This is a very, very subjective question. There really is no answer to it and I don't believe that it has a whole lot to do with Harm Reduction. No harm done of course, but for now I'm gonna move this out of the HR forums and see if it can find new life in DC.
As far as subjectivity is concerned, it is really going to depend heavily upon how close your relationship with that person is. If one of my students is on speed during class, I will probably just interpret that as enthusiasm for the material. If my girlfriend has taken Meth and we're hanging out after work, I'm almost certainly going to notice some difference in how she acts. She might just want to talk more than usual. Maybe she starts talking about buying a boat. Maybe she wants a pet Komodo Dragon.
Basically, if you know a person well, you can almost always ascertain that something is not quite right. You might not be able to identify the precise drug involved, but I believe it's hard to hide. Think about all the times you were baked, walking around school, town etc. like nothing's wrong. The second you walk in the house though, it's like your Mom was there waiting for you.