The randomized controlled trial (RCT) design assumes a drug's specific effect can be separated from nonspecific context and person effects, but ample evidence shows that physical, social, and cultural variables not only add to but also shape drug effects. Harnessing these placebo effects for patient benefit is challenging due to conceptual and normative obstacles. A new framework inspired by psychedelic science's 'set and setting' concept acknowledges that drug and nondrug factors interact synergistically, suggesting ways to reintegrate nondrug variables into biomedical practice to ethically use placebo effects for improved clinical care.
A Delphi consensus study with 89 experts from 17 countries identified 30 extra-pharmacological variables that are important or very important for reporting the setting in psychedelic clinical trials. These variables, forming the ReSPCT guidelines, cover physical environment, dosing session procedure, therapeutic framework and protocol, and subjective experiences. The findings reveal significant ambiguities in current conceptualizations of set and setting. The guidelines provide a new standard for designing and documenting contextual factors in psychedelic research.