In JAMA Network Open, Wing et al1 report an intriguing and insightful analysis of state-level incidences of electronic cigarette (e-cigarette)– or vaping–associated lung injury (EVALI), determined from case rates from the Centers for Disease Control and Prevention and Surveillance, Epidemiology, and End Results estimates of state populations. They found that the incidence of EVALI is lower in states that have legalized recreational marijuana and its active ingredient, tetrahydrocannabinol (THC), compared with states where it remains illegal or available only for medicinal uses. This finding withstood adjustment for variation in vaping rates among states. The cross-sectional nature of the analysis and inherent limitations of the available data mean that the ecological fallacy and other sources of confounding may be at play. In part because of its preliminary nature, interesting questions arise from the analysis, answers to which are likely to ultimately be found at the intersection of sociology, public health, and the law. It is illuminating to examine some of these questions through a wide historical lens.
One hundred years ago, on January 17, 1920, the Eighteenth Amendment of the US Constitution went into effect, prohibiting the manufacture, sale, or transport of intoxicating liquors. Moral and social sentiments, rather than a concern for public health per se, were the impetus for the amendment. Nonetheless, the desired but imperfectly realized result of Prohibition—curtailment of alcohol consumption—brought welcome salutary effects, some recognized only in retrospect. Rates of liver cirrhosis,2 psychiatric admissions for alcoholic psychosis,3 and infant mortality4 declined, as did arrests for drunkenness and related offenses.3 Not all secondary effects were positive, however. Bootlegging was rampant and criminal syndicates proliferated, fueling a wave of organized crime. Bootleggers fortified their distillates with methanol to increase apparent potency, causing blindness and death in unwary consumers.5 They also procured industrial ethanol, exempted from Prohibition and mass produced cheaply, as raw material for alcoholic beverages. In response, at the behest of the US government, industrial ethanol stocks were intentionally adulterated with methanol, benzene, and other poisonous substances to deter their consumption. The resulting concoctions, known as denatured alcohol, were responsible for thousands of deaths during the 14 years that Prohibition was in effect.5 The history of Prohibition thus serves as a cautionary tale about unintended and unforeseen consequences of legislation regulating substances that affect public health.
Nearly 100 years later, in 2012, Colorado became the first of several states to enact legislation serving as a de facto override of a federal ban on marijuana that has been in effect since shortly after the repeal of Prohibition. These laws form the basis of the analysis reported by Wing et al,1 showing that EVALI rates are lower in states that have legalized recreational marijuana. Is legalizing marijuana somehow protective against EVALI? If so, how does the protective effect come about? Some additional historical background is necessary.
e-Cigarettes were first introduced in 2004 and touted as a safer alternative to traditional combustible tobacco products.6 Marketing initially targeted adult smokers trying to quit, akin to other nicotine delivery methods, such as nicotine gum and transdermal patches. Used in this way, e-cigarettes are viewed by some as a harm-reduction strategy, similar to needle-exchange programs for intravenous drug users. However, in the last decade (coincident with the rise of recreational marijuana legalization), use of e-cigarettes has expanded dramatically to former nonsmokers, notably adolescents and young adults, among whom usage rates have skyrocketed.6,7 Even if the assumed relative safety of e-cigarettes compared with combustible tobacco products is valid—a matter of considerable controversy—the surge in popularity of e-cigarettes among young never-smokers has raised serious and legitimate concerns about the long-term public health consequences of this dramatic trend.6
These concerns were magnified in 2019 when numerous reports of a serious and sometimes fatal respiratory syndrome, now known as EVALI, emerged. As of February 2020, nearly 3000 cases of EVALI have been reported with at least 60 deaths attributed to the illness. Uncertainty about the cause of EVALI remains, but ample evidence suggests that vitamin E acetate (VEA), a constituent of culprit vaping products, is the causative agent. Strong associations between the illness and use of THC-containing vaping products, especially those obtained from black-market sources, suggest that VEA is being used to dilute or stretch THC concentrates that constitute the active ingredient of the implicated products—a scenario reminiscent of the unscrupulous bootleggers of the Prohibition era.
How could a state’s legalization of recreational marijuana inadvertently protect its citizens against EVALI? The obvious answer is that THC-containing vaping products in states where recreational marijuana is legal are uncontaminated with VEA. If so, another question follows: why would THC products in these states be less likely to be contaminated (ie, diluted) with VEA? One salient possibility is that there is less financial incentive to dilute THC concentrates in states where raw THC material is readily available without legal risk and compensatory markup. If THC concentrates are transported from states where they are legal and can be relatively cheaply mass produced (like industrial ethanol stocks during Prohibition) to other states where they are illegal and must be guarded jealously as a rare and precious commodity, there may be a strong economic inducement to dilute them, thereby increasing profits. Thus, legalization of marijuana may have protective local effects but untoward collateral effects.
These and many other questions about the epidemiology of EVALI remain unanswered. The analysis by Wing et al points to promising avenues for further research by highlighting the geographic heterogeneity of EVALI and suggesting a potential explanation for it. It also underscores the complex realities of social movements and resulting legislation that may have unforeseen and unforeseeable public health consequences, for better and for worse, that are recognized only in retrospect. If history teaches us anything, it is to be careful.
Published: April 6, 2020. doi:10.1001/jamanetworkopen.2020.2238
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2020 Cirulis MM et al. JAMA Network Open.
Corresponding Author: Scott K. Aberegg, MD, MPH, Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Utah School of Medicine, 26 N 1900 E, Salt Lake City, UT 84112 (firstname.lastname@example.org).
Conflict of Interest Disclosures: None reported.
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Cirulis MM, Callahan SJ, Aberegg SK. Marijuana Legislation and Electronic Cigarette– or Vaping–Associated Lung Injury: A Historical Perspective. JAMA Netw Open. 2020;3(4):e202238. doi:10.1001/jamanetworkopen.2020.2238
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