Placebo and nocebo effects: a complex interplay between psychological factors and neurochemical networks

Abstract

Placebo and nocebo effects have recently emerged as an interesting model to understand some of the intricate underpinnings of the mind-body interaction. A variety of psychological mechanisms, such as expectation, conditioning, anxiety modulation, and reward, have been identified, and a number of neurochemical networks have been characterized across different conditions, such as pain and motor disorders. What has emerged from the recent insights into the neurobiology of placebo and nocebo effects is that the psychosocial context around the patient and the therapy, which represents the ritual of the therapeutic act, may change the biochemistry and the neuronal circuitry of the patient's brain. Furthermore, the mechanisms activated by placebos and nocebos have been found to be the same as those activated by drugs, which suggests a cognitive/affective interference with drug action. Overall, these findings highlight the important role of therapeutic rituals in the overall therapeutic outcome, including hypnosis, which may have profound implications both in routine medical practice and in the clinical trials setting.

Keywords: anxiety; cholecystokinin; conditioning; dopamine; endocannabinoids; expectation; nocebo; opioid system; placebo; reward.