Vaping has gained incredible pop- ularity in the United States1 and in the United Kingdom2 over the last decade. Likely, this is due to the confluence of certain conditions that, together, bolstered an environment conducive for explosive growth. These conditions include the long existence of vaporizer technology, the growth of the legal cannabis industry, the continued marketing efforts of the tobacco industry, intense marketing campaigns of alternative and safer nicotine delivery systems, and youth culture in a hyper-connected broadband/Internet era. Tangentially, emerging “gray market” industries that are largely unregulated or underregulated have also contributed to a broader vape culture. This includes the manufacture of alternative cannabis products, such as cannabidiol (CBD), that have expanded wildly since the passage of the Agriculture Improvement Act of 2018.3 While the U.S. Food & Drug Administration and the U.K. Home Office continue to create clear and comprehensive guidelines, a regulatory vacuum continues to exist in both countries allowing products to flourish in stores and online. Facets of the legal/illegal cannabis4 and CBD markets continue to exploit the broadening vape culture. In all, the following products are available in vape form: cannabis oil and other concentrates (e.g., wax, butter, “shatter,” or butane-extracted compounds—all containing THC), CBD and “cannabis alternatives,” nicotine and nicotine/tobacco alternatives, and essential oils (or “herbal vape” products that can include “flavor” combinations such as jasmine, lime, and patchouli; orange, frankincense, and ylang ylang; fennel, thyme, and vanilla). The following sections describe this emerging vaping trend in these ways: its history, the known and unknown pharmacology (including toxicity), legal considerations, and regulatory concerns. It does so while focusing on both the products of consumption (e.g., the vape “juice,” salts, or organic matter) as well as the devices used to produce the aerosol for their consumption.
July 01, 2020 Feature
A Review of the History, Pharmacology, and Legal Regulation of Vaporizers and Vape Products
David N. Khey, PhD, Chase J. Edwards, JD, and O. Hayden Griffin III, JD, PhD
A History of Vaporizer Devices and Products
According to the 2016 Surgeon General’s Report on e-cigarette use among youth and young adults, “e-cigarettes include a diverse group of devices that allow users to inhale an aerosol, which typically contains nicotine, flavorings, and other additives.”5 In its 2016 report on e-cigarette use among youth and young adults, the CDC cites recent research6 to suggest a shared difficulty among public health officials in surveillance of vaping due to “the diverse and nonstandard nomenclature for the devices.”7 Indeed, they do come in many different forms, such as the first-generation self-contained device and second-, third-, and post-third generation devices that are rechargeable and refillable. The report takes note of other variants, such as e-pipes and e-cigars, but it is important to point out that even this list is not exhaustive (e.g., e-hookahs exist!). Other devices include technologies that serve to generate a vapor from dried organic matter (e.g., cannabis, most popularly) or salts. Thus, it is important to note that there is a diversity of both products and devices on the market that continue to expand.
The Surgeon General’s report also provides one of the most robust and well-researched histories of the development of cigarette alternatives, namely e-cigarettes. In particular, it focuses on the harm reductionist nature of experimental products that began as far back as the 1880s. It was not until Herbert A. Gilberts patented8 the “smokeless nontobacco cigarette” that the foundation of a vaporizer revolution was seeded. Yet, it appears that the demand for such an alternative came much later.
Multiple sources attribute the direct lineage of the modern e-cigarette device to a Chinese pharmacist named Hon Lik in 2003–2004.9 Driven by the loss of his father to lung cancer, Mr. Lik worked closely with investors to launch a company by the name of Ruyan to produce a device/product combination marketed both as a smoking cessation device and an alternative cigarette. The products produced by Ruyan began to creep into the U.S. and UK markets just four years later.10 Now, just the e-cigarette industry is estimated to generate $4 billion in revenue in the U.S. alone, with some scholarship suggesting that the vape industry will surpass the traditional combustible tobacco sales within five to ten years; importantly, this estimate seems to exclude the vape-adjacent products such as CBD “juices” and cannabis products.11
Literature on Pharmacology and Toxicity
Pharmacology broadly considers the absorption, distribution, metabolism, and excretion of drugs. The literature on vaporizing THC and nicotine products typically focuses on the differences found in absorption, distribution, and, less commonly, metabolism between them. While the vast majority of the literature focuses on either nicotine or THC, it is important to note a shift in research focus. Namely, the proliferation of unregulated products in both the U.S. and UK that combine tobacco and cannabis extracts with other compounds—such as vitamin E acetate, other plant oils and terpenes, medium-chain triglyceride oil, coconut oil, petroleum distillates, propylene glycol, glycerin, and flavoring agents—comprises the bulk of scientific attention in the last few years. The vast majority of these substances have previously never been taken into the lungs via aerosol until now, and public health officials are only beginning to understand the ramifications of the sharp increase in their consumption. Thus, at this point, we are mostly in uncharted territory. Just to highlight the overwhelming nature of this territory, Herrington and Myers12 reveal that sixty to seventy known and unknown compounds were found in liquid nicotine products they examined. In another study, by Kucharska and his colleagues,13 113 compounds were found across fifty brands of e-juice nicotine products. Comparing these to the sixty-seven known compounds in the marijuana plant, science has much to learn.
