[criticaltinker]

It’s a valid concern and many folks have raised it here on threads concerning this topic.

The short answer is yes: beyond mannitol, niacin, and even bespoke substances designed to mimic the organoleptic properties of ayahuasca have been used effectively as placebos.

At modest dosages (above the threshold of perception but within the therapeutic window) the side effects can be surprisingly similar in the general population, and thus difficult to distinguish for the average joe.

Of course studies vary widely in quality and rigor, so one must critique experimental design on a case by case basis.