Federal health officials announced Nov. 8 that vitamin E acetate has been found in the lung fluids of 29 patients affected by the outbreak of vaping-related lung injuries—a breakthrough that identifies the vape cartridge additive as the likely culprit in the epidemic.
The Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), state and local health departments, and multiple public health and clinical partners have been investigating the nationwide outbreak of vape-related illnesses—referred to as “e-cigarette, or vaping, product use-associated lung injury (EVALI)—which first grabbed national headlines in early September.
Based on data collected as of Oct. 15, 86% of 867 affected patients reported using THC products in the three months before the onset of symptoms, according to the CDC’s announcement, and subsequent analyses of THC-containing product samples revealed potentially harmful additives, including vitamin E acetate and medium chain triglyceride oil (MCT oil). These additives, particularly vitamin E acetate, are primarily used as a thickening agent in THC products.
Bronchoscopy and bronchoalveolar lavage (BAL) fluid samples were collected by the clinical teams caring for patients afflicted with vape-related lung injuries, according to the announcement. Public health laboratories from California, Connecticut, Hawaii, Illinois, Maryland, Michigan, Minnesota, Texas, Utah and Wisconsin then submitted samples from 29 patients to the CDC, which developed and validated testing methods to analyze the specific substances of concern and active compounds found in the BAL fluid.
Vitamin E acetate was detected in all 29 BAL fluid samples.
THC or its metabolites were detected in 23 of the samples, according to the CDC, and nicotine metabolites were detected in 16.
“These findings provide direct evidence of vitamin E acetate at the primary site of injury among EVALI patients and are consistent with FDA product testing and media reports of state public health laboratory testing documenting vitamin E acetate in product samples used by EVALI patients,” the CDC said. “Other diluents and additives of concern (e.g., plant oils, MCT oil, petroleum distillates, and diluent terpenes) were notably not detected in BAL fluid specimens from EVALI patients.”
Even so, the CDC added that additional studies are needed, including a comparison of BAL fluid samples from healthy volunteers and animal studies, to determine whether there is a causal link between vitamin E acetate exposure and the lung injuries.
“Based on these data from 29 patients, it appears that vitamin E acetate is associated with EVALI; however, it is possible that more than one compound or ingredient could be a cause of lung injury, and evidence is not yet sufficient to rule out contribution of other toxicants to EVALI,” the CDC said.
Industry stakeholders, such as the Cannabis Trade Federation (CTF), view the CDC’s discovery as a major step forward in solving the vape epidemic.
“We applaud the CDC and other federal and state health officials for their efforts thus far to identify the cause or causes of the reported outbreak of pulmonary-related illnesses associated with the use of vaporization products,” the organization said in a public statement. “While it still appears these health incidents are primarily associated with the use of illicit THC vape products, we urge members of the regulated cannabis industry to be vigilant and review all of their vaping products to ensure they are free of vitamin E acetate. CTF also urges officials in states that have regulated cannabis for medical or adult use to review their states’ regulations to ensure vitamin E acetate is clearly prohibited from being used in any inhalable cannabis products.
“This health crisis and the recent breakthrough in the investigation underscore the importance of existing state cannabis regulations, as well as the need for strict cannabis regulation at both the state and federal levels.”
Some states have indeed started more tightly regulating vapes and their additives, while others have banned vape products altogether. Colorado regulators, for example, have taken steps to ban polyethylene glycol (PEG), vitamin E acetate and MCT oil, while Washington and Oregon adopted emergency rules that ban the sale of flavored vape products. Massachusetts is working through the legal technicalities of banning all vape products in the state, although a judge ruled earlier this week that the ban must be lifted on medical cannabis vapes.
Other states have not yet responded to the vape crisis.
“The CDC’s announcement highlights the urgent need for Michigan to crack down on bad actors and black-market operators who are selling untested, dangerous products and passing it off as medicine,” said Michael Elias, CEO of Michigan Pure Med and Common Citizen, in a public statement. “There have been more than 2,000 vaping-related lung injuries and more than three dozen deaths because of harmful cutting-agents found in illicit vape products, and this is unacceptable, which is why we need stronger enforcement of the illicit cannabis market.”
Vitamin E acetate has long been the suspected culprit in the outbreak of vape-related lung injuries, although, as the CDC pointed out in its announcement, many unanswered questions still remain.
The CDC concluded that until the relationship of vitamin E acetate and lung health is better understood, vitamin E acetate should not be added to vaping products.
nik0.0kin | Adobe Stock
Type I, Type II, Type III: How Science Is Changing the Way the Industry Describes Cannabis Varieties
Leaving behind the sativa-indica dichotomy, cannabis businesses must consider the chemistry of the plant.
