Researchers at Stellenbosch University say they have identified a rare class of chemical compounds – flavoalkaloids – in the leaves of cannabis plants, which could open new doors for the pharmaceutical use of the plant beyond its well-known cannabinoids, reports the Cape Argus.
Published in the Journal of Chromatography A, the study details the work of analytical chemists who used cutting-edge laboratory techniques to investigate the phenolic content of three cannabis strains grown commercially in South Africa.
Out of the 79 phenolic compounds identified, 25 were previously unreported in cannabis: 16 of those are believed to be flavoalkaloids, compounds so rare that they’ve barely been detected in nature.
Dr Magriet Muller, lead author and researcher at SU’s Central Analytical Facility, said the discovery was exciting.
“We know that cannabis is extremely complex, that 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.
“The first evidence of flavoalkaloids, particularly, was very exciting.”
Muller’s research focused on phenolic compounds, widely recognised for their therapeutic properties.
While flavonoids, another group of phenolics, are common in plants, flavoalkaloids are scarcely found. They are highly valued in biomedical research for their potential in combating inflammation, oxidative stress, and even cancer.
Using a powerful combination of two-dimensional liquid chromatography and high-resolution mass spectrometry, the researchers were able to separate and identify the flavoalkaloids, which were mainly present in the leaves of one specific cannabis strain.
Professor André de Villiers, head of the Analytical Chemistry Research group at SU and senior author on the study, said the excellent performance of two-dimensional liquid chromatography allowed separation of the flavoalkaloids from the much more abundant flavonoids.
“This is why we were able to detect these rare compounds for the first time.”
The discovery also sheds light on the broader chemical complexity of cannabis. The plant is known to contain more than 750 metabolites, but most research has focused narrowly on cannabinoids like THC and CBD.
“Our analysis again highlights the medicinal potential of cannabis plant material, currently regarded as waste,” said De Villiers.
“Cannabis exhibits a rich and unique non-cannabinoid phenolic profile, which could be relevant from a biomedical research perspective.”
The findings add to a growing body of evidence suggesting that cannabis, when properly studied and characterised, could yield a much broader range of therapeutic compounds than previously thought.
Study details
Comprehensive two-dimensional liquid chromatographic analysis of Cannabis phenolics and first evidence of flavoalkaloids in Cannabis
Magriet Muller, André de Villiers.
Published in Journal of Chromatography A on 2 August 2025
Abstract
Cannabis contains a large number of diverse metabolites. Compared to the well-studied cannabinoids and terpenoids, characterisation of the phenolic composition of Cannabis has received little attention. With studies reporting synergistic effects in Cannabis, the importance of investigating polyphenols in Cannabis is becoming more apparent. We report an on-line comprehensive 2D HILIC × RP-LC method hyphenated to high resolution (HR) MS for the detailed characterisation of polar phenolics in Cannabis inflorescence and leaf samples of three commercial strains. Optimal HILIC × RP-LC conditions were derived using an automated method optimisation programme, and provided excellent separation performance (peak capacity > 3000) and high orthogonality. Diode array and HR-MS data enabled tentative identification of 79 compounds, comprising mainly flavone and (hydroxy)cinnamic acid derivatives. Compound assignment was facilitated by the group-type separation obtained between the phenolic acids and flavonoids, as well as the structured elution patterns for the flavone glycosides. The presence of three C-glycosylated flavones, as well as several of their O-glycosylated derivatives, distinguished one of the strains from the other two. In the same strain, flavoalkaloids were detected, mainly in the leaf extracts. The structures of the alkaloid moieties could not be unambiguously assigned based on the available HR-MS data, but four classes of flavoalkaloids comprising 16 flavone derivates could be tentatively identified. This is the first time that this relatively rare and chemically interesting class of compounds has been detected in Cannabis. These findings highlight the diversity of Cannabis, and the utility of HILIC × RP-LC-HR-MS for the in-depth study of its phenolic composition.
Cape Argus article – Don’t discard Cannabis leaves – they contain rare flavoalkaloids (Open access)
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