Researchers Uncover Origins of Key Cannabis Compounds THC, CBD

Researchers at Wageningen University & Research have made significant strides in understanding the origins of key cannabis compounds, including THC, CBD, and CBC. A study published online on December 26, 2025, in the Plant Biotechnology Journal reveals how cannabis plants evolved to produce these important cannabinoids, shedding light on potential biotechnological applications for medicinal use.

The research team, led by scientists Robin van Velzen and Cloé Villard, demonstrated experimentally for the first time that cannabis acquired the ability to synthesize these cannabinoids through the evolution of specialized enzymes. The study highlights the transition from generalist enzymes, which produced multiple cannabinoids, to specialized enzymes that focus on specific compounds. This evolutionary shift occurred over millions of years, driven by gene duplications that refined the production process.

Using a technique known as ancestral sequence reconstruction, the researchers reconstructed enzymes from cannabis’s ancient ancestors. By analyzing the DNA of modern cannabis plants, they inferred the characteristics of these enzymes from millions of years ago. The team then resurrected these “ancestral enzymes” in the laboratory and conducted experiments to assess their capabilities. The findings provide the first experimental evidence that cannabinoid biosynthesis, particularly for THC, originated from a relatively recent ancestor of cannabis.

Implications for Biotechnology and Medicine

This research not only enhances our understanding of cannabis evolution but also opens new avenues for biotechnological innovation. The reconstructed ancestral enzymes exhibited properties that made them easier to produce in microorganisms, such as yeast cells, compared to their modern counterparts. This is particularly relevant as the demand for biotechnological production methods for cannabinoids continues to grow.

“What once seemed evolutionarily ‘unfinished’ turns out to be highly useful,” said van Velzen. He noted that these ancestral enzymes are more robust and flexible than their modern descendants, making them appealing for new applications in biotechnology and pharmaceutical research. One enzyme of particular interest produces CBC, a cannabinoid recognized for its anti-inflammatory and analgesic properties. Currently, no cannabis strains naturally contain high levels of CBC, raising the potential for developing innovative medicinal varieties by introducing this enzyme into cannabis plants.

The study underscores the importance of fundamental research into plant DNA and its implications for both evolutionary science and practical applications in medicine. As scientific understanding deepens, the potential for creating new cannabis strains with enhanced therapeutic benefits becomes increasingly promising.

For more detailed insights, refer to the original study: Cloé Villard et al, “Resurrected Ancestral Cannabis Enzymes Unveil the Origin and Functional Evolution of Cannabinoid Synthases,” Plant Biotechnology Journal (2025). DOI: 10.1111/pbi.70475.