Part 1

Part 1 - 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/THCCBD-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
How Cannabigerol (CBG) May Help Battle Huntington's Disease Symptoms

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Part 2

Part 2 - Cannabidiols (CBD's) including Cannabidiolic acid (CBD-a)

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.

Cannabidiolic acid (CBD-a)
Until recently, CBD-a was thought to be a minor cannabinoid, only a small part of the overall cannabinoid profile. However, higher amounts have been seen in ruderalis strains and some recent hybrids have exhibited elevated levels of CBD-a, at potentially higher than THC-a. Just like THC-a, when heated, CBD-a decarboxylates; as THC-a becomes THC, so CBD-a becomes CBD. Like CBD, CBD-a is not psychoactive.

Cannabinoids, when heated (smoked, vaporised or baked into edibles) decarboxylate (decarboxylated forms might be produced biosynthetically and while drying, but acidic forms are the major product). Decarboxylation products are Δ9-THC, CBD and CBC. The 'first cannabinoid' also decarboxylates, from CBG-a to CBG.

CBD-a's therapeutic and medicinal values include:
Anti-emetic (reduces vomiting and nausea),
Anti-bacterial agent (slows growth of bacteria),
Anti-inflammatory (reduces inflammation systemically),
Anti-proliferative (inhibits cancer cell growth).

And while there hasn’t been much research done on CBD-a yet, the research that has been done is quite promising. Using the search term, Cannabidiolic acid, Google Scholar returns over 400 results for 2015 alone (1,420 since 2014 [over 10,000 all told]) and (US federal government resource) returns 520 results (from over 16,000).

Cannabidiolic Acid (CBD-a)

CBD-a requires a temperature of 120°C (248°F) to decarboxylate and the LD50 (lethal dose) is 5,000 mg/kg (for rats) with a toxic concentration in humans (Inhalation TCLo, Toxic Concentration Low) of 15,000 mg/kg.

Cannabidiol (CBD)

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.

Several studies have documented CBD’s role as a PPAR-gamma agonist (peroxisome proliferator activated receptors, PPAR's, a group of three nuclear receptors; PPAR-alpha, PPAR-gamma and PPAR-delta). Cannabidiol also promotes PPAR-alpha activity by inhibiting FAAH; the metabolic enzyme that breaks down several endogenous fatty acid compounds known as N-acylethanolamides. Two other N-acylethanolamides, N-palmitoylethanolamide (PEA) and N-oleoylethanolamide (OEA), bind directly to PPAR-alpha. By suppressing the FAAH enzyme and increasing PEA and OEA levels, cannabidiol indirectly activates PPAR-alpha. Higher levels of PEA and OEA result in enhanced PPAR-alpha transmission. Deficient PPAR-alpha signalling has been linked to schizophrenia.

Whereas CBD does not bind to either of the two known cannabinoid receptors, it has been shown to directly interact with other, so-called 'G-protein-coupled' receptors, to confer its medicinal effect. CBD binds to the TRPV-1 receptor which is known to mediate pain perception, inflammation and body temperature. TRPV or 'transient receptor potential cation channel subfamily V' is referred to by scientists as the 'vanilloid receptor' (named after the vanilla bean). Vanilla contains eugenol, an essential oil that has antiseptic and analgesic properties which also helps unclog blood vessels. Historically, the vanilla bean has been used as a folk cure for headaches. Capsaicin (a vanilloid), the pungent compound in hot chilli peppers, is a well known activator of the TRVP-1 receptor. CBD is a TRPV-1 'agonist' or stimulant and this seems to be one of the reasons why CBD-rich cannabis may be a particularly effective treatment for neuropathic pain.

There is also growing medical interest in the gene-regulating properties of CBD. In 2012, Israeli scientists identified more than 1,200 genes affected by CBD: 680 'gene transcripts' were up-regulated (turned on) and 524 were down-regulated (turned off) by CBD in a probe that focused on CBD’s role in zinc homoeostasis. “The results show that CBD ... affects the expression of genes involved in zinc homoeostasis and suggest that the regulation of zinc levels could have an important role through which CBD may exert its anti-oxidant and anti-inflammatory effects”, the Israeli research team concluded.

Studies indicate that CBD influences the expression of some genes by directly activating PPAR-gamma which has promising therapeutic implications, particularly with respect to cancer and metabolic disorders. PPAR's are triggered by hormones, endogenous fatty acids and various nutritional compounds. When activated, PPAR's bind to certain segments of DNA to promote or prevent transcription of specific genes. Many of the genes regulated by PPAR's are involved in energy homoeostasis, lipid uptake and metabolism, insulin sensitivity and other metabolic functions. Big Pharma recognises the importance of these nuclear receptors. Thus far, two classes of pharmaceutical PPAR activators - fibrates and thiazolidinediones - have been approved by the US Food and Drug Administration.

