Effect of Exposure to e-Cigarettes With Salt vs Free-Base Nicotine on the Appeal and Sensory Experience of Vaping
Authors: Adam M. Leventhal, Danielle R. Madden, Natalia Peraza, Sara J. Schiff, Lucas Lebovitz, Lauren Whitted, Jessica Barrington-Trimis, Tyler B. Mason, Marissa K. Anderson, Alayna P. Tackett
Journal: JAMA Network Open (2021)

<h3>Importance</h3> 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. <h3>Objective</h3> 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. <h3>Design, Setting, and Participants</h3> 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. <h3>Interventions</h3> 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. <h3>Main Outcomes and Measures</h3> Self-reported appeal (mean of<i>like</i>,<i>dislike</i>[reverse-scored], and<i>willingness to use again</i>ratings) and 4 sensory attributes (<i>sweetness</i>,<i>smoothness</i>,<i>bitterness</i>, and<i>harshness</i>; analyzed individually) on visual analog scales with<i>not at all</i>and<i>extremely</i>anchors (range, 0-100). <h3>Results</h3> 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;<i>P</i> &lt; .001), sweetness (b = 9.3; 95% CI, 7.1-11.4;<i>P</i> &lt; .001), and smoothness (b = 17.4; 95% CI, 15.2-19.6;<i>P</i> &lt; .001) and lower ratings of bitterness (b = −13.3; 95% CI, −15.4 to −11.2;<i>P</i> &lt; .001) and harshness (b = −21.0; 95% CI, −23.2 to −18.7;<i>P</i> &lt; .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. <h3>Conclusions and Relevance</h3> 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. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT04399031