Cannabis: An Emerging Occupational Allergen?

Abstract

Cannabis is the most commonly used psychoactive drug. In recent years, Cannabis access has expanded for both medicinal and non-medicinal has grown. This is also marked with an increasing number of individuals gaining employment in this emerging industry. In this article, we briefly discuss the health hazards associated with Cannabis exposure with an emphasis on the potential for allergic reactions in workers who handle and process Cannabis plant.

Introduction

Currently, Cannabis is the most commonly used psychoactive drug globally (UNODC, 2017) and is classified as a Schedule I substance under the Federal Controlled Substances Act in the USA. Current trends indicate that consumption of Cannabis-derived products for relieving ailments and for non-medical effects is likely to increase in the near future (Manthey, 2019). This has been prompted in part by increased legalization/decriminalization of Cannabis and evolving social attitudes (Williams et al., 2016). Cannabis has been legalized in Canada and over 30 American states including the District of Columbia for non-medical and/or medicinal use and more are expected to follow suit. This has resulted in sustained expansion of primary (cultivators) (Jensen and Roussell, 2016) and ancillary businesses (retailers, dispensaries) within the Cannabis industry. This is an expanding industry of approximately 150 000 workers that are employed in growing, harvesting, processing, and distribution of Cannabis. Current estimates suggest that by 2021 over 300 000 workers will be employed within the industry. As the scope and access of Cannabis use broadens, we presume that the Cannabis industry will continue to grow and employ more workers.

Occupational exposures to Cannabis

While significant emphasis has been placed on examining the broader effects of Cannabis and its derivatives on human health (NAS, 2017), we have very little understanding of the occupational exposures to Cannabis. Cannabis, being an organic entity is likely to present health issues that have been commonly observed within other industries involved in processing naturally existing raw materials. Workers in Cannabis facilities may be at risk of inhaling the organic dust, endotoxin, and fungi emerging from handling and processing of Cannabis (CDPHE, 2017). A series of investigations over the last five decades have emphasized the physiological and immunological effects of working with industrial hemp (Cannabis strains with low tetrahydrocannabinol levels) (Velvart and Stavrovska, 1963; Valic et al., 1968; Zuskin et al., 1990, 1992, 1994; Er et al., 2016). Collectively, these investigations have underscored the prevalence of pulmonary deficits and respiratory issues among hemp workers. Furthermore, many hemp workers have been demonstrated to exhibit high levels of serum IgE to hemp. Although modern practices for Cannabis cultivation and processing have changed significantly owing to the diversity in consumer application of Cannabis products (Parker et al., 2019), the occupational risks of handling and processing Cannabis raw materials remain. Several decades ago, another plant-based product, natural rubber latex, drove a worldwide epidemic of allergic disease within the healthcare industry (Charous et al., 2002a,b; Amr and Suk, 2004; Hamilton, 2017). Healthcare workers and patients experienced an unprecedented wave of sensitization and allergic disease as latex rubber use broadened. While we do not have sufficient data to comment on the possibility of a similar scenario occurring within the Cannabis industry, expanded growth within the industry may become a source of a substantial number of cases of allergic sensitization to the plant.

Allergic sensitization in Cannabis workers and contrast with non-occupational exposures

Beyond studies conducted in hemp worker populations, there is significant dearth in studies reporting allergic reactions in workers involved with frequent and direct exposures to Cannabis (growers, trimmers, etc.). Concern for occupational allergies to Cannabis extends to other vocations that are not directly associated with the Cannabis industry. For instance, law enforcement officers and forensic laboratory workers (who frequently analyze Cannabis samples) are periodically exposed to Cannabis and its products and could be at risk of being sensitized (Lindemayr and Jager, 1980; Majmudar et al., 2006; Mayoral et al., 2008; Herzinger et al., 2011). These reports have been primarily presented as case reports and the generalizability and even the allergic nature of these encounters has been questioned (Decuyper et al., 2019b). For instance, the lipid transfer protein of Cannabis, Can s 3, is considered to be a key driver of allergic reactions to Cannabis and a mediator of cross-reactive allergies to other foods in Europe (Ebo et al., 2013; Larramendi et al., 2013; Faber et al., 2015, 2017). However, in a study involving Cannabis symptomatic police officers, all diagnostic tests were negative (except a single case of borderline IgE) (Decuyper et al., 2019b). The presence of multiple allergens in Cannabis has been reported (Larramendi et al., 2013; Nayak et al., 2013); however, more studies are essential to assess their relevance to Cannabis exposures (Nayak et al., 2017; Decuyper et al., 2019a). It should be noted here that specific Cannabis-derived allergens relevant to occupational exposures remain unreported. Thus, allergens that may be relevant to non-occupational exposures may not sufficiently explain occupational sensitization to the plant.

