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Special Report: Cannabis Researchers, Scientists Confront Vaping-Related Lung Disease Debate

Vitamin E acetate, terpene content and the illicit market are in the spotlight, but plenty of unanswered questions remain.

Vape Science Lung Disease
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At Diego Pellicer in Denver, Colo., dispensary employees are confronting the question that’s landed on the doorsteps of all cannabis businesses in recent weeks: How should the legal cannabis industry engage the sudden rise in vaping-related illnesses in the U.S.?  

With five reported deaths, more than 450 other cases of vaping-related illnesses in 33 states and a rollicking series of headlines in national news media, cannabis business owners and scientists are educating a general public—and an industry—that's not yet entirely informed on vape technologies, the bioactivities of molecules and compounds in vape products and the disparities between the legal and illicit cannabis markets (and the popular e-cigarette market).

Nick Jack, chief retail officer of Diego Pellicer, says that it’s not so much the potential sales hit that has his company worried—rather, it’s the public education gap that’s become clear this summer.  

“We are working with our staff to ensure they understand the testing and regulatory procedures that recreational and medical cannabis oil companies must go through before their products are available on our shelves,” Jack says. “It's important that we're able to educate the consumer on product safety and regulatory guidelines that help reduce the chance of an unsafe product reaching the market.”  

cdc map vaping lung disease illnessescdc map vaping lung disease illnesses
CDC
The dark-blue shading represents U.S. states that have reported cases resembling the vaping-related lung disease.

His staff is not alone. 

The most visible hypothesis is that illicit-market operators are distributing and selling untested cannabis vape cartridges with high levels of vitamin E acetate, a preservative often found in nutritional supplements or beauty products. (Vitamin E acetate is safe in its typical commercial forms, but this record of safety is upended when consumption methods change.) The New York State Department of Health specifically cited the chemical when calling out the flood of unregulated cannabis products that have hit streets around the Northeast, Midwest and beyond. 

“I would hope that the recent series of unfortunate events will persuade [illicit] market users to purchase products—if they're available to them—that go through regulatory testing and compliance procedures that have been put into place in the legal cannabis market, rather than purchasing a product from unverified and unregulated sources,” Jack says.

And while public education is a vital job duty for anyone working the front lines of cannabis retail, the entire supply chain is involved in this conversation now. Nicole Howell Neubert, attorney-at-law at Clark Neubert, says that anyone involved in the legal marketplace should be taking a temperature check on every contract and every product that’s passing through his or her business. 

“To mitigate potential risk, all operators in the supply chain should take a look at their production, distribution chains, testing, and insurance coverage, and discuss with their attorneys in view of the state law in their jurisdiction,” Neubert says. “Proving a products liability case is based on many factors, but it's important to know that anyone in the supply chain can be brought in as a defendant regardless of whether the retailer sold the specific product or not.”  

So, What’s Happening, Exactly? 

While most major news media outlets have picked up the New York State Department of Health advisory on vitamin E acetate (including Cannabis Business Times), the actual public understanding of oil vaporization and degradation is a bit murkier.  

Arup Sen, CEO of Infusion Biosciences, says that the cannabis industry is missing a complete picture of the myriad chemical constituents that end up in legally manufactured vape products.  

“All preparations offered at the present time focus on a small subset of molecules as far as the purity and content in the whole product,” he says. “The obsession with THC and CBD as the primary molecules that are responsible for the actions of cannabis and hemp products is only based on anecdotal science. If you evaluate the knowledge from benzodiazepines, opiates and antidepressants, you will realize that bioactivities of highly related molecules can be dramatically different. Given the shockingly low bioactivities reported for THC and CBD preparations of the present day, I would not be surprised if we find compounds in the current preparations that are 100 to 1,000 times more potent than THC or CBD. In fact, synthetic molecules similar to THC have been reported to be more than 2,000 times more potent in a number of cell culture assays that determine biochemical effects at the cellular level.” 

“I am not convinced that anyone really knows what vitamin E acetate preparation is being used and what impurities there might be,” Sen says. “Little also is known about thermal degradation products of the primary component and minor components in the cannabis liquids used in the vape pens. Very little is known about the interaction between the materials used to make the cartridges and compounds present in vape liquids at high temperatures.” 

Of course, cannabinoids are far from the only chemical compounds found in the oil that cannabis consumers and patients are vaping. Much of the industry conversation has turned to terpenes—both organic and synthetic—and their role in the safety of these products.  