CBD is usually taken orally as a cannabis-based concentrate or extract. However, compared to smoking or vaporising, ingesting cannabinoids orally poses a number of drawbacks, including inconsistent absorption and a delayed effect. Vaporising is considered a healthier alternative to smoking and decarboxylation is reached at 160-180°C (320-356°F). However, when vaporised, CBD produces dense vapour that can be irritating to the throat for some and generate significant coughing, with the vapours produced visibly different to the less dense vapours produced by THC.

Scientific and clinical studies underscore CBD’s potential as a treatment for a wide range of conditionsCBD's therapeutic and medicinal values include:

♋ Alzheimer’s Disease / Dementia / Memory Loss - CBD’s strong neuro-protective and anti-oxidative effects work together to counteract ageing in the brain, fighting off memory loss and dementia. In 2011, an Italian research team reported that PPAR-gamma activation degrades amyloid-beta plaque, a key molecule in the development of Alzheimer’s disease. Cardiovascular, autoimmune, neurological disorders, cancers and the ageing process itself are all thought to have free radicals as a causative agent. Further, they are implicated in the formation of protein amyloid plaques - plaques that can attack neural synapses and prevent normal chemical and electrical signalling. By binding up these free radicals, antioxidants can minimise the plaque formation cycle associated with the progression of Alzheimer’s disease. 

♋ Analgesic - relieves pain, including chronic and neuropathic.

♋ Anti-bacterial agent - slows growth of bacteria.

♋ Anti-inflammatory - reduces inflammation systemically. "CBD affects the expression of genes involved in zinc homoeostasis and suggest that the regulation of zinc levels could have an important role through which CBD may exert its anti-oxidant and anti-inflammatory effects,” an Israeli research team concluded. Nutritional factors also influence PPAR signalling. At the 2013 International Cannabinoid Research Society Conference, Wageningen University (Netherlands) reported that the omega-3 fatty acid derivative docosahexaenoyl ethanolamine (DHEA) acts as an inhibitor of the COX-2 enzyme. So does CBD; this is one of the major reasons why CBD has potent anti-inflammatory properties. COX-2 is an enzyme that creates prostaglandins, a class of inflammatory compounds. Aspirin and all the other non-steroidal anti-inflammatory drugs are COX inhibitors.

♋ Anti-oxidant – prevents the damage of oxidation to other molecules in the body. The antioxidant properties of CBD exceed the antioxidant potency of either Vitamin C or E. CBD has been shown to be a potent anti-oxidant that mitigates the negative effects of oxygen free radicals. When combined with THC, the anti-oxidant properties of CBD grow even stronger. Once again, whole-plant cannabis therapeutics have been shown to be far greater than the sum of the herb’s individual medicinal components.

♋ Angiogenesis (development of new blood vessels). According to a 2008 report by the University of Rome, both PPAR-alpha and PPAR-gamma agonists regulate angiogenesis, the creation of new blood vessels, particularly capillaries. In cancerous tumours, dysregulated angiogenesis leads to new blood vessels which provide tumours with nutrients, helping them to grow and metastasise. By directly activating PPAR-gamma and indirectly promoting PPAR-alpha activity, CBD may inhibit tumour angiogenesis. Three major complications associated with Diabetes Mellitus - retinopathy, neuropathy and nephropathy are all worsened by aberrant angiogenesis. Although numerous PPAR agonists have shown efficacy in preventing retinal angiogenesis, some studies report that activating PPAR's can amplify angiogenesis. But the overall scientific consensus seems to be that PPAR-alpha and PPAR-gamma agonists prevent angiogenesis.

♋ Anti-diabetic – CBD is the only cannabinoid identified that helps lower blood sugar levels. 

♋ Anti-emetic – reduces vomiting and nausea.

♋ Anti-epileptic – reduces seizures and convulsions. In October 2013, the US FDA approved two clinical trials assessing the therapeutic uses of CBD in treating intractable epilepsy in children (Dravet Syndrome). The CBD preparations were made by British pharmaceutical company GW Pharmaceuticals. Dravet is a rare seizure disorder wherein children usually suffer their first intractable seizure before their first birthday and in exceptional cases seizures can last over 24 hours. In Australia, whole, organic cannabis extracts for intractable forms of epilepsy have been formulated from high-CBD cannabis strains that also include THC ('Entourage Effect').

♋ Anti-insomnia – aids with sleep.

♋ Anti-ischemic – CBD is the only cannabinoid identified that reduces the risk of artery blockage.

♋ 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. GPR55a 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.

♋ Anti-spasmodic – suppresses muscle spasms.

♋ 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.

