If you want to judge the safety of a drug by the what it takes to overdose you should know that nicotine is one of the deadliest poisons known to man. The tobacco in cigarettes is shit, smoking the uncured tops of a tobacco plant as the natives did could put you into a coma or kill you. Nicotine is also one of the most addictive drugs known the man.
Then of course are the natural anticholinergenic deleriants such as datura that could easily kill you, or make you go temporarily insane.