Acute Effect of Electronic Cigarette-Generated Aerosol From Flavored CBD-Containing Refill Solutions on Human Bronchial Epithelial Cells.

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. 2020 Oct 21;11:592321.

doi: 10.3389/fphys.2020.592321. eCollection 2020.

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Noel J Leigh et al. Front Physiol. .

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Abstract

Introduction: Although electronic cigarettes (e-cigarettes) were originally developed to deliver aerosolized nicotine to lungs, recent data have shown that consumers also use them for inhalation of other drugs, including cannabidiol (CBD). The aim of this study was to test the acute inhalation toxicity of flavored CBD-containing aerosols emitted from e-cigarettes. Methods: Bronchial epithelial cells (H292) cells were exposed to aerosol generated from e-cigarettes refilled either with (1) propylene glycol solvent only (PG, control), (2) commercially purchased unflavored solution with CBD, or (3) commercially purchased solutions with and without CBD and with different flavors. The in vitro toxicological effects were assessed using the following methods: (1) trypan blue exclusion assay (cell viability), (2) neutral red uptake assay (metabolic activity), and (3) ELISA (concentrations of inflammatory mediators). Results: Most flavored products with or without CBD were cytotoxic as compared to the air control. Overall, aerosols with CBD were more cytotoxic than aerosols without CBD irrelevant of the flavoring used in the product. Although, unflavored aerosols containing CBD in PG were significantly more cytotoxic than aerosols containing only PG, not all flavored products containing CBD were significantly more toxic than the same flavored products without CBD. Most CBD containing products significantly increase the concentration of cytokines released as compared to the same flavored products without CBD. Conclusion: Different flavors show different cytotoxic effects in CBD-containing e-cigarettes. Aerosols emitted from CBD containing e-cigarettes were more cytotoxic than those emitted from CBD-free e-cigarettes.

Keywords: cannabinoids; e-cigarettes; electronic cigarettes; electronic nicotine delivery systems; flavorings; inhalation; toxicity.

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Figure 1

Figure 1

Comparison of cellular toxicity (A,B) and levels of released inflammatory mediators (cytokines/myokine, C-H) from H292 bronchial epithelial cells directly exposed at the air-liquid interface to 55 puffs of flavored and unflavored cannabidiol (CBD)-containing and CBD-free aerosols. All aerosols were generated from an eGO tank system, with battery output voltage set to 3.8 V and refilled with propylene glycol (PG)-only solution with the same CBD concentrations (1.7 mg/ml). Flavored refill solutions include: “Dark Side of the Moon” (Flavor 1, F1), “Midnight Express” (Flavor 2, F2), “Easy Rider” (Flavor 3, F3), “Lizard King” (Flavor 4, F4), and “Nice Dreams” (Flavor 5, F5) *Indicates significant difference from the air control and #indicates significant difference from the PG only solvent control (p < 0.05; Kruskal-Wallis test). Values are mean ± SEM. Results for Cell Metabolic Activity (A) were normalized to the air control.

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