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 of like, dislike [reverse-scored], and willingness to use again ratings) and 4 sensory attributes (sweetness, smoothness, bitterness, and harshness; analyzed individually) on visual analog scales with not at all and extremely anchors (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 < .001), sweetness (b = 9.3; 95% CI, 7.1-11.4; P < .001), and smoothness (b = 17.4; 95% CI, 15.2-19.6; P < .001) and lower ratings of bitterness (b = -13.3; 95% CI, -15.4 to -11.2; P < .001) and harshness (b = -21.0; 95% CI, -23.2 to -18.7; P < .001). Nicotine formulation effects largely generalized across different flavors and the smoothness-enhancing and harshness-reducing effects of nicotine salt were stronger in never vs ever cigarette smokers. 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. This randomized clinical trial assessed whether controlled exposure to e-cigarette puffs with salt vs free-base nicotine formulations improved the appeal and sensory experience of vaping among adult current nicotine or tobacco product users. Question Does exposure to electronic cigarettes (e-cigarettes) in salt vs free-base nicotine formulations improve the appeal and sensory experience of vaping? Findings In this randomized clinical trial, 119 adult nicotine or tobacco product users rated puffs from e-cigarettes in nicotine salt (benzoic acid added) and nicotine free-base (no benzoic acid) formulations. Salt vs free-base nicotine formulations resulted in statistically significant higher ratings of appeal, sweetness, and smoothness, and lower ratings of bitterness and harshness. Meaning In this study, acid additives in e-cigarettes that change nicotine from free base to salt appeared to enhance the appeal and sensory experience of vaping and merit consideration in e-cigarette regulation.

Automated summary

In this randomized clinical trial, exposure to e-cigarettes with salt vs free-base nicotine formulations resulted in higher appeal, sweetness, and smoothness ratings, and lower bitterness and harshness ratings among adult nicotine or tobacco product users. The findings suggest that acid additives in e-cigarettes may enhance the sensory experience of vaping and should be considered in e-cigarette regulation.