♋ Bone Stimulant – promotes bone growth. Some studies indicate that CBD may function as an antagonist that blocks, or deactivates, GPR55 which is widely expressed in the brain, especially in the cerebellum. It is involved in modulating blood pressure and bone density. GPR55 promotes osteoclast cell function, which facilitates bone re-absorption; over-active GPR55 receptor signalling is associated with osteoporosis.

♋ Immunosuppressive – CBD is the only cannabinoid identified that reduces function in the immune system.

♋ Inflammatory Bowel Disease (Syndrome) / Crohn’s Disease - CBD shows a lot of promise for controlling the inflammatory responses and discomfort caused by Crohn’s disease and IBD/IBS. CBD has so much potential to regulate these diseases that it is being considered for a new class of IBD drugs.

♋ Intestinal Anti-prokinetic – CBD is the only cannabinoid identified that reduces small intestine contractions.

♋ Neuroprotective – slows damage to the nervous system and brain.

♋ Obesity and Metabolic Syndrome - most genes regulated by PPAR's (peroxisome proliferator activated receptors) are involved with lipid metabolism and energy storage. PPAR activation typically promotes glycolysis (glucose breakdown), lipolysis (lipid breakdown) and insulin sensitivity. These properties make PPAR activation a promising treatment for Type II Diabetes and obesity. The PPAR-activating drugs, fibrates and thiazolidinediones (PPAR-alpha agonists and PPAR-gamma agonists, respectively) have been approved to treat dyslipidemia (obesity) and insulin insensitivity in Type II Diabetics by the US FDA.

♋ Vasorelaxant – CBD is the only cannabinoid identified that reduces vascular tension.

List of Conditions treatable with Cannabidiol (Project CBD)

A search for 'Cannabidiol' in the US National Library of Medicine National Institutes of Health website, 'PubMed', returns 1,341 resultsIf you need more examples of research into CBD, check out Cannabis Research A-Z and/or CBD Research and Studies from 'Medical Jane'.

This is Part 2 of a four-part series on a lot of what is currently known about cannabinoids and covers one of the three major branches; Cannabidiols (CBD's) including Cannabidiolic acid (CBD-a). Part 1 covered CBG-a, The Precursor, and CBG. Part 3 will cover another of the three major branches of cannabinoids; Cannabichromenes (CBC's), including Cannabichromenic acid (CBC-a).

Reference sources included;

Study:New Cannabinoids Discovered
Safety Data Sheet-CBDa
A Chemotaxonomic Analysis of Cannabinoid Variation in Cannabis (Cannabaceae)
How Cbd Works Within Cells
Cannabinoid Profile CBDa
Cannabinoid Profile - CBD
How CBD Works

Cannabinoid Profile CBG
Granny Storm Crows List 2015

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Part 3

Part 3 - Cannabichromenes (CBC's), including Cannabichromenic acid (CBC-a)

In 2015, University of Mississippi scientists discovered seven new naturally occurring cannabinoids. There are now around 111 known natural cannabinoids as reported in the scientific literature. 

Cannabichromic (cannabichrome carboxylic) acid (CBC-a)

CBC-a is regarded as the fourth major cannabinoid, found in almost every cannabis strain, but more commonly in 'tropical' varieties, and but a small part of the overall cannabinoid profile. However, some cannabis strains have been developed with higher amounts of CBC-a and studies have shown mild to moderate anti-fungal and strong anti-bacterial activity. PubMed returns 8 results for a search on Cannabichromic acid

Cannabichromene (CBC)

CBC is the third cannabinoid synthesised from CBG in the cannabis plant and displays several characteristics that indicate robust medicinal value. To get CBC, decarboxylation of CBC-a must occur. Naturally (over time) or quickly (if exposed to heat) the CBC-a will lose a molecule of CO2, and become CBC. Just as THC-a becomes THC, so CBC-a becomes CBC. Hebrew University research doctors, Yehiel Gaoni and Raphael Mechoulam, discovered a host of phytocannabinoids in the 1960's, with CBC being isolated in 1966. This non-psychoactive cannabinoid, usually found in low levels (<1% [more exacting analysis showed that the compound often reported as CBD may actually be CBC]), not only has benefits of its own, it works with other cannabinoids to produce a synergistic effect. It gives merit to the saying “the whole is greater than the sum of its parts” and reminds us all to never underestimate the power of the 'Entourage Effect'. A term coined by Professor Raphael Mechoulam alongside fellow research scientists, stating; "This effect ('entourage effect') may represent a novel route for molecular regulation of endogenous cannabinoid activity" (published in the European Journal of Pharmacology, 17 July 1998).

