12 May 2015

Cannabinoids Overview. CBG-a, The Precursor, and CBG

There are over 480 different identifiable natural chemical constituents known to exist in cannabis. The most distinctive and specific class of these compounds are the Cannabinoids and around 70 have been classified to date. The term 'cannabinoid' has different meanings. In a more narrow sense, it designates the natural cannabinoids of the cannabis plant. In the broadest sense, it includes all chemicals that bind to the cannabinoid receptors and related compounds. These natural chemicals are unique to the plant and include delta-9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD). There are, however, many more, including: Cannabigerols (CBG's); other Tetrahydrocannabinols (THC's); Cannabinols (CBN's); other Cannabidiols (CBD's); Cannabichromenes (CBC's); Cannabicyclols (CBL's) and more (see below).

Cannabigerolic acid (CBG-a)

In 1975 researchers found CBG-a (the acid form of CBG) to be the first cannabinoid formed in the plant, the first expression of cannabis’ unique class of constituents. From there, CBG-a gets transformed into THC-a, CBD-a or CBC-a by the action of enzymes. Thus, CBG-a is the essential precursor for all cannabinoids.

The ability to produce Cannabigerolic acid (CBG-a) is what makes the cannabis plant unique. CBG-a is formed when geranyl pyrophosphate combines with olivetolic acid within the cannabis plant. Cannabigerolic acid (CBG-a) can be thought of as the stem cell cannabinoid, which becomes THC-a/THC, CBD-a/CBD, CBC-a/CBC, and CBG. It is the precursor to the three major branches of cannabinoids:

Cannabidiolic acid (CBD-a);

Cannabichromenic acid (CBC-a); and,

Tetrahydrocannabinolic acid (THC-a).

It is thanks to CBG-a that all the medicinal effects of cannabis are possible. It does this through different types of biosynthesis, where chemicals combine to form new compounds. The cannabis plant has natural enzymes called synthases that break the CBG-a down and mould it toward the desired branch. The plant’s synthases (CBD biosynthase, CBC biosynthase and THC biosynthase) are named after the cannabinoids they help create. It is effectively impossible to overdose on CBG as it usually exists only in trace amounts in a processed plant. This makes the already very high LD50 (lethal dose) of 22.44g/kg even less. CBG, CBD and the CBC’s all share the same molecular formula but have a different structure. 'Industrial' hemp has higher amounts of CBG due to what is described as a recessive trait, which may imply higher amounts of CBG-a are present in those strains as well.

In 2005 it was found that the enzyme controlling the conversion of CBG-a into THC-a and further, THC, is held within the trichomes of the plant. This makes sense, as the trichomes have long been known to be the home of THC. A follow-up study showed THC-a could be grown in a laboratory using a yeast culture as a host. The THC-a synthase was the first biosynthase to be studied, in 2009. It wasn’t until 2014 that any research turned back to focus on CBG-a when it was identified how and where CBG-a binding happened, then, how it was converted into THC-a.

Therapeutic and medicinal values include:

♋Analgesic (relieves pain).

♋Anti-bacterial agent (slows growth of bacteria)

♋Anti-inflammatory (reduces inflammation systemically).

♋Anti-proliferative (Inhibits the growth of tumours / cancer cells). CBG-a has been found to encourage apoptosis, also known as programmed cell death. Defective apoptosis is believed to be a major reason for the formation and progression of cancer, research shows cannabinoids appear to stimulate apoptosis in previously unknown ways, posing a novel way to mitigate and potentially cure cancer.

Cannabigerol (CBG)
Scientists first discovered this phytocannabinoid (occurring naturally in plants, as opposed to endocannabinoids which are produced in the body) in 1964.

CBG is a minor cannabinoid component in most varieties of cannabis, sometimes less than 1%. Nevertheless, narrow-leafleted strains from the Indian-subcontinent have been found to have slightly higher levels of CBG than others. Relatively high amounts of CBG can be extracted from budding plants about three-quarters of the way through flowering. CBG is not considered psychoactive and is known to block the psychoactive effects of THC.

Studies have shown its therapeutic and medicinal values include:

♋Analgesic (relieves pain) - research suggests that CBG has analgesic and anti-inflammatory properties and recommends further study.

