Scientists Discover New Cellular Processes Within Cannabis Trichomes

The world inside a cannabis leaf is clearer than ever before.

After freezing cannabis leaves and observing the cells via a quantitative electron microscope, scientists at the University of British Columbia say they have made new discoveries about the inner workings of cannabis trichomes – the minute “hairs” of cannabis leaves that produce the plant’s coveted cannabinoids.

According to the researchers, these discoveries could help inform the synthetic production of cannabinoids in yeast and cell cultures.

Their work was published in Current Biology.

Under the trichome

While much is known about the chemicals cannabis produces – such as THCA and CBDA, which, when heated, form THC and CBD – much less is known about how the plant produces them.

“What was known before we started this project was that the non-photosynthetic plastids [plant “micro-organs”] were very unusually shaped, and were involved in making the precursors of cannabinoids, and that cannabinoids were eventually stored outside the cells in the mushroom shaped storage cavity at the top of the trichome,” Dr. Sam Livingston, a botanist at the University of British Columbia who led the research, told Analytical Cannabis.

“What we didn’t know was where the final step of cannabinoid formation (THC, CBD etc.) happened, and how the precursors are able to get from where they are made to where they get converted into THC.”

To uncover more, Livingston and his colleagues froze leaf samples with liquid nitrogen (to immobilize the inner cell activity) and imaged the leaves’ trichomes with a transmission electron microscope. And they made some remarkable observations.

They noticed, for instance, that the THCA-producing cells that make up the secretory disc of the trichome are highly interconnected. These connections allowed for the transfer of plastids, the “micro-organs” that produce metabolites like geranyldiphosphate, which is required to make cannabinoids like THCA. The researchers say these interconnected cells constitute a “supercell” for THCA production.

On further inspection of the trichomes’ plastids, the researchers found that, unlike typical plant plastids (which contain chloroplasts for photosynthesis), the cannabis trichome plastids contained elaborate membranes. The research team hypothesize that these membranes support cannabinoid and terpene metabolite biosynthesis and trafficking.

The team also made another discovery about THCA synthase, the enzyme that catalyzes THCA production. By binding the enzyme with antibodies that gave off a visual marker, they observed that THCA synthase was primarily located in the apical cell wall of the disc cells. This finding, for the first time, confirms a long-held prediction that THCA synthase is extracellular.

Multiphoton microscopy image of glandular trichomes. Image credit: Samuels Lab/UBC.

“What we show for the first time in cannabis is evidence that THC is exclusively made outside of the cells – in the so-called storage cavity of the glandular trichome,” Livingston told Analytical Cannabis.

“This raised important questions for us. In particular, how do the precursors of THC get from the plastid out of the cell, without causing a toxic buildup of those chemicals? The previous microscopy studies suggested a cellular mechanism that wasn’t consistent with what we now know from 30+ years of research on other plants since those studies were published.”

“Our methods of preserving these trichomes was done with the most modern methods, called cryofixation, and these result in the best representation of their living state. This allowed us to see structures previous studies could not, and led us to propose an entirely new model of how cannabinoids and their precursors get from their site of production to their final destination in the storage cavity.”

Microbe-made marijuana

Livingston and his colleagues say that their findings – particularly the discovery of trichomes’ interconnected “supercells” – could rewrite the accepted model for cannabinoid production. And this new model, they say, could go on to inform the industrial, synthetic production of cannabis in yeast and other microorganisms.

This kind of synthetic production relies on genetically transplanting the cannabinoid-producing genes out of the cannabis plant and into a microorganism that can churn out cannabis chemicals continuously. One company invested in this new age of cannabinoid production is Farmako GmbH, a German pharmaceutical company.

Speaking to Analytical Cannabis back in 2019, Patrick Schmitt, Farmako’s chief scientific officer and co-founder, remarked that the humble, green-fingered practices of cannabis cultivation may be too limited to cope with the large market demands of the new cannabis industry.

“I think that is a process to try 100 years ago, but not in the 21st century,” he said.

“There’s a high demand for cannabinoids. But, for a plant, you need a lot of space, you need a lot of water, you have to build up greenhouses, and you have to cultivate lands under GMP [good manufacturing practices] conditions for medical users. I just think the whole process doesn’t match the possibilities we have today from technology.”

The company’s synthetic method rests on the actions of a bacterium, Zymomonas mobilis, a microbe commonly used in the production of tequila. But instead of converting sugar into alcohol,Schmitt and his team genetically modified the bacteria to turn out cannabinoids. 

“Our bacteria has [sic] a specific advantage: it spits out the cannabinoids into the outer medium,” he said. “So we can have way higher amounts because there are no limits in the production process.”