CBC has the same chemical formula and weight as CBD and THC but differs from its chemical cousins by the arrangement of its atoms (may explain why analysis showed that the compound often reported as CBD may actually be CBC). The lack of research hasn’t stopped it from being the subject of multiple patents recognising its wide range of medical uses. CBC is an analgesic, anti-microbial, anti-inflammatory, anti-bacterial, anti-viral, bone stimulant, neurogenic, anti-proliferative (slows tumour growth/combats cancer), just like CBD and THC. CBC has also been shown to be ten times more effective than CBD in treating anxiety and stress. 

Therapeutic and medicinal values include:
Targeting the spinal cord can reduce pain signals sent to the brain (Photo:
Targeting the spinal cord can reduce
pain signals sent to the brain

♋ Analgesic – CBC has been found to reduce pain in animal models, although its effect may not be as strong as THC. study in 2011 by The British Pharmacological Society concluded that CBC and CBD could both fight pain by  “interacting with several targets involved in the control of pain”  at the spinal level. When combined, CBC and CBD pack a powerful healing punch, “these compounds might represent useful therapeutic agents with multiple mechanisms of action”, wrote the researchers. In this case, two cannabinoids are better than one! CBC has also been used successfully to remedy migraines, minimising the pain by reducing inflammation. CBC improves the pain-relieving effects of THC as a result of synergies or 'interplay' with THC. It is theorised that CBC’s pain fighting ability is derived from its role in increasing THC’s pain relieving properties, not necessarily CBC’s ability to do so independently. CBC also provides a sedative effect (it is not known whether it does so independently or in conjunction with another cannabinoid). Other studes have confirmed that CBC enhances analgesia, and that it is one of the compounds responsible for the 'Entourage Effect' on pain relief.  CBC has been identified as working for acute pain. Since CBC is non-psychoactive, it can provide medical benefits without making the patient 'high'. 

♋ Anti-bacterial and Anti-fungal - in a 1981 study from the University of Mississippi, US, researchers found that CBC exhibited strong anti-bacterial effects on a variety of gram-positive, gram-negative and acid-fast bacteria, including E. coli and staph (S. aureus). CBC showed mild to moderate activity against different types of fungi too, including a common food contaminant known as black mould (Aspergillus niger). CBC was shown to be superior to both THC and CBD in most instances.

(Photo: Psychology Today)
Cannabis is known to improve mood
♋ Anti-depressant - a study from the University of Mississippi identified a significant anti-depressant effect of CBC in rat models, concluding that CBC and a number of other cannabinoids may “contribute to the overall mood-elevating properties of cannabis”. Scientists are still trying to figure out more about how CBC does this, since it doesn’t seem to activate the same pathways in the brain as THC. Research has also shown that this relatively rare cannabinoid has an anti-depressant effect 10 times greater than that of CBD. It is believed that CBC’s primary purpose is to enhance the effects of THC. It has been suggested that elevated CBC levels will make a high-THC strain of cannabis even more potent. In this respect, think of CBC as THC’s amplifier, or booster. Like the cannabinoids CBD and CBG, CBC lacks psychoactive properties, but helps THC deliver them with greater effect. It is found in the highest concentrations in strains of cannabis native to the tropics. In what is called the entourage effect, researchers theorise that dozens of cannabinoids and terpenes are involved in forming an overall therapeutic efficacy that is greater than the sum of the individual cannabinoids. Research also points to the fact that these plant-based cannabinoids interact not only with each other, but also with the body’s internally produced cannabinoids (endocannabinoids).

♋ Anti - diarrhoeal - In another study CBC was demonstrated to alleviate diarrhoea without causing constipation, which is unique among treatments for diarrhoea, a useful if somewhat obscure use for this particular extract of cannabis.

Inflammation is an immune reaction and plays a key role in many diseases (Photo:
Inflammation is an immune reaction
 Anti-inflammatory - studies show CBC has superior anti-inflammatory abilities, and tested superior to phenylbutazone as early as 1988. The abstract of a 2010 report states "CBC, THC, and a combination of both phytocannabinoids were examined and found that the anti-oedematous effects of these  cannabinoids in combination were additive. Although CBC produced pharmacological effects, unlike THC, its underlying mechanism of action did not involve CB1 or CB2 receptors. In addition, there was evidence of a possible pharmacokinetic component in which CBC dose-dependently increased THC brain levels. In conclusion, CBC reduced oedema through a non-cannabinoid receptor mechanism of action. These effects were augmented when CBC and THC were co-administered". By inhibiting inflammation, CBC (in synergy with other cannabinoids and terpenes etc) helps the body establish homeostasis (balance).

CBC is promising as a gastro-intestinal anti-inflammatory aid, as shown in a 2012 study by The British Pharmacological Society. The researchers induced inflammation in the small intestine of a mouse and studied the effect of the phytocannabinoid on the animal’s intestinal motility. They drew the conclusion that “CBC selectively reduces inflammation-induced hypermotility in vivo in a manner that is not dependent on cannabinoid receptors”, thus, CBC can reduce both swelling and inflammation and produces a stronger anti-inflammatory effect when combined with other cannabinoids like THC. Not involving CB1 or CB2 receptors may explain why CBC produces a stronger anti-inflammatory effect when combined with other cannabinoids like THC. 

