Evidence for pharmacological versus sensory influences on puffing behavior and nicotine extraction during ENDS use: Implications for compensation and product regulation.

Abstract

Tobacco products designed to emit less nicotine can prompt longer and more frequent puffs, a compensatory response that may undermine nicotine reduction policies. Although this behavior is often attributed to central nervous system-mediated nicotine titration, immediate sensory cues from nicotine in the mouth and throat may also contribute. We conducted a novel secondary analysis of puff topography data from two previously published laboratory studies of electronic nicotine delivery systems (ENDS). Across 129 participants, we examined minute-to-minute variations in puff duration and frequency during one-hour sessions under 11 conditions varying in nicotine concentration (0-30mg/mL), formulation (freebase vs. salt), and electrical power. Time-resolved estimates of extracted nicotine dose were computed within each session. First-puff duration differed significantly across conditions (p < .001), well before nicotine could reach the brain. These differences persisted throughout the 60-min sessions (p < .001): puff duration remained stable (p < .001), with no compensatory increases in low-flux or decreases in high-flux conditions. Extracted nicotine dose rose proportionally with flux (p < .001) and linearly over time (p < .001), showing no within-condition behavioral adjustments in response to accumulating nicotine dose. Together, these findings indicate open-loop sensory regulation, in which puffing is shaped by immediate sensory cues, rather than the closed-loop control, in which puffing would be dynamically titrated based on systemic nicotine feedback. Puffing behavior stability persisted across a wide range of nicotine dosing conditions. These results suggest that nicotine-reduction strategies that account for sensory features, in addition to nicotine content, may reduce reinforcing potential without eliciting compensatory puffing.