What is CBG?

Cannabis has been used for thousands of years due to the many opportunities the plant carries. It is only in recent times that scientists have begun to give the cannabinoids, and their descendants, the attention they deserve. The mechanisms of the molecules were an unsolved mystery until tetrahydrocannabinol (THC) and the first cannabinoid receptor, CB1, were discovered, followed by endocannabinoids, anandamides (arachidonoylethanolamide, AEA) and 2-arachidonoylglycerol (2-AG). The AEA, 2-AG and CB receptors have been regrouped and classified by physiologists in the endocannabinoid system (ECS).

ECS is a complex network of neurotransmitters and receptors that work together to signal and transmit information throughout the body. They modulate essential neurovegetative functions and help maintain the body's homeostasis. AEA is most often tonic signaling agents for ECS and regulates synaptic transmissions, while 2-AG acts as a phasic signal activator in neuronal depolarization and mediator of synaptic plasticity.

Phytocannabinoids are terpenophenolic compounds that naturally occur in cannabis plants. Among them are not only the psychoactive tetrahydrocannabinol (THC), but also several non-psychoactive molecules such as cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC) and many more. CBG-type molecules are the natural precursors of cannabinoids, and have shown, through several independent studies, to have therapeutic properties and are therefore promising tools in developing current therapies for a wide range of disorders. We are determined to inform the scientific community about the latest developments in the research of CBG's properties and therapeutic capabilities.

Cannabis has been used for thousands of years due to the many opportunities the plant carries. It is only in recent times that scientists have begun to give the cannabinoids, and their descendants, the attention they deserve. The mechanisms of the molecules were an unsolved mystery until tetrahydrocannabinol (THC) and the first cannabinoid receptor, CB1, were discovered, followed by endocannabinoids, anandamides (arachidonoylethanolamide, AEA) and 2-arachidonoylglycerol (2-AG). The AEA, 2-AG and CB receptors have been regrouped and classified by physiologists in the endocannabinoid system (ECS).

ECS is a complex network of neurotransmitters and receptors that work together to signal and transmit information throughout the body. They modulate essential neurovegetative functions and help maintain the body's homeostasis. AEA is most often tonic signaling agents for ECS and regulates synaptic transmissions, while 2-AG acts as a phasic signal activator in neuronal depolarization and mediator of synaptic plasticity.

Phytocannabinoids are terpenophenolic compounds that naturally occur in cannabis plants. Among them are not only the psychoactive tetrahydrocannabinol (THC), but also several non-psychoactive molecules such as cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), cannabichromene (CBC) and many more. CBG-type molecules are the natural precursors of cannabinoids, and have shown, through several independent studies, to have therapeutic properties and are therefore promising tools in developing current therapies for a wide range of disorders. We are determined to inform the scientific community about the latest developments in the research of CBG's properties and therapeutic capabilities.

The isolation of CBG was first discovered in 1964 when Y. Gaony reported the structure and parts of the synthesis of many cannabinoids, including CBG. Although CBG is represented in most types of cannabis (though only in relatively small quantities), researchers have concentrated their energy on the more prominent cannabinoids, THC and CBD. In contrast to naturally occurring cannabinoids, synthetic cannabinoid-inspired compounds, which have become leading drugs in the pharmaceutical market, have been invented in recent decades. Some of these chemically modified cannabinoids do not have the psychoactive effects that THC has, but at the same time have some of the therapeutic properties of already known cannabinoids. It is important to point out that synthetic drugs often have poor side effects, due to solvent residues. Since we are dealing with very new compounds, the side effects can be drastic and, in extreme cases, fatal. By contrast, the cannabinoids, used for recreational use and with therapeutic effect, have been for an incredibly long time - and no life-threatening cases have ever been reported.

Phytocannabinoids such as CBD, CBN and CBG contain most of the therapeutic effects of THC, without being psychoactive. These cannabinoids have been shown to be effective against a growing number of diseases and conditions. Although positive results are seen, treatment is very limited for the population. Furthermore, while many scientific and medical studies use CBD, CBG is not used yet, as it is being investigated and tested.

