How CBG Derivatives Can Treat Inflammation, Pain and Reduce Obesity

The  ‘Father  of  Cannabis  Research’  Raphael  Mechoulam  has  studied  how  new  cannabigerol  derivatives can reduce inflammation, pain and treat obesity.

The Israeli researcher who isolated in 1969 tetrahydrocannabinol (THC), the main psychoactive compound  of  the  cannabis  plant,  has  published  a  new  study  in  Molecules,  a  peer-reviewed,  open-access journal of chemistry.

 

Cannabigerol (CBG), formed in most young cannabis plant varieties, is one of the hundred compounds present in the cannabis plant. It was discovered even before THC. In, 1964 Mechoulam and his colleague Yechiel Gaoni considered this cannabinoid the missing link in the biosynthesis of THC.

 

Unlike the most famous THC, CBD has no psychotropic effects: in other words, it doesn’t get you high. Although CBG is a minor constituent of cannabis, researchers think it has anti-inflammatory and analgesic effects on the human body.

 

Like THC and CBD, CBG is processed through the body’s endocannabinoid system.

 

The endocannabinoid system comprises molecules and receptors responsible for keeping bodies in an optimal state regardless of the external environment.Researchers said that the anti-inflammatory activity of CBD derivative HU-320, as previously demonstrated by us in various experimental systems, has led them to explore the potential of CBG derivatives, which are much less studied, to evaluate therapeutic potential.

 

This study shows that CBG derivatives, named HUM-223, HUM-233, and HUM-234, have anti-inflammatory and analgesic properties. But what is even more interesting is that, unlike the CBG compound, its derivative HUM-234 also prevents obesity in mice fed a high-fat diet.

 

In particular, CBG has therapeutic potential for treating neurological disease, gastrointestinal disease, and some metabolic disorders that have grown over the years.  As CBG has some common and distinct mechanisms with THC and CBD, researchers have explored its anti-inflammatory and analgesic properties.

 

Researchers reported that the synthesis of the three new synthetic CBG derivatives possesses anti-inflammatory and pain-resolving properties in preclinical models. But most importantly, the molecule HUM-234 has shown prominent activity in obesity prevention in mice fed a high-fat diet.

 

Regarding the CBG anti-Inflammatory activity, CBG itself did not show a consistent pattern of efficacy. However, when comparing its derivative HUM-223 to CBG, researchers observed significant improvement in the inflammatory sensation.The biological results revealed that both HUM-233 and HUM-234 have anti-inflammatory activity as both compounds showed improvement of inflammation and pain sensation.

 

The CBG derivative HUM-234 showed an opposite trend at elevated doses when treating inflammatory conditions. However, it is much more active than CBG in the prevention of obesity. Researchers have tested adult female mice fed with a high-fat diet, which gradually gain weight faster than standard diet-fed ones.

 

Researchers observed that CBG doesn’t limit weight gain, but it has the opposite effect as the weight gain is even higher for the mice fed with a standard diet than the high-fat diet group.

 

But when mice get HUM-234, they gain weight much slower than the mice groups fed with a high-fat diet with CBG. So, researchers could affirm that the HUM-234 significantly reduces weight gain levels much better than CBG.

 

Inflammation contributes to the pathogenesis of many diseases. For instance, chronic inflammation can lead to cardiovascular diseases, gastrointestinal diseases, obesity, asthma, arthritis, neurodegenerative diseases, cancer, and more. The drugs currently used to treat inflammation are mostly corticosteroids and non-steroidal anti-inflammatory drugs. Although they can reduce inflammation, they also increase the risk of gastrointestinal ulcers/bleeds and may have several side effects, including increased risk of gastrointestinal ulcers and bleeds, heart attack, and kidney disease.

 

Researchers concluded that the synthesis of HUM-223, HUM-233, and HUM-234 uses CBG as starting material, or in other words, as an intermediate drug substance to express their properties.

 

“Regarding HUM-233 and HUM-234, both showed anti-inflammatory activity comparable to CBG in all three assays. They were all able to reduce swelling and decrease evoked pain responses upon applying localized pressure on the inflamed paw. We observed an inverse dose-response trend upon increasing the dose of the compounds,”  the study read.

 

But what most attracted the researchers’ interest was the CBD derivative HUM-234 on weight gain.

 

“We chose HUM-234 to be assayed on diet-induced obesity, as we previously established a similar derivative of CBD, HU-435, could prevent weight gain in mice,” they explained in the study.

 

The effect of HUM-234 on diet-induced obesity is of great interest to researchers as obesity leads to a series of physiological, psychological, and social problems. Furthermore, obesity is a crucial risk factor for diseases such as hypertension, hyperlipemia, diabetes, and even cancer, and it is closely associated with the emergence of many chronic diseases. For researchers, the activity of HUM-234 in diet-induced obesity may be a candidate therapeutic for obesity.

 

“We believe that CBG derivatives HUM-223, HUM-233, and HUM-234 have the potential to be further developed as novel drug candidates for use in inflammatory conditions, and potentially also as anti-obesity treatment, where there is a huge unmet need,” the study concluded.

Written and Published by Dario Sabaghi in Weed World Magazine issue 155