Placebo and nocebo effects.

Abstract

We introduce the Psychoneurobiology, Individualization, and Normalization (PIN) framework of placebo and nocebo effects. Traditionally, research primarily focused on psychoneurobiological mechanisms of these effects, the Psychoneurobiology phase. Recently, AI-driven tools are being used to predict placebo/nocebo responses, whereas digital therapeutics like virtual reality and artificial intelligence-assisted cognitive training are being used to enhance and personalize these effects, the Individualization phase. We envision the Normalization phase, where insights from the 2 phases are integrated into mainstream medicine. This includes incorporating open-label and dose-extending placebos into treatment protocols and providing healthcare professionals with formal training in placebo and nocebo effects, as well as expectation management interventions.