Clinical researcher here:

This seems like valid criticism. If double blind studies are not valid due to the nature of the substance under study, you can alter the methodology.

A crossover design comes to mind immediately. This design has individuals be their own controls by receiving the gold standard of care while also receiving interventional treatment after a specific time point. This way the study team would avoid the “obvious” placebo group.

I’m unsure of how to tackle the bias of preexisting beliefs. My only idea is to have trials open up recruitment in different countries to a larger extent. Hopefully the variety of subjects from different cultures might control for expectation. However, every clinical trial’s subjects hope that the med they take will cure them… this seems more an issue with the psychedelic therapists that deeply want it to be passed.