Cracking the complex biology of cannabis
A year and a half after legalization, researchers are just starting to understand a crop worth $5 billion a year in Canada
By Silvia Moreno-Garcia, UBC Science
In 2017, University of British Columbia botanist Lacey Samuels applied for her first permit from Health Canada to study cannabis. It was a complex process–even the smallest detail, like the size of frames and type of lock used on her lab doors had to be verified for security.
After legalization of cannabis in Canada in 2018, scientists like Samuels expected it would become much easier to study the valuable and complex plant. The process is now much more stream-lined, but the reporting and physical security issues are still stringent.
“It’s still easier to grow four plants at home for personal use than to grow four plants in the lab for research use,” says Sam Livingston, a Botany department PhD candidate who is part of the Samuels lab.
It’s a sentiment echoed by other UBC researchers, such as Judith Booth, who studies the aromatic components of cannabis plants, and Jonathan Page, the first scientist to sequence the cannabis genome and Chief Science Officer at Aurora Cannabis. They all say that, due to prohibition, many aspects of chemistry and biology of cannabis remain a mystery, and we need to do more to crack its secrets.
Unanswered questions
Canada’s cannabis industry is worth five billion dollars a year. Yet, unlike other crops such as corn or grapes, researchers, growers and producers still know very little about it.
Booth, for example, studies the enzymes that make cannabinoids, the main psychoactive ingredient in cannabis. Although scientists have identified the enzymes that create cannabinoids, they haven’t been able to identify all the steps in its production. It’s like viewing a Google Map and being able to see your destination but not the streets you’ll take to get there.
“What we do know now, which we didn’t understand before, is the genes involved,” says Samuels. “Every single cannabis plant cell is like a very dense city of processes, and the metabolites need to be produced in one place and shipped to another, and we don’t quite know how that happens.”
Another aspect of cannabis growth that scientists don’t understand yet is flowering time. Only female cannabis plants flower and produce the resin that contains cannabinoids. Flowers bloom under specific light conditions, when days begin to shorten in the fall. This is inconvenient for growers because they must carefully manage light conditions. The genetic basis of this auto-flowering trait is an area of intense research.
Cannabis terpenes are also poorly understood. Terpenes are the compounds that give a plant its aroma and flavor. What we call essential oils, such as lavender or mint oil, are mostly made of terpenes. Cannabis is universally associated with a musky aroma, but each strain of cannabis actually has its own specific scent.
“Generally, the major difference in scent between marijuana strains has to do with the terpenes in them, but we don’t really know why. At a genetic level, at a causal level, we don’t know what makes them smell differently from one another,” Booth explains.
Cannabis has a Lego kit of enzymes that it can reach into to create a variety of compounds. But there’s a lot of duplication in the instructions — selections from 10 different enzymes could produce any particular terpene.
A bud by any other name
This incredible chemical diversity and variety of strains has created another issue: misclassification. Because cannabis has been an illegal crop for so many decades, growers haven’t kept track of many varieties.
In 2015, when Jonathan Page led the first large-scale genetic study of cannabis, he discovered that the genetic identity of a marijuana strain can’t be accurately determined by its name or reported ancestry.
“You can buy a cannabis product by name but you’re not really getting any consistent product under that name,” says Booth. “When we looked at eight different plants that were called Afghan Kush, they had no relationship to one another at all.”
It’s the equivalent of going to the store, asking for a bag of Doritos and getting Cheetos instead.
The other gap, Samuels says, is the lack of attention to ‘folk knowledge’ — numerous books, pamphlets and stories that have documented cannabis production through the decades.
“Some of it is really consistent with what we’re finding scientifically, and some really isn’t consistent with the science,” says Samuels. “But it’s interesting to look at it and try to apply what we’re finding to traditional knowledge.”
Samuels points to an old book that shows a man trimming flowers with scissors to improve the quality of the plant. Cannabis flowers are covered with what look like tiny crystals. They almost resemble frost. These frosty growths are called trichomes, from the Greek word tríchōma, meaning “growth of hair,” and they function as tiny resin glands that hold the compounds that are responsible for cannabis’ effects: tetrahydrocannabinol (THC) and cannabidiol (CBD).
For a long time, marijuana growers have recommended trimming the plants, both for aesthetic reasons and to remove the “sugar leaves” from the bud — the smaller leafs look like they are frosted in sugar due to their coating of trichomes. These little leafs do not have as many trichomes as the buds themselves, so if you leave them on the potency of cannabinoids (THC- and CBD) per total weight of the bud decreases.
Recent microscopy work has shown that the density of trichomes varies on different parts of the flowers. Large mushroom-shaped trichomes are the richest source of THC- and CBD-forming metabolites and terpenes. This explains why growers might want to trim away certain parts of the plant.
All of these questions and mysteries provide an exciting space for researchers. But the problem we are currently facing is the imbalance between industry and pure research. Companies are conducting numerous studies, but behind closed doors. UBC researchers agree that Canada is in a good position to become a leader in cannabis research, ensuring it’s not only private companies that tackle these scientific questions. The result will otherwise be lopsided knowledge — as if all our knowledge of grapes was developed by wine makers. Now that cannabis is a legal crop, more attention should be given it to it by a wide variety of researchers.
Making cannabis research ordinary
UBC researchers believe there are ways to improve the panorama. Canada could support the creation of an umbrella organization that allows companies to share the costs of research. This would avoid the duplication of research efforts and allow smaller companies to still have access to important information. Booth points to Mitacs — a nonprofit national research organization that, in partnerships with Canadian academia, private industry and government, operates innovative research programs — as a possible model.
“Access to funding is a bottleneck,” Page says. “I think the federal government should commit to investing some of the taxes and regulatory fees from legal cannabis to funding research, in particular, on health properties of medical cannabis.”
Meanwhile, Health Canada could tackle research license delays by transferring the authority for cannabis research licensing to universities, which already manage aspects of biosafety, radiation safety and ethics approvals.
“On the one hand, cannabis science has a lot of glamour right now,” says Page. “Part of that is because it was illegal for so long. But I hope eventually it’ll be treated just like any other crop. In the end it’s just a plant and we can’t manage it better if we don’t understand it as fully as we understand potatoes or corn.”
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