The wide variety of e-juice vape products on store shelves and online—in particular, the vast variations in product ingredients and consistency—should give any scientist pause in making broad statements about their safety or expected pharmacology. For example, even something as simple as pH can have a profound impact on absorption of nicotine by the body; specifically, in basic environments, nicotine may cross membranes with greater ease, having sizeable ramifications on absorption. Products sold in the United States have been found to have wide variation in pH in recent literature. It so happens that when researchers contrasted the pH of combustible tobacco products to e-juice products, e-juice products tended to be more basic. Critically, “[t]he abuse liability of tobacco products increases with greater delivery, faster rate of absorption, and higher blood nicotine concentrations”14—and it appears that vaporizers and e-juice products have the potential to have higher abuse liability relative to combustible tobacco products due to differences in something as simple as product pH.
In addition, the possibility of a substantial difference in the pattern of consumption could exist between combustible products versus an aerosol. The on-demand availability of a product without having to think about using a lighter or getting out another dose (e.g., knowing that you have used one dose, say, one cigarette, and have to start another dose by lighting another) may influence how people consume or “titrate” their dosage. Much more research needs to be done on real-world consumption patterns of aerosolized e-juice products and their impact on pharmacology.
With regard to toxicity of the inhaled vapor plume (e.g., the aerosol), it is important to highlight that many unknown hazards exist at this time. One prominent hazard noted in the literature is the potential existence of carbonyl compounds, likely as a result of when e-juice liquids are heated and aerosolized. In other words, the liquid formulation of these products may not be toxic (or as toxic) as packaged—yet, when used as directed, the resulting aerosol yields known carcinogens. These compounds include formaldehyde, acetaldehyde, acrolein, and glyoxal.15 With a bit of Internet research, prospective users can find quasi-scientific information among vaporizer products that promote options, such as voltage modulators, to minimize or eliminate carbonyls and thus the formation of carcinogens. The underlying science that supports such assertions does not take into account how performance may change as vaporized products age and their components experience wear; nor does this literature account for the wide variation of the consistency of e-juice products on the market.
At the time of this writing, the science on nicotine aerosols suggests:
[1.] There is conclusive evidence that in addition to nicotine, most e-cigarette products contain and emit numerous potentially toxic substances. [2.] There is conclusive evidence that, other than nicotine, the number, quantity, and characteristics of potentially toxic substances emitted from e-cigarettes are highly variable and depend on product characteristics . . . and how the device is operated. [3.] There is substantial evidence that except for nicotine, under typical conditions of use, exposure to potentially toxic substances from e-cigarettes is significantly lower compared with combustible tobacco cigarettes.16
Importantly, these findings do not include other e-juice products, such as those derived from cannabis or essential oils.
The toxicity of cannabis-derived vape products has been particularly concerning over the last two years. Specifically, the U.S. Centers of Disease Control and Prevention have been aggressively researching a national outbreak of e-cigarette, or vaping use–associated lung injury (EVALI). As of February 2020, the CDC has identified segments of THC-infused e-juice vape products—particularly those sourced from friends, family, or in-person or online dealers—are linked with EVALI. The analysis of these products by the FDA and state-run labs points to one adulterant at the heart of this outbreak, vitamin E acetate. Most critically, “[e]vidence is not sufficient to rule out the contribution of other chemicals of concern [to EVALI cases], including chemicals in either THC or non-THC products.”17 Perhaps ironically, the science supporting the safety of products such as the Volcano has become voluminous in extant literature. This could, perhaps, be a substantial issue. If end users misinterpret the safety of the science to extend to devices that vaporize liquids with unknown consistency or quality assurance/control, it could have substantial consequences to their acute and long-term health.
