Abstract
The 2018 U.S. Farm Bill inadvertently paved the way for a market of unregulated, hemp-derived cannabinoid vaping products, including cannabidiol (CBD) and Δ8-tetrahydrocannabinol (Δ8-THC). These products contain extremely high cannabinoid concentrations, contaminants, and potentially harmful byproducts from heating, raising concerns about respiratory toxicity. This review examines the regulatory landscape, manufacturing practices, composition, and toxicological mechanisms associated with hemp-derived cannabinoid vaping products. While vaping-related lung injuries, such as E-cigarette or Vaping, Product use-Associated Lung Injury (EVALI), have been linked to vitamin E acetate (VEA), a definitive mechanism of injury has not been established, and cases continue to be reported. Studies reveal multiple mechanisms of lung toxicity associated with cannabinoid vaping, including inflammatory responses, oxidative stress, and damage from contaminants like heavy metals and flavoring agents. Emerging evidence also highlights the formation of reactive cannabinoid quinones (e.g., CBDQ) during vaping, which form covalent adducts with protein cysteine residues, potentially altering their function, and also have the potential to drive oxidative damage through redox cycling. These electrophilic quinones may act as pleiotropic modifiers of cellular function and represent an important, yet understudied, contributor to cannabinoid vaping toxicity. This review identifies key research gaps, including the need for studies on chronic exposure models, mechanisms of lung injury, and the interplay between VEA, cannabinoid quinones, and other harmful byproducts. Additionally, given the potential for both therapeutic benefits and toxic effects, research should investigate optimal temperatures and formulations that balance efficacy and safety over potential toxicity caused by thermal oxidation. Overall, a comprehensive understanding of the toxicological mechanisms of cannabinoid vaping products is essential to guide public health decisions, inform regulatory frameworks, and support the development of safer products.