What is cannabigerol?

Cannabigerol (CBG) is a type of cannabigerolic acid, which is formed in the trichomes of cannabis inflorescences. At the end of the growing season, cannabigerols trigger the process of leaf rejection, after which the plant uses the released resources for flowering. Having completed their mission, the acid and its derivatives break down into three compounds:

-tetrahydrocannabinolic acid (TGKK, THCA, TGKA) – under the action of heat and UV rays, it is converted into THC;
-Cannabidiolic acid (CBD) – converted to Cbd;
-Cannabichromenic acid (KBHC) is a precursor to cannabichromene.

When there is an abundance of heat and light, CBD is split directly into two bioactive substances – harmless CBD and psychoactive THC. Therefore, a ripe cone cannot boast a high content of CBD; as a rule, the percentage of cannabigerol in plant raw materials does not exceed 1%.

How is CBG (cannabigerol) produced?

Israeli scientists Rafael Mechulam and Yehiel Goni were the first to isolate CBD from the cannabis plant. Yes, yes, the same guys who isolated THC and CBD and cleared the way for several generations of researchers into the medicinal properties of cannabis. However, the discovery of CBG went unnoticed for a long time; like many minor components of the gifts of Ja, this mysterious substance has long been hidden in the shadow of its famous brethren.

For some time it was believed that it was impossible to isolate a cannabinoid from a photographic material in an amount sufficient for serious study. But when the success of the legalize movement freed the hands of experimenters, it was found that it was quite possible to extract Cbg from the plant mass if extraction was carried out from the 6th to the 8th week of flowering, when the cleavage of CBG had already begun, but most of the decomposition products had not yet transformed. The isolates and CBD oil obtained in this way are part of naturopathic preparations – drops, therapeutic ointments, balms and sprays, skin and hair care products.

Breeding also does not stand still. The breeding of many varieties of medical cannabis with high CBG levels has become possible due to a spontaneous gene mutation that causes delayed cleavage of CBGA. Hemp obtained by crossing mutant plants contains a lot of CBD even during the flowering period – from 2 to 4% versus 0.1–1% in non-specialized varieties.

Cannabis is cultivated from feminized cannabis seeds with elevated levels of CBD on farms that grow cannabis for the pharmaceutical industry. Since cannabigerol and cannabidiol together inhibit THC synthesis, feminized seeds are planned to be used to grow light cannabis enriched with CBG. Canna therapists all over the world highly appreciated the non-narcotic Bediol variety, patented by the Dutch company Bedrocan BV Medical Cannabis. There is also a French variety of Santica with a CBG content of more than 1%, from which hemp tea and other dietary supplements are produced.

At the University of Dortmund, cannabigerol KBG is extracted by genetic engineering methods for research purposes. Genetically modified yeast fungi produce an enzyme that activates the synthesis of BCG.

How does CBG work?

The mechanism of action of CBG has not been sufficiently studied – there is little data, and the results of few studies are ambiguous. Experts have some ideas, but it’s too early to draw final conclusions. According to the working hypothesis, the cannabinoid CBG is not among the psychotropic drugs, but binds two types of endocannabinoid receptors – CB1 and CB2.

High after a joint is a joke of nature, made possible by the similarity of cannabis phytohormones to compounds that are produced by nerve cells to regulate conduction in synapses. In 1988, researchers at St. Louis University in the United States identified receptor complexes with affinity for THC and CBD in CNS neurons. Four years later, the Hebrew University of Jerusalem isolated a substance called anandamide from brain tissue that binds cannabinoid receptors.

A year later, a second type of cannabinoid receptors was found in peripheral neurons, glandular and immune cells, which coincided by 44% with the receptors of the first type in the sequence of amino acids. Currently, two types of receptors are designated as CB1 and CB2. As it turned out later, they differ in preferences: the CB1 receptor is sympathetic to THC and its derivatives, and CB2 has a great affinity for non-narcotic cannabinoids.

CB1 receptors have chosen brain structures associated with the dopamine reward system:

-prefrontal cortex;
-the cingulate gyrus;
-hippocampus;
-hypothalamus;
-black and striped body;
-Amygdala.

Anandamide and psychoactive phytocannabinoids have been found to enhance the effects of dopamine, which causes euphoria and recovery. At the same time, the conduction of impulses from the limbic system to the cerebral cortex is inhibited, and first of all, impulses caused by pain and fear are attenuated.