The Regulatory Scheme of Vaporizers and Vape Products
Within the United States, the Controlled Substances Act of 1970 (CSA) provides a framework for the classification and regulation of drugs. The most important contribution of the CSA was the establishment of different regulatory categories of substances, known as “schedules” within the legislation. Numbering Schedules I through V, with Schedule I providing the most stringent regulations, substances are placed within different schedules based upon eight criteria, with medical utility and potential for abuse being the most important.18 Scheduling decisions are often controversial, with the evaluation of medical utility and the calculation of the harm of a particular substance producing a majority of the controversy.19 In some instances, controversy exists because a substance is perceived to be “over-scheduled,” and some people believe a particular substance should be placed in a more lenient schedule (cannabis, psilocybin, and LSD are common examples). In other instances, it may be perceived that a substance was not scheduled quickly enough (synthetic marijuana or pseudoephedrine are often mentioned) or that some substances are not scheduled because regulatory agencies do not perceive substances as a threat (Salvia divinorum is one example).20
While it can be debated whether some substances are too stringently regulated or too leniently regulated, two substances, alcohol and tobacco, are seemingly exempted from such regulations. As Goode21 has noted, although alcohol and tobacco cause a great deal of harm to users, it is the failure of American society to generally perceive either substance as a drug that has seemingly exempted the two substances from the same type of regulation that other drugs receive.22 While tobacco has been exempted from the CSA, there have been other efforts to regulate the substance that could portend more stringent regulating of vaping products.
In 1979 the Secretary of the Department of Health and Human Services (DHHS) requested that the Director of the National Institute on Drug Abuse (NIDA) investigate whether nicotine should be considered an “addictive drug” and if cigarette smoking could be considered a form of drug dependence. Three years later, in 1982, both the secretary and director testified at a congressional hearing that not only should cigarette smoking be considered a form of drug dependence, but it represented the most widespread example of drug dependence in the United States.23 Throughout the 1980s, a plethora of behavioral pharmacological studies reinforced that tobacco use produced dependency; and in 1995, the Food and Drug Administration (FDA) proposed that the agency should be able to regulate tobacco products.24
David Kessler, the head of the FDA, announced on February 25, 1995, that the agency was considering whether to regulate tobacco as “drug delivery devices.” The announcement was made without White House approval and seemingly violated eighty years of policy that the FDA had no regulatory authority over tobacco. Later, with a blessing from President Bill Clinton, the FDA declared such authority and that the agency would regulate the sale, distribution, and use of tobacco products. Among the specific actions the FDA would take were to outlaw cigarette vending machines and restrict tobacco advertising that the agency deemed was targeted at young people. After the announcement, several tobacco companies, as well as one advertising agency, sued in federal court, arguing that the FDA had exceeded its authority and that the Food, Drug, and Cosmetic Act provided no such authority to the FDA to regulate tobacco products.25 Ultimately, in FDA v. Brown & Williamson,26 the Supreme Court ruled that the FDA had exceeded its authority and lacked the ability to regulate the tobacco industry.27
It would not be until nearly a decade later, on June 22, 2009, that President Barack Obama would sign the Family Smoking Prevention and Tobacco Control Act and the FDA would receive legal authority over tobacco products. Within the legislation was regulatory framework for the approval of new tobacco products, product performance standards, and standards for the authorization and sale of “modified risk tobacco products.”28
From Disruption to Assimilation to Implosion
In May 2016, the FDA announced that the agency would extend its control of tobacco products (through the Deeming Rule) to include the regulation of electronic nicotine delivery systems (ENDS).29 This has allowed for the expansion of regulation seen through this day. Since their large-scale introduction more than fifteen years ago, e-cigarette use has increased exponentially worldwide due to aggressive marketing as a cigarette replacement, a healthier alternative, and a permissible indoor activity.30 When concerns about the safety of these devices arose, they were ameliorated, in part, by peer-reviewed scientific articles published by researchers funded by Juul.31 This sharp rise in the use of vaping devices was seen as the epitome of disruptive technology, and some experts predicted the displacement of traditional cigarettes within the foreseeable future.32
Seemingly overnight, the vape market has disrupted America’s centuries-old tobacco industry, which continues to reel from the smoking cessation campaigns that have continually cut the number American users each year.33 From 2016 to 2017, for instance, the number of cigarettes sold in the United States dropped by 3.5 percent from 258 billion to 249 billion.34 When considering that the loss of those 9,000,000,000 cigarettes fell mostly on just two companies that control the lion’s share of the American tobacco market, the resulting acquisitions were practically inevitable.
Investors flocked to all levels of vape market segmentation, from small-town vape shops to flavor manufacturers to the device makers themselves. One of the largest bets ever made on an emerging market leader was completed in December 2018 when Altria paid $12.8 billion for a 35 percent stake in Juul.35 Shortly thereafter, the first hospitalizations and deaths due to excessive vaping were reported.
