Terps are double-edged swords. They include a family of cannabinoid acids and terpenes but are conversely toxic to cannabis plants. Thankfully, terp production occurs within cannabis trichomes — glandular hairs that cover your favourite frosty nugs. And trichomes have many tricks to prevent a toxic leak of cannabinoids and terpenes, which includes their mushroom shape.
Almost more important than the mushroom shape, though, are cellular transporters that carry CBGa and other non-polar metabolites through cannabis trichomes. But four researchers only recently elucidated part of that vital transportation system. To help understand their discovery, this author spoke with one of the researchers, Sam Livingston, Ph.D. — a Postdoc botanist and plant biologist from UBC.
Oxidative auto-toxicity and oily metabolites
Cannabinoid acids begin as non-polar metabolites inside the cellular matrix (within plastids) of a glandular trichome. And their journey continues until they reach a cavity underneath the waxy cuticle — an entirely separate part of the trichome. The physical structure and internal mechanisms all serve a purpose, though.
That [cavity] is where all the non-polar metabolites are stored throughout the course of plant development and when we harvest the flowers for consumption.
Beyond the study, this author’s thinking suggests that non-polar metabolites — especially CBDa and limonene byproducts — function as natural pesticide agents. Cannabinoids further help plants survive by unintentionally attracting humans that harvest and spread them throughout the world. In any case, the literature does agree that non-polar metabolites are conversely toxic to certain cells.
Non-polar metabolites are toxic to plant cells, and they’re toxic to other systems like yeast, bacteria, and even human cells. And the way that they exert this toxicity could be through several different mechanisms.
Cannabinoids also function as molecular antioxidants. (4) In contrast, their passage through cannabis’s resinous trichomes likely connects to oxidative stress. (3, 5, 6) Moreover, non-polar metabolites in the synthesis pathway are oil-based and might cause toxic fluid disruption in plants.
We proposed that these metabolites are probably getting into membranes and disrupting them somehow — or changing their fluidity. And at high enough concentrations, we suspect normal membrane components might fall apart.
How plants hold herbicides
The reasons that non-polar botanical components induce auto-toxicity within plant cells remain unclear. Cellular transportation within trichomes likely provides protection, though.
It’s strange that we have this interconnected supercellular oil factory communicating clearly with itself, but it’s completely separated from everything below it.
Basal cells that sit beneath the trichome’s secretory head comprise a unique cellular system atypical of the stalk or cuticle. And the trichome’s different structures and mushroom shape help hold terpenes and cannabinoid acids away from defenceless plant cells without a storage cavity.
That’s why we hypothesize that the supercells are compartmentalized away from other plant cells — to prevent leakage and toxic effects from occurring in cells that can’t deal with these metabolites.
Covering an umbrella of cannabinoids
Sam’s team grew high-THC cultivars of Purple Kush rather than CBD cultivars for their most recent study. (1) Yet, trichomes produce CBDa in the same part of the cell as THCa. (2, 3) Cells arrange both molecules once transporters bring CBGa to the surface. Sam, therefore, proposed that the process should apply to all cultivars regardless of their variety or type.
THCa and CBDa both use CBGa as their input molecule. And the only thing that’s actually different is the two enzymes that either make THCa or CBDa. [Enzymes] rearrange cannabinoids into different end products, and we suspect this all happens inside the cell wall, anyway.
Whether THCa synthase is in the cell wall in, say, Purple Kush or CBDa synthase is in the wall of a CBD cultivar like Finola. We suspect that the same mechanisms for CBGa trafficking are present inside the cell, moving CBGa out to the cell wall.
Sam Livingston, Postdoc.
Understanding how CBGa transfers into THCa can help inform breeders of new tricks to create better CBG strains, for example. And similar developments can center on THCa production outside the polar membrane and its storage in the cavity beneath the cuticle. That said, capitate stalked trichomes are essentially shaped like mushrooms to avoid toxic leakage. So keep your glands intact.
How cannabis trichomes make CBDa and THCa from CBGa
Inside a cannabis trichome’s plastid
TPS-beta, an enzyme, converts a major terp precursor known as GPP (geranyl pyrophosphate) within the plastid (yellow circle). The process spits out monoterpenes (MTs).
In the presence of olivetolic acid (OA), the enzyme known as PT (aromatic prenyltransferase) consumes GPP and spits out CBGa into the plastid’s membrane.
