Ugh... Romanticism, the perennial poisoner of liberal political thought. Rousseau was an idiot, savages aren't noble, the murder rates in pre-state societies were far higher than in the most violent modern ghetto, and "natural" is a (barely) descriptive term that carries no connotations of morality, desirability, or safety.
That having been said, there is a little something to the idea that compounds in use for thousands of years have been road-tested and may be safer than something we just made last week. However, plenty of mind-altering substances -- nicotine and ethanol being the prime examples, and yes, both of them have been very widely used in ritual contexts -- are highly toxic. And it's not like our ancestors had the statistical tools to figure out who died a few years earlier than average, or developed senile dementia earlier, etc. So I personally wouldn't feel very much safer if I restricted my intake to the "old standbys". Using any drug on a regular basis is, ultimately, a gamble. New research could come out tomorrow showing that caffeine causes some horrible condition, or that 2C-I regenerates brain cells. Who knows? It's all a spin of the wheel, folks, and you're fooling yourself if you think you can shade the odds more than a little bit.