Intended for healthcare professionals

Clinical Review State of the Art Review

Placebos in chronic pain: evidence, theory, ethics, and use in clinical practice

BMJ 2020; 370 doi: (Published 20 July 2020) Cite this as: BMJ 2020;370:m1668
  1. Ted J Kaptchuk, professor of medicine1*,
  2. Christopher C Hemond, assistant professor of neurology2*,
  3. Franklin G Miller, professor of medical ethics3
  1. 1Beth Israel Hospital/Harvard Medical School, Boston, MA 02139, USA
  2. 2University of Massachusetts Medical School, Worcester, MA 01655, USA
  3. 3Weill Cornell Medicine, New York, NY 10065, USA
  4. *Contributed equally
  1. Correspondence to: T J Kaptchuk ted_kaptchuk{at}


Despite their ubiquitous presence, placebos and placebo effects retain an ambiguous and unsettling presence in biomedicine. Specifically focused on chronic pain, this review examines the effect of placebo treatment under three distinct frameworks: double blind, deception, and open label honestly prescribed. These specific conditions do not necessarily differentially modify placebo outcomes. Psychological, clinical, and neurological theories of placebo effects are scrutinized. In chronic pain, conscious expectation does not reliably predict placebo effects. A supportive patient-physician relationship may enhance placebo effects. This review highlights “predictive coding” and “bayesian brain” as emerging models derived from computational neurobiology that offer a unified framework to explain the heterogeneous evidence on placebos. These models invert the dogma of the brain as a stimulus driven organ to one in which perception relies heavily on learnt, top down, cortical predictions to infer the source of incoming sensory data. In predictive coding/bayesian brain, both chronic pain (significantly modulated by central sensitization) and its alleviation with placebo treatment are explicated as centrally encoded, mostly non-conscious, bayesian biases. The review then evaluates seven ways in which placebos are used in clinical practice and research and their bioethical implications. In this way, it shows that placebo effects are evidence based, clinically relevant, and potentially ethical tools for relieving chronic pain.


  • Series explanation: State of the Art Reviews are commissioned on the basis of their relevance to academics and specialists in the US and internationally. For this reason they are written predominantly by US authors

  • Contributors: All authors contributed and provided input to the entire manuscript. TJK drafted the first outline of the manuscript, did primary literature reviews, and provided the first draft of the sections on different types of placebo interventions and evidence/theory. CCH wrote the first draft of the predictive coding/bayesian brain portion of the manuscript. FGM wrote the first draft of the practice and ethics section. All authors reviewed all sections of the manuscript, engaged in interactive discussions, and made suggestion for content and references. TJK is the guarantor.

  • Funding: TJK is partially funded by NIH/NCCIH grants #R01AT008573 and #R61/33AT009306 and the Foundation for the Science of the Therapeutic Encounter.

  • Competing interests: We have read and understood the BMJ policy on declaration of interests and declare the following interests: none.

  • Provenance and peer review: Commissioned; externally peer reviewed.

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