Litigation costs skyrocketed as a spike in hospitalizations resulted in suits from coast to coast. Many of these hospitalizations were patients who presented with inhalation injuries after vaping. Biopsies consistently revealed bilateral pulmonary opacities, spots on the lungs.36 The causes of action in many of these cases include Juul’s alleged failure to warn consumers of the dangers of over-inhalation. Others take aim at the industry’s marketing methods. During the rapid growth of the industry, vaping was routinely touted as harmless, a safe alternative to smoking, or a healthier alternative to satisfy a nicotine addiction.37
Other suits are the result of catastrophic oral and maxillofacial injuries caused by exploding devices.38 Injuries in these cases include third-degree burns, tissue loss, facial scarring, and tooth loss, all of which carry the potential for significant jury awards. Altria would write down the value of that investment by $4.5 billion less than a year later in October 2019. In three months, Altria recharged its Juul investment another $4.1 billion, cutting the value of its massive investment by two-thirds. Even before the market correction of March 2020, Altria’s stock price had dropped by 23 percent over the previous twelve months due to decreased sales forecasts and continuing litigation that exacerbated the Juul losses.
On the regulatory front, the Federal Trade Commission filed an administrative complaint on April 1, 2020, alleging that Altria’s exit from the e-cigarette market while acquiring a significant stake in Juul was essentially an agreement not to compete.39 The Commission alleges that the deal between Altria and Juul thus violates section 1 of the Sherman Act, section 5 of the FTC Act, and section 7 of the Clayton Act.
An Uncertain, but Highly Regulated Future
While these major market players fight with the FTC, the industry as a whole faces several existential risks, including multiple regulatory constraints and hurdles. In December 2019, U.S. lawmakers amended the Federal Food, Drug, and Cosmetic Act to raise the minimum age to purchase tobacco products from eighteen to twenty-one years. If this change is successful in its stated goal of reducing tobacco and vaporizer use by teens and young adults, it will greatly reduce the demand for nicotine-based products of all types over time.
Even more unpredictable is a mandatory review of all vaping products by the Food and Drug Administration pursuant to an order from a U.S. district court in Maryland. All vaping products, including fluids, additives, and the devices themselves, must apply for review by May 12, 2020. Afterward, the Trump administration could take any number of actions, ranging from no action at all to completely banning all vaping devices.
To summarize, vaporizer technologies are not new to the market; yet the explosion of vape products has been rapid, dynamic, and largely under- or unregulated. As insinuated above, an era of regulation reckoning is dawning upon vaporizers and vape products—particularly vape products. At this time, the ire of regulatory muscle seems affixed on the tobacco industry while the acute harms of the gray or black markets of cannabis and cannabis-related products are at the heart of public health concerns. Could our youth and young adults who are already hip to the vape culture merely migrate from regulated vape products that are out of reach to under- or unregulated products that may put them at more risk? Could this trend vary by states that regulate cannabis products, including aerosol products, rigorously versus those that do not? Or by legalization status, more broadly? We continue to be at a precipice of change. Many known unknowns exist. However, there does not seem to be a sense of how many unknown unknowns exist. Given the continued popularity of these products across tobacco and cannabis realms, much more research is needed to inform policy, regulatory schemes, public health, and legal exposures.
Endnotes
1. Lawrence O. Gostin & Aliza Y. Glasner, E-cigarettes, Vaping, and Youth, 312 JAMA 595 (2014).
2. M. S. Blundell, P. I. Dargan & D. M. Wood, The Dark Cloud of Recreational Drugs and Vaping, 111 QJM: Int’l J. Med. 145 (2018).
3. Agriculture Improvement Act of 2018, Pub. L. No. 115-334, 132 Stat. 4490 (popularly known as the 2018 Farm Bill).
4. Products with the ingredient delta-9-tetrahydrocannibidinol—the active psychoactive ingredient in cannabis.
5. U.S. Dep’t of Health & Human Servs., E-Cigarette Use Among Youth and Young Adults: A Report of the Surgeon General (2016), https://www.ncbi.nlm.nih.gov/books/NBK538679/ [hereinafter Surgeon Gen. Rep.].
6. Jennifer P. Alexander et al., Smoke and Vapor: Exploring the Terminology Landscape Among Electronic Cigarette Users, 2 Tobacco Reg. Sci. 204 (2016).
7. See Surgeon Gen. Rep., supra note 5, at 3; see also Alexander et al., supra note 6.
8. U.S. Patent No. 3,200,819 (1965).
9. Alison M. Wallace & Robert E. Foronjy, Electronic Cigarettes: Not Evidence-Based Cessation, 8 Translational Lung Cancer Res. (Suppl. 1) S7 (2019).
