A Cannabis High, No Plant Required

Scientists think they can re-create marijuana’s active ingredients with brewer’s yeast.

Richard Vogel / AP

Fermentation-powered brewing has been getting people drunk for thousands of years. Soon, it could be getting them high, too.

In research announced on Wednesday by the University of California at Berkeley, a team of synthetic biologists modified brewer’s yeast to produce a range of cannabinoids, which are compounds in cannabis that affect the brain and body. The technique opens up the possibility of circumventing the need for large-scale plant cultivation, and the findings could conceivably make high-quality, reasonably priced cannabinoids much more accessible for pharmaceutical development and recreational consumer products.

For longtime cannabis advocates, though, this new technology might bring corporate interests one step closer to controlling a market they’re fighting to keep democratic.

To brew cannabinoids—the most famous of which are tetrahydrocannabinol and cannabidiol, or THC and CBD—the operation looks much like a traditional brewery, says Jay Keasling, the Berkeley professor of chemical and biomolecular engineering who led the research. “Essentially what we’ve done is taken yeast, which would normally produce ethanol for beer or wine, and we put in it the gene for producing cannabinoids,” he says. “We have the opportunity to produce very pure molecules.”

THC and CBD are only two of about 100 documented cannabinoids in existence. THC is the psychoactive element of cannabis that makes users feel high, while CBD is the element that can provide a feeling of calm. Beyond primarily recreational consumer products such as the gummies and oils currently found in legal weed dispensaries, preliminary research is promising on both THC’s and CBD’s potential uses as pharmaceutical therapies for managing conditions such as pain and anxiety.

Obtaining large quantities of reliably high-quality cannabinoids can be a major obstacle for scientific researchers looking for medicinal applications of the compounds, and supplying those efforts might be the most immediate upside of large-scale vat fermentation. As recreational cannabis legalization expands across America, there could be other upsides. “When they’re incorporated into products—whether that be skin creams or edibles or whatever else—you’re going to know exactly how much you’re getting,” Keasling says.

Concerns over variable CBD quality and strength have caused problems for cannabis entrepreneurs recently, especially when the debatably legal extract is incorporated into consumer products such as food.

For the dozens of other cannabinoids, no one really knows what might be possible, or what effect they might have on humans in larger, isolated doses. Because most of them appear in cannabis as trace or rare chemicals—and some of them, known as unnatural cannabinoids, don’t appear in the plant at all—meaningful research on them has so far been impossible. “We haven’t had access to test, and this will give us access to those compounds,” Keasling says. “The yeast would produce the cannabinoids in, say, a day or a couple days.”

Keasling is one of the research pioneers of this yeast-based approach to chemical production, which is a type of synthetic biology. The technique is still in its exploratory stages and has been met with some skepticism, but it is currently being used to manufacture a number of products, including insulin and lab-grown leather.

In 2014, Keasling used yeast to produce the antimalarial drug artemisinin, which occurs naturally only in the sweet wormwood plant. Agricultural supplies of the drug have traditionally been erratic, but as Keasling’s synthetic-biology alternative went to market, the natural supply of the drug stabilized and the price dropped, which neutralized the economic need for alternatives.

The cannabis market provides the opportunity for better timing. Large-scale cultivation of the plant in legalized U.S. states is only just beginning to move forward. With more states likely to soften their position on weed in the near future, demand could skyrocket not just for the plant’s flowers, but especially for the cannabinoid-based extracts that provide an easier point of entry for novice experimentation or health products. Fermentation has the potential to provide a quicker and more sustainable way to meet those needs: Conventional cannabis cultivation is, ironically, not so green.

Fermentation is also less expensive, according to Keasling, because it uses less land, smaller facilities, and more limited manpower. Its waste product is mostly water, which can be safely treated with existing technologies that large-scale fermenters already use. In the case of artemisinin, Keasling says that production cost about $400 a kilogram once everything was up and running at scale. In contrast, a pound of wholesale cannabis in legalized states currently costs anywhere from $595 to nearly $3,000. That raw material would then have to be processed down to much smaller quantities of pure extracts.

Keasling has bought in to the business potential of his research. In 2017, he founded a company called Demetrix that so far has $4 million in venture-capital seed funding, and it licenses the technology he has helped develop in order to explore research and consumer-business models for vat-fermented cannabinoids. Other companies are also keen to use synthetic biology to enter the cannabis market, including the Boston-based Ginkgo Bioworks.

When it comes to research opportunities, the predictable, cost-effective production of cannabinoids is likely good news, but it could be a problem for people who want legalization to preserve individual citizens’ right to grow their own weed and to sidestep the drug’s looming corporatization. A bill introduced to legalize cannabis in New York has been criticized by cannabis advocates for excluding home growers at what they say is the behest of corporate interests, and the potential to circumvent the plant entirely could give Big Pharma easier control over who can or cannot access cannabis’s potential, and how much they have to pay to do so.

Still, synthetic biology’s potential to give scientists a deeper and more complete understanding of cannabinoids’ possible benefits could help people with any number of ailments. “I wouldn’t be surprised if there’s a blockbuster drug in there,” Keasling says. “We just don’t know.”