♋Anti-bacterial agent - slows growth of bacteria and proven superior to THC, CBD and CBC against gram-positive bacteria, mycobacteria and fungi.

♋Anti-depressant - evidence suggests therapeutic potential. CBG appears to do something at the 5-HT1a receptor that is not fully understood (Agonist/Antagonist?). It modulates the effects of other cannabinoids at this brain site, which is the hub of emotions and depression regulation in the brain. Depending on the study, evidence suggests that CBG may help with depression and anxiety, or possibly block certain anti-depressant drugs. One study in rodents showed that if the right combination of CBG and CBD were present the CBG would block some anti-nausea effects of CBD, but it couldn't quite identify why (other than it related to the 5HT1a receptor).

♋Anti-emetic - anti-vomiting, however, one study showed CBG reversed CBD’s anti-emetic properties.

♋Anti-epileptic - reduces seizures and convulsions. Anecdotal evidence and some studies suggest CBG may be beneficial to patients with Dravet and other seizure conditions. A 2014 study suggests that CBG may help with seizure management, but the mechanisms aren’t fully understood.

♋Anti-glaucoma - relieves pressure behind the eyes. A 2009 study on glaucoma concluded that both THC and CBG reduce intra-ocular pressure and increase aqueous outflow.

♋Anti-inflammatory - reduces inflammation systemically. Research suggests that CBG has anti-inflammatory and analgesic properties and recommends further study. A 2013 Italian study suggested CBG has strong anti-inflammatory properties and may benefit patients with Inflammatory Bowel Disease (IBD). Much like CBD, CBG shows a lot of potential for controlling the inflammation that leads to IBD and like CBD warrants further research.

♋Anti-insomnia - aids with sleep.


♋Anti-nausea - along with an anti-emetic (anti-vomiting) effect
found in rats, although research has not yet been replicated in humans.

♋Anti-proliferative - inhibits growth of tumours / cancer cells). CBG slowed down progression of colon cancer in mice, a promising result that may lead to a new treatments.

♋Anti-psoriatic - eases symptoms and treats psoriasis.

♋Bone stimulant (promotes bone growth)

♋Neurogenic - stimulates growth of new brain cells (CBG is the only cannabinoid identified that is neurogenic and neurogenic compounds are extremely rare, which makes CBG a worthwhile subject for research)

♋Neuro-protective - In January 2015, researchers discovered that CBG had neuro-protective effects in mice with Huntington’s Disease (HD), which is degeneration of nerve cells in the brain. The study illuminated several mechanisms by which CBG may help treat symptoms. Researchers used two different in vivo models to most comprehensively ascertain CBG’s benefits. The first model gave mice a toxin to induce HD-like symptoms. CBG countered a number of the toxin’s effects by reducing pro-inflammatory markers and reactive microgliosis (a form of neuro-inflammation). It also restored the antioxidant defences that were damaged by the toxin administration, ultimately protecting neurons and improving motor function. In the second model, researchers used R6/2 transgenic mice, genetically modified to display features of HD, to examine CBG’s effects. The improvement in motor function was not as strong as the intoxicated mice, but it was still significant. Most interestingly, CBG had a significant effect on at least seven genes linked to HD. The cannabinoid was able to partially normalise the expression of the genes, all of which were impaired in the R6/2 mice. Furthermore, it reduced the accumulation of mutant Huntington protein, which may be responsible for the majority of HD symptoms. Several of the physiological problems associated with HD may be treated with phytocannabinoids. Like many neuro-degenerative disorders, excitotoxicity (over-stimulation of neurons) and oxidative stress (imbalance of oxidants and antioxidants) likely contribute to the cell death seen in HD. Although no clinical trials have been carried out, cannabinoids almost certainly have a place in the future treatment of Huntington’s Disease.

CBG needs temperatures higher than 200°C (392°F) to vaporise, increasing by 90% from 200°C to 230°C (392°F to 446°F).

Searching for Cannabigerol using Google Scholar returns over one thousand and forty results.

This is Part 1 of a four-part series on a lot of what is currently known about cannabinoids. Part 2 will cover one of the three major branches of cannabinoids; Cannabidiols (CBD's) including Cannabidiolic acid (CBD-a).

Reference sources included;

Hemp Edification February 2015 Cannabinoids

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