 Anti-proliferative - inhibits cancer cell growth. Studies have shown CBC to have anti-proliferative effects, meaning it can inhibit cancerous tumour growth, particularly breast-cancer and colorectal cancer. It works because of anandamide, a cancer-fighting endocannabinoid that our bodies produce naturally. CBC inhibits the uptake of anandamide, making it stay in the blood stream for a longer period of time meaning it basically improves the immune system’s ability to use its own healthy chemicals, such as anandamide, to rid itself of cancer. 

 Anxiolytic – Relieves anxiety. Studies have demonstrated that CBC has sedative effects, promoting relaxation. 

♋ Bone Stimulant – promotes bone growth. CBC has been shown to stimulate bone growth.

Brain growth continues in adulthood through a process called neurogenesis (Photo: Sixty & Me)
Brain growth continues during
adulthood through neurogenesis
 Neurogenesis – promoting the growth of new brain cells. Research in 2013 on CBC highlighted one of the most unique benefits of this compound, neurogenesis: it may actually help your brain grow. Specifically, CBC appeared to increase the viability of developing brain cells. Contrary to popular belief, neurogenesis doesn’t stop once you reach a certain age. However, it only occurs in a specific part of the adult brain called the hippocampus. The hippocampus is important for memory and learning and a lack of growth in this area is believed to contribute to a number of disorders, including depression and Alzheimer’s. While CBC’s ability to promote neurogenesis is a recent finding, previous studies suggest THC and CBD can do the same. As Dr Xia Jiang of the University of Saskatchewan, one of the first scientists to uncover this remarkable effect of cannabis explained: Most ‘drugs of abuse’ suppress neurogenesis. Only 'marijuana' promotes neurogenesis”. Opiates, alcohol, nicotine and cocaine are all known to inhibit brain growth. Thankfully, CBC and other compounds in cannabis are proving to have the opposite effect.

Many experts, care-givers and patients have concluded that therapy involving a single cannabinoid - such as the CBD oils being used to treat children with intractable epilepsy - may be insufficient for the majority of patients. Many proponents of whole plant therapy point toward the 'Entourage Effect' and the subtle ways in which one cannabinoid, such as CBC, may buffer or enhance the effect of another, like THC (or an endocannabinoid like anandamide). With more than 110 cannabinoids having been discovered, additional research is necessary to understand the nuanced interaction of these specialised chemicals that fit perfectly into receptors throughout the human brain and nervous system. Greater knowledge of cannabinoids and the efficacy of particular cannabinoid profiles is needed before patients can be administered solutions targeted to their particular endocannabinoid system and the specific disease or ailment they are attempting to treat. 

CBC requires a temperature of 220°C (428°F) to decarboxylate and the LD50 (Lethal Dose) is 270mg/kg for monkeys (compared to nicotine for humans, 40–60 mg, 0.5-1.0 mg/kg).

A search for the compound Cannabichromene in PubMed returns over 70 results.

Cannabicyclol (CBL)
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
Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects

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Part 4a


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. 

Cannabinoids have been found to work synergistically with the human body and, more specifically, the Endogenous Cannabinoid System (ECS). The human body produces its own cannabinoids, called endocannabinoids (endogenous means produced internally). Phytocannabinoids (literally, 'plant' cannabinoids) from the Cannabis plant are a perfect fit for the specialised cannabinoid receptors found throughout the brain, nervous and immune systems. In addition, cannabinoids do more than work independently to deliver a particular therapeutic effect, they also work in tandem to regulate one another, something that has been labelled the Entourage Effect. These miracle molecules give the herb a wide variety of therapeutic benefits, from reducing inflammation to managing pain and many researchers and patients have begun to recognise the fact that single cannabinoid extracts may not be the best solution for the majority of patients.
The Endocannabinoid System (ECS) is a coordinated network that consists of the canonical Cannabinoid Receptors (CB1 and CB2), their endogenous ligands, Anandamide (the 'bliss' molecule) and 2-arachidonoyl glycerol (2-AG) and their synthesising and degrading enzymes. THC mimics the actions of Anandamide and 2-AG and has been shown to be an effective treatment for a variety of neurological, gastrointestinal and psychological ailments. It is an especially effective treatment for Crohn’s disease. This is primarily because of the way in which this cannabinoid decreases inflammation, the core cause of Crohn's. In fact, THC is such an effective treatment for Crohn’s, it has been shown to put the disease into remission. Strains high in THC are also effective in treating PTSD and even preventing heart attacks. Strains high in THC can sometimes deliver a strong dose of paranoia but this is easily ameliorated with everyday household pantry items like Black Pepper, and patients who suffer from acute anxiety often find strains lower in THC to be more therapeutic. Cannabichromene (CBC) another cannabinoid, has been found to enhance the potency of THC. Thus, a strain that is high in both THC and contains enough CBC to enhance its psychoactive properties will be especially potent, providing greater efficacy for some patients. Likewise, another cannabinoid, Cannabigerol (CBG), has the opposite effect on THC, serving to buffer its effects and decrease its psychoactive properties. Strains that are high in THC, but also with sufficient amounts of CBG, may be more tolerable for some.

