Effect of Exposure to e-Cigarettes With Salt vs Free-Base Nicotine on the Appeal and Sensory Experience of Vaping: A Randomized Clinical Trial

Importance Alkaline free-base nicotine is bitter and a respiratory irritant. High-nicotine electronic cigarette (e-cigarette) products contain acid additives that change nicotine from a free-base to a protonated salt chemical form, which could improve the sensory experience of vaping, particularly among never smokers unaccustomed to inhaling free-base nicotine. Objective To determine whether exposure to e-cigarettes with salt vs free-base nicotine formulations improves the appeal and sensory experience of vaping e-cigarettes and whether nicotine formulation effects differ by e-cigarette flavor and ever combustible cigarette smoking status. Design, Setting, and Participants Single-visit double-blind within-participant randomized clinical trial was conducted in an academic medical center outpatient clinical research facility in Southern California. Participants were 119 individuals with past 30-day e-cigarette or combustible cigarette use aged 21 years or older recruited from November 2019 to March 2020. Interventions Participants self-administered standardized puffs of each 10 differently flavored e-cigarette solutions using a pod-style device. Each flavor was administered in salt (benzoic acid added) and free-base (no benzoic acid) nicotine formulations with commensurate nicotine concentrations (mean, 23.6 mg/mL). The 20 solutions were administered in randomly assigned sequences. Immediately after puffing each solution, participants rated appeal and sensory attributes. Main Outcomes and Measures Self-reported appeal (mean oflike,dislike[reverse-scored], andwillingness to use againratings) and 4 sensory attributes (sweetness,smoothness,bitterness, andharshness; analyzed individually) on visual analog scales withnot at allandextremelyanchors (range, 0-100). Results Of the 119 participants; 39 (32.8%) were female. The mean (SD) age was 42.1 (14.4) years; 105 (88.2%) were ever combustible cigarette smokers, and 66 (55.5%) were current e-cigarette users. Salt vs free-base nicotine formulations produced higher ratings of appeal (salt vs free-base mean difference effect estimate: b = 12.0; 95% CI, 9.9-14.1;P  Conclusions and Relevance In this randomized clinical trial of adult current nicotine or tobacco product users, controlled exposure to e-cigarette puffs with salt vs free-base nicotine formulations appeared to increase product appeal and improve the sensory experience of vaping, particularly among never smokers. Regulatory policies limiting acid additives in e-cigarettes might reduce the appeal of high-nicotine e-cigarettes among populations deterred from vaping e-cigarettes that emit harsh aerosol. Trial Registration ClinicalTrials.gov Identifier:NCT04399031