nicotine. Yet, plenty of people quit cigarettes effortlessly. Nicotine is one of the most variable, but caffeine, alcohol and cocaine vary widely too. I imagine we'd find this is the case for most substances if we had the data. In a sane world, we'd give every kid their addiction predisposition profile when they turn 13.
Not necessarily. I only have one cup in the morning, that's it, but I enjoy it just the same so long as the beans are good and it's done right.
I also enjoy my morning ritual of preparing the grinds and brewing a fresh pot. But I'll be honest, at the end of the day it doesn't really matter where I get it -- brunch at a nice restaurant, Starbucks, McDonalds, a cheap hotel buffet, lukewarm from a flight attendant ... as long as I get it. Sounds healthy, right?! ;)
The problem is, most Americans don't drink coffee, they drink sugary mix with coffee flavor
"The mechanism of action of ketamine primarily involves modulation of mitochondrial metabolism as opposed to NMDA receptor antagonism"
More evidence for Chris Palmer's 'Metabolic Theory of Mental Disorders'
It kinda makes sense if you consider depression to be a mechanism to get into winter hibernation. It's just we can't hibernate and even if we could, somebody has to pay them bills.
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.
Completely anecdotal but I've found Ujjayi Breathing from yoga to have an enormously calming effect.
Long exhales in general with a short pause at the end, before inhaling, are also incredibly useful. I try to do this as often as I need.
I’ve found wim hof no more effective than laughing gas. Very short euphoric high then back to where I was plus a slight headache.
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.
Agreed. It even has the classic “this not that” and “from this to that” LLM tells in the headline.
I would suggest ignoring this document and reading the Nature article linked in the comment above.
Glad I wasn't the only one to suspect AI slop. The language is too self promoting and vacuous in parts. Just doesn't feel like a human wrote it to me.
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?
Not an expert, but the standout thing about ketamine in particular is that it targets an entirely different neurotransmitter pathway than almost all traditional anxiety and depression meds. Traditionally, people treating serious depression or anxiety rotate through a variety of drugs that all hit same small set of neurotransmitters and settle on the one that works the best/sucks the least.
This is why people get excited about ketamine and psychedelics as therapeutics. Otherwise, we're just sitting around waiting for the next round of "new" drugs that manipulate the same pathways as all the old drugs (and carry much of the same risks).
Nice read, I've been wondeling if coffee really had an effect on mental health too
TIL coffee is extra good for your brain
This also helps explain why extremely early waking or late sleeping is common in depression.
ChatGPT conclusion about this:
> sleep deprivation can temporarily boost mood in some depressed people, and research suggests this may involve a short-term surge in adenosine and other metabolic changes, similar to rapid antidepressants.
This is also true that sleep deprivation can act as shock therapy! But it seems to still indicate that depression can be caused by chronic adenosine dysfunction. So temporary sleep deprivation will put the adenosine system in a state it isn't usually in, and alleviate symptoms.
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?