Research from Wageningen University & Research (WUR) in the Netherlands has unveiled significant insights into the evolution of cannabis and its bioactive compounds. By resurrecting ancient enzymes responsible for synthesizing key cannabinoids, including tetrahydrocannabinol (THC) and cannabidiol (CBD), scientists are paving the way for new medicinal applications.
The study, led by researchers Robin van Velzen and Cloé Villard, focused on understanding how cannabis evolved its capacity to produce these complex compounds. Historically, the pathways that led to THC, CBD, and cannabichromene (CBC) have remained unclear. The findings not only clarify the evolutionary trajectory of cannabis but also suggest innovative methods for leveraging these compounds in medicine.
Ancient Enzymes Offer New Possibilities
Utilizing a technique called ancestral sequence reconstruction, the research team reconstructed cannabinoid-producing enzymes from early cannabis ancestors. When these enzymes were expressed in laboratory settings, they demonstrated the ability to produce multiple cannabinoids from a shared precursor. Unlike today’s specialized enzymes that target specific cannabinoids, these ancient variants acted as generalists.
“What once seemed evolutionarily ‘unfinished’ turns out to be highly useful,” stated van Velzen. He emphasized that the ancestral enzymes exhibit greater robustness and flexibility compared to their contemporary counterparts, making them promising candidates for biotechnology and pharmaceutical research.
The implications of this research extend particularly to CBC, a cannabinoid that has received less attention than THC and CBD. Modern cannabis typically contains less than 1% CBC, which complicates large-scale studies and production. Van Velzen noted, “At present, there is no cannabis plant with a naturally high CBC content. Introducing this enzyme into a cannabis plant could therefore lead to innovative medicinal varieties.”
Exploring the Therapeutic Potential of CBC
Preliminary studies suggest that CBC may possess a range of therapeutic benefits, including anti-inflammatory, anticonvulsant, and antibacterial properties. Despite its potential, research into CBC remains limited compared to more widely studied cannabinoids.
The ancestral enzymes not only offer a method for producing cannabinoids more efficiently but also provide a pathway to synthesize rare cannabinoids without relying on traditional plant cultivation. This could significantly impact both research and drug development, allowing for the exploration of cannabinoids that are currently difficult to obtain.
The team elaborated on their findings, stating, “Through rational engineering of these ancestors, we designed hybrid enzymes which allowed identifying key amino acid mutations underlying the functional evolution of cannabinoid oxidocyclases.” This innovation leads to unique activities in the enzymes, facilitating easier production in microorganisms, such as yeast.
The study was published in the Plant Biotechnology Journal, contributing to the broader understanding of cannabinoid oxidocyclases’ origins and evolutionary mechanisms. The researchers hope that these discoveries will open new avenues for breeding, biotechnological applications, and medicinal uses of cannabis.
As the exploration of cannabinoids continues to evolve, the insights gained from these ancient enzymes may redefine how cannabis is utilized in modern medicine, enhancing its therapeutic potential and accessibility.
