Nature of the placebo and nocebo effect in relation to functional neurologic disorders

Placebos have long been considered a nuisance in clinical research, for they have always been used as comparators for the validation of new treatments. By contrast, today they represent an active field of research, and, due to the involvement of many mechanisms, the study of the placebo effect can actually be viewed as a melting pot of concepts and ideas for neuroscience. There is not a single placebo effect, but many, with different mechanisms across different medical conditions and therapeutic interventions. Expectation, anxiety, and reward are all involved, as well as a variety of learning phenomena and genetic variants. The most productive models to better understand the neurobiology of the placebo effect are pain and Parkinson's disease. In these medical conditions, several neurotransmitters have been identified, such as endogenous opioids, cholecystokinin, dopamine, as well as lipidic mediators, for example, endocannabinoids and prostaglandins. Since the placebo effect is basically a psychosocial context effect, these data indicate that different social stimuli, such as words and therapeutic rituals, may change the chemistry of the patient's brain, and these effects are similar to those induced by drugs.