CBD dominates the market for non-intoxicating medicinal cannabis products by a wide margin today. However, more and more manufacturers have recently been including another cannabinoid – CBG – in their range. What makes cannabigerol interesting, how does it work and what potential does it offer?
Like CBD, CBG is non-psychotropic, but it has two historical disadvantages compared to its more famous relative. First, it was discovered almost thirty years later, and second, until recently, no cannabis strains were known to contain more than one percent CBG.
This ultimately meant that this cannabinoid could only be obtained in larger quantities through costly processing of huge volumes of plant material or even more costly laboratory synthesis.
Professor Mechoulam's team again
CBG in cannabis was first discovered by Yehiel Gaoni at the Hebrew University of Jerusalem in 1964, in collaboration with his teacher, cannabis research legend Raphael Mechoulam. The material they had at the time contained only trace amounts of cannabigerol. However, they were later able to synthesize it and, five years after the discovery, were able to test the effects of CBG on cell cultures and animals.
They soon noticed both its significant antibacterial efficacy and the fact that it was not psychoactive. At the time, cannabis research was focused almost exclusively on elucidating its intoxicating effects, so CBG did not generate much interest.
However, in 1975, a team of Japanese scientists first described the chemical processes by which the cannabis plant forms cannabinoids. Their research showed that at the origin of all cannabinoids known at that time is cannabigerolic acid (CBGA), which is enzymatically processed to, for example, THCA or CBDA.
Under the influence of heat, CBGA is converted into its neutral form, i.e. CBG. Thanks to this discovery, cannabis varieties were later bred that genetically lost the ability to convert CBGA into other cannabinoids, because they cannot produce the necessary enzymes. Thanks to this, in recent years, we have also found representatives of these varieties rich in CBG in today's offer of the largest seed banks.
CBG values in dry matter
The ability of breeders to create CBG-rich varieties can also be assessed today by the maximum values achieved, which range up to around twenty percent CBGA + CBG in the dry matter of the flower. Why “CBGA + CBG”? Like other cannabinoids, cannabigerol is present in the fresh plant in its acidic form, i.e. CBGA.
However, in the dry state, it slowly converts to neutral CBG, so the analysis of the total amount of this cannabinoid should always be based on determining the values of both its forms. Compared to the better-known acidic forms THCA and CBDA, CBGA is slightly more susceptible to decarboxylation, or conversion, due to temperature, but on the other hand, it is more resistant to oxidation, i.e. reaction with atmospheric oxygen.
In practice, this means that a cannabis sample with a high CBGA content stored in the cold will retain the acid in its unchanged form. It can then be extracted using gentle low-temperature extraction. This can be advantageous because CBGA is the cannabinoid with the strongest antibacterial effects recorded, especially against multidrug-resistant Staphylococcus aureus (MRSA).
In this regard, it significantly outperforms its neutral version, the cannabinoid CBG (see below). However, as with other cannabinoid acids, the biological activity of CBGA is still poorly understood.
If for some reason you decide to convert all the CBGA content in the dry matter to CBG, a lower temperature than THCA and CBDA, around 100°C, will suffice. It is important to seal the material airtight before decarboxylation. Once CBG is formed, it goes into a gaseous state, as its boiling point is 52°C (up to 180°C for CBGA). It is therefore strongly recommended that containers containing decarboxylated material are not opened until they have cooled.
Effect on the endocannabinoid system
Unfortunately, CBG lags far behind THC and CBD in terms of studies investigating its effects on specific diagnoses or mechanisms of action. However, as this cannabinoid gains popularity in the supplement market, scientific interest in it is growing.
Under the influence of heat, cannabigerolic acid is converted into its neutral form, i.e. CBG.
Among other things, the subject of interest is thorough research into the effect of CBG on the endocannabinoid system. Like CBD, CBG has a significant effect on the TRPV and TRPA receptors, which are essential for processes associated with chronic pain, inflammation, and especially neurological diseases related to seizures.
