It would be especially harmful if we ended up suppressing the processes that make you feel sleepy when you need sleep, while the harmful effects of sleeplessness remained.
Now here's the kicker. When your body builds 'tolerance' for caffeine, what this usually means* is the post-synaptic cell adjusts how much adenosine it's pumping out so that the "I'm tired" signal can cut through the caffeine. And when you go through caffeine withdrawal, it takes a while for those levels to re-adjust to normal.
* in the brain. Caffeine also has effects on your digestive tract, blood pressure, and some other non-brain parts. :)
Edit: corrected cAMP -> adenosine (simple recall error from a lecture that was 9 years ago). The gist of the reply remains the same.
In moments of weakness and pushing a deadline, I have sometimes rationalize the trade-off of future time/health to present time, and sometimes, that sticks me with tolerance that it takes time to wean off. I have made a conscious effort to quit caffeine dozens of times in my life, and the most recent time it has stuck, and I plan to stick with it. The thing is, when I gain "time" with caffeine, it's not necessarily time with high-quality cognition or productivity compared to my well-rested self, and it's easy to forget to take that into account when you're making trade-off decisions when tired. You still perform like a tired person, you're just not subjectively feeling the tiredness.
FWIW, drinking decaf gives you the health benefits of coffee with 5% (kinda negligible) amounts of caffeine.
That said, a lot of the risky solvents used in the usual methods of making decaf are no longer commercially used these days, so I don't think there's a serious health risk in drinking any ol' decaf you want.
Notes for below:
* CHB/CHC -> chronic hepatitis B/C
* NAFLD -> Non-alcoholic fatty liver disease
When discussing possible mechanisms for their findings:
"We postulate that the observation of the benefit of coffee on the progression of liver disease may be due to its effects on the oxidative stress/lipotoxicity pathway, which underlie the pathogenesis of cirrhosis related to alcohol, NAFLD and possibly, in part, CHC. However, since oxidative stress is not the predominant mechanism of injury seen in CHB, coffee has no beneficial effect. Polyphenols and melanoidins, which are major components of coffee, have been shown to mediate multiple protective mechanisms in a rat model of steatohepatitis, ranging from increased fatty acid β oxidation, mitigating oxidative stress and curtailing liver inflammation (47). The other components of coffee, cafestol and kahwoel, can induce phase II detoxifying enzymes, including sulfotransferase, UDP-glucuronosyl transferase, glutathione transferase and peroxidase, and thus contribute to the anti-oxidant properties of coffee (14, 48). In addition, chemicals in coffee such as polyphenols and the diterpenes have been shown to down-regulate proinflammatory, fibrogenic cytokines such as transforming growth factor beta (TGF-β) and its downstream modulator, connective tissue growth factor (CTGF), collagen and stellate cell activation (13–16).
Epidemiologic studies on caffeine have been inconsistent in demonstrating a protective effect in liver disease since other caffeine-containing beverages such as tea have not shown to be protective (19–21). Similarly, in our study, the inverse association with caffeine became null after adjustment for coffee, suggesting that ingredients of coffee other than caffeine appear to be responsible for this beverage’s effect on risk reduction. Furthermore, other caffeine-containing beverages like green tea and black tea had no significant effects with cirrhosis mortality in this study."
Caffeine is more like an adenine analog, not a cAMP (3'-5' cyclic adenosine monophosphate) analog. It binds adenosine receptors, not primarily cAMP receptors. It has indirect effects on cAMP, but I am not aware of direct ones. Also, your description of cAMP signaling sounds confused, since cAMP is an intracellular second messenger. I am not aware of an extracellular retrograde signaling process for this molecule.
Sorry, and your implication that cAMP is a byproduct of ATP consumption is totally wrong. cAMP is synthesized directly from ATP, a reaction catalyzed by the regulated enzyme adenylate cyclase.
(My thesis was on auditory cognition and I haven't touched ion channel biophysics in that long. I have a long-ago memory that adenosine (now corrected) operated as a retrograde transmitter, though since I'm probably not going to spend my afternoon looking for the citations, I'll delete as well for now. Not because I believe it's wrong, just that I can't immediately back it up.)
Are you still doing research yourself or have you left for startup land like most of HN?
since bioscience isn't on my radar i'm not sure if you'd find anything useful there, however, it feels like a more concentrated version of HN which specializes in some of the other stuff that interests you (e.g. learning algos, data analysis, etc.).
"Caffeine competitively inhibits phosphodiesterase, the enzyme that degrades cyclic AMP...By blocking the degradation process of cyclic AMP, caffeine indirectly affects regulation of cAMP-dependent protein kinases". TIL.
[1] http://www.ncbi.nlm.nih.gov/pubmed/20164566
[2] http://www.sciencedirect.com/science/article/pii/S0301008204...
* not diagnosed with narcolepsy or depression already
Looking up some primary source just now: http://www.oncologypractice.com/fileadmin/content_pdf/cpn/ar...
(for some reason the UI doesn't let me reply to the reply, so here goes)
Now that I'm looking around at papers, it seems like there is evidence that it helps patients who are already depressed get some energy back.
In my opinion, efficiently using our current methods for deferring sleep boils down to understanding that you're merely deferring it, and using it to "schedule" your most awake/concentrated periods when you need it most, rather than try to force yourself to work well all the time.
Maybe one day we have something that can let us cut sleep entirely, but we're still far away from that.
EDIT: As I've clarified in another comment below, my sleep amounts without anything are already fairly low, and that may certainly affect my ability to push it further down with modafinil over the long term.
It also builds tolerance in a kind of annoying way; it prevents me from napping or sleeping even when it no longer makes me not tired.
Interesting. I can sleep just fine on modafinil, but I still have greatly increased focus if I just choose to stay awake. Also, I've never noticed any increase in tolerance (which I get very quickly with caffeine and alcohol), even taking it every day for two weeks, although maybe that's not very long.
Is there any information (affirmative or negative) about Modafinil's effects on this plaque? Considering how recent this whole discovery seems to be, I doubt there's much conclusive info on this specific interaction.
You'll probably fall asleep earlier in the day, but you'll only sleep for 8 hours. This is why it's useful for offsetting your rhythm.
Ritalin/Adderall is very different. If you use it to stay up for 8 hours, you'll sleep for 16 hours the next time you pass out.
Again, though, the data is ambiguous AFAIK.
I tend to prefer to use it to offset sleep for relatively short periods - e.g. get an extra night of work, and then sleep a bit longer for the next couple of nights - as I feel it's more productive to get a longer block of time where I'm fully alert, and give up late evenings when I'd feel tired anyway to recover.
From my subjective experience, this isn't necessarily true. All-nighters with modafinil vs. all-nighters with adderall require the same amount of catch-up sleep for me. Modafinil just gives me a less jittery wakefulness.