The cannabinoid receptor CB1, major goal of THC within the mind, is understood for mediating the hashish excessive. And its counterpart CB2, primarily expressed in immune cells all through the physique, is known to play an necessary function in inflammatory processes. These abstractions are correct so far as they go, however as with something associated to the endocannabinoid system, actuality is way extra advanced.
Venture CBD’s current article on the passing of Raphael Mechoulam famous that the esteemed scientist believed CB2 must be a spotlight of future cannabinoid science. The CB2 receptor interacts with THC, CBD, endocannabinoids, and different compounds in a large number of organs together with pores and skin and bone.
Latest analysis — together with papers co-authored by Mechoulam effectively into his 80s — has confirmed that aberrant CB2 signaling is implicated in a raft of autoimmune, neurodegenerative, metabolic, and psychiatric issues. CB2 can be an more and more sizzling matter in most cancers analysis.
On this two-part sequence, Venture CBD will discover a number of the newest research and what they reveal about what we all know — and nonetheless don’t know — about this ubiquitous, considerably mysterious cell receptor.
This week: most cancers. Subsequent week: cognitive and temper issues, together with a few of Mechoulam’s closing work earlier than his demise in March on the age of 92.
Prostate Most cancers & a New CB2 Ligand
Three research from the primary few months of 2023 probe the perform of CB2 in three totally different most cancers fashions. Whereas their findings are advanced and never essentially conclusive, they contribute to a rising physique of data concerning the potential efficacy of cannabinoids in most cancers therapy.
A paper printed in February in Worldwide Journal of Molecular Sciences1 affords two insights for the value of 1: first, one other take a look at how the CB2 receptor features in a mobile mannequin of most cancers; and second, new proof {that a} compound known as 3-3′-Diindolylmethane (DIM) — current in cruciferous greens akin to cauliflower, cabbage, broccoli, Brussels sprouts, and numerous leafy greens — exerts anti-cancer results via the CB2 receptor.
By testing DIM on two totally different human prostate most cancers cell traces, the Italy- and UK-based researchers noticed that the compound activated naturally expressed CB2 receptors in each traces — and that in a single, generally known as “PC3,” CB2 activation led to cell demise, an impact that was reversed when the researchers blocked the CB2 receptor with an antagonist.
DIM was already identified to have an anti-cancer impact extra broadly. What had not been beforehand noticed, the authors be aware, is CB2’s function in mediating this impact in a human most cancers cell line. “We will conclude that DIM is a CB2 receptor ligand with a possible anti-prostate most cancers impact,” they write.
If true, cruciferous greens be part of saffron, black pepper, cloves, oregano, and another spices as meals containing compounds that work together with the CB2 receptor in useful methods.
However don’t head to the marketplace for a cartload of cauliflower and cabbage simply but. The concentrations of DIM used within the examine are too excessive to be obtained via eating regimen alone, the authors be aware, and administration by dietary supplements could also be required.
Colon Most cancers: Case Closed?
A second February 2023 examine within the Worldwide Journal of Molecular Sciences2 involves the same conclusion concerning CB2’s function in colon most cancers. Researchers in Israel investigated how the CB2 receptor functioned in a mouse mannequin of colon most cancers (using “knockout” mice lacking the receptor altogether), they usually analyzed genomic knowledge in a big human inhabitants to find out the connection between CB2 variants and colon most cancers incidence.
In each instances, the authors write, their findings point out that “endogenous CB2 activation can modulate the immune response and consequently cut back tumorigenesis” and that “CB2 protects towards the event of colon most cancers.”
But regardless of their seemingly unambiguous findings, the authors additionally acknowledge that earlier research have come to very totally different conclusions concerning the function of CB2 in most cancers.
“CB2 has been investigated in a number of most cancers varieties and fashions of irritation,” they write, “and there are controversial outcomes concerning the impact on tumor development.” For instance, previous research have discovered that CB2 expression is related to a poor prognosis in people; that CB2 antagonists, or blockers, suppress tumor development; that CB2 activation promotes tumor development in fashions of colon most cancers; and that CB2 agonists inhibit tumor development. The researchers attribute this ambiguity to variations in animal most cancers fashions and most cancers cell traces.
Lung Most cancers: A Completely different Reply
Certain sufficient, a unique examine printed a month earlier in Frontiers in Immunology3 utilizing a unique mouse mannequin of non-small cell lung most cancers appears to indicate one thing else altogether.
Inside knockout mice poor of CB2 within the “tumor microenvironment” — the conventional cells, molecules, and blood vessels that encompass a tumor cell, together with immune cells expressing excessive ranges of CB2 — a crew of Austria-based researchers noticed a discount in tumor burden relative to “wild-type” mice. In addition they discovered that CB2-deficient mice responded considerably higher to a type of immunotherapy generally known as anti-PD1.
Collectively, these findings point out that CB2 receptors within the tumor microenvironment of non-small cell lung most cancers “might act as an immunosuppressor … thereby selling tumor development.”
You learn that proper: the other of what the opposite two papers discovered. Be that as it could, it nonetheless appears clear sufficient that CB2 modulates mobile immune response in methods immediately related to most cancers development — and that the scientific implications of this hyperlink nonetheless have to be labored out.
Read part 2 of this 2-part series: Psychological Well being & the CB2 Receptor
Nate Seltenrich, Venture CBD contributing author, is the writer of the column Bridging the Gap. An impartial science journalist based mostly within the San Francisco Bay Space, he covers a variety of topics, together with environmental well being, neuroscience, and pharmacology. © Copyright, Venture CBD. Might not be reprinted with out permission.
Footnotes
- Tucci, Paolo et al. “The Plant Derived 3-3′-Diindolylmethane (DIM) Behaves as CB2 Receptor Agonist in Prostate Most cancers Mobile Fashions.” Worldwide journal of molecular sciences vol. 24,4 3620. 11 Feb. 2023, doi:10.3390/ijms24043620
- Iden, Jennifer Ana et al. “The Anti-Tumorigenic Function of Cannabinoid Receptor 2 in Colon Most cancers: A Research in Mice and People.” Worldwide journal of molecular sciences vol. 24,4 4060. 17 Feb. 2023, doi:10.3390/ijms24044060
- Sarsembayeva, Arailym et al. “Cannabinoid receptor 2 performs a pro-tumorigenic function in non-small cell lung most cancers by limiting anti-tumor exercise of CD8+ T and NK cells.” Frontiers in immunology vol. 13 997115. 9 Jan. 2023, doi:10.3389/fimmu.2022.997115
