For a plant that humans have been cultivating, smoking, weaving, eating, and arguing about for thousands of years, cannabis still keeps a surprising amount of its history locked away at the molecular level. A new study just cracked part of that vault open by resurrecting enzymes that went extinct millions of years ago, revealing how cannabis learned to make THC, CBD, and CBC in the first place.
The research, led by scientists at Wageningen University and published in Plant Biotechnology Journal, focused on a family of enzymes called cannabinoid oxidocyclases. These enzymes sit at a crucial point in cannabis chemistry. They take a precursor molecule called cannabigerolic acid, or CBGA, and convert it into the cannabinoids people know best, including THC and CBD. Today’s cannabis plants rely on separate, highly specialized enzymes for each compound. That wasn’t always the case.
Using a technique known as ancestral sequence reconstruction, the researchers worked backward from modern cannabis DNA to rebuild the genetic blueprints of long-extinct enzymes. Those ancient sequences were then brought back to life in the lab and tested to see what they could do. What they found suggests early cannabis chemistry was less specialized and more flexible than it is now.
Scientists Just Figured Out How Cannabis Makes THC, CBD, and CBC
Instead of producing a single cannabinoid, the ancestral enzymes could generate several different ones at once. Over time, gene duplications led to the more narrowly focused enzymes seen in modern plants. In evolutionary terms, specialization came later. Early cannabis appears to have been a biochemical multitasker.
“These ancestral enzymes are more robust and flexible than their descendants,” said biosystematics scientist Robin van Velzen in a statement accompanying the study. “That makes them very attractive starting points for new applications in biotechnology and pharmaceutical research.”
That flexibility isn’t limited to academic curiosity. Compared to modern enzymes, the reconstructed versions were easier to produce in microbes like yeast. That has implications for the growing interest in manufacturing cannabinoids through fermentation rather than farming, especially as regulations and supply chains continue to evolve.
One compound drawing particular interest is cannabichromene, or CBC. While research has linked CBC to anti-inflammatory and pain-relieving effects, modern cannabis plants produce it in very small amounts. One of the resurrected enzymes turned out to be especially good at making CBC, representing what the researchers describe as an evolutionary intermediate.
“At present, there is no cannabis plant with a naturally high CBC content,” van Velzen said. “Introducing this enzyme into a cannabis plant could therefore lead to innovative medicinal varieties.”
The study also found that cannabis developed its cannabinoid-producing abilities independently from other plants, such as rhododendrons, that make similar compounds. That suggests cannabinoid chemistry emerged as a useful biological tool, not a fluke.
What looks unfinished from a modern perspective turns out to be anything but. As van Velzen put it, “What once seemed evolutionarily unfinished turns out to be highly useful.”
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