Reconceptualizing addiction as metabolic-arousal dysregulation: a structured theory-synthesis across neurobiological, physiological and psychological domains

BACKGROUND: Prevailing models of addiction emphasize reward dysregulation, stress neuroadaptation and impaired executive control, but typically treat metabolic disturbance as secondary. Convergent evidence across neuroimaging, physiological and endocrine domains suggests that instability in energy mobilization and utilization may play a more central role in addiction-related neuroadaptation than is currently formalized. OBJECTIVE: To develop a structured theory-synthesis reconceptualizing addiction as a disorder of metabolic-arousal regulation. METHODS: A theory-synthesis approach was applied to integrate findings from addiction neuroscience, metabolic physiology and stress psychology, mapped onto the Koob-Volkow addiction cycle. Evidence relating to cerebral glucose metabolism, autonomic regulation, endocrine function, inflammation and temporal cognition was synthesized within a unified framework. MODEL: Two dynamically interacting states are proposed. Hyperarousal, characterized as anticipatory mobilization or "living in the future," involves increased metabolic demand, sympathetic predominance and cue-driven salience. Hypoarousal, characterized as energetic constraint or "living in the past," involves reduced metabolic availability, cortical hypometabolism and ruminative cognition. These states are hypothesized to map onto phases of the addiction cycle and to be measurable via biomarkers including cerebral glucose metabolism, heart-rate variability, cortisol dynamics and inflammatory indices. CONCLUSIONS: Addiction may be usefully conceptualized as a disorder of metabolic-arousal regulation that organizes, rather than replaces, established neurobiological accounts. The model integrates findings across levels of analysis and generates testable predictions for biomarker-informed, phase-specific intervention.