Half joking. I found out the hard way that I have abnormal tolerances to opiates, surgeon switched me around several times, found something that worked, although not well enough on its own. It runs in the family I found out, morphine has no effect on my grandfather, which they didn't try, dilaudid worked best on both him and I, but still didn't do much at administered dosage. For reference, this was sex reassignment surgery, so not exactly something minor.

Its hard to quickly find a paper that discusses innate opiate tolerance, though I was able to quickly find a paper acknowledging it exists. In all honesty, I fear the next time I need a major surgery as I know to expect them to not really do anything. As for the tolerance, it runs in the family, as would be expected in an innate tolerance. On a molecular level, it has to do with genetic variances in receptor type and frequency. I could go into nauseating detail, but I'm pretty sure we all know that its something covered at the undergrad level. Psychiatrics sees a lot of this, as individual variance has a huge impact on which medication has a meaningful impact, if any. If the key doesn't fit the lock, you are sol.

In my case, don't bother with morphine, it won't do a damn thing, same goes for hydrocodone, hydromorphone works, though not as effectively as it seems to work with others, don't bother with oxycodone as I build too much of a tolerance to it within days. The surgeon tried another opiate that I don't recall the name of, well, it did nothing. We settled on hydromorphone. Looking back, the hydromorphone would have likely bee more effective if paired with an anxiolytic, something like 0.5 mg lorazepam administered twice daily over the interval where pain is expected to be worst probably would have been sufficient. Why a benzo? The relationship between anxiety and pain.

First two lines of that quote were entirely sarcasm, though as explained, I have a genetic tolerance that makes things a pain, both figuratively and literally.