The purpose of endocannabinoids is probably to protect neurons from overexertion. The release of anandamide into the nerve synapse inhibits the synthesis of gamma-aminobutyric acid and other mediators that alter the membrane potentials of neurons. As a result, the postsynaptic neuron temporarily loses its ability to excite and transmit an impulse.

A more active THC captures more cannabinoid receptors and is not content with a modest role as a regulator. A sharp change in brain metabolism leads to emotional uplift, peace and joy. The well-established neural connections of the prefrontal cortex, responsible for processing sensory signals, are replaced by chaotic impulses of arousal; there is a feeling of heightened sensitivity and intuition. Sounds and colors acquire fantastic expressiveness and depth, new and unusual facets open up in familiar things.

Receptors of the second type are present in many internal organs and on the membranes of immune cells, therefore, the effects of CBD and CBG are more complex and multifaceted than those of endocannabinoids and THC acting on the receptor of the first type. At the same time, the molecules of phyto- and endocannabinoids, such as anandamide and its analogues, are arranged in approximately the same way; all these compounds belong to the class of paraphenols.

Unlike THC, the non-psychoactive cannabinoids CBD and CBG do not replace anandamides in central synapses, but only enhance their effect by reuptake. Therefore, light cannabis with a minimum THC content does not cause intoxication; the effect on the nervous system is limited to an antidepressant and relaxing effect.

Even at high doses, CBD-rich cannabis does not provoke the paradoxical reactions characteristic of THC; anxiety attacks and paranoia have not yet been noticed in the voluntary participants of the experiments. Attention, memory and intelligence also do not suffer; on the contrary, there is evidence that increased blood flow to the hippocampus against the background of taking CBD and CBD makes it easier to remember large amounts of information and make quick decisions in conditions of uncertainty.

In addition to modulating nerve conduction, the mammalian endocannabinoid system is involved in the regulation of muscle and vascular tone, immune response, and energy metabolism. Endogenous and exogenous cannabinoids are used as consumables in the main processes of vital activity and have a versatile effect on the reactivity and adaptive ability of the body.

What is the difference between CBD and CBG?

CBD and CBG have a lot in common: both substances interact with CB1 and CB2 receptors without intoxicating effect and reduce the “arrival” from THC. Experienced followers of Ja use CBD and CBD isolates when they need to sober up quickly or relieve side effects after high doses of THC. Moreover, cannabinoids prevent the reuptake of acid and serotonin, a mediator with antidepressant properties. As a result, a high concentration of serotonin is maintained in synapses, which has a powerful tonic effect on the body.

However, the difference between the two related compounds is very significant. Unlike CBD, cannabigerol binds all three types of alpha-adrenergic receptors, resulting in a wide range of physiological effects of interest to pharmacology:

suppression of inflammatory reactions;

-vasodilation;
-neuroprotective effect;
-stimulation of general and local immunity;
-accelerated healing of fractures.

In addition, CBG communicates with peroxisome proliferation receptors, which control the intensity of oxidative processes. Interestingly, in healthy tissues, the substance behaves as an antioxidant, and in cancerous tumors, on the contrary, accelerates the activity of oxidizing enzymes, triggering a powerful oxidative stress that destroys malignant cells.

CBD has its own superpower – proven anticonvulsant activity. So far, it is the only one of the cannabinoids approved by the FDA for the treatment of epilepsy. Although CBG is theoretically capable of dampening pathological activity in the cerebral cortex by blocking the sodium channels of neurons that provide the occurrence of excitation potentials during a seizure, the anticonvulsive effect of cannabigerol has not been experimentally confirmed.

Finally, CBG and CBD have different effects on appetite and digestion. Unlike cannabidiol, which dulls hunger, CBD stimulates appetite and improves the digestibility of food, but does not lead to weight gain due to the high intensity of metabolic processes.

What are the potential benefits of CBG?

The prospects for the use of CBG in medicine look tempting, but there are still many years of research ahead. All known results were obtained on cell cultures, experimental animals and small groups of volunteers; there is no information about side effects, interactions with other medications and the long-term effects of taking cannabinoids. Nevertheless, there are possible applications of cannabigerol extracts for therapeutic purposes, which we will discuss.

Is dementia being cancelled?

