Hahaha, oh man. College AU, definitely. I don’t even want to imagine a plausible high school AU for these guys. XD
Sherlock is doing a Chemistry program and dabbling in criminal justice and music, despite the fact that nobody can figure out how he manages to carry that many credits, while John is of course in the med program. Everybody knows Sherlock. He’s as infamous among the professoriate as he is famous. He seemingly can do no wrong and yet they all want to wring his scrawny over-achieving neck.
John, meanwhile, is the good boy. Pulling great grades, doing everything right, etc. etc. They cross paths in an organic chemistry class they’re both taking.
From there, I…am short on ideas, honestly. Perhaps Sherlock stumbles upon what he’s convinced is a dastardly conspiracy spearheaded by the unspeakably brilliant Maths professor, Jim Moriarty. He drags John along for the ride, and John is at first convinced that Sherlock is high, then becomes in danger of failing his classes, and then discovers that he’s in real danger, embroiled hip-deep in a criminal conspiracy that he and Sherlock may not escape alive.