The most significant difference between CBG and THC is its negligible ability to bind to CB1 and CB2 receptors . Due to the absence of this activity, CBG is not psychotropic. Little is known about the effects of CBG on other endocannabinoid receptors, such as GPR-55, but they do not appear to play a significant role in the actions of CBG.
Beware of serotonin receptor blockade
However, CBG differs significantly from other known cannabinoids in two effects. The first is the ability to partially block the serotonin receptor 5-HT 1A , and the second is the ability to activate the α 2 receptor .
When 5-HT 1A receptors are activated by CBD, it exerts many effects on the body, most notably antidepressant, anxiolytic (anti-anxiety) and antiemetic (anti-vomiting). Since the activity of CBG is opposite in this regard, the simultaneous use of CBD with CBG may lead to a decrease in the effectiveness of the treatment.
This is a risk, for example, when using products containing CBD and CBG at the same time due to nausea. In contrast, the antiemetic effect of THC or its semi-synthetic derivatives (e.g. nabilone) works on a different principle and is therefore not affected by the administration of CBG.
It is also very likely (although unconfirmed) that CBG interacts with synthetic drugs that affect the serotonin system, especially antidepressants. Therefore, the simultaneous use of preparations containing cannabigerol is not recommended for patients taking antidepressants, especially from the SSRI group, which includes the most widely used drugs, such as citalopram or venlafaxine.
Interestingly, even at high doses, CBG alone does not produce adverse symptoms associated with serotonin receptor blockade, such as anxiety or nausea. This is likely due to its complex action at multiple sites in the endocannabinoid system, meaning it does not cause a decrease in the effectiveness of serotonin in the body.
Unique anti-anxiety effect
Somewhat paradoxically, CBG has also been shown to have significant anxiolytic and antidepressant effects, which are likely related to its second characteristic activity, which is unparalleled among cannabinoids.
CBG is able to very effectively activate the α 2 receptor (which is practically its most significant pharmacological effect). This is a so-called feedback receptor; in simple terms, if a molecule of noradrenaline or a chemically similar substance binds to this receptor, the body evaluates its level as too high and stops producing it.
In pharmaceuticals, α 2 receptor activators have been used for a long time and frequently. They are usually used to treat high blood pressure (e.g. clonidine), but they can also be used to treat anxiety, especially when it is associated with significant psychosomatic symptoms such as palpitations.
CBG's ability to lower blood pressure makes it an ideal candidate for the treatment of metabolic syndrome.
In a survey on self-medication with CBG, more than half of respondents cited anxiety as a reason for using CBG, and nearly three-quarters said that CBG helped them more than prescription medications. α 2 activators also have a place in the treatment of ADHD and Tourette syndrome, and recent studies suggest that they increase the success rate of opioid addiction treatment.
The combination of α2 activators and stimulants (e.g. methylphenidate) in the treatment of ADHD is advantageous not only because of the reduction of the effective dose of stimulants, but also because of the attenuation of their side effects, such as tics or hypertension. The potential of CBG as an adjunctive drug in the treatment of these diagnoses is therefore clearly worthy of closer investigation.
However, the significant activity of CBG at the α 2 receptor could pose certain complications for people who are also taking highly potent antihypertensive drugs, as the simultaneous use of CBG may apparently mean a drop in blood pressure well below the desired level.
Metabolic syndrome
Although some effects of CBG and CBD are contradictory (see above), others are complementary, and therefore there are diagnoses for which their combination is significantly more effective than the administration of these cannabinoids alone. These include, for example, metabolic syndrome. This is a civilization disease manifested by obesity, increased cholesterol and lipid levels, hypertension and type 2 diabetes.
