A recent study claimed to show vaped CBD is more harmful than vaped nicotine, and while several news outlets have reported on it, they all missed numerous flaws in the methodology. As a result of numerous confounding variables, there is no way to actually show that any of the harms they found were from CBD, and not one of the many other chemicals in the oil. High Times spoke to several cannabis vaping experts in an effort to nip this story in the bud, and stop it before it can spread further.
Seeing Through the Hazy Cloud of Vaped Variables
Rather than test a range of CBD and nicotine products, Dr. Yasmin Thanavala and her colleagues only looked at one CBD and one nicotine product, using the same Juul device to aerosolize both. The study was done on groups of ten mice, and rather than direct inhalation, the mice were in chambers filled with vapor. Things got off to a rocky start, with Table 1 showing the CBD sample used propylene glycol (PG) and vegetable glycerin (VG) and the nicotine sample used medium chain triglycerides (MCT), yet every other part of the study reported the CBD sample used MCT and the nicotine sample used PG/VG.
Source: “Not All Vaping is the Same: Differential Pulmonary Effects of Vaping Cannabidiol Versus Nicotine”
Dr. Thanavala told High Times “that is an error in Table 1,” confirming the CBD sample used MCT oil, which is banned by five legal cannabis states due to concerns over EVALI-like symptoms. Despite being “aware that ~ 5 states have banned MCT oil as a vape additive,” Dr. Thanavala and her colleagues used a CBD sample with MCT. Paradoxically, given their choice to use samples with MCT, VG, and PG, the researchers noted that “any respiratory toxic effects of vaping could potentially be exacerbated by the presence of other constituents,” like MCT, VG, PG, and terpenes.
Dr. Jeff Raber is the CEO, CVO, and a co-founder of the cannabis analytical laboratory, the Werc Shop, and is an expert on vaped cannabis and common vape additives. “VG/PG blends can be irritating to the vapor pathway,” which is one reason why they are not widely used in the cannabis industry today. Dr. Raber said “the concern with MCT is that it could stay in the lungs and lead to lipid pneumonia,” which is normally caused by “long chain fats” with over 40 carbons in their chain, cautioning “we don’t know the ‘magic number’ on what is safe to inhale.” Dr. Raber is an advocate for using alternatives that are “naturally in the plant” like terpenes or cannabinoids, and thinks terpenes are a great alternative to PG, VG, or MCT.
Dr. Peter Grinspoon is a primary care doctor, cannabis specialist at Harvard Medical School, and author of the upcoming book Seeing Through the Smoke. Dr. Grinspoon echoed some of Dr. Raber’s concerns, “I can’t see the rationale for dissolving them in different solvents, as the solvents themselves could be responsible for some of the findings.” Dale Gieringer Ph.D. is the Director of Cal NORML and a vaporizer research pioneer, who told High Times, “It’s impossible to draw meaningful conclusions about vaped CBD from this study.”
The next thing you see in Table 1 is there are a dozen terpenes in the CBD sample and seven terpenes in the nicotine sample, which all are “confounding variables,” in other words, potential sources for the supposed harm of CBD which were not controlled for by their study. When asked about their attempts to limit the myriad of confounding variables, Dr. Thanavala said, “Our goal was to test commercial pods the way a user would.”
“That’s a fair point to test the pods consumers buy,” said Dr. Raber “but they did not clearly delineate that the CBD was the culprit.” Dr. Raber then fired off some questions for the researchers: “How pure was the CBD? Could it be the combination of that formula with that hardware? How consistent was the hardware made? How was it stored? Did they use a new battery or an old one?” Dr. Raber noted the “time and cost limitation to studies” but would have preferred to see “2-3 different CBD and tobacco samples tested to see if they all behaved the same way.”
When pressed about the variables clouding their data, Dr. Thanavala told High Times, “Our goal was not to dissect out the effects of the individual components.” As that was their goal, one major question remains: Why did they “dissect out” the CBD and blame all the reported harms on it? If they truly wanted their study to demonstrate real-world harms of consumer-available products, they should have reported on that, rather than singling out CBD, which their study was not constructed to control for.
