Nicotine
I found a post from a long time ago where someone described having a POIS-like reaction to nicotine. He described it as unusually dysphoric and anxiety-inducing, and definitely not the usual focus enhancing effect nicotine has. He said even after one regular use of nicotine (I think he was talking about vaping) his head-space would be slightly altered for the rest of the day. This is true for myself as well.
I’m wondering if anyone else has had similar experiences. If it turns out to be the case that POIS-ers generally don’t react to nicotine normally, this could be a clue as to what neurological differences, such as altered receptor behavior, could have a part in POIS. (If not, of course, then this is a dead end. But my own reaction to nicotine is so strange that after seeing a post on here detailing a similar experience I thought there’s at least a decent chance this line of thought will yield something interesting.)