Kali-Extracts Announces Second Bidder On Its Cannabis Biopharmaceutical Technology Valued At $50 Million

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 sativa L.—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Out of Date and Out of Touch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

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?

Researchers have already taken an interest in finding out what the lesser-known cannabis compounds are capable of. In fact, the National Center for Complementary and Integrative Health (NCCIH) recently announced that they will be funding nine new studies that will investigate minor cannabinoid therapeutic potential.

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 refer 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.”