As we mentioned before, CBG was first isolated by Y. Gaoni, in 1964, when he was able to show the structure and parts of the synthesis of many cannabinoids, including CBG. CBG is a terpenophenolic compound and, like many other cannabinoids, may be divided into three distinct parts. The components not only carry different chemical and pharmaceutical properties, but also influence the absorption potential of the molecules in different ways. The hydrophilic moiety is represented by a phenolic ring believed to carry the antibacterial and antimicrobial properties of the cannabinoids. The ring is joined by two lipophilic chains at each of their diagonal ends. One is the n-alkyl chain, while the other is represented by a terpenoic function that contains therapeutic powers and appears to be related to many of the medical properties of CBG. By having two lipophilic moieties, CBG, like other cannabinoids, has a very difficult time dissolving in water, while it is very readily absorbable by cell membranes and tissues.

As you already know, CBG is the natural precursor for THC, CBD and CBN. CBG's phenolic moieties are probably created via the polyketide method, where a triketo acid can bear some of the responsibility. Its cyclization leads to olivetoic acid, which turns into C-acylate of geranyl diphosphate, based on the CBGa synthase. The carboxylic acid form of this phytocannabinoid, cannabigerolic acid (CBGa), is very important for the synthesis of other phytocannabinoids, and it is exactly this chemical form that phytocannabinoids have when they are in fresh cannabis plants. The corresponding cannabinoids are subsequently absorbed through decarboxylation (heat) (Figure 1). The conversion from CBG acid to THC, CBD and CBN acid is also catalyzed by specific enzymes, and is called THC, CBD and CBN acid synthase.

Despite the fact that relatively few in-depth studies of CBG have been conducted, there is evidence of pharmacological action at a number of targets. CBG has been shown to have relatively weak agonistic effects at CB1 (Ki 440 nM) and CB2 (Ki 337 nM), which explains the non-psychotropic properties of the molecule. However, it affects endocannabinoid tone by preventing the escalation of AEA and therefore higher levels of AEA. Older studies point to CBG as a gamma aminobutyric acid (GABA) escalation inhibitor, in a range of affiliations comparable or superior to THC or CBD, which may explain its anti-anxiety and muscle-relaxing properties. In 1991, Evans and his colleagues found that CBG offers analgesic and antiarrhythmic effects, by blocking lipoxygenase activity and thus reducing the risk of inflammation to a wider extent than the usual medication. CBG has also been shown to be useful as antidepressant medication and antihypertensive medication on rodents. Most of the effects mentioned are mediated by their potent activity as β-adrenoreceptor agonists and by their moderate conductive binding conditions to 2-HT5A. Furthermore, CBG inhibits keratinocyte proliferation, suggesting to be useful in psoriasis, and combined with being a relatively potent TRPM1 antagonist, is thought to lead to the possibilities of relieving prostate cancer and bladder pain. Recently, CBG has been shown to be an effective cytotoxic molecule in human epithelioid carcinoma, as well as the second most effective phytocannabinoid, just after CBD, against breast cancer. CBG has also been shown to have antibacterial and antimicrobial properties (including methicillin-resistant staphylococcus aureus, MRSA), to have moderate antifungal effects.

Numerous studies have shown evidence of CBG for enhanced effect when associated with terpenoids. Terpenoids are quite potent and can affect animal and human behavior if only slightly inhaled through the air. They show unique therapeutic effects that can contribute to many of the medicinal effects that cannabis extract has. For example, limonene has been shown to synergize with both CBG and CBD by promoting apoptosis in breast cancer cells, while Myrcene, a terponide known from hops, synergizes with CBG and CBD by inhibiting hepatic carcinogenesis induced by aflatoxin. Linalool, a terpenoid known from lavender, appears to work with CBD and CBG in the treatment of anxiety. Furthermore, CBC and CBG have been shown to have cooperating properties in cooperation with the terpenoid, caryophylene oxide, which is naturally present in lemon balm, as a fungicide, and with effect similar to commercial fungicides such as sulconazole and ciclopiroxolamine. CBGa has been shown to have synergy with the lemon balm terpenoids, as CBGa keeps the insects away and ensures that the plant is not eaten, suggesting that CBGa may be a promising alternative to protecting crops and vegetables from insects and parasites.

CBG has shown promising results in many treatments. Unfortunately, CBG with a relatively low concentration in the plant, resulting in therapeutic administration of CBG oil, will be limited by the amount of compound obtained from plant extraction.

However, recent breeding work has shown that cannabis chemotypers - with their lack of downstream enzymes - phytocannabinoid content is 100% CBG. After 9 years of hard work and breeding programs, Endoca has created a CBG oil and 99% CBG insulation. That being said, more studies and studies are needed before one can confirm and determine the wide range of therapeutic properties that CBG oil contains.