Question Do salt-based nicotine and menthol flavoring additives in e-cigarettes increase abuse potential among young adults?
Findings In this crossover randomized clinical trial of 72 participants aged 21 to 25 years who used e-cigarettes, salt-based (vs freebase) nicotine resulted in higher nicotine intake after both 5-minute standardized and 30-minute ad libitum vaping, particularly at 5% (vs 1%) nicotine. Compared with freebase nicotine, nicotine salts yielded more positive subjective effects ratings and intense puffing behaviors, and menthol (vs tobacco) flavor yielded more positive subjective effects ratings.
Meaning The findings imply that salt-based nicotine formulations prevalent in the market may increase nicotine dependence among young adults already using e-cigarettes and warrant regulation.
Abstract
Importance Concerns have been raised about the abuse liability of modern e-cigarettes that use acidic additives to form nicotine salts, making the inhalation of nicotine smoother than freebase nicotine.
Objective To examine the effects of nicotine form and concentration and e-liquid flavor on subjective effects ratings, vaping behavior, and nicotine uptake among young adults who use e-cigarettes.
Design, Setting, and Participants In this single-blind, within-participant, crossover randomized clinical trial, a convenience sample of young adults aged 21 to 25 years who currently used e-cigarettes was recruited from December 2021 to August 2023, for in-person research laboratory visits in Columbus, Ohio.
Interventions Participants completed up to 9 vaping sessions, starting with their usual e-cigarette brand in the first session followed by 1 of 8 laboratory-prepared e-liquids in a randomly assigned order in each subsequent session. Prepared e-liquids varied by nicotine form (salt-based vs freebase), nicotine concentration (5% vs 1% weight per weight), and flavor (menthol vs tobacco). Each session included a 5-minute, 10-puff standardized vaping period followed by 30 minutes of ad libitum vaping.
Main Outcomes and Measures At 4 time points (0, 5, 10, and 35 minutes) during each vaping session, plasma samples were collected for assessing nicotine uptake, and self-reports of urges, craving, and withdrawal were collected via questionnaires. Positive subjective effects were self-reported after 35 minutes of vaping using a visual analog scale; urges and cravings were reported using the Questionnaire of Smoking Urges (QSU). Puff topography data were collected throughout each vaping session.
Results Seventy-two participants (mean [SD] age, 22.4 [1.4] years; 42 [58.3%] female) who sampled at least 1 laboratory-prepared e-liquid composed the analytic sample. Salt-based (vs freebase) nicotine e-liquids increased nicotine intake, with 5% salt-based e-liquids delivering the highest mean plasma levels of nicotine (11.2 ng/mL [95% CI, 9.3-13.2 ng/mL] at 5 minutes; 17.2 ng/mL [95% CI, 14.3-20.1 ng/mL] at 35 minutes) irrespective of flavors. Higher positive subjective effect ratings (eg, for liking) were received by salt-based (42.8; 95% CI, 39.4-46.1) vs freebase (32.0; 95% CI, 28.6-35.3) nicotine, 1% (43.4; 95% CI, 40.2-46.6) vs 5% (31.2; 95% CI, 27.7-34.6) nicotine, and menthol-flavored (43.2; 95% CI, 39.7-46.7) vs tobacco-flavored (31.5; 95% CI, 28.4-34.7) e-liquids. Salt-based and 1% but not menthol-flavored nicotine elicited more intense puffing (eg, 25% [95% CI, 12%-40%] more total puffs for nicotine salts vs freebase). All study e-liquids reduced urges and cravings, with 5% vs 1% nicotine being more effective (mean [SE] QSU-Desire score at 35 minutes, 15.4 [0.5] vs 16.7 [0.5]).
Conclusions and Relevance In this crossover randomized clinical trial among young adult e-cigarette users, salt-based (vs freebase) nicotine e-liquids increased nicotine intake and yielded more positive subjective effects ratings and intense puffing behaviors, suggesting higher abuse potential. Restricting the level of acidic additives and menthol flavoring may reduce the addictiveness of e-cigarettes.
Trial Registration ClinicalTrials.gov Identifier: NCT05458895
Related coverage:
Study reveals how salt-based nicotine and menthol flavors influence e-cigarette use in young adults
https://www.news-medical.net/news/20240814/Study-reveals-how-salt-based-nicotine-and-menthol-flavors-influence-e-cigarette-use-in-young-adults.aspx
“We analyzed the effects of the two major components, PG/VG [propylene glycol/ vegetable glycerin] and nicotine, on tumor development in preclinical models. We found that PG/VG promoted tumor cell migration in migration assays and contributed to more aggressive, metastatic, and immunosuppressive tumors in vivo, aggravated by the presence of nicotine… These findings suggest that the major components used in e-cigarette fluid can impact tumor development through induced immunosuppression.”
E-cigarette exposure disrupts antitumor immunity and promotes metastasis
Front. Immunol., 15 August 2024
Marcel Arias-Badia, Chien-Chun Steven Pai, PeiXi Chen, Anthony Chang, Yee May Lwin, Aahir Srinath, Jeffrey E. Gotts, Stanton A. Glantz, Lawrence Fong
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1444020/full
Note: Open Access.
