Cannabis leaves harbor rare medicinal compounds, study finds

Analytical chemists at Stellenbosch University in South Africa have identified a class of rare medicinal compounds in cannabis leaves that had never been documented in the plant before. The discovery emerged from a detailed chemical analysis of three commercially grown cannabis strains, revealing 79 phenolic compounds in total—25 of which had never been reported in cannabis at all. Most striking among these findings was the tentative identification of 16 flavoalkaloids, a rare family of plant chemicals that researchers had not previously known to exist in cannabis leaves. The work, published in the Journal of Chromatography A, suggests that plant material typically discarded as waste may harbor a surprisingly rich collection of potentially useful compounds.

Flavoalkaloids belong to a broader category of naturally occurring plant chemicals called phenolic compounds, which plants produce for pigmentation, defense, and protection against environmental stress. Within this family, flavonoids are well known to researchers and have drawn pharmaceutical interest because many carry antioxidant, anti-inflammatory, and anti-carcinogenic properties. Flavoalkaloids, however, are exceptionally uncommon in nature, making their presence in cannabis leaves a notable finding. What made the discovery even more unexpected was the variation across strains: most of the flavoalkaloids appeared primarily in just one of the three varieties tested, suggesting that different cannabis plants may produce markedly different phenolic profiles.

Dr. Magriet Muller, an analytical chemist at Stellenbosch University's Central Analytical Facility and lead author on the paper, explained that studying plant phenolics presents significant technical challenges. These compounds typically exist in very low concentrations within plant tissue, and their chemical structures vary enormously, making it difficult to separate and identify individual compounds within the already complex mixture that any plant contains. Cannabis presented a particularly demanding case: the plant is known to contain more than 750 metabolites—small molecules produced through biological and chemical processes. The researchers had not anticipated finding such dramatic variation in phenolic profiles between just three strains, nor had they expected to encounter so many compounds being documented in cannabis for the first time.

The breakthrough grew from analytical methods Muller had developed during her postgraduate work in the Department of Chemistry and Polymer Science. Her approach combines two-dimensional liquid chromatography with high-resolution mass spectrometry. In conventional liquid chromatography, different chemicals in a mixture are separated so researchers can examine them individually. Two-dimensional chromatography performs this separation twice, using different methods each time, which dramatically increases the resolving power when dealing with samples containing many closely related chemicals. High-resolution mass spectrometry then identifies those separated compounds by measuring their molecular masses with extreme precision. Together, these techniques allowed researchers to examine cannabis phenolics in far greater detail than previous methods had permitted. Muller had successfully tested these methods on rooibos tea, grapes, and wine before deciding to apply them to cannabis, knowing the plant was chemically complex and that its phenolic chemistry had not been well characterized.

Professor André de Villiers, Muller's study leader and co-author, emphasized that the separation power of two-dimensional liquid chromatography was essential to the discovery. The technique successfully separated the rare flavoalkaloids from the much more abundant flavonoids, which had previously obscured them from detection. This points to a fundamental challenge in plant chemistry: rare compounds can easily be hidden by other chemicals that occur in much larger quantities. More powerful separation methods can therefore reveal substances that were present all along but were simply impossible to distinguish using less sophisticated techniques.

Historically, scientific attention on cannabis has concentrated on cannabinoids—the compounds responsible for many of the plant's well-known pharmacological and mood effects. De Villiers argues that these new findings demonstrate how much remains unknown about the plant's non-cannabinoid chemistry. Cannabis leaves, currently treated as low-value waste material or discarded entirely, may contain phenolic compounds with properties relevant to future biomedical research. The plant exhibits what researchers describe as a rich and unique non-cannabinoid phenolic profile that could prove valuable if the compounds demonstrate antioxidant, anti-inflammatory, or anti-carcinogenic activity. What was once considered waste may, with further investigation, become a source of medically useful compounds.