It is plausible that both the duration and the qualitative nature of occupational exposures contribute towards the differences between occupational and personal exposures (non-medicinal or medicinal). Even among heavy Cannabis users, most personal exposures are unlikely to reach the levels of occupational exposures where contact may last for extended hours at a stretch. In personal exposures to Cannabis, particularly smoke has an irritant effect on airways with greater incidences of rhinitis, cough, wheeze, dyspnea, and may also result in aggravation of underlying asthma (NAS, 2017). While this is an unlikely scenario in workplaces, direct handling of Cannabis is a concern. Reports have emerged where some users commonly exhibit contact urticaria and angioedema following direct contact with the plant (Lindemayr and Jager, 1980; Majmudar et al., 2006; Tessmer et al., 2012; Decuyper et al., 2019b). These symptoms are not universal, and more studies are essential to link the exposures to specific symptoms, particularly in occupationally exposed cohorts.

Diagnostic tests: challenges and opportunities

A critical impediment in separating immunological and non-immunological reactions upon exposure to Cannabis has been the lack of specific diagnostic tests (Nayak et al., 2017; Decuyper et al., 2018, 2019b). Improvements in diagnostic tools and reagents could significantly enhance our ability to capture the spectrum and prevalence of Cannabis allergy in occupational settings. However, multiple challenges exist. Current tests for definitively determining Cannabis allergy are still in nascent stages of development and tools currently available may fail to capture the diversity of allergens present in Cannabis. Cannabis is also composed of various metabolites and volatile organic compounds (including cannabinoids, terpenes, flavonoids, etc.) and dissecting the contribution of individual components towards broader allergy symptoms is a subject of current research efforts. Cannabis plants are also frequently vulnerable to contamination by microbial sensitizers such as bacteria and mold owing to requirement of high humidity conditions for plant growth, particularly during seedling stages and can be an additional risk to workers (McKernan et al., 2016; CDPHE, 2017). For instance, using sequencing approaches (16S ribosomal RNA and Internal Transcribed Sequencing), molds such as Botrytis cinerea have been shown to commonly contaminate samples collected from Cannabis grow facilities (Green et al., 2018).

Concluding remarks

Unlike medicinal or non-medicinal use of Cannabis, where allergic reactions can be prevented by ceasing voluntary exposures to Cannabis or its derivatives, managing occupational exposures can be very challenging. Use of appropriate personal protective equipment and engineering controls may assist in mitigating exposures. In the context of occupational allergies, it is also essential to expand our understanding of the current practices involved in Cannabis cultivation, processing, and product development in order to identify specific exposure risks. Other factors to consider are the evolving list of newly available strains of Cannabis plant and the route of exposures for different derivatives/products processed within the Cannabis industry. Such efforts have already begun and will continue to contribute to our growing knowledge (Couch et al., 2017, 2019a,b; Green et al., 2018; Victory et al., 2018). The development of sensitive and specific diagnostic tools in the near future could provide us with an ability to objectively establish allergic sensitization to Cannabis in workers in a timely manner. Collaborative efforts of basic scientists and clinicians will continue to drive our understanding of identifying unique exposure scenarios and specific molecular factors that contribute to occupational allergies to Cannabis.

Funding

This work was supported in part by the National Institute of Allergy and Infectious Diseases (NIAID)/National Institutes of Health (NIH) Grant R21AI140411 to AN. The findings and the conclusions in this report are those of the authors and do not necessarily represent the views of the National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention.

Conflict of interest

Dr Silvers and Zeiger are members of the Canna Research Group, which as commercial interests in outcomes associated with benefits and adverse effects of Cannabis use. All other authors declare no conflict of interest.