Like cosmic charlie I've had years of "experience" with mary jane (I quit awhile ago and have been sober for almost 6 months) and I've never come across any negative side effects. It is a misunderstood and horribly slandered drug, one that is safer than alcohol and tobacco (I do not condone the smoking of weed, being a reformed addict I wouldn't want any one to fall into the trap I was in, however, I think it is ludircrous that our society accpets alcohol as "legal" when it causes more harm, more deaths and a mirriad of other problems compared to weed.)
Switching back to the topic at hand, honestly I think all of them would try it at least once, but I think Twilight would be the most likely to use. Having numerous anxiety issues (something I can relate too) she would find that weed helps to calm her down and provide her with the ability to stabilize her mind (again I can relate, I smoked because it helped to control my anxiety and panic attacks, as well as other issues). The other candidates would be dashie and fluttershy (again weed helps with extreme shyness). As for pinkie, I doubt should would use long term, as it would curb her ability to party and I doubt Rarity would smoke as it would impact her ability to design.
Lastly, in regards to the weed debate there are a tremendous amount of medical benefits (ie. pain management for cancer patients, increased appetite for eating disorders, pain management for patients who cannot take pain killers...) and it would be great to see the medical community continue to utilize and evolve marijuana for medical purposes.
*again I do not condone the smoking of weed, but I'm not against it, in fact I think it should be legalized.