Between the plastid’s membrane and the cell wall
Unusually large pores throughout trichome supercellular structures allow CBGa to venture to the cell’s surface.
An unidentified vehicle in the ATP binding cassette (ACB) family then drives CBGa to the surface — a critical journey.
The ER (endoplasmic reticulum / green bubbles) and its contact sites (cER / blue bubbles) must first authorize CBGa’s passage to the surface.
ER passage, in most cases, comes with a minor toll of oxidative stress. (3, 5, 6)
THCa outside the wall
Lipid Transfer Proteins (LTPs) likey take CBGa through the cell wall to THCAS (THC-acid synthase enzymes).
THCa production completes outside the cell beneath a detached polar cuticle.
THCa and non-polar metabolites live in a storage cavity outside the cell wall, protected by the cuticle.
Disconnected structures throughout the trichome, alongside transport vehicles inside a polar supercell, stop non-polar metabolites from leaking onto defenceless plant cells. (1, 3)
Unrelated to cannabis and terps, the Rab proteins, ytp31 more than ytp32, induce resistance against anti-fungal azole compounds in yeast cells (pseudohyphae.) And ytp31 traffic might depend on an ACBG transporter, PDR5P. (7, 8)
Separating terps from flowers
There are three different types of trichomes. Sitting atop the Stalked Trichome’s multi-cellular stem and base is an inner supercell. And that supercell is responsible for cannabinoid production. An outer waxy cuticle, while itself polar, is separate from the internal supercellular structure. The cuticle is a different organ surrounding the trichome’s storage cavity and secretory interior.
Trichomes produce modified terpenoids such as THCa and CBDa. And, of course, cannabis’s glandular hairs also make terpenes. And the mushroom shape that certain trichomes grow into helps keep non-polar metabolites away from the plant.
Let us know in the comments if you want to dive deeper into the transportation system. And check out this story on how the team froze trichomes using the most modern techniques.
Title photo is a multi-photon scan of stalked and sessile trichomes from a Hindu Kush calyx by Sam Livingston, Ph.D. and Postdoc, UBC | Wiley.
Sources explaining cannabis trichomes
Samuel J. Livingston, Kim H. Rensing, Jonathan E. Page, A. Lacey Samuels. A polarized supercell produces specialized metabolites in cannabis trichomes. Current Biology, 2022;
Livingston SJ, Quilichini TD, Booth JK, et al. Cannabis glandular trichomes alter morphology and metabolite content during flower maturation. Plant J. 2020;101(1):37-56. doi:10.1111/tpj.14516
Communication with Sam Livingston, Ph.D. and Postdoc. 08/2022.
Borges RS, Batista J Jr, Viana RB, et al. Understanding the molecular aspects of tetrahydrocannabinol and cannabidiol as antioxidants. Molecules. 2013;18(10):12663-12674. Published 2013 Oct 14. doi:10.3390/molecules181012663
Depaepe T, Hendrix S, Janse van Rensburg HC, Van den Ende W, Cuypers A, Van Der Straeten D. At the Crossroads of Survival and Death: The Reactive Oxygen Species-Ethylene-Sugar Triad and the Unfolded Protein Response. Trends Plant Sci. 2021;26(4):338-351. doi:10.1016/j.tplants.2020.12.007
Micci A, Zhang Q, Chang X, et al. Histochemical Evidence for Nitrogen-Transfer Endosymbiosis in Non-Photosynthetic Cells of Leaves and Inflorescence Bracts of Angiosperms. Biology (Basel). 2022;11(6):876. Published 2022 Jun 7. doi:10.3390/biology11060876
Yoshiyuki Tsujimoto; Daisuke Takase; Hajime Okano; Naohiro Tomari; Kunihiko Watanabe; Hiroshi Matsui (2013). Functional roles of YPT31 and YPT32 in clotrimazole resistance of Saccharomyces cerevisiae through effects on vacuoles and ATP-binding cassette transporter(s). , 115(1), –. doi:10.1016/j.jbiosc.2012.08.011
Paumi CM, Chuk M, Snider J, Stagljar I, Michaelis S. ABC transporters in Saccharomyces cerevisiae and their interactors: new technology advances the biology of the ABCC (MRP) subfamily. Microbiol Mol Biol Rev. 2009;73(4):577-593. doi:10.1128/MMBR.00020-09