Human brains are wired for categorization. These systems help us navigate the world and communicate with one another more efficiently. But with more than 400 active chemical compounds associated with the many variations of Cannabis sativaL.—and an infinite number of combinations these phytochemical constituents can take in flower-form—arriving at an appropriate and accurate consensus on chemovar categorization across the cannabis industry has been tough. This is especially problematic within the context of the market’s binary legacy.
How we talk about cannabis chemovars matters. Now, more than ever before, science is revealing new ways to categorize this plant’s effects.
Out of Date and Out of Touch
The indica-sativa-hybrid model of classification has continued to dominate the markets—both regulated and illicit. Separate from their intended taxonomy, these terms have been adopted as a way to describe the likely experiential and therapeutic effects of a given strain, or phytochemical varietal. But in a world where expansive hybridization of cultivated types is the norm and wild-type landraces have been taken out of their natural growing environments, this system of taxonomy does little to predict chemical constituents or describe experiential outcomes. The industry is at a loss for words to adequately convey the plant’s chemistry to consumers.
Leaving aside disagreements on the accuracy of classifying drug-type cannabis as either indica or sativa, categorizing a chemovar within this binary system—especially in the absence of comprehensive phytochemical data or, even, genetic assuredness—presumes a predicted effect based solely on stable genetic inheritance and disregards variation in profile due to environmental factors. It’s not as simple as the old yarn that an indica strain leaves the consumer “in da couch.” A more complex set of phytochemical constituents is at play here.
Comprehensive data now demonstrates that the morphology of the plant is not indicative of the effects it will produce in a general population; only the final ingredients matter. This phenotypic amalgamation of chemical compounds is a product of both genetic inheritance and environmental factors (light, temperature, pests, soil microbiome, etc.—all of which influence the phytochemical output and, in turn, the Ensemble Effect of how these myriad molecules engage with one another.
So how do we categorize these differences in a way that is both accurate and approachable? How do we create a segue from an inherently subjective system based on incomplete taxonomy toward a more scientific vernacular that will, at least, set the stage for whatever comes next?
One way, of course, would simply be to adhere to the ingredients—the phytochemical data. By acquiring full-spectrum lab reports, training employees to navigate those reports and communicating that data to consumers in an approachable way, producers and retailers can introduce a deeper understanding of the complexity of the plant and its nuanced effects. More on that can be found here.
But, as ethnobotanist, BioAgronomics Group co-founder and CBT columnist Robert C. Clarke commented during a recent phone conversation, that’s “a lot of fine print. … It’s like reading the Dr. Bronner’s soap label. We have to simplify things. We have to leave out some of the details or we won’t see a distancing from indica-sativa.”
A Segue Into Science
In a 1973 paper published in Nature, Ernest Small and H.D. Beckstead introduced the idea of categorizing varietals according to cannabinoid content. Cultivators shooting for a more accurate approach to classification, like Oregon’s Prūf Cultivar, have taken up this system to distinguish between broad cannabinoid profiles.
Three primary chemotypes are recognized:
Type I – THC-dominant with a concentration of >0.3% and CBD content of <0.5%.
Type I flower makes up the majority of the current market and can reach upwards of 30% THC as cultivators push the limits of what the cannabis plant is capable of producing. These cultivations are likely to induce intoxicating effects with low levels of secondary cannabinoids that could otherwise influence specific therapeutic or experiential outcomes. A more colloquial interpretation of Type I could be “intoxicating” types.
However, as Dr. Giuseppe Mandolino from the Council for Agricultural Research and Analysis of Agricultural Economics (CREA) in Italy pointed out in a recent email exchange with CBT, a Type I varietal can refer to any THC-dominant chemotype, including one with a relatively low cannabinoid content overall and is not necessarily indicative of intoxicating potency. Granted, these low-potency products are less likely to be selected for breeding, much less make it onto dispensary shelves, but it is worth noting that a system based on chemotype classification is still reliant upon detailed phytochemical data to convey likely effects.
Type II – a mixed ratio profile with CBD and THC in varying moderate concentrations, almost always presenting as CBD-forward.
The CBD-rich content of Type II flower can help mitigate unwanted intoxication from the still present THC content while increasing therapeutic benefit—both from the ensemble of the mixed ratio profile working on receptors, as well as through the greater likelihood of patient adherence to daily dosing when negative outcomes are attenuated. For this reason, a 1:1 ratio of THC to CBD is often considered by industry professionals and medical practitioners alike as an effective starting point for consumption. The FDA-approved pharmaceutical Sativex is an isolated cannabinoid product in this ratio and has been increasingly used in clinical trials.
