I have a strange relationship with psilocybin where microdoses reliably give me an almost unbearable headache, but a large dose will reliably get rid of a headache (even a migraine in one case).

I haven’t tested it in many years (boring parent mode engaged) but that was my first experience with bizarre dose response relationships where one effect was very acutely inverted.

It took me months to figure out the source of headaches. I felt certain it couldn’t be the psilocybin because it was so good at fixing my headaches prior to that. Sure enough, I could turn the headaches on and off like a switch by taking a tiny dose or not taking it.

This reminds me of hydrogen sulfide that at low levels smells awful but at little higher doesn't smell at all, because it just fries receptors.

I wonder if it has something to do with different receptor activity at low vs. high levels. Must have been frustrating trying to figure that out, though!