Finding rare cannabinoids in plants other than cannabis | CBD project

Special glands that protrude from cannabis flowers express a number of unique molecules. Cannabinoids, as they are known, exist in cannabis. But it turns out that identical molecules are also present in plants other than cannabis. Researchers at Israel’s Weizmann Institute recently reported finding cannabigerolic acid (CBGA) and other rare cannabinoids in Helichrysum umbraculigerum, a perennial shrub informally known as wool umbrella.¹

A South African botanist

Ferdinand Bohlmann and Evelyn Hoffman first discussed the chemical irregularity of helichrysum. In a 1979 article published in Phytochemistry², analyzed the South African species H. umbraculigerum, native to the eastern part of the country, where it was used in traditional medicine and in fumigation rituals.

Bohlmann and Hoffman argued that plants atop both leaves and flowers produce compounds specific to cannabis. But a follow-up study by Italian researchers in 2017 failed to find CBG or its acidic precursor in H. umbraculigerum flowers. However, they identified a CBG analog known as Heli-CBG (also found in some fiber hemp varieties), which binds to the CB2 cannabinoid receptor.^3.4

In a May 2023 article in Nature plantsWeissman Institute scientists confirmed that woolly umbrella produces CBGA in the trichomes on its leaves, but almost no CBGA was present on its flowers. It is different from cannabis, where CBGA and other cannabinoids are concentrated in the trichomes on the flower buds.¹

The trichomes found on cannabis inflorescences (flowers) have a special cellular structure, according to a 2022 study by researchers at the University of British Columbia in Current biology. The bulbous head of the glands contains large porous cells that allow acidic cannabinoids (CBGA, CBDA, THCA, etc.) to move through the trichome.⁵ The Weizmann Institute team reported that H. umbraculigerum produces a similar cannabinoid transport network on its leaves.¹

Finding rare cannabinoids in shrubs other than cannabis

How did Israeli scientists figure this out? They fed precursor compounds of the woolly umbrella responsible for the production of cannabinoids in cannabis. When given two precursors (hexanoic acid and phenylalanine), the shrub produced more cannabinoids than plants fed the nutrients regularly. This means that the same biosynthetic pathway exists in both cannabis flowers and woolly umbrella leaves.

The woolly umbrella shrub naturally produces over 4% cannabigerolic acid along with other rare cannabinoids on its leaves. The shrub also contains water-soluble cannabinoids, which are not found in cannabis.

Essentially, two different plant species have developed the same machinery to produce CBGA. However, woolly umbrella is evolutionarily distinct from cannabis. And unlike the shrub, cannabis produces two unique enzymes that transform CBGA into THCA and/or CBDA.

Exploring a new phytocannabinoid toolkit

Thus, there are two toolboxes for cannabinoid phytosynthesis in the phylogenetic tree. Terpenes and some flavonoids accompany lipophilic cannabis flowers, while a complex array of water-soluble flavones and cannabinoids develops in H. umbraculigerum. By understanding their similarities and differences, we can better assess the therapeutic potential of each plant.

The cannabinoid compounds found in the woolly umbrella dissolve more easily in water and can affect specific areas of the body, such as the deeper intestines. But higher bioavailability, an argument in favor of water-soluble cannabinoids, doesn’t necessarily equate to higher potency. What is absorbed quickly and easily also leaves the body and loses effectiveness faster. And cannabinoid receptors have more affinity for fat-loving compounds than water-soluble agonists.^6.7

Travis Cesarone is a freelance writer and communicator covering the sciences of medical cannabis. Copyright, CBD Project. May not be reprinted without permission.

References

1. Berman, P., de Haro, LA, Jozwiak, A. et al. Parallel evolution of cannabinoid biosynthesis. Nat. Installations (2023).
2. Cannabigerol-hnliche verbindungen aus Helichrysum umbraculigerum. Phytochemistry. 1979;18(8):1371-1374.
3. Pollastro, F., De Petrocellis, L., Schiano-Moriello, A., Chianese, G., Heyman, H., Appendino, G., & Taglialatela-Scafati, O. (2017). Amorfrutin-type phytocannabinoids from Helichrysum umbraculigerum. Herbal medicine, 1231317.
4. Pollastro F, Taglialatela-Scafati O, Allar M, Muoz E, Di Marzo V, De Petrocellis L, Appendino G. Bioactive prenylogue cannabinoid from hemp fiber (Cannabis sativa). J Nat Prod. 2011 Sep 23;74(9):2019-22. doi:10.1021/np200500p. Epub 2011 8 September. PMID: 21902175.
5. Livingston, SJ, Rensing, KH, Page, JE & Samuels, AL (2022). A polarized supercell produces specialized metabolites in the cannabis trichomes. Current biology: CB, 32(18), 40404047.e4. https://doi.org/10.1016/j.cub.2022.07.014
6. Li, X., Chang, H., Bouma, J. et al. Structural basis of the selective activation of the cannabinoid CB2 receptor. Nat Commun 14, 1447 (2023).
7. Stadel, R., Ahn, KH and Kendall, DA (2011). The terminal carboxyl cannabinoid receptor type 1, more than just a tail. Journal of Neurochemistry, 117(1), 118. https://doi.org/10.1111/j.1471-4159.2011.07186.x