Inventi Rapid: Ethnopharmacology

Inventi:prep/113466/25

Anticipatory Harm as a Neuropsychological Modifier of Drug Response: A Novel Review of the Nocebo Effect for Contemporary Pharmacology

The nocebo affect-adverse physiological or psychological responses emerging from negative expectations-has re-emerged as a dominant modifier of therapeutic outcomes in contemporary. While placebo research has historically emphasized the enhancement of healing, nocebo science probes the darker counterpart: how anticipatory harm, fear and negative cognitive schemas exacerbate symptoms, reduce drug efficacy and modulate neurobiological pathways. Despite major advances, no comprehensive synthesis situates anticipatory harm within its evolving neuropsychological, neurobiological and socio-technical context. This review integrates findings from neuroimaging, molecular neuroscience, psychoneuroimmunology, cognitive psychology and digital-era communication theory to provide a unified framework for understanding nocebo-driven drug modulation. Mechanistic insights are drawn from expectancy theory, dopaminergic attenuation, heightened cholecystokinin (CCK) signaling, hyperalgesic circuitry and altered prefrontal–limbic dynamics. Emerging concerns—digital nocebo, misinformation amplification, global pharmacovigilance distortions and clinical communication failures—are critically assessed. Finally, the article argues that “anticipatory harm” represents a distinct neuropsychological construct that modifies drug response via layered processes involving expectancy, socio-contextual priming, cognitive threat modeling and neurobiological sensitization. Incorporation of anticipatory harm into pharmacological modelling could transform drug development, regulatory science and clinical risk communication beyond 2025....