Designing a Better Study
Dr. Raber had an easy solution to control for the numerous confounding variables,“they could have gotten rid of concerns by just filling the cartridges themselves.” That would allow them to test terpene and solvent free samples, limiting confounding variables significantly. As a result, Dr. Raber was “disappointed” and felt they didn’t run “the right blanks and controls.” He also brought up a meta level issue of risks vs. rewards. Any potential harms need to be weighed against the potential benefits in what Dr. Raber called a “medicinal cost benefit risk analysis.” Considering the benefits of cannabis will be one way to improve a follow up study.
Another confounding variable they did not properly control for was the temperature samples were heated to. When asked if they knew how hot their samples got, Dr. Thanavala pointed to their supplemental section, which only had information on the room temperature, not device temperature. A 2021 study found that some “vape pens” heated to temperatures far above the point of combustion (450 °F, 232 °C), in worst cases as high as 633 °F/334 °C when containing liquids or 1000 °C when dry heating the coils. “Temperature is a key parameter but very hard to determine,” said Dr. Raber, because the temperature around the coil is hotter than the vapor stream. “The rate of molecular change doubles every 10 degrees celsius you go up,” said Dr. Raber, “a jump of 50 degrees can lead to a lot of changes.” The study hinted to these concerns saying, “Numerous potential degradation byproducts were detected … suggesting that both products are susceptible to high temperatures.” The CBD sample “may have been more susceptible to thermal degradation compared with nicotine product.”
One final way to improve their methodology is to use more accurate puff topography. “At present there is no information on CBD user topography,” said Dr. Thalanavala, so their study “followed the same puffing protocols for both products.” They did note that “users of cannabis-based vaping products may use these products in a very different way than nicotine vapers.”
Arnaud Dumas DeRauly is the CEO of the Blinc Group, and Chair of the ISO & CEN Vaping Standards Committees, and has researched cannabis user puff topography. DeRauly told High Times that this study used a puffing regime similar to Coresta Recommended Method 81, which “is totally different” than what Blinc’s research showed. In the study, “Animals were exposed … to a total of 20 puffs generated over 1 hour (1 puff every 3 min), 5 days/week.” Blinc’s research found that, while rates were different for U.S. and Canadian cannabis consumers, most needed only 20 puffs per day rather than 20 puffs per hour like the mice. Beyond puff topography, DeRauly was critical of the decision to use the Juul atomizer for both samples, and said “the Juul coil is not compatible with lipids like CBD oil.” Finally, DeRauly pointed out that one of the researchers, Maciej L Goniewicz, received funding from Pfizer and Johnson & Johnson, which the study noted was “outside of this work.”
Source: “Blinc Group and Labstat”
Mice: Nice Animals, Definitely Not Humans
As previously mentioned, this was a study done on small groups of mice, which means the results might not even be generalizable to the broader population of rodents, let alone, humans. While Dr. Thanavala said that ten mice per group is an “adequate group size,” the study’s discussion section said “larger numbers of mice could have further strengthened our study conclusions.” Dr. Raber viewed the findings as “not generalizable” and said, when it came to rodent lungs and humans, “It is a model, it is not an exact replica.” The mouse lung is not just smaller than human lungs, it “is considerably different in structure,” namely, while both mice and humans have five lobes in their right lung, “unlike the human the mouse has only a single left lung.” Research on mouse lungs also shows they lack “mast cells in the peripheral lung” and “extensive pulmonary circulation.”
Another way this study could be improved is to actually do it on humans, which currently is very difficult due to the federal ban on cannabis research with a positive hypothesis. If a researcher sought to prove the claim that vaped CBD is more harmful than nicotine, they could be eligible for funding, but if they wanted to disprove that claim, they would not. While a lot of research is done on mice, in the words of the recently deceased Father of Cannabis Research, Raphael Mechoulam, “Mice are nice animals but they are definitely not humans.”