I agree with your question's points about representing the effect of Substance D and the shifting nature of reality. In the case of both A Scanner Darkly and Richard Linklater's earlier rotoscoped film, Waking Life, the medium of animation is used to challenge the audience's perception of reality.

We're constantly aware that the film is not merely creating its own world/reality (as, say, with Disney or Pixar animation), but that it is re-representing reality as we know it. We are hyper-aware that the characters in the film are animated from human actors. (And I, for one, am acutely aware that the character are the actors Keanu Reeves, Robert Downey, Jr., Woody Harrelson, etc.)

The effect is surreal and postmodern in the sense that it acknowledges that reality & experience as subjective. This is purposefully done, I believe, because it fits with the themes of the film and of its source material, written by sci-fi and speculative fiction author Philip Dick. It's an old quote, but true, that the "medium is the message."

And with A Scanner Darkly I can't think of a better way to represent the slippery nature of reality than to use rotoscoping that continues resembles the human actors, yet never quite stays stable (that shifting, watery effect); the scramble suit realized by the animation!

And for what it's worth, I think that while the drug culture is big part of the story and its representation of reality, I also believe that the themes of surveillance and paranoia play into the question of reality as well. We have characters who are constantly aware of being watched and of watching, and how those things shift our behavior and understanding of ourselves.

Richard Linklater addresses some of his motivations in this Wired article, noting his interest in representing the science fiction world Dick created and his interest in animation for an adult audience. The article also provides some background on Waking Life as well as the long process of animating A Scanner Darkly.

The video I attached also deals with Linklater's interest in how the animation affects the audience, challenging their perceptions.

As you can tell, I really liked the film – in part because I really like Dick's story. If I had one disappointment, it was that I thought the animation stayed TOO stable throughout the film. I would have played with it event more, had I been the director. Then again, the process was so time-consuming...and it's far too easy for me to criticize what should have been done because I didn't actually have to do the work. ;)

I think it was for two reasons:

1. Just because people think rotoscoping is cool. I think it looked good in the movie

2. The crazy suit Keanu Reeves' character wears fits perfectly with the weird effect of rotoscope produces. I think the whole drug theme of the movie fits with rotoscoping because some of the characters are in an altered state.