CBGA: Cannabigerolic Acid

Cannabinoids, the chemical compounds housed in the cannabis plant, along with hundreds of other complex organic molecules are responsible for the plant’s therapeutic effects.

The two most abundant cannabinoids are THC and CBD. However, without cannabigerolic acid (CBGa), these cannabinoids would not exist because the cannabis plant uses CBGa as a precursor to create several cannabinoids, including THC and CBD.

Although evidence suggests that CBGa may have its own therapeutic uses, its role in the formation of other cannabinoids currently dominates CBGa research. 

What is CBGa? 

CBGa is formed when olivetolic acid and geranyl pyrophosphate, two organic compounds contained in the cannabis plant, combine. CBGa is a critical building block in the formation of cannabinoids THCa, CBDa, CBCa, and CBG.

The scope of possible medical uses of these cannabinoids is largely responsible for the 180-degree attitude shift toward cannabis. A once demonized plant has now become a therapeutic answer for patients all over the world. However, producing cannabinoids is an inefficient and costly process. Scientists have been interested in harnessing CBGa’s biosynthetic role to produce natural cannabinoids through methods beyond growing and extracting cannabis plants.  

Carboxylic acids are found in many places in nature, and the most common carboxylic acids are formic acid and acetic acid. Each carboxylic acid is equipped with a carboxyl group (COOH) comprised of carbon, oxygen, and hydrogen. In the case of cannabinoid acids like CBGA, these carboxyl groups are attached to the end of the cannabinoid’s main structure.

When CBGA is heated to 110° C, it decarboxylates into CBG. In this process, the carboxyl group at the end of the CBGA molecule is converted into a unique chemical structure, and it is no longer considered to be an acid.

CBGA doesn’t always decarboxylate into CBG, however. This cannabinoid acid is often called the “stem cell cannabinoid” since it is also the chemical precursor for CBD, THC, and cannabichromene (CBC). CBGA does not directly turn into any of these other cannabinoids, however, and it is impossible to decarboxylate non-intoxicating CBGA into intoxicating THC.

Instead, a chemical process can happen during the development of Cannabis sativa flower that transforms CBGA into the carboxylic acid precursors of other cannabinoids. Depending on the genetics of the strain in question, CBGA can turn into either CBDA, THCA, or CBCA. These cannabinoid acids then turn into their stable cannabinoid forms when decarboxylated.

CBGA is primarily a subject of interest among cannabis scientists due to its ability to transform into other cannabinoid acids. However, this carboxylic acid also appears to have its own unique benefits that make it a legitimate target of continued research.

Again, CBGa played a crucial role in the creation of THCa. The significance of this research is that it provides a relatively sustainable mechanism by which scientists can create natural and unnatural cannabinoids for continued research and therapeutic use. 

CBGA: The mother cannabinoid

CBGA, or cannabigerolic acid, plays a cornerstone role in the creation of cannabinoids in the cannabis plant. Through a series of chemical reactions, cannabis trichomes create olivetolic acid (OA) and geranyl diphosphate (GPP). Both of these molecules are converted into CBGA by a specific enzyme—CBGA synthase. Once synthesised, CBGA has the potential to become a multitude of cannabinoid acids, depending on which enzyme catalyses the reaction. THCA synthase, CBDA synthase, and CBCA synthase convert CBGA into THCA, CBDA, and CBCA, respectively.

However, CBGA can also be converted into the cannabinoid CBG if exposed to the right conditions before these reactions. When exposed to heat, a carboxyl group detaches from the molecule. This process—known as decarboxylation—creates CBG. Known mostly as a minor cannabinoid, CBG is beginning to gain traction in the world of cannabis. An increasing amount of CBG products are hitting the market, and breeders have developed cultivars that possess cannabinoid profiles consisting of 100% CBG.

CBGA also plays other fundamental roles in the cannabis plant. As a secondary metabolite, it helps to direct resources towards the flowers for resin and seed production. The molecule achieves this impressive feat by supporting programmed cell death in the leaves, which spares up critical energy.

What is the endocannabinoid system and what is its role?

Performing a protective function for cannabis, CBGA is produced in the plant’s  trichomes and triggers targeted plant cell necrosis for natural leaf pruning to allow the plant to maximize energy directed toward the flower.

CBGA is a foundational compound of the cannabis flower. In fact, you might think of CBGA as the “granddaddy” of cannabinoids. Why? Because CBGA is at the top of the cascade reaction that produces the three major cannabinoid lines:

• THCA (tetrahydrocannabinolic acid)
• CBDA (cannabidiolic acid)
• CBCA (cannabichromenic acid)

These eventually become THC, CBD, or CBC, respectively. CBGA may also convert to CBG, but in a majority of strains, CBGA eventually converts into either THC or CBD.

