This article was co-authored by Steve J. Bannister, PhD, of Hightower Pharmaceutical Services. He has over thirty years of experience applying the fundamentals of physical and analytical chemistry to development of drug-delivery devices.
This article was co-authored by Steve J. Bannister, PhD, of Hightower Pharmaceutical Services. He has over thirty years of experience applying the fundamentals of physical and analytical chemistry to development of drug-delivery devices. His projects have included the development of a standardized e-cigarette for use in NIH-sponsored clinical studies.
Electronic nicotine-delivery systems (ENDS or e-cigarettes) are potentially reduced-risk products—relative to conventional combustible cigarettes—that have been making headlines. The entire category has come under intense scrutiny by regulators, policy makers, plaintiffs’ attorneys, activists, and the public. While there are multiple issues that have led to this convergence of attention, some stakeholders may be inappropriately conflating two product categories: nicotine-containing e-liquids and illicit THC-containing liquids (by illicit we are referring to black market/informal sources/off the street versions, and not the legal ones obtained at legal dispensaries). Case in point: Massachusetts recently placed a four-month ban on all vaping products (update: as of October 21, 2019, a judge has given the state 1 week to fix flaws associated with the ban). In this post, we discuss why these two product categories should not be lumped together.
While a full description of the chemistry and delivery characteristics of these devices is beyond the scope of this article (i.e., the phenomena are quite complex!), we provide a high-level summary of the fundamental differences between nicotine-containing e-liquids and illicit THC-containing liquids. Our goal is to provide a better understanding as to why and how nicotine vaping products (ENDS or e-cigarettes) and illicit THC delivery devices are indeed different.
Nicotine Vaping Products
ENDS are deemed to be tobacco products and are therefore subject to regulation by FDA, though no products in this category are currently the subject of an approved Premarket Tobacco Application (PMTA). In July 2019, a U.S. District Court in Maryland ordered that PMTAs for a variety of deemed tobacco products, including ENDS, must be submitted to FDA no later than May 12, 2020. The products in this category are manufactured and marketed by a growing number of reputable brands including JUUL Labs/Altria, Logic/JTI, NJOY, RJ Reynolds/British American Tobacco, among others. An approvable PMTA will include a complete description of raw materials (and their specifications and quality-control laboratory testing), and of the design and performance specifications of the hardware (i.e., the delivery mechanism).
Mass-marketed nicotine-vaping products are composed of a nicotine solution (the e-liquid) in a battery-powered heating device (the atomizer). Nicotine-containing e-liquids typically contain varying compositions of nicotine, food-grade flavorings, and possibly other components, in a high-boiling mixture of propylene glycol and vegetable glycerin. These liquids are heated – usually in the temperature range of 100-250 °C (212-482 °F) – and vaporized in the atomizer. The vaporized e-liquid then condenses to form an aerosol that the user inhales.
THC Vaping Products
Vaping products delivering tetrahydrocannabinol (THC) are legally available in states permitting the medical or recreational use of cannabis and include cannabis oil, an inherently viscous extract of one or more cultivars of marijuana. The cost of legitimate cannabis oil production is significant and includes costs associated with growing or acquiring the biomass, processing equipment, and quality-control testing. For a number of reasons, cannabis oil has recently become increasingly scarce.
Illicit THC vaping products, which the FDA and CDC have warned consumers to stop using, contain e-liquids with cannabis oil which may be produced in uncontrolled processes, and may contain one or more inexpensive diluents, such as Vitamin E acetate ( tocopherol acetate). Black-market cannabis oil is frequently diluted to lower the cost of goods. Since many diluents will lower the viscosity of cannabis oil, viscosity has become a property associated with higher quality. Low viscosity (runny) e-liquids with bubbles are viewed as low-quality/less pure and could potentially introduce a factor that could lead to safety or efficacy concerns. Thus, it has become more common for manufacturers to utilize thickeners (such as vitamin E acetate) to dilute cannabis oil. The use of such high-viscosity cutting agents masks the dilution of the viscous cannabis oil.
But Vitamin E is safe isn’t it? Yes and no. Vitamin E has been safely used in topical and ingested consumer products—such as cosmetics and dietary supplements—for many years. However, there is a lack of rigorously performed scientific studies to definitively demonstrate the safety of vitamin E when it is inhaled into the lungs as an aerosol. For instance, there is some reason to believe that aerosolized vitamin E can cool to an oily substance in the respiratory tract where it can interfere with the normal functioning of the respiratory system. This mechanism may be consistent with the broad types of VAPIs (Vaping Associated Pulmonary Injuries) that have been reported in the literature, including lipoid pneumonia, alveolar hemorrhage, and cryptogenic organizing pneumonia. Concerns have been raised that these VAPIs could be associated with symptoms that could occur when oily substances enter the lungs.
On the other hand, this is probably not the whole story. According to a recent report in the New England Journal of Medicine, while some investigators speculate that vaping-related lung injuries may be due to the role of lipids, other scientists suggest that VAPIs may represent “a form of airway-centered chemical pneumonitis from one or more inhaled toxic substances.” Nevertheless, the agents responsible such toxicity remain unknown. According to the FDA, among the hundreds of vaping products tested by States or by the FDA, the majority have been found to contain THC, and that the majority of patients that have been afflicted with VAPI (Vaping Associated Pulmonary Injury) “reported using THC-containing products [from illicit sources], suggesting THC products are playing a role in the these illnesses.” Not surprisingly, the FDA has warned consumers to “not use vaping products that contain THC.”
Illicit THC vaping products have also been found to contain unsatisfactory levels of some pesticides (such as myclobutanil) and solvents like butane. Through the process of extracting THC from cannabis, these chemicals — and others that have likely not been yet identified — may be concentrated into the final product. These adulterants create significant potential health risks due to direct toxicity and/or the formation of toxic degradants when vaporized.
The e-cigarette landscape continues to evolve rapidly, which presents both risks and opportunities for manufacturers. To effectively navigate this complex environment, manufacturers and their counsel must maintain an awareness of the science and regulatory landscapes (See our previous post on how to keep up with the e-cigarette science). Experts will increasingly play a key role in legal cases as they make their way through the courtroom (See our previous post on E-Cigarette Expert Teams). These experts may include chemists, physicians, epidemiologists, and other disciplines.
If you need help staying current on the e-cigarette science or are looking to build your ideal expert team, get in touch to begin a discussion.
On Wednesday July 8, 2020, Dr. David Schwartz of Innovative Science Solutions presented at the IADC 2020 Virtual Annual Meeting on a panel titled The Use of Genetic Testing in the Courtroom. A complimentary copy of the panel presentation is now available for download. Read more
Dr. David Schwartz of Innovative Science Solutions will be presenting at the IADC 2020 Virtual Annual Meeting on a panel titled The Use of Genetic Testing in the Courtroom. Read more
Plaintiff experts having been asserting for decades that all mesotheliomas must be linked to some asbestos exposure. Indeed, this has led to the erroneous (but widespread) view that mesothelioma is a signature disease, only caused by asbestos exposure. Read more
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