According to current knowledge, this disorder is largely caused by a malfunction of the endocannabinoid system. The PPARα and PPARγ receptors, which are closely related to this system, have been the subject of interest to the pharmaceutical industry for over forty years. Synthetic activators of these receptors, known as glitazones, are commonly used to lower blood sugar and lipid levels. CBG – like CBD – can activate PPAR receptors with an efficacy comparable to glitazones. In addition, its ability to lower blood pressure makes CBG an ideal candidate for the treatment of this fatal disease.
Anti-inflammatory effects
CBG has a very strong anti-inflammatory effect, which is probably mainly related to the activation of the TRPV 1 receptor , also known as the capsaicin receptor. Like CBD, CBG has the ability to reduce the heat of capsaicin (the active ingredient in chili peppers), but this effect is more pronounced in CBG.
The great hope is the use of CBG in the treatment of chronic inflammatory diseases of the digestive tract, such as Crohn's disease or ulcerative colitis. These diseases affect an increasing proportion of the population and currently their treatment is focused only on alleviating symptoms and improving quality of life.
CBG has strong antimicrobial activity – it showed significantly greater effectiveness against some strains of MRSA than commonly used antibiotics.
Although there is no large-scale clinical study of the effects of cannabinoids on human patients, the use of cannabinoid preparations for these diagnoses has a long tradition. Most often, it is self-medication, but in some countries, such as Israel, cannabis is also prescribed for this indication.
Several recent studies in cell and animal models have shown that CBG has exceptional effects in this regard. For example, in 2013, it was found that it not only has the ability to significantly reduce inflammation, but also to reduce intestinal damage. This is often associated with these disorders. A recent study in mice also reached similar results. Interestingly, the effect of CBD on intestinal inflammation was found to be insignificant in this study.
Other chronic inflammatory conditions that cannabigerol could help with include psoriasis. Several studies have confirmed CBG's ability to reduce excessive skin cell division, thereby suppressing the formation of typical scaly skin.
Neuroprotective effects
Chronic inflammation of nerve tissue is the most common cause of nerve damage, and drugs that can reduce it are called neuroprotective. In a 2015 study, the authors examined the effects of CBG on Huntington's disease, an inherited neurodegenerative disease. In mice that had been chemically induced to exhibit symptoms resembling the disease, administration of CBG reduced inflammation and neuronal loss. The reduction in mobility was also less pronounced.
Neuroprotective effects of CBG have also been noted in models of Parkinson's disease or multiple sclerosis.
Antitumor activity
CBG has also been documented to have antitumor activity in laboratory models. In an in vitro study investigating the effect of cannabinoids on a tumor of the nervous tissue (glioblastoma), the effectiveness of CBG, CBD, THC, and their combinations were compared. CBG and CBD were similarly effective in reducing tumor cells and inhibiting metastasis, their effect was comparable to that of the standard chemotherapeutic agent temozolomide. When CBD and CBG were administered simultaneously, they acted synergistically. On the other hand, the effect of THC alone was negligible, and administration of CBD or CBG together with THC did not increase the antitumor effect.
For problems with urination and glaucoma
Other effects of CBG include inhibiting excessive bladder contractions, which could be useful for stress incontinence, for example, or its ability to reduce intraocular pressure in glaucoma.
CBG also has strong antimicrobial activity. It was significantly more effective than commonly used antibiotics against some strains of MRSA, i.e., resistant Staphylococcus aureus. According to a 2020 study, cannabigerol was as effective as vancomycin in suppressing staph infection in mice. This is great news, because this drug is now only used as a so-called reserve antibiotic in cases where the infection is caused by extremely resistant bacteria. In addition, CBG has negligible side effects compared to vancomycin.
Synthetic future
Natural substances with interesting biological activity are often the template for the development of more effective semi-synthetic derivatives. The structure of CBG is also subject to laboratory modifications and some of these molecules could find application in medical practice. The substance HUM-234 is very interesting in this regard. It has been shown to reduce the likelihood of obesity in mice fed a high-calorie diet.
In conclusion, CBG, like CBD, is not a panacea… but it has great potential!
The author is a pharmacist.
Source - Cannabis Magazine