The first thing that came to mind was Ultimate X-Men 94 when Colossus revealed that he took the drug Banshee for several reasons. I've been reading the X-Men for half my life and to have a member on drugs really shocked me, even with it being the Ultimate version of the team. I also loved the idea that he had this steel body but didn't have the strength to support all that weight. It was one of the most original ideas I've seen in a while.