The commercial value in most jurisdictions where use of Cannabis is still illegal is typically dictated by the amount of THC it contains. Cannabis strains with larger percentages of THC (12-21% is purportedly the average) are capable of delivering more potent therapeutic and medicinal efficacy. Some strains of Cannabis, such as Train Wreck and OG Kush, feature THC in quantities as high as 24-30%. Concentrates, such as hash and wax may feature as much as 85% THC. One method of isolating the THC contained in whole plant Cannabis is to vaporise it, allowing it to be consumed without the tars and toxins of smoking.

THC is a bronchial dilator, an effective treatment for asthma and related respiratory conditions, again this is due to its anti-inflammatory properties. It is also very helpful for those suffering from autoimmune deficiencies, such as wasting syndrome and HIV/AIDS, because of its ability to stimulate a patient’s appetite. THC allows sufferers to maintain body weight and enjoy proper nutrition so they are most capable of battling their disease. THC is a powerful treatment for nausea caused by chemotherapy and other toxic treatments. It allows patients to keep down food or critical pharmaceutical drugs that otherwise would be lost through vomiting. Like its cousin Cannabidiol (CBD), THC also provides neuroprotective qualities, making it well suited to treating diseases like Multiple Sclerosis (MS), Parkinson’s and Epilepsy. Like CBD, CBG and CBC, THC has also been proven to fight cancer and can be an effective analgesic (pain killer). 

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):

♋ Analgesic (Pain Killer) – Understanding the mechanism of cannabinoid-induced analgesia has been increased through the study of cannabinoid receptors, endocannabinoids, and synthetic agonists and antagonists. The CB1 receptor is found in both the central nervous system (CNS) and in peripheral nerve terminals. One of the most common uses of Cannabis is for pain relief and THC is the cannabinoid responsible for its pain-relieving effects. A 2010 double-blind study titled "Smoked Cannabis for Chronic Neuropathic Pain: A Randomized Controlled Trial", published in the Canadian Medical Association Journal stated: "Adults with post-traumatic or postsurgical neuropathic pain were randomly assigned to receive Cannabis at four potencies (0%, 2.5%, 6% and 9.4% THC) over four 14-day periods in a crossover trial. Participants inhaled a single 25-mg dose through a pipe three times daily for the first five days in each cycle, followed by a nine-day washout period. Daily average pain intensity was measured using an 11-point numeric rating scale. Conclusion: A single inhalation of 25mg of 9.4% THC herbal Cannabis three times daily for five days reduced the intensity of pain, improved sleep and was well tolerated". A 2012 study shows THC activates pathways in the central nervous system which work to block pain signals from being sent to the brain. Likewise, in a 2013 study, Cannabis is shown to be especially effective against neuropathic pain, or nerve-related pain. Another 2013 study titled, "Low Dose Vaporized Cannabis Significantly Improves Neuropathic Pain", published in the Journal of Pain stated; "Cannabis has analgesic efficacy with the low dose (1.29%) being, for all intents and purposes, as effective a pain reliever as the medium dose (3.53%). Psychoactive effects were minimal and well-tolerated, and neuropsychological effects were of limited duration and readily reversible within 1–2 hours. Vaporised Cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain". A quick search via Google Scholar returns around 26,900 results for THC as an analgesic and over 3,000 of those results are from 2015.

♋ Anti-emetic (Nausea and Vomiting) – In 2001 a Post-doctoral Fellow in the Department of Psychiatry at the University of Chicago (Illinois, US) wrote an article, "Antiemetic Efficacy of Smoked Marijuana: Subjective and Behavioral Effects on Nausea Induced by Syrup of Ipecac" in the journal Pharmacology, Biochemistry and Behavior which stated; "The present study examined the antiemetic effect of smoked Cannabis cigarettes (8.4 and 16.9mg THC) compared to a highly potent antiemetic drug, ondansetron (8mg) in 13 healthy volunteers. Nausea and emesis were induced by syrup of ipecac. Cannabis significantly reduced queasiness and slightly reduced the incidence of vomiting compared to placebo. Ondansetron completely eliminated the emetic effects of ipecac. These findings support and extend previous results, indicating that smoked Cannabis reduces feelings of nausea and also reduces emesis in this model". THC has to be dosed relatively highly, so any resultant side effects may occur comparatively frequently and more recent investigations have shown THC in low doses improves the efficacy of other anti-emetic drugs if given together. There is evidence from clinical studies that cannabinoids are effective in nausea and vomiting due to radiotherapy and after surgery. Cannabinoids are popular in alternative and complementary medicine and are often used in other causes of nausea including AIDSHepatitis and nausea in pregnancy.

