Aren’t most “artificial” substances more likely to be carcinogenic or toxic than something occurring naturally? Or is that just my wacky personal bias talking?
I don't know if this addresses the root of the question though, which is - of things occurring naturally vs those man-made, is there a statistically significant difference in safety of ingesting those found in nature.
I'd imagine there is, or at the very least we'd have millions of years worth of evolution to learn to dislike the taste of naturally occurring things that are bad for us in the vast majority of cases.
Absolutely, there are few weight loss / irritable bowel syndrome drugs more effective, though it is of course horribly addictive. But tobacco is a lot more than just pure nicotine, and that's where the problems come in.