Effects of "Tobacco Free" Language in Warning Labels on Perceptions of Electronic Cigarettes and Nicotine Pouches among Young Adult Men: A Randomized Trial.

Background: Manufacturers of Puff Bar electronic cigarettes (e-cigarettes) and Fre nicotine pouches claim that their products contain synthetic nicotine. The packages for Puff Bar and Fre have modified versions of the warning labels required by the Food and Drug Administration (FDA) for tobacco products, which specify that Puff Bar and Fre products contain "tobacco free" or "non-tobacco" nicotine, respectively. We evaluated whether exposure to these "tobacco free" warning labels was associated with differing perceptions about the products. Method: N = 239 young adult men who were enrolled in a cohort study completed a short online experiment. Participants were randomly assigned to view either packages of Puff Bar and Fre nicotine pouches with the standard FDA warning or packages with the standard FDA warning + the tobacco free descriptor. We compared harm and addictiveness perceptions and products' perceived substitutability for cigarettes and smokeless tobacco (SLT) by exposure to a "tobacco free" warning. Results: Viewing a Puff Bar package with a "tobacco free" warning label was associated with increased perceived substitutability of the product for cigarettes and smokeless tobacco (p's<.05). Viewing a Fre package with a "non-tobacco" warning label was associated with thinking the product was less harmful than SLT (p<.01). Conclusions: "Tobacco free" descriptors in warning labels for e-cigarettes and nicotine pouches affect young adults' perceptions of the products. To date, it is unclear whether the FDA will continue to permit "tobacco free" descriptors in warning labels. As e-cigarettes and nicotine pouches are increasingly marketed with "tobacco free" language, urgent action is needed.

Perceptions of Oral Nicotine Pouches on Reddit: Observational Study.

BACKGROUND: Oral nicotine pouches are a new form of tobacco-free nicotine products launched in recent years with a variety of flavors. OBJECTIVE: This study aims to examine the public perceptions and discussions of oral nicotine pouches on Reddit, a popular social media platform for sharing user experiences. METHODS: Between February 15, 2019, and February 12, 2021, a total of 2410 Reddit posts related to oral nicotine pouches were obtained over a 2-year period. After the removal of unrelated or commercial posts, 653 Reddit posts related to oral nicotine pouches remained. Topics and sentiments related to oral nicotine pouches on Reddit were hand coded. RESULTS: The number of Reddit posts related to oral nicotine pouches increased during the study period. Content analysis showed that the most popular topic was "sharing product information and user experience" (366/653, 56%), in which sharing oral nicotine pouch products and user experiences were dominant. The next popular topic was "asking product-related questions" (product properties and product recommendations; 115/653, 17.6%), followed by "quitting nicotine products" such as vaping or smoking through use of oral nicotine pouches or quitting the oral nicotine pouches themselves (83/653, 12.7%) and "discussing oral nicotine pouch-related health" symptoms or concerns related to oral nicotine pouches (74/653, 11.3%). The least popular topic was "legality and permissions" related to oral nicotine pouches (15/653, 2.3%). In addition, a greater number of Reddit posts described positive attitudes compared to negative attitudes toward oral nicotine pouches (354/653, 54.2% vs 101/653, 15.5%; P<.001). CONCLUSIONS: Reddit posts overall had a positive attitude toward oral nicotine pouches and users were actively sharing product and user experiences. Our study provides the first insight on up-to-date oral nicotine pouch discussions on social media.

Evaluating the effects of nicotine concentration on the appeal and nicotine delivery of oral nicotine pouches among rural and Appalachian adults who smoke cigarettes: A randomized cross-over study.