Type II, or “mixed ratio” flower, does not currently make up a large percentage of available product but will likely take a leading role in future production as more and more consumers seek balance over inebriation.
While not technically a Type II, labeling a product as “mixed ratio” could also allow for the inclusion of other minor cannabinoid mixed ratio profiles as they are developed, like the THCV-rich (tetrahydrocannabivarin) Black Beauty chemovar.
Type III – CBD-dominant with low THC content that provides little to no intoxication.
This chemotype may be classified as hemp or “marijuana”—the racially motivated term that has been adapted to refer to any cannabis that falls above the 0.3% THC content arbitrarily allotted for legal hemp production. THC content for Type III flower can be as high as 1%. Therefore, Type III can be cultivated for fiber or drug-production. Further sub-classification may be warranted wherein craft hemp, rich in cannabinoids and terpenes, may need to be distinguished from material grown for industrial goods like paper, fabric, and cellulose plastics.
Retailers and producers seeking a more approachable translation of type categorization for consumers could consider labeling Type III cultivations as “non-intoxicating.” Accessible vernacular such as this could embrace other non-intoxicating chemovars as they hit the market as well. However, retail educators should be wary of over-promising benign effects as some consumers and patients may still feel unwanted intoxication from these chemovars, depending on individual tolerances.
Courtesy of Dr. Giuseppe Mandolino
Beyond THC: Types IV and V
As medical access increases and more and more consumers seek out effective therapies that don’t leave them intoxicated from too much THC, cultivators are exploring varietals rich in other cannabinoids. Utilization of a types-based system allows for the introduction of “minor” cannabinoid-rich profiles like these in real-time that differentiate themselves from a Type I, II, III classification. This distinction becomes particularly important as clinicians take a more active role in cannabinoid therapies.
First identified in 1987 by a team of French researchers led by Dr. Genevieve Fournier, a fourth, CBG-rich profile was noted. Like Type III varietals, Type IVs also contain low levels of THC but with potent percentages of CBGA, or cannabigerol-acid, the raw stem cell cannabinoid from which all other cannabinoids synthesize during plant growth. When heated, CBG has demonstrated potential therapeutic benefits ranging from appetite stimulation to reduction in neuroinflammation and increased neuroprotection in mouse models via engagement with both cannabinoid receptors 1 and 2 as well as other G protein-coupled receptors found throughout the body.
Dr. Mandolino was the first to describe a fifth type—Type V—in 2004. This chemotype refers to cannabis plants that produce little to no cannabinoid content (cannabinoid-null or -zero).
Cannabinoid-null plants are still a bit of a mystery within the cannabis market. However, as Director of Production Sciences at Prūf Cultivar Jeremy Plumb has pointed out, Type V plants may be useful in stabilizing Type III plants for the consumer market. Or they may have an important role all their own yet to be uncovered.
The Future of Flower
And what of other minor-rich cannabinoid profiles? How does the type classification system create a useful jumping off point as the market expands beyond the THC vs. CBD conversation?
Varietals like Black Beauty, known for its THCV-rich content, are already on the market and other minor-rich profiles containing CBC (cannabichromene) and CBDV (cannabidivarin) dominant expressions are not far behind. These minor cannabinoids have far less intoxicating value than their THC cousin whose varying phytochemical expressions have been the primary target of the indica-sativa vernacular. How, then, can this dichotomy be adapted to a future market where THC doesn’t dominate? It simply doesn’t translate. Furthermore, using a types classification reinforces the fact that not all cannabis is created equal. In many areas of the U.S., there is still a profound stigma associated with cannabis as an intoxicant and the adult-use market as a liability, not a right. Fortunately, the 2018 Farm Bill helped to encouraged open-minded curiosity once CBD was seen as legal and accessible. Many folks who once cried reefer madness have now found real relief through access to non-intoxicating compounds. Others are now discovering that they need more than just CBD to hit their ideal therapeutic window.
As the market responds to the needs and desires of this increasingly sophisticated consumer market in search of truly personalized cannabis medicine and “Goldilocks” ratios, there will need to be a new method of navigating the nuances flooding the shelves. A system of classification based on scientifically accurate chemotypes, whether taken at face value or translated into more approachable vernacular, can be that needed segue toward creating a consistent language across the consumer and scientific communities.
