Placebo and nocebo effects - a synthesis of main underlying mechanisms

Abstract

Introduction. Although the effects of placebo have been known in medicine for several centuries, the research of the underlying mechanisms has developed relatively recently. Consequently, in the last decades, numerous studies and researches have been published, most of them focused on symptoms such as pain, fatigue, nausea and itching. Aim of the study. To disclosure the main mechanisms underlying the placebo and nocebo effects. Materials and methods. The study was performed in the base of reviewes of various researches and scientific materials (articles in specialized journals, monographs and articles on the Internet etc.) that refer to placebo/nocebo effects description and observation. Results. The classical conditioning theory and the response expectancy model were considered for a long time the most accepted theories explaining the underlying processes of placebo/nocebo phenomena. Numerous researches revealed that suggestions, thoughts and beliefs could have an important influence on human body, thus giving rise to specific therapeutic processes. However, placebo and nocebo effects are not mediated only by psychological mechanisms. There is a clear evidence of neurobiological changes at different levels and areas of the brain, involving endogenous opioids, as well as dopamine, especially in the case of the analgesic placebo effect. Similarly, such neuromodulators as cholecystokinin play a significant role in the nocebo effect. The findings concerning the involvement of the genetic mechanisms in the process of manifesting placebo/nocebo effects cannot be neglected. In the last years, the studies reveal that genetic variations in the brain's neurotransmitter pathways could influence placebo effects, the incipient evidence being provided with regard to existence of genes that mediate placebo effects in individual patients. Placebo/nocebo genetics is an area in which research is only in a quit early phase. Conclusions. The study results evoke the complexity of the placebo and implicitly nocebo phenomena and the difficulty of formulating a generally valid theory, which could explain in a clear and complete manner how they function. The described mechanisms have to be regarded in a complementary manner and must be analyzed and regarded as a whole. It is worth to continue the investigations of placebo/nocebo mechanisms so as to optimize the therapeutic interventions and to improve the design of clinical trials.