For the first time, scientists at Stellenbosch University report the identification of a previously unreported class of rare compounds in cannabis called flavoalkaloids.
A majority of cannabis research to date has centered on well-known cannabinoids like tetrahydrocannabinol (THC) and cannabidiol (CBD). Found in the leaves of the cannabis plant, flavoalkaloids are plant molecules that combine structural features of flavonoids and alkaloids.
The new findings expand the chemical landscape of cannabis and point to new possibilities for biomedical research beyond its established psychoactive components.
A New Look at a Familiar Plant
Phenolic compounds, including flavonoids, are well studied in plants for their antioxidant, anti-inflammatory, and anti-carcinogenic properties. These molecules already play an important role in pharmaceutical development, with compounds from sources such as tea and grapes possessing applications for biomedical research and related areas.
Cannabis, with more than 750 known metabolites, has traditionally been known for its cannabinoids. While these molecules drive its psychoactive and therapeutic effects, far less is known about the plant’s non-cannabinoid chemistry.
“Cannabis is extremely complex,” said author Dr. Magriet Muller, an analytical chemist at Stellenbosch. “We did not expect such high variation in phenolic profiles between only three strains, nor to detect so many compounds for the first time in the species.”
Cracking the Chemical Puzzle
To investigate the less-studied compounds in cannabis, Muller applied advanced analytical techniques previously used in the studies of rooibos tea, grapes, and wine. By combining comprehensive two-dimensional liquid chromatography with high-resolution mass spectrometry, the team was able to separate and identify compounds that are often overlooked in standard analyses.
The study, published in ScienceDirect, identified 79 different phenolic compounds in three commercial cannabis strains grown in South Africa. Among these compounds, 25 were newly identified in cannabis. Sixteen of them were provisionally assigned to the flavoalkaloid class, a group of molecules that are rarely observed in plants. Notably, most of these flavoalkaloids were detected only in the leaves of a single strain, highlighting the potential for chemical variation that may occur even between closely related strains.
Professor André de Villiers, Muller’s study leader, said he was astonished by the findings. “The excellent performance of two-dimensional liquid chromatography allowed separation of the flavoalkaloids from the much more abundant flavonoids, which is why we were able to detect these rare compounds for the first time in cannabis,” he explained.
The Illusive Flavoalkaloid
Flavonoids are common and well characterized, but flavoalkaloids are rarely observed in nature, and their biological activity is not well understood. Previous studies of flavoalkaloids suggest that they may share or even extend some of the beneficial properties of flavonoids, including antioxidant and anti-inflammatory effects.
This discovery also reframes cannabis waste. Leaves, typically discarded during cultivation, may hold overlooked reservoirs of valuable compounds. “Our analysis again highlights the medicinal potential of cannabis plant material, currently regarded as waste,” de Villiers said. “Cannabis exhibits a rich and unique non-cannabinoid phenolic profile, which could be relevant from a biomedical research perspective.”
Looking Beyond Cannabinoids
These results illustrate how much remains unknown about the full chemical profile of cannabis. For decades, research focused almost entirely on cannabinoids, leaving other metabolites largely unexamined. As legal restrictions ease, there is an increasing opportunity to investigate the broader pharmacology of the plant.
The study also demonstrates the importance of advanced analytical chemistry. Detecting flavoalkaloids requires specialized tools that can distinguish them from flavonoids with similar structures. In the absence of such analytical approaches, these uncommon molecules might never be found. This serves as a reminder that technological capabilities frequently shape advances in science.
The Future of Cannabis
While the discovery is promising, the researchers note that flavoalkaloids were present at low concentrations, and their pharmacological properties remain unknown. Further studies will be necessary to isolate these molecules, confirm their structures, and assess their potential medical effects.
Still, this marks a shift in how cannabis is understood by researchers. Instead of being defined solely by THC and CBD, cannabis is revealed as a chemically diverse plant with potential for new biomedical applications.
“Especially the first evidence of flavoalkaloids in cannabis was very exciting,” Muller emphasized.
Cannabis-based medicines are already established for certain uses, but future applications could extend well beyond known cannabinoids. By identifying a rare class of compounds in the leaves, this research points to the potential therapeutic value of plant material that was previously regarded as waste.
The study also demonstrates that even well-known plants like cannabis can reveal new compounds with potential medical significance through advanced analysis, offering unexpected opportunities for drug discovery.
Austin Burgess is a writer and researcher with a background in sales, marketing, and data analytics. He holds a Master of Business Administration and a Bachelor of Science in Business Administration, along with a certification in Data Analytics. His work combines analytical training with a focus on emerging science, aerospace, and astronomical research.