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Review
. 2025 Nov 1;166(11S):S111-S115.
doi: 10.1097/j.pain.0000000000003637.

Placebo and nocebo effects

Belina Rodrigues  1 , Nandini Raghuraman, Roni Shafir, Yang Wang, Lakota Watson, James Cottam, Mumtahana Nabi, Titilola Akintola, Luana Colloca
Affiliations
Review

Placebo and nocebo effects

Belina Rodrigues et al. Pain. .

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.

Keywords: Clinical trials; Conditioning; Expectancy; Expectations; Learning; Pain; Predictors; Verbal suggestions.

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