Part 1 - Cannabinoids Overview. CBG-a, The Precursor, and CBG
Cannabigerolic acid (CBG-a)
Cannabichromenic acid (CBC-a); and,
♋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.
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.
♋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-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)
Hemp Edification February 2015 Cannabinoids
There are now around 111 known natural cannabinoids as reported in the scientific literature. In 2005, researchers from the University of Mississippi published a detailed review of the then 70 known cannabinoids. They have since isolated and described about 28 more cannabinoid derivatives, and a couple were reported by a group in Italy. In 2015, University of Mississippi scientists discovered seven new naturally occurring cannabinoids.
The flowers and leaves of some 'industrial' hemp strains may be a viable source of CBD, but hemp is by no means an optimal source. Hemp typically contains far less CBD than CBD-rich cannabis. Huge amounts of industrial hemp are required to extract small amounts of CBD, raising the risk of toxic contaminants (hemp is a 'bio-accumulator'; drawing heavy metals from the soil). Single-molecule CBD synthesised in a lab or extracted and refined from industrial hemp lacks critical medicinal terpenes and secondary cannabinoids found in cannabis strains. These compounds interact with CBD and THC to enhance their therapeutic benefits.
CBD indirectly stimulates endogenous cannabinoid signalling by suppressing the enzyme 'fatty acid amide hydroxylase' (FAAH). This enzyme breaks down anandamide, a naturally occurring endogenous cannabinoid neurotransmitter, or 'endogenous ligand' which binds CB1 receptors which are concentrated in the brain and central nervous system. Because FAAH is responsible for breaking down anandamide, less FAAH means more anandamide (and greater CB1 activation) in the body for longer. By inhibiting the enzyme that metabolises and destroys anandamide, CBD enhances the body’s innate protective endocannabinoid response. At the same time, CBD powerfully opposes the action of THC at the CB1 receptor, thereby muting the psychoactive effects of THC. CBD also stimulates the release of 2-AG, another endocannabinoid that activates both CB1 and CB2 receptors. CB2 receptors are predominant in the peripheral nervous and immune systems.
|Role of Endocannabinoid Activation of Peripheral CB1 Receptors in the Regulation of Autoimmune Disease|
♋ Anti-proliferative - inhibits the growth of tumours / cancer cells. A study published in 2007 showed that CBD inhibited a particular gene, Id-1, which is responsible for the growth of cancer cells in the body. By inhibiting this gene CBD shuts down the growth of cancer cells, potentially stopping or even reversing tumour growth. Researchers at the California Pacific Medical Center have shown that CBD reduces brain cancer and breast cancer cell proliferation and metastasis by inhibiting the expression of the Id-1 gene. GPR55, a G protein-coupled receptor that some researchers postulate may actually be a third cannabinoid receptor type (CB-3?), when activated, promotes cancer cell proliferation, according to a 2010 study by researchers at the Chinese Academy of Sciences. CBD is a GPR55 antagonist, as University of Aberdeen discovered, also in 2010. By blocking GPR55 signalling, CBD might act to decrease both bone re-absorption and cancer cell proliferation. This is one of many molecular pathways through which CBD exerts an anti-cancer effect. Best results were obtained when CBD was administered in combination with THC. ID-1 expression is implicated in several kinds of aggressive cancer.
♋ Anti-psioratic – CBD is the only cannabinoid identified to treat psoriasis.
♋ Anti-psychotic – tranquilising effects relieve symptoms of psychosis; two terpenoids, Linalool and Myrcene, also help. CBD is a powerful anti-psychotic currently being considered for use in treating schizophrenia and other psychoses. CBD appears to have a very similar chemical profile to certain atypical anti-psychotic drugs. PPAR-alpha agonists in particular are indicated as an adjunct treatment for schizophrenia. Polymorphisms or mutations in the gene encoding PPAR-alpha are associated with schizophrenia. Furthermore, PPAR-alpha activation is both anti-inflammatory and can decrease dopamine release, thereby minimising schizophrenic symptoms. This may help to explain how and why CBD has anti-psychotic effects.
♋ Anxiolytic (anti-anxiety) / Anti-depressant – CBD is the only cannabinoid identified that relieves anxiety, but two terpenoids also help (Linalool and Limonene). CBD may exert its anti-anxiety effect by activating adenosine receptors. Adenosine receptors play significant roles in cardiovascular function, regulating myocardial oxygen consumption and coronary blood flow. The adenosine (A2A) receptor has broad anti-inflammatory effects throughout the body. Adenosine receptors also play a significant role in the brain as they down-regulate release of other neurotransmitters (dopamine and glutamate). CBD also stimulates the 5-HT1a (hydroxytryptamine) receptor in the brain involved in the re-uptake of serotonin and other processes that aid depression and anxiety. The anti-depressant properties of CBD are very similar to the trycyclic anti-depressant Imipramine (also being evaluated for panic disorder). At the University of San Paulo in Brazil and King’s College in London, pioneering research into CBD and the neural correlates of anxiety have been studied. At high concentrations, CBD directly activates the 5-HT1A serotonin receptor, thereby conferring an anti-depressant effect. This receptor is implicated in a range of biological and neurological processes, including, but not necessarily limited to, anxiety, addiction, appetite, sleep, pain perception, nausea and vomiting. 5-HT receptors are activated by the neurotransmitter serotonin, found in both the central and peripheral nervous systems. 5-HT receptors trigger various intracellular cascades of chemical messages to produce either an excitatory or inhibitory response, depending on the chemical context of the message. CBD triggers an inhibitory response that slows down 5-HT1A signalling. In comparison, LSD, mescaline, magic mushrooms and several other hallucinogenic drugs activate a different type of 5-HT receptor that produces an excitatory response.
|Inflammation is an immune reaction|
|Brain growth continues during|
adulthood through neurogenesis
A search for the compound Cannabichromene in PubMed returns over 70 results.
