Harnessing placebo: Lessons from psychedelic science

J Psychopharmacol. 2023 Sep;37(9):866-875. doi: 10.1177/02698811231182602. Epub 2023 Jun 30.


The randomized controlled trial (RCT) research design assumes that a drug's "specific" effect can be isolated, added, and subtracted from the "nonspecific" effect of context and person. While RCTs are helpful in assessing the added benefit of a novel drug, they tend to obscure the curative potential of extra-pharmacological variables, known as "the placebo effect." Ample empirical evidence suggests that person/context-dependent physical, social, and cultural variables not only add to, but also shape drug effects, making them worth harnessing for patient benefits. Nevertheless, utilizing placebo effects in medicine is challenging due to conceptual and normative obstacles. In this article, we propose a new framework inspired by the field of psychedelic science and its employment of the "set and setting" concept. This framework acknowledges that drug and nondrug factors have an interactive and synergistic relationship. From it, we suggest ways to reintegrate nondrug variables into the biomedical toolbox, to ethically harness the placebo effect for improved clinical care.

Keywords: Placebo; additive model; interactive model; placebo effect; psychedelics; set and setting.

Publication types

  • Review

MeSH terms

  • Hallucinogens* / pharmacology
  • Hallucinogens* / therapeutic use
  • Humans
  • Randomized Controlled Trials as Topic


  • Hallucinogens