Drug effects can be heavily culturally mediated; Hanson has posted some material on alcohol in particular.

(Another n=1: I was surprised and dismayed the first time I had enough alcohol to qualify as even partially drunk, and realized that I felt incredibly depressed. This happened twice more, and I eventually gave up alcohol as a bad job. This is annoying because it limits my mead consumption, even though it also means I never need to worry about alcoholism.)