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  • Writer's pictureTravis Cesarone

What type of inflammation does this minor cannabinoid affect?

Inflammation protects our blood vessels, at least, in moderation. But of course, an excessive amount of inflammatory agents becomes harmful and toxic. Healers and physicians continue treating symptoms caused by inflammation with plant oils after thousands of years. A new study by authors from South Korean and American institutes assesses the roles that cannabichromene (CBC), an ingredient in some cannabis oil, plays as an anti-inflammatory. Results are generally positive, yet the cannabinoid produced negligible effects on one immune component. (1)


What is CBC?

Cannabichromenic acid (CBCa), a rare ingredient known as a cannabinoid, is found in a limited number of plants. It is a precursor for the active compounds ― (-) and (+) CBC. Research released earlier in 2023 before peer review revealed greater details about cannabichromene, which occurs in nature in two forms. They simply mirror each other. This means that cannabis contains two variations of CBC — two chirals. And molecules that mirror each other’s physical orientation can produce drastically different effects. One variation of CBC, for example, exclusively activates the cannabinoid 2 (CB2) receptor, whereas the other form possesses no known ‘cannabimimetic’ activity. (2)


More recently, the journal Plants published a study assessing CBC extracted from the hemp cultivar — Pink Pepper. They exposed one group of mice to lipopolysaccharide (LPS) and another to a combination of CBC and LPS. They also left one group untreated. LPS, which is known as a glycolipid, is essentially a type of fat combined with a sugar molecule. Gut bacteria, for example, produce large amounts of this glycolipid. A poor microbiome can, therefore, cause inflammation in animals. But, according to recent results, CBC isolated from a hemp cultivar mitigates complications caused by excessive LPS accumulation. (1)




CBC and the inflammatory gut

Cannabinoid (CB) receptors comprise a biological system coined the endocannabinoidome (ECBome). And, one of those receptors has a regulatory relationship with glycolipids, especially LPS. Like other agents in the body, LPS encourages endocannabinoid synthesis by spiking enzymes in the biological process. Further published in the last quarter of 2023, however, is a conclusion suggesting that CB2 receptors induce mechanisms that depend on LPS. Gut bacteria, therefore, connects directly to the cannabinoid receptor and the ECBome. (3) Immediate dependency on glycolipids adds to indirect ties between the ECBome and gut bacteria.


TRPs (transient receptor potential channels) sense chemicals, temperature, and even light. And while some TRPs interact with bacteria. Their relationship is poorly understood. CBC desensitizes a specific few TRP channels, reactivated by heat but also some microorganisms. CBC potently targets TRPs that drive inflammatory mechanisms, yet the cannabinoid performs poorly in this regard when isolated from other plant components. (4) While CBC targets these special chemical sensors seemingly without activating the cannabinoid 2 receptor. The two targets do crosstalk. CB receptors convert the activity of most TRP channels in a way that forces a desensitized response to stimuli.


What about the spectrum?

More than a decade ago, a study found a divide between full-spectrum cannabis extracts and cannabinoid isolates. Researchers tested several cannabinoids in isolated formulations and whole-plant extractions to compare their effects. As an example, CBC isolates could not significantly inhibit an enzyme known as NAAA. Combined with the whole botanical cannabinoid extract, however, cannabichromene significantly blocked the enzyme. This means that ‘full spectrum’ cannabis oils rich in CBC can regulate poor fatty acid metabolism; a driving force in numerous inflammatory diseases.


The body produces an important fat and endocannabinoid derivative known as PEA, which is broken down by NAAA. This means that CBC helps restore and retain natural PEA levels, which in turn regulates fat balance. (4) Despite the decade-old results, though, CBC isolated from Pink Pepper mitigated inflammation, in part, by blocking NAAA in the new study. (1)


Inflammation and CBC

Nitric oxide is a cytokine that induces vascular inflammation, which helps keep blood vessels dilated. A constricted vascular system is more at risk for damage and complications. The cytokine, however, becomes a problem when biological regulatory systems that keep in check, such as the ECBome, fail. Mice treated with around six milligrams of cannabichromene isolated from a hemp cultivar expressed a 50% nitric oxide reduction. Doses of cannabichromene further reduced a cascade of other inflammatory mechanisms induced by λ-carrageenan.


CBC, a cannabis and hemp ingredient, will calm inflammation stirred up by excessive LPS produced by bad gut bacteria. But it likely depends on the inverse synchronicity of the cannabinoid 2 receptor and the microbiome. Secondly, CBC helps to regulate numerous biological processes by retaining PEA lipid levels. Do you think whole plant extracts will provide dramatically improved results compared to isolated compounds?

Photo courtesy of Hong et al. 2023, by Plants. (1)



Photo courtesy of Hong et al. 2023, by Plants. (1)


Sources

  1. Hong M, Kim J-H, Han J-H, Ryu B-R, Lim Y-S, Lim J-D, Park S-H, Kim C-H, Lee S-U, Kwon T-H. In Vitro and In Vivo Anti-Inflammatory Potential of Cannabichromene Isolated from Hemp. Plants. 2023; 12(23):3966.

  2. Udoh M, Santiago M, Haneef S, et al. Activation of cannabinoid CB2 receptors by (−)-cannabichromene but not (+)-cannabichromene. bioRxiv. Published online August 2, 2023:2023.08.01.551199.

  3. Liu, M., Tandorost, A., Moludi, J., & Dey, P. (2023). Prebiotics Plus Probiotics May Favorably Impact on Gut Permeability, Endocannabinoid Receptors, and Inflammatory Biomarkers in Patients with Coronary Artery Diseases: A Clinical Trial. Food Science & Nutrition, 00, 1–11. doi/10.1002/fsn3.3835

  4. De Petrocellis L, Ligresti A, Moriello AS, et al. Effects of cannabinoids and cannabinoid-enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. Br J Pharmacol. 2011;163(7):1479-1494. doi:10.1111/j.1476-5381.2010.01166.x

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