Synthetic THC has been available in pill form and used for treating nausea and vomiting in cancer patients since the 1980's. In the US, a growing number of cancer patients and oncologists view Cannabis as a viable alternative for managing chemotherapy’s effects, as well as some of the physical and emotional health consequences of cancer, such as bone pain, anxiety and depression. Marinol® was the first synthetic THC pharmaceutical to be approved by the US Food and Drug Administration (FDA) for this purpose. Since then, other THC pills have been developed and prescribed to patients undergoing chemotherapy. However, the danger with synthesising any plant extract is that you lose the intrinsic checks and balances provided by nature and undesirable side-effects ensue. For example, Marinol® causes more psychoactive effects than natural, organic THC! Nature is always best, even when the pharmaceutical industry tries to tell us otherwise!

♋ Appetite Stimulant - Along with its ability to reduce nausea, THC is known to work as a powerful appetite stimulant in both healthy and sick individuals (whole organic Cannabis promotes a healthy appetite). As Professor of Clinical Medicine (University of California, San Francisco), Dr Donald Abrams says Cannabis “is the only anti-nausea medicine that increases appetite”. Cannabis also helps Dr Abrams' patients sleep and elevates their mood which is no easy feat when someone is facing a life-threatening illness. “I could write six different prescriptions, all of which may interact with each other or the chemotherapy that the patient has been prescribed. Or I could just recommend trying one medicine”Dr Abrams said.

♋ Asthma - THC’s ability to improve breathing in asthmatics is supported by research examining the anti-asthmatic effect dating from the 1970's. In Australia, up until the 1920's, 'Cigares de Joy' (Joy's Cigarettes), which were Cannabis cigarettes or 'joints' were sold. "Joy's Cigarettes afford immediate relief in cases of Asthma, Wheezing and Winter Cough, and a little perseverance will effect a permanent cure", read the 1920's advertising blurb! Following trials in the first half of the 1970's that showed smoking Cannabis could help calm asthma attacks, scientists tried to develop an inhaler that could deliver THC, and some say vaporisers might be the solution. The effects of a Cannabis cigarette (2% THC) or oral THC (15 mg), respectively, approximately correspond to those obtained with therapeutic doses of common bronchodilator drugs (for example, salbutamol).

Crohn's♋ Crohn's Disease – A prospective trial in Israel showed complete remission in five of eleven patients suffering Crohn's Disease who were given Cannabis twice daily. Authors of the study said it had been reported for years that Cannabis lessened the painful symptoms of the inflammatory bowel disease, but findings had not been proven in a controlled trial. The 2013 study, published in Clinical Gastroenterology and Hepatology compared 21 patients who did not respond to conventional treatment. Half were given Cannabis cigarettes and the other half were given placebo (Cannabis cigarettes with the THC removed). Results showed improvement in the group treated with the THC-intact Cannabis. Those subjects also reported improved sleep and appetite. The 8-week treatment with THC-rich Cannabis caused a decrease in the Crohn's Disease activity index in 90% of patients without producing significant side effects. The mechanisms involved most likely include peripheral actions on cannabinoid receptors 1 and 2 (CB1 and CB2) and may also include central actions.

Epilepsy♋ Epilepsy – One of the mechanisms underlying the anticonvulsant properties of cannabinoids is through their activation of CB1. THC has shown CB1-dependent anticonvulsant activity in experimental models of seizure and epilepsy. Cannabis has some contradictory effects in Epilepsy which likely has to do with the complexity of the plant itself. Cannabis not only exhibits many cannabinoids, it exhibits other compounds including potentially neuroactive substances such as terpenes, hydrocarbons, ketones, aldehydes and other hydrophobic compounds capable of crossing the blood–brain barrier. The variability of the strain-specific ratios of the most common cannabinoid, THC, and the second most common cannabinoid, CBD, offers further complexity in utilising whole Cannabis as an anti-epileptic. In addition, the mode of administration likely affects bio-availability and neuroactivity. However, there is evidence that Oral Cannabis Extracts (OCEs) are well tolerated by children and adolescents with Epilepsy, according to a 2015 studyParental reporting of response to oral cannabis extracts for treatment of refractory epilepsy, in the journal, Epilepsy & Behavior.