Neurodegenerative diseases and widespread senile dementia are the price to pay for an increase in life expectancy. According to WHO, there are 35.6 million dementia patients worldwide. By 2030, the number of patients with senile psychoses may double, but the use of CBG-based neuroprotectors may reverse the sad trend.

The neuroprotective effect of cannabigerol in experiments on mice was manifested in three directions:

-protection of nerve cell membranes from oxidative stress;
-reduction of motor deficits in Parkinson’s and Huntington’s disease;
-reduction of autoimmune inflammation foci and resorption of amyloid plaques in Alzheimer’s disease.

In another study, which was covered in 2015 in the pages of the journal Neurotherapeutics, scientists managed to restore the normal expression of genes associated with the development of Huntington’s disease using CBG. In addition, this interesting substance acts as a biostimulator – it blocks alpha-adrenoreceptors and receptors of the PPAR system, slowing down aging and pathological processes that increase the risk of dementia:

-reduces blood pressure;
-breaks down cholesterol plaques;
-reduces blood sugar levels and prevents the development of type II diabetes.

Currently, the biotechnology corporation Emerald Health Pharmaceuticals is developing a drug EHP-102 based on CBD. In case of successful clinical trials, the drug is planned to be used for Huntington’s disease and Parkinson’s disease.

Control of multiple sclerosis

Multiple sclerosis is one of the most common causes of disability in working age among the population in Europe and North America. According to WHO estimates, within 10 years of diagnosis, more than half of patients become disabled; in total, about 2.5 million people in the world live with multiple sclerosis. An autoimmune disease with a tendency to progression is difficult to control, traditional means of suppressing pathological immune reactions are difficult to tolerate and undermine the patient’s health. Preclinical studies at Royal Holloway University inspire cautious optimism: perhaps taking CBD and CBG will slow down destructive processes in nervous tissue at the cellular level and improve the quality of life of patients.

In cell cultures obtained from healthy people, cannabigerol and cannabidiol increase the activity of targets of the natural immunosuppressant rapamycin mTORC1 – specific proteins that are part of membrane signaling complexes. In cultures obtained from patients with multiple sclerosis, the opposite is true – the target of mTORC1, which shows excessive activity, is partially inactivated by cannabinoids, as a result of which the immune attack fades and the loss of nerve cells decreases. Previously, there were reports from Spain about the suppression of autoimmune inflammation of the spinal cord in multiple sclerosis by CBD and CBG.

CBG in inflammatory bowel diseases

Prospects for the use of CBG in inflammatory bowel diseases such as ulcerative colitis and Crohn’s disease are being actively discussed in Israel and the United States. The first precedent was documented in 1976, when a young woman, after four years of unsuccessful treatment for ulcerative colitis, got hooked on weed out of grief and soon felt relieved.

Later, in Israel, they tried to compare the effectiveness of medical cannabis, THC and CBD in Crohn’s disease in a small sample of 32 people who were observed by a gastroenterologist from 2011 to 2017. 45% of patients who smoked weed in the old-fashioned way noted an improvement in the quality of life:

-relieving intestinal cramps and reducing the frequency of seizures;
-eliminating nausea and improving appetite;
-normalization of the stool;
-improvement of intestinal absorption function;
-making up for weight loss.

Pure CBD, contrary to expectations, turned out to be ineffective; THC had no effect on the health of the subjects. American and British colleagues who conducted similar studies came to the same conclusions. As a result, it was proposed that the improvement of the gastrointestinal tract is achieved through the synergy of various cannabinoids, among which CBD plays an important role.

Almost simultaneously, an experiment was conducted in the USA on mice with induced intestinal inflammation. The intake of isolated CBG contributed to the restoration of mucous membranes by suppressing the production of inflammatory mediators and the antioxidant activity of the cannabinoid. At the next stage of research, it is planned to test the drug on humans.

CBG in dermatology

The anti-inflammatory effect of CBG persists with external use. In 2016, AXIM Biotech initiated the testing of medicinal ointments with CBD against eczema and psoriasis at the Moritz Clinic in the Netherlands. For eczema, psoriasis and atopic dermatitis, CBG is indicated to be used in the form of an ointment, cream or lotion.

In another project, the effect of different phytocannabinoids on the activity of the sebaceous glands was studied:

-cannabichromene (CBC) and tetrahydrocannabivarin (THCV) – reduce sebum production, reduce acne manifestations;
-Cannabidivarin (CBGV) – slightly reduces secretion;
-cannabigerol (CBG) and cannabigerovarin (CBGV) – increase the production of sebaceous secretions, prevent dryness and cracking of dry skin.

