Cannabis’s Evolutionary Origins of THC, CBD, and CBC Revealed in New Study
Cannabis is a remarkable plant with a rich pharmacopeia hidden in its flowers and foliage. While many of its compounds evolved millions of years ago as defense mechanisms, humans have discovered additional uses for them over time.
A recent study delves into the evolutionary history of cannabis to uncover the origins of some of its most well-known bioactive compounds – tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabichromene (CBC).
Researchers at Wageningen University & Research in the Netherlands employed ancestral sequence reconstruction (ASR) to investigate long-extinct enzymes that were responsible for producing these compounds in an ancient ancestor of cannabis. By “resurrecting” these ancient enzymes, they were able to study their functions.
According to biosystematics scientist Robin van Velzen, the ancestral enzymes discovered in the study are more robust and flexible than their modern counterparts, making them promising candidates for applications in biotechnology and pharmaceutical research.
The cultivation of cannabis dates back to prehistoric times, with the plant being used for various purposes such as food, fabric, medicine, and recreation. Today, researchers have identified hundreds of different cannabinoids, terpenes, flavonoids, and other phytochemicals in cannabis, each with unique medicinal or psychoactive properties.
The study focused on cannabinoid oxidocyclases, enzymes responsible for converting cannabigerolic acid (CBGA) into various cannabinoids with distinct bioactive effects. These enzymes play a crucial role in determining the therapeutic potential of cannabis.
Despite the significance of cannabinoid oxidocyclases, their mechanisms are not fully understood. By reconstructing their evolutionary history and studying their extinct ancestors, researchers aimed to gain insights into these enzymes.
While modern cannabis plants rely on three specialized enzymes to produce THC, CBD, and CBC, the study suggests that ancient cannabis ancestors had more versatile enzymes capable of producing multiple cannabinoids simultaneously. The specialization of enzymes for specific cannabinoids evolved later in cannabis history through gene duplications.
The study’s findings also indicate that the ability to metabolize CBGA likely emerged in a recent ancestor of cannabis and that early cannabinoid oxidocyclases were “promiscuous” enzymes, producing precursors for multiple cannabinoids rather than specializing in one.
Compared to modern enzymes, the reconstructed ancestral enzymes were easier to produce in microbes like yeast cells, hinting at the potential for biotechnological approaches to cannabinoid production.
One of the reconstructed ancient enzymes showed a strong affinity for producing CBC, a cannabinoid known for its anti-inflammatory and analgesic properties. This enzyme could potentially be introduced into modern cannabis plants to create new medicinal varieties with high CBC content.
The study, published in Plant Biotechnology Journal, sheds light on the evolutionary origins of THC, CBD, and CBC in cannabis and opens up new possibilities for harnessing the plant’s medicinal potential.
