Are these shrubs a source for CBGp and other rare cannabinoids?

Special glands protruding from cannabis flowers express a series of unique molecules. Cannabinoids, as they are known, exist in cannabis. But, according to a four-decade-old study, one family of shrubs produces identical molecules. And recently, researchers from Israel’s Weizmann Institute found CBGp and other rare cannabinoids in the same perennial shrubs, informally known as the woolly umbrella. (1, 2)

A deeper look into a forty-year-old discovery

Ferdinand Bohlmann and Evelyn Hoffman discussed, in 1979, the chemical irregularity of Helichrysum. In a paper published in Phytochemistry, they analyzed the South African species from the country’s east — H. umbraculigerum. They tested the roots but found that the plant’s tops — leaves and flowers — produce cannabis-specific compounds. (1) Conversely, a follow-up study conducted in 2017 failed to find the same conventional cannabinoids in H. umbraculigerum flowers. (3)

Trichomes found on cannabis inflorescence (flowers) have a special cellular build, according to research from the University of British Columbia published last year. The gland’s bulbous head holds large porous cells that let acidic cannabinoids move through the trichome. (4) Published in Nature Plants, researchers from Weizmann Institute utilized similar imaging techniques to confirm that this special shrub produces a similar cannabinoid transport network on its leaves. (2)

Helichrysum umbraculigerum, informally known as Woolly Umbrella, is a perennial shrub that produces CBGa in trichomes on leaf material, but not on its flowers. Photo courtesy of Helcman, Martin & Karel, Šmejkal. (2021).

Sourcing rare cannabinoids in non-cannabis shrubs

The researchers fed the shrubs precursor compounds responsible for making cannabinoids in cannabis. It turns out that woolly umbrella plants fed two precursors (hexanoic acid and phenylalanine) produced more cannabinoids compared to plants fed regular nutrients. This means that the same biosynthetic pathway exists between cannabis flowers and woolly umbrella leaves. But the shrubs naturally produced over 4% cannabigerolic acid (CBGa) alongside other rare cannabinoids. Yet, the plant is evolutionarily distinct from cannabis.

Interestingly, Weizmann Institute found the phorol and hexyl derivatives, CBGPa and CBGHa, which were not previously found in nature — not in cannabis plants or any shrub. Further found in the Woolly Umbrella shrub and not found in cannabis are water-soluble cannabinoids. Essentially, two species of distinct plants developed the same machinery to produce CBGa. Unlike the perineal shrub, though, cannabis makes two unique enzymes that flip CBGa into either THCa or CBDa. Plus, cannabis sticks to non-polar metabolite production.

Exploring a new phytocannabinoid toolkit

We have two toolboxes for cannabinoid phyto-synthesis in the phylogenetic tree. Terpenes and a few flavonoids accompany cannabis flowers, whereas a complex array of flavones develop in H. umbraculigerum. This author surmises that cannabinoids act as pesticide and herbicide agents in their non-polar confirmation. But these compounds are also strongly anti-oxidant while also correlating to abscission — the loss of leaves. Overall, non-polar cannabinoids maintain plant homeostasis until an attack or after natural decay. By understanding the differences and similarities in each plant’s use of cannabinoids, and Woolly Umbrella’s use of water-soluble varieties, we can better understand their purpose.

This author further notes that cannabinoid polarity (water-loving versus fat-loving) is not linear with potency or effect. Polar compounds take an alternate route into cannabinoid receptors. (5) Otherwise, water-soluble molecules break down into prodrugs in the body, which might have benefit targetting specific areas such as the deeper bowel. But in layman’s terms — greater bioavailability does not necessarily equal greater potency.

Deeper chemical analyses are required to better understand the rare occurrence of cannabinoids in nature. Let us know in the comments why you think two different plants produce CBGa.

Sources

1. Cannabigerol-ähnliche verbindungen aus Helichrysum umbraculigerum. Phytochemistry. 1979;18(8):1371-1374.

2. Berman, P., de Haro, L.A., Jozwiak, A. et al. Parallel evolution of cannabinoid biosynthesis. Nat. Plants (2023).

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. Fitoterapia, 123, 13–17.

4. Livingston, S. J., Rensing, K. H., Page, J. E., & Samuels, A. L. (2022). A polarized supercell produces specialized metabolites in cannabis trichomes. Current biology : CB, 32(18), 4040–4047.e4.

5. Li, X., Chang, H., Bouma, J. et al. Structural basis of selective cannabinoid CB2 receptor activation. Nat Commun 14, 1447 (2023).

6. Stadel, R., Ahn, K. H., & Kendall, D. A. (2011). The cannabinoid type-1 receptor carboxyl-terminus, more than just a tail. Journal of neurochemistry, 117(1), 1–18.

7. Helcman, Martin & Karel, Šmejkal. (2021). Biological activity of Cannabis compounds: a modern approach to the therapy of multiple diseases. Phytochemistry Reviews. 21. 10.1007/s11101-021-09777-x.