10. Id.
11. T. DeAngelis, Are E-Cigarettes a Game Changer?, 45 Monitor on Psychol., no. 3, Mar. 2014, at 48.
12. Jason S. Herrington & Colton Myers, Electronic Cigarette Solutions and Resultant Aerosol Profiles, 1418 J. Chromatography A 192 (2015).
13. Malgorzata Kucharska et al., Testing of the Composition of E-Cigarette Liquids—Manufacturer-Declared vs. True Contents in a Selected Series of Products, 67 Medycyna Pracy 239 (2016).
14. Nat’l Acad. of Scis. + Eng’g + Med., Consensus Study Report. Public Health Consequences of E-Cigarettes 99 (Kethleen Stratton, Leslie Y. Kwan & David L. Eaton eds. 2018).
15. Id. at 182.
16. Id. at 198.
17. For State, Local, Territorial, and Tribal Health Departments, Ctrs. for Disease Control & Prevention: Smoking & Tobacco Use, https://www.cdc.gov/tobacco/basic_information/e-cigarettes/severe-lung-disease/health-departments/index.html.
18. Id. at 21–22.
19. O. Hayden Griffin III, A Democracy Deficit Within American Drug Policy, 26 S. Cal. Rev. L. & Soc. Just. 103, 121–22 (2017).
20. Carolyn Coulson & Jonathan P. Caulkins, Scheduling of Newly Emerging Drugs: A Critical Review of Decisions over 40 years, 107 Addiction 766, 770–71 (2011).
21. Erich Goode, Drugs in American Society 13–15 (2015).
22. Id. at 217–18.
23. Jack E. Henningfield, August R. Buchhalter & Reginald V. Fant, Behavioral Pharmacology Contributions to the Regulation of Drug and Tobacco Products by the Food and Drug Administration, 16 Behav. Analysis: Res. & Prac. 179, 180 (2016).
24. Id. at 185.
25. Jeffrey R. Lax & Mathew D. McCubbins, Courts, Congress and Public Policy, Part I: The FDA, the Courts, and the Regulation of Tobacco, 15 J. Contemp. Legal Issues 163, 169 (2006).
26. 529 U.S. 120 (2000).
27. Lax & McCubbins, supra note 25, at 172.
28. Henningfield, Buchhalter & Fant, supra note 23, at 185.
29. Cathy L. Backinger, Helen I. Meissner & David L. Ashley, The FDA “Deeming Rule” and Tobacco Regulatory Research, 2 Tobacco Reg. Sci. 290, 290 (2016).
30. Oren Rom et al., Are E‐Cigarettes a Safe and Good Alternative to Cigarette Smoking?, 1340 Annals N.Y. Acad. Sci. 65 (2015).
31. Andy S.L. Tan et al., JUUL Labs’ Sponsorship and the Scientific Integrity of Vaping Research, 394 The Lancet 366 (2019).
32. Surgeon Gen. Rep., supra note 5, ch. 4 (Activities of the E-Cigarette Companies).
33. Paul T. Harrell et al., Patterns of Youth Tobacco and Polytobacco Usage: The Shift to Alternative Tobacco Products, 43 Am. J. Drug & Alcohol Abuse 694 (2017).
34. John C. Maxwell Jr., The Maxwell Report: Year End & Fourth Quarter 2017 Cigarette Industry (2018).
35. Juul, a company with $3.4 billion in revenue in 2019 (up from $1.3 billion in 2018), is also 35% owned by Altria, the maker of Marlboro cigarettes. Rakesh Sharma, The Company Behind JUUL, Investopedia, https://www.investopedia.com/news/which-company-behind-popular-ecigarette-juul/ (accessed Apr. 10, 2020).
36. Yasmeen M. Butt et al., Pathology of Vaping-Associated Lung Injury, 381 New Eng. J. Med. 1780 (2019).
37. Marisa De Andrade, Gerard Hastings & Kathryn Angus, Promotion of Electronic Cigarettes: Tobacco Marketing Reinvented?, 347 BMJ f7473 (2013).
38. Elisha G. Brownson et al., Explosion Injuries from E-Cigarettes, 375 New Eng. J. Med. 1400 (2016).
39. Press Release, Fed. Trade Comm’n, FTC Sues to Unwind Altria’s $12.8 Billion Investment in Competitor JUUL (Apr. 1, 2020), https://www.ftc.gov/news-events/press-releases/2020/04/ftc-sues-unwind-altrias-128-billion-investment-competitor-juul.