A degradative product like Cannabinol (CBN), during extraction, light converts CBC to CBL. It is found in small amounts, if at all, in fresh plant material, and there are, as yet, no reports on its activity in humans. It remains hidden in the shadows of other more prevalent cannabinoids. Its positive medical values have yet to be researched but it is expected that future studies will decipher its properties. Official research reports include 15 records on PubMed and Pubfacts.
This is Part 3 of a four-part series, covering one of the three major branches; Cannabichromenes (CBC's), including Cannabichromenic acid (CBC-a). Part 1 covered CBG-a, The Precursor, and CBG and Part 2 covered Cannabidiols (CBD's) including Cannabidiolic acid (CBD-a). Part 4 will cover the last of the three major branches of cannabinoids; Tetrahydrocannabinols (THC's), including Tetrahydrocannabinolic acid (THC-a) along with Delta-8 and Delta-9-Tetrahydrocannabinol, and Cannabinolic-acid (CBN-a) and Cannabinol (CBN).
Reference sources included;
CBC: THC Enhancer and Cancer Killer
Part 4a - Delta-9-Tetrahydrocannabinol
In Israel in 1964 the most prominent compound in Cannabis sativa L., a non-toxic herb commonly referred to simply as 'Cannabis', delta-9-Tetrahydrocannabinol (THC), was discovered. THC starts out in the Cannabis plant as geranyl pyrophosphate and olivetolic acid. Through enzyme catalisation (an increase in the rate of chemical reaction, without which most biochemical reactions would not occur) they become Cannabigerolic acid (CBG-a), the essential precursor for all cannabinoids. CBG-a becomes THC-a, a cannabinoid which has very different effects to THC. But, with heat or over time, THC-a decarboxylates into THC. Cannabinoids are specialised molecules that mimic similar chemicals in the human body and fit into special receptors within the brain, nervous and immune systems and as reported in the scientific literature at this time there are around 111 known natural cannabinoids.
THC has been proven completely safe to consume with decades of research revealing the impossibility of overdose. According to the United States (US) National Cancer Institute, “Because cannabinoid receptors, unlike opioid receptors, are not located in the brain-stem areas controlling respiration, lethal overdoses from Cannabis and cannabinoids do not occur”. Lethal doses are simply not possible due to the lack of cannabinoid receptors in the brain stem, responsible for respiration and heart function, unlike drugs such as cocaine and heroin, which can easily result in overdose. In 2008, researchers in universities in both Montreal and Vancouver, Canada, reviewed 23 clinical investigations of cannabinoid drugs (typically oral THC or liquid pharmaceutical Cannabis extracts) and eight observational studies conducted between 1966 and 2007. Investigators "did not find a higher incidence rate of serious adverse events associated with medical cannabinoid use" compared to non-using controls over these four decades.
Regulation of THC by other cannabinoids like CBG also affect potency and overall effect, providing another buffer. A 2009 study revealed that using only 10 times the “effective” dose of alcohol can be fatal, whereas 1,000 times the effective amount would be necessary to achieve a fatal dose of Cannabis, a quantity impossible to consume! More research has indicated additional reasons why humans don’t die from Cannabis poisoning. In 2014, the journal Science published results from a French study, Pregnenolone Can Protect the Brain from Cannabis Intoxication, which documented the discovery and presence of a natural hormone that reverses Cannabis intoxication - in rats, at least. According to the researchers: “When the [rat] brain is stimulated by high doses of THC, it produces pregnenolone - a 3,000% increase - that inhibits the effects of THC”.
Therapeutic and medicinal values include (but are certainly not limited to):
♋ HIV/AIDS (Acquired Immunodeficiency Syndrome) – The American Academy of HIV Medicine (AAHIVM) stated in 2007, "When appropriately prescribed and monitored, Cannabis can provide immeasurable benefits for the health and well-being of our patients". Also in 2007, Dr Donald Abrams, Professor of Clinical Medicine (University of California, San Francisco) wrote an article; Cannabis in Painful HIV-Associated Sensory Neuropathy: A Randomized Placebo-Controlled Trial, in the journal Neurology: "Objective: To determine the effect of smoked Cannabis on the neuropathic pain of HIV-associated sensory neuropathy, and an experimental pain model ... Patients were randomly assigned to smoke either cannabis (3.56% THC) or identical placebo cigarettes with the cannabinoids extracted three times daily for 5 days ... Conclusion: Smoked Cannabis was well tolerated and effectively relieved chronic neuropathic pain from HIV-associated sensory neuropathy. The findings are comparable to oral drugs used for chronic neuropathic pain". A group of researchers from Louisiana State University (US) published a study in 2014 in the journal AIDS Research and Human Retroviruses which suggests Cannabis can help stop the progression of HIV/AIDS and its associated symptoms of chronic pain, nausea, fatigue and more. The specific compound that halts the spread of HIV compounds into other healthy cells is none other than THC.
This is Part 4a of a series covering the major branches of cannabinoids. Parts 1 to 3 covered the other major branches; Part 1 - CBG-a, The Precursor, and CBG. Part 2 covered Cannabidiols (CBD's) including Cannabidiolic acid (CBD-a). Part 3 covered Cannabichromenes (CBC's), including Cannabichromenic acid (CBC-a). Parts 4b and 4c will cover Tetrahydrocannabinolic acid (THC-a) along with Delta-8-Tetrahydrocannabinol, Cannabinolic-acid (CBN-a) and Cannabinol (CBN).