The Power of Expectation – Understanding the Placebo and Nocebo Phenomenon

Although placebo pills are supposed to have no pharmacological activity, people taking placebo pills describe a variety of positive (i.e., placebo phenomenon) and negative (i.e., nocebo phenomenon) reactions. This has major clinical implications. Placebo reactions account for a substantial part of improvement when treating patients with hypertension, mental disorders, and even after surgical procedures. The nocebo phenomenon on the other hand is responsible for non-compliance and discontinuation of many pharmaceutical interventions. Mechanisms that underlie the placebo and nocebo effects may be related to expectation and/or classical conditioning, but some methodological issues should also be considered. Most experimental studies investigating the placebo effect have used paradigms to induce ‘placebo analgesia’, the reduction of pain perception after receiving an inert substance and an instruction that this medication would relieve pain. This paradigm allows investigators to examine the neurobiological circuitry of the placebo response using neuroimaging techniques. The term placebo is rooted in the Latin word ‘placare’ meaning ‘to please you’. The placebo effect refers to the positive consequences of unspecific factors that are associated with a treatment. Placebos are usually chemically inert substances that do not act directly at the biochemical substrate of medical conditions. Instead, it is assumed that placebos work through unspecific psychological factors, such as patient expectancy of treatment benefits. However, this notion is problematic because there is no commonly accepted definition of the placebo effect, and because the effect is accompanied by many biochemical changes as we will outline in this paper. The distinction between ‘specific’ treatment effects (e.g., the ‘real’ drug action) vs. ‘unspecific’ treatment effects (the placebo reaction) is problematic. Rather than distinct categories, both terms should be considered as theoretical endpoints of a continuum of specificity of treatments. The middle of the last century was crucial for recognizing the relevance of placebo effects. Beecher (Beecher, 1955) published an article entitled ‘The powerful placebo’. In this article, the author reported that about one