Cannabis Vaping: Existing and Emerging Modalities, Chemistry, and Pulmonary Toxicology

Abstract

The outbreak of e-cigarette or vaping product use-associated lung injury (EVALI) has been cause for concern to the medical community, particularly given that this novel illness has coincided with the COVID-19 pandemic, another cause of severe pulmonary illness. Though cannabis e-cigarettes tainted with vitamin E acetate were primarily associated with EVALI, acute lung injuries stemming from cannabis inhalation were reported in the literature prior to 2019, and it has been suggested that cannabis components or additives other than vitamin E acetate may be responsible. Despite these concerning issues, novel cannabis vaporizer ingredients continue to arise, such as Δ8-tetrahydrocannabinol, Δ10-tetrahydrocannabinol, hexahydrocannabinol, and cannabichromene. In order to address cannabis e-cigarette safety and vaping in an effective manner, we provide a comprehensive knowledge of the latest products, delivery modes, and ingredients. This perspective highlights the types of cannabis vaping modalities common to the United States cannabis market, with special attention to cartridge-type cannabis e-cigarette toxicology and their involvement in the EVALI outbreak, in particular, acute lung injurious responses. Novel ingredient chemistry, origins, and legal statuses are reviewed, as well as the toxicology of known cannabis e-cigarette aerosol components.

Hexahydrocannabinol on the Light Cannabis Market: The Latest “New” Entry

“…Hexahydrocannabinols (HHCs, refer to as (9R)-HHC and (9S)-HHC diastereoisomers, compounds 4(R) and 4(S), Figure 1) are relatively low-studied cannabinoids naturally found in small concentrations in the pollen and the seeds of the hemp plants that are emerging on the lightcannabis (hemp) market. 1 Firstly described by Roger Adams in 1944 2 , HHCs have recently kept the attention of toxicology researchers and analysts since laboratories all over the world started to synthesize them, applying old semi-synthetic approaches. 3 Indeed, HHCs can be obtained in two steps, by acidic treatment and successive hydrogenation, starting from cannabidiol (CBD, 1), or by direct reduction of  9 -tetrahydrocannabinol ( 9 -THC, 2) or  8 -tetrahydrocannabinol ( 8 -THC, 3) present in hemp 4 , as shown in Figure 1, in order to add them to hemp-derived products.…”

The E-cigarette or Vaping Product Use–Associated Lung Injury Epidemic: Pathogenesis, Management, and Future Directions: An Official American Thoracic Society Workshop Report

“…are known to be present at varying concentrations ( 96 – 98 ). Cannabinoid e-cigarettes can deliver up to 5 mg Δ 9 -THC per puff depending on composition and applied power ( 99 ). In addition to primary constituents of e-cigarettes, it is well understood that the heat applied in aerosolization combined with instability of some chemical constituents can result in degradation products that potentially contribute to underlying pathogenesis, including metals, carbonyls, and other organic compounds ( 100 – 102 ).…”

Clearing up the smoke: Physical and mental health considerations regarding cannabis use in adolescents with cystic fibrosis

“…Cannabis, independent of CF status, is associated with developing pneumothorax 25 and hemoptysis 26 . Cannabis‐based e‐cigarette products are formulated with additives which can adversely affect the pulmonary system, as seen in e‐cigarette or vaping use‐associated lung injury 27 . Potential effects of oral consumption of cannabis on pulmonary function is not currently well described, yet may have possible indirect implications on lung function through drug‐drug interactions with medications used in the treatment of CF, such as the CFTR modulators 28 …”