Yeah I don't know about the alcohol combo but pretty much all the APs say not to do it....it reminds me of the old-fashioned abstinence teachings where all the kids were getting pregnant because they didn't know about protection/birth control. Point blank no's just aren't super effective when it comes to people. Anyway all I could find associated with alcohol was sedation and increased side effects of the med...I didn't see anything about ineffectiveness. The smoking though cuts the drug levels in half or more which is major I'm just not sure if it takes into account levels of smoking or if it's a smoking vs not smoking thing that doesn't seem to have been specifically studied but logically it makes sense that tripling your smoking rate would increase the impact.