Genetics and the placebo effect: the placebome

Trends Mol Med. 2015 May;21(5):285-94. doi: 10.1016/j.molmed.2015.02.009. Epub 2015 Apr 14.


Placebos are indispensable controls in randomized clinical trials (RCTs), and placebo responses significantly contribute to routine clinical outcomes. Recent neurophysiological studies reveal neurotransmitter pathways that mediate placebo effects. Evidence that genetic variations in these pathways can modify placebo effects raises the possibility of using genetic screening to identify placebo responders and thereby increase RCT efficacy and improve therapeutic care. Furthermore, the possibility of interaction between placebo and drug molecular pathways warrants consideration in RCT design. The study of genomic effects on placebo response, 'the placebome', is in its infancy. Here, we review evidence from placebo studies and RCTs to identify putative genes in the placebome, examine evidence for placebo-drug interactions, and discuss implications for RCTs and clinical care.

Keywords: COMT; RCT; no treatment control; pharmacogenomics; placebo.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Clinical Trials as Topic
  • Genetic Variation / genetics*
  • Genetics
  • Humans
  • Neurotransmitter Agents / genetics
  • Placebo Effect*
  • Randomized Controlled Trials as Topic
  • Signal Transduction / genetics*


  • Neurotransmitter Agents