The Discovery of CBGA

Scientists have known about CBG (cannabigerol) for over 50 years. Israeli researchers were the first to isolate the cannabinoid, and 30 years later, Japanese researchers were the first to reveal that CBGA was its precursor. Despite the long history, minimal research has been conducted on CBGA to date.

Most of that CBGA research has focused on sustainable production of THCA for pharmaceutical and research uses. This research specifically has looked at the mechanism of converting CBGA into THCA.

CBGA was not identified during the initial taxonomification of compounds present in Cannabis sativa. It wasn’t until the 1970s that Israeli scientists were successful in isolating CBGA from cannabis, and it took until 1996 for Japanese researchers to discover that CBGA is the chemical precursor of CBG.

Based on this timeline alone, it’s understandable that research into CBGA remains in its infancy. Combined with the fact that worldwide prohibition efforts have made it very difficult for scientists to research cannabis compounds, the current status of CBGA research is even easier to justify.

CBGA has started receiving significantly more attention over the last few years, however, due to the discovery that this cannabinoid can also turn into the chemical precursors of THC and CBD. Contemporary research into CBGA has primarily centered around this cannabinoid’s ability to turn into THCA, which some scientists believe may make this carboxylic acid a prime source of recombinant THC.

While nearly the entirety of the world’s cannabinoid supply is currently derived from mature Cannabis sativa flower, the process of cultivating and processing cannabis is highly inefficient. While hemp and cannabis flower will surely remain important parts of the connoisseur or artisan cannabinoid economic landscape for the foreseeable future, researchers are keen to derive cannabinoids from other sources for the mass-production of pharmaceutical-grade cannabinoid products.

Research from 2017 indicates that it is relatively simple to derive CBGA from various genetically altered yeast strains, and this recombinant CBGA can then be converted into THCA. Then, this THCA is decarboxylated into THC, completing the process of deriving THC from yeast without the land-use and resource-application concerns inherent to mass-scale outdoor cannabis agriculture.

Researchers are currently in the process of developing techniques to derive cannabinoids from yeast at commercial scales. It’s likely that the relative ease of deriving CBGA from yeast will continue to make this carboxylic acid a primary target of recombinant cannabinoid research for the foreseeable future.

How to Consume CBGa 

One way to consume the greatest quantity of CBGa is to ingest raw hemp. Raw hemp refers to freshly harvested Cannabis sativa containing little to no THC. The more recently harvested, the greater the likelihood of a higher quantity of CBGa.

That’s because regular exposure to heat and light, oxidation, and decarboxylation synthesize the acidic forms of cannabinoids into their activated forms. The longer cannabis is exposed to those variables, the less CBGa and the more CBG (and eventually CBN) will be present.  Hemp tends to contain more CBGa than cannabis strains which contain higher levels of THC. 

It is important to note that there is a lack of research on the risks, benefits, and methods of consuming CBGa.

Consult your doctor before incorporating cannabis/hemp into your diet or health regimen. 

The Benefits of CBGa

There have been some fascinating studies on how CBGa affects the various medical conditions. It should be noted that the following studies are some of the first of their kind and do not equate to a scientific consensus. They’re merely interesting and provide a good basis for future research.

We can’t stress enough that you should consult your doctor before you attempt to treat yourself with products containing CBGa.

While there is very little medical research yet conducted on CBGA, early studies provide some hints about its potential applications down the road.

Cardiovascular Disease

CBGA may help diabetic patients combat some of the disease’s complications and comorbidities like cardiovascular disease. CBGA was studied in vitro and found to greatly inhibit the enzyme aldose reductase, a major contributor of the oxidative stress that leads to heart and other problems. As expected, the results of the CBGA tests were highly dose dependent. Synthetic inhibitor medications have severe side effects for many patients, so a CBGA plant-derived drug is a promising prospect.

Side effects

Unfortunately, CBGA remains relatively under-researched. A lack of human trials leaves a big gap in knowledge on the cannabinoid. No solid data exists regarding possible side effects. We do know that, like CBD, CBGA doesn’t bind to CB1 receptors and thus doesn’t cause psychoactive effects. However, the lack of data also means we don’t know whether the cannabinoid interacts with medications. More studies will hopefully elucidate the answers to these queries soon.