Cannabigerol as an antibiotic

The emergence of antibiotic–resistant bacteria is a serious challenge for medicine, prompting to expand the range of scientific research and discard prejudices. At McMaster University (Canada), the antibiotic properties of cannabis have been studied since the early days of marijuana legalization.

Of the 18 cannabinoids tested, cannabigerol turned out to be the most effective means of combating methicillin-resistant staphylococcus aureus. CBG not only slows down the growth of the microbial population, but also kills harmful bacteria. If the result can be transferred from animal models to humans, the treatment of nosocomial pneumonia and postoperative complications will become more successful and predictable.

Zero toxicity is an additional advantage of CBG over traditional antibiotics; after a course of treatment, no violations of the gastrointestinal microflora were observed in experimental mice. Although the development of innovative antibiotics based on CBD is definitely beneficial to medicine, scientists are not rushing to conclusions and plan to conduct additional research with the involvement of volunteers.

CBG against cancer: one step closer to victory

Oncologists have high hopes for medical cannabis: in addition to relieving nausea during chemotherapy, reducing pain and stimulating appetite, bioactive substances of cannabis can restrain the proliferation of malignant cells.

According to a number of preclinical studies, CBG is one of the most promising drugs for the adjunctive therapy of leukemia, brain, colon, prostate and breast cancers. Cannabigerol stimulates natural defense mechanisms that cause cancer cell death and slow down metastasis:

-tumor regression due to increased formation of free radicals in cancer cells;
-reducing the number of vessels feeding the neoplasm;
-stimulation of the anti-cancer immune response;
-blocking the synthesis of tumor proteins;
-neutralization of toxic products.

In 2014, Italian scientists led by Francesca Borrelli from the Institute of Biomolecular Chemistry from Naples presented impressive results of their experience with the treatment of intestinal cancer with CBG drugs in rats. Although the disease could not be defeated, the rate of tumor progression slowed down significantly.

Prevention of glaucoma with CBG

A 1990 West Virginia University scientific paper reported that CBG in combination with THC and other cannabinoids dilates the vessels of the eyeball and reduces intraocular pressure, preventing the development of glaucoma. In parallel, the positive effect of cannabinoids on the production of intraocular fluid was noted.

Pacification of the bladder

In the course of studying the interaction with CB2 receptors of smooth muscles in some cannabinoids, including CBD and THC, the property of suppressing the activity of acetylcholine, the leading mediator of muscle contraction, was announced. Reducing acetylcholine emissions normalized bladder tone in rats and prevented involuntary urination. The combination of CBG and THCV can become the basis of a drug against enuresis and urinary incontinence, saving millions of sufferers from embarrassment.

Cannabigerol in psychiatry and neurology

Disorders of brain metabolism create prerequisites for the development of mental illness and cognitive impairment. A lack of dopamine is observed in schizophrenia, autism, tic syndromes and hyperactivity, and insufficient production of serotonin tends to depression.

The deficiency of key CNS mediators has traditionally been compensated by taking drugs that are addictive and have severe side effects. In particular, autistic people and children with ADHD are often prescribed amphetamines to increase the endurance of the nervous system. Recently, a safe alternative has been available – medical cannabis, which acts on the central nervous system gently and delicately.

The legalize countries have accumulated rich practical experience in correcting the behavior of autistic and hyperactive children with the help of cannabinoid concentrates. In 2019, CBG was among the drugs recommended for patients with neurodifferentiation. Based on information obtained during the observation of 188 autistic schoolchildren in the period from 2015 to 2017, researchers from Ben-Gurion University noted progress in 80.1% of children who received extracts of CBD in combination with CBD, THC and THC within six months:

-reducing anxiety and irritability;
-reducing stereotypes;
-improving sleep quality;
-improving intellectual productivity and academic performance;
-development of communication skills;
-improving speech skills in non-verbal autistic people;
-reducing the need for stimulants up to complete withdrawal.

The best results were achieved when using a complex drug containing 30% CBD and no more than 1.5% THC; there was no narcotic “arrival”.