As Plumb noted, while chemotype classification may add nothing more than a “layer of geekery” for some, “for patients [and consumers] looking to establish a lifelong positive relationship with the plant, it’s not a bridge too far.”
petert2 | Adobe Stock
Petitions to Legalize Cannabis in Florida Run Short on Signatures as Deadline Looms
Two petitions that would place adult-use cannabis initiatives on Florida’s 2020 ballot need 766,200 signatures before Feb. 1 to qualify.
Two petitions that would place adult-use cannabis legalization initiatives on Florida’s 2020 ballot are running short on signatures as a Feb. 1 deadline looms.
Regulate Florida has collected about 92,000 of the required 766,200 verified signatures to qualify, while Make It Legal Florida has gathered 57,000, according to an Orlando Sentinel report.
The groups’ initiatives take two different approaches to legalization; Regulate Florida aims to broadly legalize adult-use cannabis, while Make It Legal Florida’s proposal would allow only the dispensaries currently selling medical cannabis in the state to serve a broader adult-use market.
Regulate Florida has been largely funded through small donations, the Orlando Sentinel reported, while Make It Legal Florida is financed by the cannabis industry.
If they make the ballot, the initiatives—both constitutional amendments—would need 60 percent of the vote to pass, according to the Orlando Sentinel.
Lulla | Adobe Stock
Alabama Medical Cannabis Study Commission Begins Work on Legislation
The group is working on a medical cannabis legalization bill that will be introduced to the legislature early next year.
The Alabama Medical Cannabis Study Commission has been weighing the pros and cons of legalizing medical cannabis in the state, and the group is now entering discussions on a draft version of legislation that will be introduced to the legislature early next year.
The commission, which held its first meeting in August, was charged with recommending medical cannabis legislation that could be considered in the 2020 legislative session. The group was created by lawmakers as a compromise after a bill to legalize medical cannabis in the state stalled earlier this year. It consists of representatives from fields such as medicine, law enforcement, drug addiction treatment, agriculture and pharmacy, according to an AL.com report.
The draft bill would create a Medical Cannabis Commission responsible for establishing a regulatory framework for the issuance of medical cannabis cards for patients with qualifying conditions, which include agitation associated with dementia, autism spectrum disorder, chemotherapy-induced nausea, Chron’s Disease or irritable bowel syndrome, a condition causing chronic pain such as fibromyalgia and migraines, epilepsy or other condition causing chronic seizures, HIV/AIDS-related nausea or weight loss, post-traumatic stress disorder (PTSD), sleep disorders, spasticity associated with a motor neuron disease, multiple sclerosis or spinal cord injuries, terminal illnesses and Tourette’s Syndrome.
Sen. Tim Melson (R-Florence), the commission chairman, has urged members to study the draft legislation and make any recommended changes ahead of the legislative session, which begins Feb. 4, AL.com reported.
sergign | Adobe Stock
Judge Rules Racial Quotas in Ohio Medical Cannabis Program Are Unconstitutional
A section of the law requires that 15 percent of licensed companies in the program are owned by members of “economically disadvantaged groups.”
A judge has ruled that a section in Ohio’s medical cannabis law that requires 15 percent of licensed companies to be owned by members of “economically disadvantaged groups” is unconstitutional.
Madison County Common Pleas Judge Eamon Costello also ordered that Pure Ohio Wellness LLC should get another hearing before the Ohio Board of Pharmacy to decide whether it should be granted a dispensary license, according to a Cleveland.com report.
All parties involved in the lawsuit have agreed that Pure Ohio had the highest score among all the dispensary license applicants in Madison, Fayette and Greene Counties, a region set to get only one dispensary, but Pure Ohio, which is not minority-owned, lost to a minority-owned applicant, Cleveland.com reported.
The Board of Pharmacy has argued that the section of the law regarding economically disadvantaged groups allows the state to address racial discrimination in the licensing process, but Costello ruled that the board’s arguments in favor of the racial quotas apply to government contracts with minority-owned businesses and not businesses that are licensees, according to Cleveland.com. Costello also ruled that the board has not provided statistical evidence that prove that there was indeed racial discrimination present in Ohio’s medical cannabis industry in the first place, the news outlet reported. Under Costello’s ruling, the law must be more specific.
The Board of Pharmacy is reviewing the ruling and discussing whether to appeal it with the Ohio Attorney General’s Office.
Legislative Map
Cannabis Business Times’ interactive legislative map is another tool to help cultivators quickly navigate state cannabis laws and find news relevant to their markets. View More