From a purely chemical standpoint, a cannabinoid is a cannabinoid and a THC molecule is a THC molecule, no matter how it’s produced, whether in a lab or grown on a farm.
From a legal perspective, a cannabinoid is a cannabinoid—at least in Canada. Production and distribution of CBD is held to the same standards as the psychoactive compounds in cannabis.
However, in the US, THC and CBD are legally distinct. After the 2018 Farm Bill passed, hemp and cannabis with extremely low percentages of THC—less than 0.3%—became federally legal. So while non-psychoactive cannabinoids may act, look, and quack like ducks, they might turn out to be swans.
This possibility has researchers and companies salivating at the medical possibilities and potential profits of the less common cannabinoids contained in cannabis plants. These rarer cannabinoids appear at such low levels that it’s impractical to extract large quantities from marijuana plants. But a little genetic engineering, a lot of research, and a few metal tanks full of yeast bacteria could make mass-production possible.
The race to study rare cannabinoids
Yeast fermentation is an age-old process, familiar to most as a source of beer or bread. But in the scientific community, it’s known as one of the primary bacteria used to produce biopharmaceuticals (the other is E. coli).
Today, the scientific race is on to study specific cannabinoids other than THC or CBD as treatments for illnesses such as epilepsy. And the commercial race is on to provide those cannabinoids to research institutions.
From a researcher’s perspective, it doesn’t matter how the cannabinoid is produced. Consistency and reliability of supply are required, not sunlight and dirt. While yeast has to be genetically modified to produce a cannabinoid, the end product is genetically identical to its plant-produced counterpart.
While there is no safety or efficacy concern, from a consumer perspective, substance origin can matter—if you know about it. But once cannabinoids have been harvested and refined into an oil, it’s impossible to tell whether they came from a plant or a test tube. They all quack like ducks.
Producing cannabinoids through yeast fermentation
“There’s so much territory to explore. We’re just taking the first steps,” said Cynthia Bryant, the Chief Business Officer at Demetrix, a US company focusing on the potential medical benefits of non-psychoactive cannabinoids for the US pharmaceutical market.
Based out of California, Demetrix is working toward large-scale, non-farming cannabinoid production. And they think yeast fermentation will take them there.
“The technology works very well to produce a rare cannabinoid,” said Bryant.
Once they are up and running, they will be able to quickly and regularly produce large amounts of specific cannabinoids, setting up a supply chain that’s reliable enough for pharmaceutical research and medicines. Sales could include oils and crystalized powders for research, clinical trials, and eventually, as active ingredients in medications.
Over a hundred different cannabinoids can be extracted from cannabis plants, but many exist at such low levels that they have never been studied as isolated medical ingredients.
Demetrix has identified the first so-called rare cannabinoid that they want to bring to market. Bryant wouldn’t name the specific cannabinoid the company plans to release to market next year, citing trade secrets, and said only that they’ve “discovered some useful effects.”
The yeast fermentation process
Insulin, the first biopharmaceutical, was once extracted from pig pancreases. In the late 1970’s scientists cloned the gene that makes the human body produce insulin, cut out a piece of DNA from a yeast cell, and inserted the engineered gene into its place. Instead of producing alcohol, the yeast cells became tiny factories that produced insulin.
Suddenly, it was exponentially easier and cheaper to manufacture insulin. The new method was fast, consistent, and scalable, allowing it to be replicated at commercial levels. It is also completely safe. Today’s yeast fermentation process is similar, if significantly advanced.
Demetrix mail orders synthetically produced DNA sequences of the enzymes in cannabis that have been identified as instigators of natural cannabinoid production. Scientists then insert the DNA sequence into yeast cells, reprogramming their purpose. The specific methods used to do this vary from company to company and are considered trade secrets. But the general tack of using a microorganism to produce a specific molecule is common across the field.
The modified yeast cultures are then left to ferment and grow in tanks, multiplying and producing large amounts of the desired cannabinoid. Workers then extract the cannabinoids from the yeast slurry, isolate, and purify them.
“I think there’s going to be a huge need for these cannabinoids,” said Bryant. The more cannabinoids are studied, the more medical solutions might be found. So it’s a good thing that the fermentation field is crowded—and that cannabinoid plant extraction is also plowing forward, Bryant explained. Competition will bring down prices and increase availability, she said. “We need all of the various sources.”
Cannabis doesn’t directly make the most famous cannabinoids associated with the plant, THC and CBD. Instead, it synthesizes several cannabinoid acids . These cannabinoid acids must be “activated” (decarboxylated), usually by heat, to yield the compounds that most consumers are after (THC or CBD). But in addition to THCA and CBDA, there are number of related cannabinoid acids that can be produced by cannabis. These are:
- CBGA (Cannabigerolic acid)
- THCA (Δ9-tetrahydrocannabinolic acid)
- CBDA (Cannabidiolic acid)
- CBCA (Cannabichromenenic acid)
- CBGVA (Cannabigerovarinic acid)
- THCVA (Tetrahydrocanabivarinic acid)
- CBDVA (Cannabidivarinic acid)
- CBCVA (Cannabichromevarinic acid)
Will consumers care?
Far north of Demetrix’s Berkeley, CA, base, Canadian company Hyasynth is just about ready for full-scale production of fermented cannabinoids, said Kevin Chen, Hyasynth’s CEO.
Hyasynth also mail orders DNA sequences, slots them into yeast genomes, and extracts the desired compounds from the slurry to produce medical grade cannabinoids for sale to pharmaceutical companies.
“It’s the modern way,” said Chen, who extolled the same virtues of fermentation over farming as Demetrix does: scale, consistency, speed, and, most especially, specificity. “We have full control over which cannabinoid we produce and which we don’t.”
Fermentation is a process that takes five days, instead of the three months it would take to plant and grow marijuana to use for enzyme extraction, he said. Farming can be difficult. Once you nail down your specific splicing method, fermentation is easy.
Engineered cannabinoids may be superior for pharmaceutical purposes, but not everyone will want cannabis grown in tanks or tubes, Chen acknowledges.
“We’re not too worried about people rejecting our product,” said Chen. “We’re using yeast to manufacture things, but the yeast isn’t what we’re selling.”
From the standpoint of personal preference, not all cannabinoids are equal. Some consumers might prefer a holistic, whole-plant product. Some might only care about results.
“Do people care that it comes from a different place? Absolutely,” said Chen. But different methods of cannabinoid production are suited to different purposes, and fermentation seems poised to win in a pharmaceutical ingredient contest. “It is different—in many ways it’s better.”