Don’t Throw Away Those Cannabis Leaves – They’re Packed With Rare Compounds

Stellenbosch University researchers identify rare phenolic compounds in Cannabis leaves for the first time.

Chemists at Stellenbosch University (SU) have uncovered the first evidence of a rare group of phenolic compounds, known as flavoalkaloids, in Cannabis leaves.

Phenolic compounds—particularly flavonoids—are highly valued in the pharmaceutical field because of their antioxidant, anti-inflammatory, and anti-carcinogenic effects.

In their study, the researchers analyzed three commercially cultivated Cannabis strains from South Africa and identified 79 distinct phenolic compounds. Of these, 25 had never before been reported in Cannabis, and 16 were tentatively classified as flavoalkaloids. Notably, these rare compounds were found primarily in the leaves of just one strain. The findings were published in the Journal of Chromatography A.

Challenges of studying plant phenolics

Dr Magriet Muller, an analytical chemist in the LC-MS laboratory of the Central Analytical Facility (CAF) at Stellenbosch University and first author on the paper, says the analysis of plant phenolics is challenging due to their low concentration and extreme structural diversity.

“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,” she explains.

“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.”

Developing new analytical methods

As part of her postgraduate work in SU’s Department of Chemistry and Polymer Science, she designed advanced analytical techniques that integrate comprehensive two-dimensional liquid chromatography with high-resolution mass spectrometry to achieve detailed characterization of phenolic compounds.

“We were looking for a new application for the methods that I developed, after successfully testing them on rooibos tea, grapes, and wine. I then decided to apply the methods to Cannabis because I knew it was a complex sample, and that Cannabis phenolics have not been well characterized,” she explains.

According to Prof. André de Villiers, her study leader and main author on the paper, he was blown away by the chromatographic results that Muller obtained: “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 leads the analytical chemistry research group in SU’s Department of Chemistry and Polymer Science.

Prof. De Villiers says it is obvious there is still much to gain from studying Cannabis, as the bulk of research in this field to date has been focused on the pharmacological properties of the mood-altering cannabinoids.

“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,” he concludes.

Reference: “Comprehensive two-dimensional liquid chromatographic analysis of Cannabis phenolics and first evidence of flavoalkaloids in Cannabis” by Magriet Muller and André de Villiers, 2 August 2025, Journal of Chromatography A.
DOI: 10.1016/j.chroma.2025.466023

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