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

Abstract

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.

Trial registration: ClinicalTrials.gov Identifier: NCT04399031.

Figure 1.. Study Flow Diagram and Schematic

eCigarette indicates electronic cigarette. ^aMean of like, dislike (reverse-scored), and willingness to use again ratings on visual analog scale. ^bSmoothness measure introduced into the study after the first 8 participants had already completed the protocol.

Figure 2.. Mean (SE) Appeal and Sensory Attribute Ratings, by Nicotine Formulation of Electronic Cigarettes

The number of participants was 119 for all outcomes except harshness (n = 111). Appeal refers to the mean of liking, willingness-to-use-again, and disliking (reverse-scored) (range, 0-100) scores.

Figure 3.. Nicotine Formulation Effect Estimates, Stratified by Flavor

The number of participants was 119 for all outcomes except harshness (n = 111). Effect estimate (salt vs free-base). Error bars are 95% CIs. Appeal refers to the mean of liking, willingness-to-use-again, and disliking (reverse-scored) (range, 0-100) scores. e-Cigarette indicates electronic cigarettes.

Figure 4.. Mean (SE) Appeal and Sensory Attribute Ratings of Electronic Cigarettes, by Nicotine Formulation in Ever and Never Smokers

Never smokers (n = 14): smoked <100 combustible cigarettes in lifetime. Ever smokers (n = 105): smoked ≥100 combustible cigarettes in lifetime. Appeal refers to the mean of liking, willingness-to-use-again, and disliking (reverse-scored) (range, 0-100) scores. ES indicates ever smoking participants; NS, never smoking participants. ^aP value for test of interaction between nicotine formulation and ever smoking status.