Uncovering the Mysteries of Cannabis: How Trichomes of Cannabis Produce their Unique Metabolites.

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Cannabis was recently made federally legal in Canada, and the recreational cannabis market is projected to be worth up to $7 billion per year. Scientifically, we know very little about the biology of this economically and socially important plant (Cannabis sativa). Despite the iconic cannabis leaf, it is the flowers of the cannabis plant that are consumed for their valuable metabolites. Tiny hairs called trichomes on the flower surface produce the chemicals called 'cannabinoids', including tetrahydrocannabinolic acid and cannabidiolic acid. When heated, these cannabinoid molecules spontaneously form the psychoactive compound tetrahydrocannabinol (THC) and the medicinal compound cannabidiol (CBD), respectively. Cannabis flowers also produce high quantities of fragrant and resinous terpenes in the same glandular trichomes, and these terpenes are responsible for the smell associated with cannabis. It is astonishing that the chemicals that determine the pharmacological effects of cannabis are all produced in tiny clusters of trichome cells on the flower surface, yet very little is known about how these cells produce and store cannabinoids and terpenes. Due to the past legal restrictions on cannabis, it has been difficult to study the cannabis plant. Now the research landscape is rapidly changing: in 2016, the Samuels lab was awarded a new Canadian Foundation for Innovation grant to build a secure cannabis greenhouse at UBC, and there are new procedures for Health Canada permits using the Cannabis Tracking and Licencing System. The goal of this discovery research program is to understand how the cells in the trichomes on cannabis flowers produce and store such large quantities of cannabinoids and terpenes. These tiny cell clusters on the surface of the flower are the biochemical micro-factories of cannabis production. This research program will have three objectives: to pinpoint the parts of the cannabis cells responsible for making the cannabinoids; to discover how the oily and potent cannabinoids and terpenes can move through the cells without having a toxic effect; and to test how the cells package the metabolites in the cell wall of the trichomes. The Samuels lab expertise is in plant cell biology, especially in using advanced microscopy tools such as live-cell multi photon imaging, cryo-fixation, and electron microscopy to probe inside of cells. We will use these tools to test hypotheses of how the cannabis cells produce, traffic, and store their metabolites. Discovering where the metabolites are made, and how toxic effects are controlled, is vital information for biotechnologists who want to produce high-value cannabinoids. How cannabis stores its products in the cell wall will influence retention or release, so this information will inform best practices in drying, extraction, and storage. The cell and molecular biology of cannabis is fundamental knowledge that is urgently required as cannabis becomes a main stream crop in Canada.