CBM - Counters insulin resistance

David Katz
Mar 18, 2020
3 min read

CBM (cannabimovone) is found in the cannabis cultivar known as “Carmagnola” [a hemp variety or also called low THC producer variety]

Author note – Carmagnola is a small Italian village in Piedmont, near Turin, specializing in weaving hemp for making ropes, sails, nets, and marine clothing.

Similar to CBM, previous studies found dual-agonist potential at both receptor types [PPARα/γ alpha/gamma] for cannabinoids: THC, CBD, CBG (cannabigerol), as well as their raw, unheated form. Of most importance, CBM was found to be the most potent phytocannabinoid at PPARgamma receptor.

Please look at the diagram below

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The target in question: Peroxisome proliferation-activated receptors (PPARs)

Why is this receptor important:

"Due to its role in adipocyte differentiation, lipid metabolism, glucose homeostasis, insulin sensitivity, inflammatory, and immune responses, PPARγ represents an attractive pharmacological target to address metabolic disorders. [1]"

Whats the future consequences of discovering CBM?

CBM has the potential to be the next medication to help treat insulin resistance. [1]

Is there anything similar to CBM on the market today?

Well actually yes there is...

Thiazolidinediones - a class of diabetes medication - acts as a PPARγ agonist
Fenofibrate and the other fibrates - a class of cholesterol lowering medication - acts as a PPARα agonist

What makes CBM different is the biochemistry...

CBM - has a smaller molecule size which prevents full occupancy at the receptor site leading to a weaker activation than the thiazolidinedione drug rosiglitazone. [1]

A weaker agonist may actually be beneficial if the side effect profile is less severe...

The use of PPARγ agonists is restricted due to their severe side effects including weight gain—which can be particularly problematic for those already suffering from metabolic disorders—"fluid retention, edema and myocardial infarction. In principle, a lower potency agonist like CBM should be associated with a better safety profile. [1]

A notable difference between CBM & rosiglitazone was shared by a study published in March 2020. They found CBM “significantly increased the expression of PPARγ, revealing that, most likely, this phytocannabinoid not only activates PPARγ, but it is also able to trigger a positive feedback loop promoting gene expression.” [1]

The author discusses how CBM may be used in the real world - CBM can boost glucose uptake in cells. Though, further studies are necessary to assess the suitability of CBM as an anti-diabetic & insulin sensitizing drug. If results are found true in humans, CBM would be a new therapeutic alternative for patients who are not yet receiving effective and safe long-term treatment. [1]

 Final question...

Is cannabis a good source of CBM?

Currently, the concentration is too low...

It isn’t cost effective to grow cannabis for CBM extraction. A possible resolution is if breeders cross chemovar (strain) Carmagnola with other high CBM producers to create new chemovars with greater amounts of CBM.
Another possibility is engineering nature to do this. Accomplished by changing the genetics of bacteria, yeast, or even cannabis itself to crank out industrial quantities of CBM.

*Do note that the information presented in this article was gathered from 3D modeling & in vitro studies. No in vivo studies have been completed to date*

Please look at the diagram below

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Author: David Katz | DavidKatz@cox.net

References:

Iannotti FA, De Maio F, Panza E, et al. Identification and Characterization of Cannabimovone, a Cannabinoid from Cannabis sativa, as a Novel PPARγ Agonist via a Combined Computational and Functional Study. Molecules. 2020;25(5). doi:10.3390/molecules25051119
Information used within diagram: Cawthorn WP, Sethi JK. TNF-α and adipocyte biology. FEBS Lett. 2008;582(1):117-131. doi:10.1016/j.febslet.2007.11.051
Information used within diagram: Tyagi S, Gupta P, Saini AS, Kaushal C, Sharma S. The peroxisome proliferator-activated receptor: A family of nuclear receptors role in various diseases. J Adv Pharm Technol Res. 2011;2(4):236-240. doi:10.4103/2231-4040.90879