Metabolic Disorders

Another research team discovered that CBGA may also help patients with other metabolic disorders. The 2019 in silico study (computer simulation) was performed to look at CBGA’s role in activating peroxisome proliferator activated receptors (PPARs) that regulate metabolism. When PPARs do not function properly, people develop diseases like diabetes and high levels of cholesterol or triglycerides (dyslipidemia). This study showed that CBGA activated the PPAR receptors, stimulating lipid metabolism and thereby reducing excess lipid accumulation. The study needs to be repeated in animal and human trials.

Colon Cancer

Finally, CBGA may one day prove crucial for patients with colorectal cancer, the third most common cancer and fourth leading cause of cancer-related death. Researchers looked at cytotoxic effects of CBGA extracted from cannabis, and found that not only did the CBGA kill colon cancer cells, but it hastened early cancer cell death and arrested the cancer cell cycle. While more research is definitely needed, the researchers were encouraged that CBGA may effectively target not only colon cancer cells, but could also prevent the growth and proliferation of polyps. Left untreated, these polyps grow into carcinomas.

CBGa and Inflammatory Bowel Disease (IBD)

In a 2013 study, researchers induced colitis in mice and then examined the effect of CBG on extracted intestinal cells from the affected mice.

The results showed that CBG had beneficial effects on the colitis in that it reduced nitric oxide production, mitigated the severity of the colitis, and reduced the creation of oxidizing agents in the small intestine.

These overall benefits led researchers to recommend CBG for clinical experimentation in human IBD patients. 

CBGa and Diabetes

Recent evidence suggests that CBGa has the potential to be used as a treatment for diabetes. The enzyme aldose reductase (ALR2) has been identified as a major contributor to the oxidative stress that leads to diabetic complications and diabetes-induced cardiovascular disease, the leading cause of death in patients with diabetes.

In 2018, Italian researchers reported astudy where it was discovered that whole plant extracts of Cannabis containing high amounts of non-psychotropic cannabinoids could be used as potential treatments for diabetic complications. 

CBGa and Metabolic Disorders

CBGa may also have a beneficial effect on metabolic disorders. Scientists have determined that the nuclear peroxisome proliferator activated receptors (PPARs) are important regulators of metabolism.

The disruption of normal PPAR functioning can lead to the progression of metabolic diseases including diabetes and dyslipidemia. In 2019 research published in Biochimica et Biophysica Acta (BBA)-General Subjects found that CBGA activates PPARs in ways that stimulate lipid metabolism and reduce excess lipid accumulation.  

CBGa and Colon Cancer Cells 

One of the most pervasive forms of cancer is colorectal cancer.  In 2018 research published in Cannabis and Cannabinoid Research by suggests that CBGa may have a therapeutic role in targeting colon cancer cells. The researchers discovered that CBGa-rich cannabis extracts were involved in cytotoxic activity on colon cancer cells by inducing apoptosis (programmed cell death) of colon cancer cells.

These extracts were seen to be active on these adenomatous polyps which if untreated can progress into carcinomas. Research is revealing that cannabis extracts including CBGa are potential candidates as chemopreventive agents to either prevent or suppress progression of neoplastic polyps.

CBGa is a Neuroprotectant 

Neuroinflammation has been implicated in an array of disorders including schizophrenia, autism spectrum disorder, Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. 

Inflammation and oxidative stress are major contributors to neuroinflammation. A 2018 International Journal of Molecular Sciences study found that CBG reduced inflammation, oxidative stress, and the expression of problematic proteins implicated in neuroinflammation.

The study concluded that “the neuroprotective effects of CBG […] may be a potential treatment against neuroinflammation and oxidative stress.” Another 2018 study published in the Journal of Neuroinflammation supports this finding, concluding that the anti-oxidative properties of CBGa demonstrated protective effects from the neurodegeneration involved in Parkinson’s disease. 

CBGA on the horizon

CBG is already an important component of the global hemp economy, and CBGA is proving to play a critical role in the fledgling recombinant cannabinoid industry. Via both of these channels, CBGA will continue to gain prominence within the world of cannabis, and in the relatively near future, it may end up being hailed as the most important Cannabis sativa compound.

In the meantime, explore the potential benefits of CBGA yourself by smoking CBG flower or going the purist’s route and finding a way to ingest this cannabinoid in its original carboxylic acid form. We’re just starting to learn about CBGA, and it’s the job of hemp enthusiasts everywhere to demand further research into this fascinating cannabinoid acid. For more guides like this, visit the Secret Nature blog, and contact us with any questions.