THCeeker: Discovery Of Cannabis ‘Pharma Factory’

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Researchers at the University of Saskatchewan have identified the chemical pipeline used by Cannabis sativa to create its signature psychoactive cannabinoids, such as delta-9-tetrahydrocannabinol or THC, according to their report published this week in the Proceedings of the National Academy of Science.

Cannabinoid production is a different kind of process that involves an enzyme, called olivetolic acid cyclase (OAC), which has never before been seen in plants, according to the U of S research team led by Jon Page, an adjunct professor of biology at the university.

“What cannabis has done is take a rare fatty acid with a simple, six-carbon chain and use it as a building block to make something chemically complex and pharmacologically active,” Page says.

The research team included PhD student Steve Gagne, who discovered OAC, and postdoctoral researcher Jake Stout, who discovered another key enzyme in the cannabinoid-producing process, hexanoyl-CoA synthetase (reported earlier this year in The Plant Journal).

Cannabis has been cultivated for thousands of years to make food, fiber, medicine and psychoactive drugs, both legal and illicit. Cannabinoids, such as THC, are produced on the flowering buds of the female plant in tiny hair-like structures called trichomes.

In the study, the researchers genetically sequenced isolated trichome cells to identify which genes are involved in cannabinoid production. After isolating these genes, they were then able to produce the newly discovered key enzymes. These enzymes have already been used to spark the production of olivetolic acid, a key metabolic intermediate, in yeast cultures.

“Now that we know the pathway, we could develop ways to produce cannabinoids with yeast or other microorganisms, which could be a valuable alternative to chemical synthesis for producing cannabinoids for the pharmaceutical industry,” Page says.

The pharmacological study of cannabinoids has typically been based on the structure of naturally-occurring herbal cannabinoids. Newer synthetic compounds have been developed by making systematic, incremental modifications of cannabinoid molecules and are either based on the structure of the naturally produced compounds or are completely unrelated to natural cannabinoids.

Many countries have either decriminalized or legalized drugs made from cannabis. More than 19,000 patients in Canada are authorized to use marijuana through a prescription and stand to benefit from the effects of cannabinoids, which includes pain relief, nausea suppression and appetite stimulation.

The United States has also been progressing toward a more THC-tolerant society with the adoption of a 2003 patent entitled “Cannabinoids as Antioxidants and Neuroprotectants“, which was awarded to the United States Department of Health and Human Services. This patent asserts that cannabinoids are useful in treating chronic conditions including “age-related, inflammatory, and autoimmune diseases.”

In addition to identifying plants for use in the production of prescription drugs, plant breeders can now look for cannabis strains that lack the mechanisms necessary for cannabinoid production.

These zero-THC varieties can be used for everything from textiles to rope. Hemp seed, which is high in omega-3 and omega-6 fatty acids, is also marketed for its healthy qualities and benefits. The seed is used in everything from lactose-free hemp milk, cereals, snacks and protein supplements for athletes.

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Image Caption: Hemp forms of Cannabis sativa are primarily grown in Canada for seed, which is produced on the female plants in this mixed plot. The seed has a healthy mix of omega 3 and 6 fatty acids is high in protein, and its oil is used in both food and cosmetic products. Credit: Jan Slaski (Alberta Innovates: Technology Futures)

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