BACKGROUND AND AIMS: Oral nicotine pouches (ONPs) probably offer reduced harm compared with cigarettes, but independent data concerning their misuse liability are lacking. We compared nicotine delivery and craving relief from ONPs with different nicotine concentrations to cigarettes. DESIGN: This was a single-blind, three-visit (≥ 48-hour washout), randomized-cross-over study. Participants were encouraged to complete all study visits in less than 1 month. SETTING: The study took place in Rural/Appalachian Ohio. PARTICIPANTS: Participants comprised 30 adults who smoke cigarettes. Participants (meanage = 34.5) were 60% men and 90% White. INTERVENTION: Participants who were ≥ 12-hour tobacco-abstinent used: (1) a 3-mg nicotine concentration ONP, (2) a 6-mg nicotine concentration ONP and (3) usual brand cigarette in separate visits. ONPs (wintergreen Zyn) were used for 30 minutes; cigarettes were puffed every 30 sec for 5 minutes. MEASUREMENTS: Plasma nicotine and self-reported craving were assessed at t = 0, 5, 15, 30, 60 and 90 minutes. The primary outcome was plasma nicotine concentration at t = 30 minutes. A secondary outcome was craving relief at t = 5 minutes. FINDINGS: At t = 30, mean [95% confidence interval (CI)] plasma nicotine was 9.5 ng/ml (95% CI = 7.1, 11.9 ng/ml) for the 3 mg nicotine ONP, 17.5 ng/ml (95% CI = 13.7, 21.3) for the 6 mg nicotine ONP and 11.4 ng/ml (95% CI = 9.2, 13.6 ng/ml) for the cigarette. Mean plasma nicotine at t = 30 minutes differed between the 3- and 6-mg nicotine ONPs (P = 0.001) and between the 6-mg nicotine ONP and cigarette (P = 0.002). Mean (95% CI) craving at t = 5 minutes was lower for the cigarette (mean = 1.00, 95% CI = 0.61, 1.39) than either the 3 mg (mean = 2.25, 95% CI = 1.68, 2.82; P < 0.0001) or 6 mg nicotine (mean = 2.19, 95% CI = 1.60, 2.79; P < 0.0001) ONP. CONCLUSIONS: Among adult smokers, using 6-mg nicotine concentration oral nicotine pouches (ONPs) was associated with greater plasma nicotine delivery at 30 minutes than 3-mg ONPs or cigarettes, but neither ONP relieved craving symptoms at 5 minutes as strongly as a cigarette. Accelerating the speed of nicotine delivery in ONPs might increase their misuse liability relative to cigarettes.

Flavor Classification/Categorization and Differential Toxicity of Oral Nicotine Pouches (ONPs) in Oral Gingival Epithelial Cells and Bronchial Epithelial Cells.

Oral nicotine pouches (ONPs) are a modern form of smokeless tobacco products sold by several brands in the U.S., which comprise a significant portion of non-combustible nicotine-containing product (NCNP) sales to date. ONPs are available in various flavors and may contain either tobacco-derived nicotine (TDN) or tobacco-free nicotine (TFN). The growth in popularity of these products has raised concerns that flavored ONPs may cause adverse oral health effects and promote systemic toxic effects due to nicotine and other ONP by-products being absorbed into the circulatory system through oral mucosa. We hypothesized that flavored ONPs are unsafe and likely to cause oral and pulmonary inflammation in oral and respiratory epithelial cells. Before analyzing the effects of ONPs, we first classified ONPs sold in the U.S. based on their flavor and the flavor category to which they belonged using a wheel diagram. Human gingival epithelial cells (HGEP) were treated with flavored ONP extracts of tobacco (original, smooth), menthol (wintergreen and cool cider), and fruit flavor (americana and citrus), each from the TDN and TFN groups. The levels of ONP-induced inflammatory cytokine release (TNF-α, IL-6, and IL-8) by ELISA, cellular reactive oxygen species (ROS) production by CellRox Green, and cytotoxicity by lactate dehydrogenase (LDH) release assay in HGEP cells were assessed. Flavored ONP extracts elicited differential toxicities in a dose- and extract-dependent manner in HGEP cells 24 h post-treatment. Both fruit TDN and TFN extracts resulted in the greatest cytotoxicity. Tobacco- and fruit-flavored, but not menthol-flavored, ONPs resulted in increased ROS production 4 h post-treatment. Flavored ONPs led to differential cytokine release (TNF-α, IL-6, and IL-8) which varied by flavor (menthol, tobacco, or fruit) and nicotine (TDN vs. TFN) 24 h post-treatment. Menthol-flavored ONPs led to the most significant TNF-α release; fruit TFN resulted in the most significant IL-6 release; and fruit TDN and tobacco TFN led to the highest release of IL-8. Subsequently, human bronchial epithelial cells (16-HBE and BEAS-2B) were also treated with flavored ONP extracts, and similar assays were evaluated. Here, the lowest concentration treatments displayed increased cytotoxicity. The most striking response was observed among cells treated with spearmint and tobacco flavored ONPs. Our data suggest that flavored ONPs are unsafe and likely to cause systemic and local toxicological responses during chronic usage.