Researchers at Stellenbosch University say they have found the first evidence of rare phenolic compounds known as flavoalkaloids in cannabis leaves, after profiling dozens of plant chemicals across three commercially grown strains.
Scientists at Stellenbosch University (SU) in South Africa analyzed phenolic compounds in three commercially grown Cannabis strains and reported identifying 79 phenolic compounds in total, including 25 that they said had not previously been reported in Cannabis.
Among the newly reported compounds were 16 that the researchers tentatively classified as flavoalkaloids—an uncommon class of phenolic compounds that the team says is rarely found in nature. The study found these tentatively identified flavoalkaloids were concentrated mainly in the leaves of one of the strains, underscoring how strongly phenolic profiles can vary across strains and plant parts.
The results were published in the Journal of Chromatography A in 2025 (DOI: 10.1016/j.chroma.2025.466023). The researchers used comprehensive two-dimensional liquid chromatography combined with high-resolution mass spectrometry to separate and detect low-abundance compounds.
Dr. Magriet Muller, the study’s first author and an analytical chemist in the LC–MS laboratory of SU’s Central Analytical Facility, said plant phenolics can be difficult to study because they occur in small amounts and come in many different structures.
“Most plants contain highly complex mixtures of phenolic compounds, and while flavonoids occur widely in the plant kingdom, the flavoalkaloids are very rare in nature.”
Muller also pointed to the broader chemical complexity of the plant.
“We know that Cannabis is extremely complex — it contains more than 750 metabolites — but 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. Especially the first evidence of flavoalkaloids in Cannabis was very exciting.”
Phenolic compounds—particularly flavonoids—are widely studied and used in pharmaceutical research, and are commonly associated with antioxidant and anti-inflammatory activity. The Stellenbosch team argued that the findings reinforce the possibility that cannabis leaves and other non-flower material, often treated as low-value byproducts, may contain overlooked compounds that could be relevant to biomedical research.
Prof. André de Villiers, who led the study and heads SU’s analytical chemistry research group, said the method’s separation power was key to spotting the rare signals.
“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.”
De Villiers added that the results point to potential value in plant material frequently regarded as waste.
“Our analysis again highlights the medicinal potential of Cannabis plant material, currently regarded as waste. Cannabis exhibits a rich and unique non-cannabinoid phenolic profile, which could be relevant from a biomedical research perspective.”
