Craving to Dose Interval: A Cascade Dynamics Framework for Objective Measurement and Protocol Design in Nicotine Cessation

Nicotine addiction is a cascade process in which repeated sub-threshold perturbations gradually shift a homeostatic attractor, progressively suppressing endogenous nicotinamide production as the body recalibrates to chronic external supply. Permanent cessation requires the structural inverse: perturbations of identical magnitude applied in the opposite direction, below the homeostatic resistance threshold, until the attractor returns to its pre-addiction state and endogenous production capacity is restored. No existing cessation modality applies this perturbation. Cold turkey applies an above- threshold perturbation that triggers maximum compensatory resistance; nicotine replacement therapy applies zero net perturbation, leaving the attractor unchanged. The observed one-year cessation rates, 3–5% unaided, 12–15% with NRT, approximately 25% with combination pharmacotherapy, are predicted consequences of these dynamics, not unexplained failures. We introduce the Craving-to-Dose Interval (CDI), the interval between craving onset (homeostatic prediction signal) and withdrawal onset (physiological deficit), as a primary, objective, and manipulable protocol variable that has not previously been operationalized in cessation research. The CDI is mandatory, present in every craving event, and physiologically flexible. A 60-second delay protocol operating within the CDI applies the sub-threshold inverse perturbation required for homeostatic recalibration and restoration of endogenous nicotinamide production, the mechanism of permanent cessation. We further propose the inter-dose interval (IDI) as a primary objective outcome measure, requiring no self-report at any stage and enabling reproducible clinical trials. Implications for opioid, alcohol, and behavioral addiction cessation are discussed.