Rethinking acute nicotine self-administration in inhaled tobacco products: A randomized clinical trial with ENDS in young adults.

Abstract

Puffing behavior is often interpreted through a nicotine titration model, which posits that individuals adjust puffing to achieve the central nervous system effects of nicotine. This model has been invoked frequently to explain the phenomenon of "compensation," in which people increase puffing intensity when using reduced-nicotine products. However, puffing patterns may also be governed by sensory feedback in the upper airways. This study tests that hypothesis using electronic nicotine delivery systems (ENDS) as a model. Within-subject, double-blind clinical study using a puff-by-puff switching protocol. Clinical Aerosol Technology Lab, American University of Beirut; December 2024. Ten adults who consume both ENDS and cigarettes completed three randomized directed puffing bouts during a single clinical lab visit. In each bout, they alternated puffs between two identical ENDS devices differing by one design factor: (1) power (20W vs 40W, 0mg/ml nicotine); (2) power (20W vs 40W, matched nicotine flux); (3) PG:VG ratio (30:70 vs 70:30). Puff topography and sensory feedback (mouthful, draw effort, throat hit) measured on a puff-by-puff basis. Puff duration responded immediately and reversibly to changes in sensory feedback. At higher power, participants reported stronger mouthful, easier draw, and took shorter puffs regardless of nicotine content (p < .05). At matched flux, computed nicotine dose was lower at 40W than 20W (p < .01). PG:VG effects were also significant. Puffing behavior appears to be driven by sensory cues, not delayed nicotine effects-highlighting an underused regulatory pathway: targeting product design features that shape perception.