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.
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."
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.