Placebo and nocebo effects: how the doctor's words affect the patient's brain

Abstract

The administration of inert treatments along with verbal suggestions of either clinical improvement (placebo) or worsening (nocebo) are known to powerfully affect the course of some symptoms and diseases. In fact, placebos and nocebos have been found to affect the brain in different conditions, like pain, motor disorders and depression. It has also been shown that this may occur through both cognitive factors, like expectation, and conditioning mechanisms. In recent years, placebo- and nocebo-induced expectations have been analyzed with sophisticated neurobiological tools that have uncovered specific mechanisms at both the biochemical and cellular level. For example, positive expectations (placebos) have been found to activate endogenous opioids whereas negative expectations activate cholecystokinin. Placebos have also been found to induce a release of dopamine in the striatum and to affect the activity of single neurons in the subthalamic nucleus in Parkinson patients. There is also experimental evidence that different serotonin-related brain regions are involved in the placebo response in depression. Recently, the placebo effect has been studied with a different experimental approach, in which hidden (unexpected) medical treatments were carried out and compared with open (expected) ones. In all cases, the hidden medical treatments were less effective than the open ones. These findings show that the patient's awareness about a therapy is of crucial importance in the therapeutic outcome. Overall, all these studies show that the psychosocial context around the therapy, particularly the doctor's words, may induce changes in the patient's brain that, in turn, may affect the course of a disease.