In 2006, Richard Musti and Richard Dayo discovered the properties of an antidepressant and antipsychotic in CBG. The principle of action is the same as that of the popular neuroleptics clozapine and olanzapine – cannabigerol blocks the uptake of serotonin and gamma-aminobutyric acid, providing a mild sedative effect and reducing anxiety. At the same time, the experimental mice did not have the destructive side effects characteristic of neuroleptics.

There is still insufficient evidence of the effectiveness of cannabigerol for humans, but CBD oil is sometimes prescribed to patients who have been diagnosed with depression, bipolar disorder or PTSD. To stabilize the emotional state, CBG isolates are used as an addition to drugs with proven efficacy, such as THC and CBD.

Fracture healing and prevention of osteoporosis

Orthopedics and rheumatology are relatively new fields of application of CBG, but the results of preclinical studies will certainly please older people experiencing problems with the musculoskeletal system. Experiments on rats have shown that CBG, CBD and THC strengthen bones, accelerate fracture healing and reduce bone loss during aging.

In 2009, the University of Edinburgh drew attention to the role of the endocannabinoid system in skeletal renewal. Scientists have traced the relationship between the number of CB1 receptors and the state of bone tissue: the more active receptors there are, the faster the bone grows and the higher its density. With an insufficient number of receptors, fat is deposited in the bones, which contributes to the development of osteoporosis. At the same time, scientists from the Hebrew University of Jerusalem noticed that rats with active CB2 receptors are less susceptible to senile osteoporosis.

Apparently, the endocannabinoid system serves as one of the links in the regulation of the mechanisms of cellular differentiation and the ratio of populations of fat cells and young bone cells that produce the basic substance of bone. Intensive formation of young bone cells under the action of CBD, THC and CBG is accompanied by enhanced mineralization and prevents osteoporosis.

In 2014, the effect of CB2 receptors on pain sensitivity in arthritis was studied at Pompeu Fabra University (Spain): in patients with lower activity of CB2 receptors, more pronounced joint soreness was recorded.

In 2016, the Medical College in Kentucky announced the successful experience of using CBD for osteoarthritis as an alternative to nonsteroidal anti-inflammatory drugs, and the British company GW Pharmaceuticals is developing regimens for symptomatic treatment of rheumatoid arthritis using CBG applications. It is claimed that cannabigerol has a complex therapeutic effect without provoking side effects typical of NSAIDs:

-relief of inflammation and pain syndrome;
-relieving puffiness;
-stimulation of local blood circulation and regenerative processes;
-restoration of joint mobility.

How to use cannabigerol?

Official medicine is in no hurry to replenish its arsenal with poorly studied substances, although the use of dietary supplements and local preparations based on cannabigerol is allowed. In countries where medical cannabis is legalized, CBD in the form of tablets, tinctures and concentrates for evaporation and dabbing is dispensed in dispensers by prescription. In Canada, chewable candies and cupcakes with cannabigerol are in demand, which are used for psychotherapeutic and recreational purposes.

Shortage in the production of CBG

Pure CBG concentrates are very rare even in countries with full legalization; due to technological limitations, manufacturers are not eager to get involved with cannabigerol. Firstly, the multi-stage cultivation of hybrid varieties increases the payback period of the product; in addition, it is difficult to grow capricious specialized varieties of cannabis. Secondly, isolating an isolate is a complex, time–consuming process that requires substantial investments in equipment and qualified personnel.

If one of the entrepreneurs dares to produce CBG isolates, it is obvious that the product will be expensive, which means that you should not hope for stable demand. For these reasons, many companies focus on the production of CBD, especially since the effects of cannabinoids are similar in many ways. As a compromise, complex drugs without a psychoactive component are offered, in which a small amount of cannabigerol is present.

Resume

Cannabigerol is a substance capable of bringing medicine to a qualitatively new level. The potential of CBG in pharmacology is huge:

• It prevents age–related diseases – osteoporosis, osteoarthritis, glaucoma, senile dementia.
• Suppresses inflammation in the intestine.
• It kills cancer cells.
• Defeats antibiotic-resistant infections.
• Relieves urinary incontinence.
• Slows down the progression of multiple sclerosis.
• Helps autistic and hyperactive children to adapt to society.
• Reduces itching and skin irritation in psoriasis and eczema.
• Improves mood, sleep and appetite; relieves depression and anxiety.

Let’s hope that further research will reveal the possibilities of this amazing substance and pave the way for the industrial production of effective and safe medicines against the “diseases of the century”.

 

 

About Author