[hilbert42]

I find discussion about caffeine sensitivity in humans rather fascinating given the very broad range of the amount required to induce an effect.

If those above are to be believed (or not suffering a psychosomatic response) and are still affected by decaffeinated coffee then the dosage between different individuals for given psychotropic effects to occur could be as high as 100:1.

As someone who can drink copious nubmers of cups of coffee in a single sitting and notice very little effect I'm curious to know why this range is so wide (heaven help patients, doctors and pharmaceutical manufacturers if all drugs had such a wide range).

Whenever I raise this the common retort is that I've developed a tolerance to caffeine, and no doubt that's true to some extent. But from experience it's pretty limited, I've been in situations where I've not had caffeinated drinks for months and not noticed any difference when I returned to them. Also, decades ago when I was a student I took up coffee to help stay awake whilst studying and it was pretty inefective. I tried evey strong brew availabe including up to five heaped teaspoons of Moccona instant coffee per cup and it was like water off a duck's back—almost useless/inefective.

The question is why do some people have a supersensitive response to caffeine whilst others do not.

[Teslazar]

There are stimulating compounds in coffee other than caffeine, so I've pondered that people who find decaf stimulating may be reacting to some of these other compounds.

Another consideration is that people seem to often report that coffee is more stimulating than caffeine pills, even if the amount of caffeine is similar.

[hilbert42]

"There are stimulating compounds in coffee other than caffeine,…"

OK, that makes sense and I'm not surprised. I claim no expertise in coffee chemistry but I'd guess there'd likely be small amounts of other xanthines including xanthine, theophyline, theobromine [we ought to stop using that confusing name] and perhaps others. Are you referring to these or another class of drugs altogether?

You know, your mention that others report coffee more stimulating than caffeine pills got me thinking. As I said in my other comment, caffeine did little for me when I was studying, heaps of instant coffee made very little difference. I'd not mentioned it but I'd also tried OTC caffeine pills and they were pretty useless (and instant coffee was cheaper).

Now to an interesting connection you've just reminded me of. Some years after I'd finished studying (trying to stay awake with caffeine), we used to frequent a little French restaurant that served an unusual type of coffee that I enjoyed very much.

Being a frequent customer I asked the owner what type of coffee he was serving and he told me it was a special New Guinea blend that he'd specifically selected for the restaurant.

Now to the interesting part: as I said, many cups of caffeine-laden coffee have little effect on me but this coffee was something else altogether. Within a short time of consuming a cup or two I'd get a sudden urge to urinate, similarly my partner and the coffee had an even stronger effect on her than it did me. This wasn't an isolated case, it happened whenever we went to the restaurant, in fact we used to joke about it.

I need to add that I've always had a pretty good bladder, for example I've crossed the Pacific from Los Angeles to Sydney numbers of times without needing to use the restroom. So there was something rather unusual about that coffee. It's only a guess but I'd reckon it likely had much more than the usual trace of theophyline in it. Perhaps there were much higher levels other xanthines as well.

Hum, now I'm wondering whether these methylxanthines can act synergistically when in certain combinations/ratios. If it wasn't one or more of them in combination in that coffee then I wonder what other drug could have caused the strong diuretic effect.

Thanks for you point, it's made me think.

[Teslazar]

I'm no coffee chemistry expert either, but the following article indicates that the main adenosine receptor antagonists are caffeine, theophylline, and theobromine, all of which are found in coffee, tea, and chocolate (https://en.wikipedia.org/wiki/Adenosine_receptor). These three are all considered purines and therefore molybdenum would be involved in breaking them down. All three also have a diuretic effect (1) and Theobromine "shows strong diuretic effects" (2). That leads me to wonder if the ratio of these three varies significantly between coffees. I'm not sure but found one paper that shows that it does in cocoa (3), so perhaps it does in coffee also (there's probably research on coffee about this and I just didn't look hard enough).

(1) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4383091 (2) http://medical-technologies.eu/upload/1.effects_of_coffee_al... (3) https://www.sciencedirect.com/science/article/pii/S030881460...

[hilbert42]

Thanks for the references. Just had an initial look and I'll return to them shortly. I was already aware the action of xanthine class drugs is centered on the adenosine receptors but I've little deeper knowledge of the subject, drugs and their biological action isn't my field so I'll have to take the documents slowly.

However, I've already noted in (2) a statement under Theobromine that it's a strong diuretic. That's interesting but what does strong mean here? I dislike simple-notion words in papers unless they're quantified (they require numbers against them).

That said, that's not a criticism of the paper having just glanced at it, and it has lots of other interesting stuff I'll need to read in detail. What's particularly relevant about the theobromine entry is this mention of the molecule's strong diuretic effect. When I made my point towards the end of my comment that that particular coffee 'likely had much more than the usual trace of theophyline in it', I deliberately left out reference to theobromine because I'd seen references that it was biologically less active than either theophyline and caffeine.

What was implied was that when evaluating the effects of coffee that theobromine was essentially considered irrelevant because it wasn't as biologically potent as either theophyline and caffeine and that its concentration in coffee is considerably lower than either of the other two.

Perhaps the earlier reference (which I've to locate again) was referring to theobromine's psychotropic effects rather than its diuretic effects. I'll now have to review and revise my understanding of common xanthines to correct my misunderstandings.

As someone who's not professionally involved in this field I sometimes think I'm a little mad for allowing my curiosity to get the better of me. :-)