Minor cannabinoids making major inroads targeting specific medical conditions
New information and research about minor cannabinoids – among the 100-200 that have been identified – is helping treat different health and wellness conditions and allowing cannabis companies to sell a wider variety of products.
The products go beyond the typical THC and CBD offerings currently on store shelves, and they incorporate lesser cannabinoids such as CBN and THCV.
The new products – including edibles and vapes – allow cannabis companies to appeal to consumers seeking ways to address conditions such as obesity, sleeplessness and nausea.
“We’re better trying to understand which plants elicit what effects and how to consistently provide that to consumers so we can get away from all the meaningless strain names and get right to the point of how do you want this plant to help you feel,” said Mike Hennesy, vice president of innovation at Colorado-based edibles maker Wana Brands.
“How is this plant going to enhance your life based off of your needs?”
At the same time, researchers are studying the cannabis plant to determine whether minor cannabinoids can be effective at treating everything from epilepsy and traumatic brain injury to other conditions that have yet to be identified.
Most of the new marijuana products being developed today involve four minor cannabinoids, none of which have the same psychotropic effect as THC:
- Cannabigerol (CBG), reputed to help fight inflammation, pain and nausea.
- Cannabichromene(CBC), one of the most abundant cannabinoids in the plant – first isolated in 1966 – and said to play a role in anti-cancer and anti-tumor capabilities.
- Cannabinol (CBN), reputed to be a sleep aid or sedative.
- Tetrahydrocannabivarin (THCV), dubbed “diet weed” and purported to help with weight loss.
The appetite for these cannabinoids is growing.
Grand View Research calculates the U.S. market for minor cannabinoids totaled $4.9 billion in 2020.
The San Francisco-based market research and consulting firm projects the market will expand at a compound annual growth rate of 20.1% from 2021 to 2028.
The firm points to “the rising trend of adopting cannabinoid-based medicines over traditional medicines, owing to their affirmative health benefits for many health conditions such as chronic pain, cancer, arthritis, neurological disorders, and metabolic disorders.”
Cannabis companies offer new products
Cannabis producers and manufacturers in Canada and the United States are rolling out products incorporating minor cannabinoids.
In December, Canadian licensed producer Cronos Group announced a new gummy featuring a 3-1 ratio of CBC to THC, called Day Trip.
In addition, Cronos has three different vape products based on those various gummy combinations.
Wana Brands recently released its Passionfruit Pineapple edible with a 1-to-1-to-1 CBG/CBD/THC ratio. That release follows last November’s debut of its Stay Asleep gummy, with a formulation of CBD, CBN, CBG and THC plus 30 specialized terpenes.
“So, instead of just a THC product alone with this formulation, you’re getting a multitude of benefits,” Hennesy said.
“And the reason this is important is that each cannabinoid has its own molecular shape and its own affinity for different receptors. So, if I have THC and CBG, those two molecules have some convergent and some different cannabinoid receptor targets.
“The pairing of these in the right ratios can lead to better effects than THC alone.”
Much research is still needed to understand the precise chemical properties of the minor cannabinoids and how they work in the human body.
Israeli cannabis scientist Raphael Mechoulam, who died earlier this month, and his team at the Hebrew University of Jerusalem have identified some of the other minor, or lesser, cannabinoids in the plant.
But it’s a difficult process.
“I never tried to count all of those,” said Oded Shoseyov, professor of plant sciences and genetics in agriculture at Hebrew University and a member of Mechoulam’s team.
“It’s actually anywhere between 100 and 200 that have been identified. And the reason I’m saying that is because there are also many synthetic cannabinoids with some chemical modifications that are still cannabinoids, maybe not natural, but they have or may have different pharmacological effects.”
Another thing researchers don’t know is if the cannabinoid profile is due to genes or to the environment, according to Daniela Vergara, an emerging crop specialist at Cornell University who founded the Agricultural Genomics Foundation.
“But if a lot of it is due to environmental effects, and has not been quantified, you need to make sure that you’re growing your strain in the right conditions for producing the compound that you want to produce.”
“I think that the pharmacological picture is still very complex,” said Shoseyov, who is working on remote sensing and machine learning of cannabis chemical composition and genetic markers.
Shoseyov was also part of the team that first isolated the THC molecule in 1964.
“Many scientists in the world are trying to isolate new cannabinoids and try to see if they work together with others that will have a certain biological effect,” he said. “But this is very tedious work.”
The role of plant genomics
Plant genomics used to develop new cannabinoids is behind the work of a number of researchers, including Colorado-based Front Range Biosciences; Montreal-based Hyasynth Bio, which is using yeast to produce cannabinoids; and both the University of California, Davis, with its Cannabis and Hemp Research Center, launched in 2019; and the Center for Research and Education Addressing Cannabis and Health at the University of Colorado Boulder.
“A lot of those minor cannabinoids are made in such tiny quantities, and we have some ideas of some of the effects that they have,” said Charles Pick, senior vice president for science and innovation at Aurora Cannabis, an Edmonton, Alberta-based licensed producer.
“But there’s the vast majority we really don’t know. So that’s sort of a tantalizing question: Is there one of those compounds available that has some sort of blockbuster impact in terms of therapeutics. We just don’t know.”
Jason MacDonald, director of cultivation operations at Native Roots, a Denver-based retail operator and grower, said he also is interested in learning more about the minor cannabinoids.
“But there’s not a ton of data behind them. And many labs have just started testing for several of these lesser cannabinoids,” he said.
“So where we’re at right now is in the beginning stages of identifying what strains contain some of these lesser-known cannabinoids and some of these rare cannabinoids, and then it’s finding out what interest there is in the market.”
Pick said Aurora is studying minor cannabinoids and company researchers are working with a cultivar that’s “sort of in an experimental stage” and has a higher-than-average level of THCV.
“With the plant, like most things in nature, you get this wonderful sort of genetic variation usually driven by mutations that have happened in the plant, so that you know the dominant cannabinoid pathway,” he said.
“But if you get mutations in some of the enzymes in that dominant cannabinoid pathway, what ends up happening is you get higher levels of sort of side products X or, in the case of CBG, which is kind of a precursor to CBD and THC, you get a buildup of that.
“When we find those sort of rare occurrences, we can essentially start to breed them and look for cultivars that have higher levels of minor cannabinoids,” Pick added.
Zac Hildenbrand, chemistry research professor at the University of Texas at El Paso, said he is trying to unearth this new understanding of what molecules are needed for specific conditions.
“So that yourself or myself could say, ‘Hey, I have condition A, and according to this literature, I need a little bit of CBD. I need some CBC, and I need these three terpenes. Show me a strain that has those components and I’ll buy that.’ Otherwise, you’re really shooting in the dark,” he said.
“People need to be making more data-driven decisions,” Hildenbrand added.
“If we’re making better, more data-driven decisions about this, then patients are going to have more favorable outcomes and then they’ll come back to cannabinoid medicine as opposed to using traditional pharmaceutical agents.”
According to Hennesy, Wana works with its suppliers and partners to establish terpene maps and then tries to match those to user outcomes and experiences.
“So it’s not only an understanding of the cannabinoid and terpene profile,” he said.
“But when you query people on how it made them feel, we can start to map these strains clustered together to produce these types of effects.
“There’s still a long way to go on that. But that’s the future for innovative companies to be working with.”