[TheFattestNinja]

While I can imagine it's possible that usage of substance A "breaks" new ground in your sensitivity to substance B by "opening" some new pathways, I find it unlikely:

The "standard" pathways for most substances is to build a tolerance to it (and similar compounds) over time of use. If you drink coffee a lot you don't get hyped by the same dose of caffeine, if you drink lots of alcohol it's harder to get you drunk, etc.

So if anything I'd expect "veterans" to be less sensitive to it. But there are substances that permanently reduce your tolerance to them, usually by causing some form of permanent damage, so it's possible that you might "break" something limiting your experience.

[scotty79]

> If you drink coffee a lot you don't get hyped by the same dose of caffeine,

Depends on the dose. If you poison yourself with caffeine later you can get very sensitive to even small amounts of it.

[andybak]

Personal experience again - there are definitely substances that exhibit "anti-tolerance".