“Terpenes can be dangerous,” says Robert Strongin, chemistry professor at Portland State University. “Their use should be limited. Our upcoming report shows they degrade more rapidly during vaping than THC. Adding relatively large concentrations of terpenes to relatively pure cannabinoid distillates is not recommended based on our work. In a mixture of 9:1 THC:terpenes, we found that when vaped with a common device, terpenes accounted for a much larger percentage of gas-phase toxins despite the 9x higher abundance [of THC].” 

Mojave Richmond and Robert C. Clarke, CBT columnists and co-founders of BioAgronomics Group, say that “Not all terpenes are good terpenes.” Richmond adds, “We should tread lightly when it comes to adding large quantities of what are essentially solvents into cannabis products.” 

Science has to play catch-up to the innovative vaping technologies that are leading broad swaths of the marketplace. As new consumers enter the legal cannabis space, vape cartridges (and other concentrated cannabis products) are outpacing the growth of traditional flower. 

“The consumption of cannabis has been deemed relatively safe in comparison to other socially acceptable substances, but this was based off a long history of consuming marijuana and hashish whose overall terpene content was significantly lower than today’s modern cannabis varieties and extracts,” Richmond says. “The devil is always in the details, and safety must come first. Anytime we add new ingredients of varying quantities into the beaker we risk an explosion in the lab. So, let's not use consumers and patients as guinea pigs and take a step backward before we tarnish cannabis' reputation as a safe, beneficial, medicinal plant that has been an integral part of the human experience.” 

Caution Ahead 

One important byproduct of the news media frenzy is a public backlash against vaping outright. While the industry, on one hand, has an opportunity to engage in widespread public education on one of its most popular consumer product segments (which has been steadily increasing in popularity over several years), the anxiety over health and safety may easily overwhelm.

“Some doctors suspect that this may have gone undiagnosed due to a lack of knowledge combined with a lack of reporting requirements for vaping illnesses or a lack of knowledge about how to report the cases,” Strongin says. “That said, I believe I read that the CDC says this is a recent phenomenon. It’s possible that a recent proliferation of counterfeit carts and new additives are culprits. However, there is no confirmation by the agencies investigating this outbreak that this is even limited to just cannabis vaping and does not pertain to tobacco product vaping as well. Hence the universal recommendation to stop vaping.” 

Indeed, the New York State Department of Health, whose advisory has become a center of gravity in this national storyline, warns against the full spectrum of vaping technologies and products, aside from those sold through the legal cannabis market there. (“The Department of Health advises people who are not certified patients in the New York State Medical Marijuana Program to consider not using any vape products,” according to the press release language.) 

Same thing in Oregon, where the Oregon Health Authority has issued a similar, though more comprehensive warning: “We are encouraging people to avoid vaping, or to quit if they’re ready. We don’t know yet which types of e-cigarettes or vaping devices are causing this serious illness, so the safest thing to do is not to vape at all.” 

But the public education component is key. Eliana Golberstein, chief scientist of Myriad Pharmaceuticals in New Zealand, has been watching the media narrative develop in the U.S. She says it’s vital for cannabis business owners and consumers to understand lung chemistry: What’s happening inside the body after a hit from a vape pen? Or a dab? 

Part of the issue, as she’s studied it, is that substances such as “MCT (medium chain triglycerides), waxes and vitamin E affect the fragile lipidic balance of this surfactant [layer of the lungs], and their occlusive behavior wets the surfaces of the lung membranes. Substances [like those] interact heavily with this surfactant, and that heavy interaction disables the gas exchange and permeations processes.” 

With the addition of so many chemical compounds in modern cannabis concentrate products, like the vape cartridges being sold in regulated marketplaces and, worse, on the street, Golberstein says it’s paramount to develop an understanding of what happens after that concentrated oil is vaporized and inhaled. 

“A person working at a dispensary should be able to educate consumers on how a safe formulation can be identified,” she says. “Products clearly displaying the ingredients in their manufacturing process should be verified, and pharmacists should be able to identify risky products that need to be recalled. Explaining the physiology ... of our lungs is important, as this increases the awareness of the importance of vaping responsibly.” 

At the very least, the past few weeks of national news coverage have brought terms like “vitamin E acetate,” “lipoid pneumonia,” even “terpenes” to the forefront of a public safety conversation with the expanding cannabis industry. The regulated marketplace is where emergent businesses and health officials continue to sort out these rules, these technological guardrails. Now, the industry and its consumer base are armed with more questions to prop up those rules. 

Editorial Director Noelle Skodzinski, Senior Editor Brian MacIver and Science Editor Andrea Sparr-Jaswa contributed to this report.

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