Eye with Glaucoma
♋ Glaucoma – Glaucoma causes patients to develop a reduced field of vision that can lead to blindness. Glaucoma is incurable and the second leading cause of blindness in the world, according to the World Health Organization. There are actually several different types of Glaucoma, but only two are common. These two are characterised by an increase in intraocular pressure (IOP), or pressure inside the eye (shown in the diagram), which damages the optic nerve. The cause of the increase in eye pressure is similar, but different between the two most common types. A benefit of THC, recognised early on, was its potential to relieve eye pressure in patients with glaucoma. Studies in the 1970's showed that smoking Cannabis could reduce symptoms in Glaucoma sufferers and scientists tried (and failed) to develop a way to administer THC in eye drops. The idea proved too complicated due to THC not being soluble in water. In 2004 in an article titled "Glaucoma", by GW Pharmaceuticals Cannabinoid Research Institute stated; "The ability of Cannabis and THC to lower intra-ocular pressure in Glaucoma was serendipitously discovered in the late 1970's by a variety of patients and researchers. Several patients in the US Compassionate Use Investigational New Drug Program maintained their vision while employing large amounts of daily Cannabis in situations where standard drug therapy failed ... An emerging concept is that Glaucoma represents a progressive vascular retinopathy that requires a neuroprotectant to preserve vision. Some of the resulting optic nerve damage accrues due to NMDA hyperexcitability, an effect that THC and CBD may counter as neuroprotective antioxidants. Thus, Glaucoma is an area where Cannabis and cannabinoids may offer particular advantages over available single ingredient ocular anti-hypertensive agents".

♋ 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.

♋ Multiple Sclerosis (MS) – A 2001 study, "Prospects for New Cannabis-Based Prescription Medicines", published by GW Pharmaceuticals in the Journal of Cannabis Therapeutics stated; "In practice it has been found that extracts of Cannabis (processed whole plant compounds) provide greater relief of pain than the equivalent amount of cannabinoid given as a single chemical entity (such as Marinol) .... Some patients with Multiple Sclerosis who smoke Cannabis report relief of spasm and pain after the second or third puff of a Cannabis cigarette. This implies very rapid transit to, and absorption into the central nervous system. The time involved is seconds rather than minutes". In a 2012 study, "Multiple Sclerosis and Extract of Cannabis: Results of the MUSEC Trial", published in the Journal of Neurology, Neurosurgery & Psychiatry, patients with stable MS across the United Kingdom (UK) were randomised to oral Cannabis Extract (CE) or placebo. This was a Double Blind, Placebo controlled, Phase III study with a screening period, a 2 week dose titration phase from 5-25mg of THC daily and a 10 week maintenance phase. The rate of relief from muscle stiffness after 12 weeks was almost twice as high with CE than with placebo. In conclusion, the study met its primary objective to demonstrate the superiority of CE over placebo in the treatment of muscle stiffness in MS. At the Hebrew University of Jerusalem in August 2015, researchers took isolated immune cells, which target and harm the brain and spinal cord, from paralysed mice and treated them with either THC or CBD. In both cases, the immune cells produced fewer inflammatory molecules, strongly associated with MS and very harmful to nerve cells and their insulating covers. Researchers concluded the presence of THC or CBD restrains the immune cells from triggering the production of inflammatory molecules and limits the molecules' ability to reach and damage the brain and spinal cord. Researchers say further studies are needed to prove the effectiveness of cannabinoids in treating MS in humans but in many countries, THC and CBD are already prescribed for the treatment of MS symptoms, including pain and muscle stiffness.

♋ Post Traumatic Stress Disorder (PTSD) - The euphoric 'high' from THC is associated with temporary impairment of memory. While this may be seen as a drawback for some Cannabis users, impaired memory is often therapeutic for those who struggle to forget painful memories, such as patients who suffer from PTSD. In 2014, research out of Israel confirmed oral doses of THC can help relieve a variety of PTSD-related symptoms including flashbacks, agitation and nightmares. In a 3-week pilot study involving 10 patients with severe PTSD, oral doses of THC led to significant improvement across a number of measures, including sleep and hyperarousal symptoms. The findings were published in the journal Clinical Drug Investigation. The researchers wrote, “The results show good tolerance and safety, reduction of PTSD hyperarousal symptoms, improved sleep quality and reduced frequency of nightmares”. Recent evidence suggests cannabinoids may enhance the ability to overcome traumatic memories. What’s more, cannabinoids are known to affect sleep in various ways, including a decrease in REM sleep — the sleep phase during which nightmares occur. Anecdotal reports also suggest Cannabis may be of benefit. Also in 2014, psychometric data on PTSD symptoms collected during 80 psychiatric evaluations of patients applying to the New Mexico (US) Medical Cannabis Program between 2009-20011 was statistically analysed. PTSD symptoms were reduced by more than 75% in patients using Cannabis ...". The 2015 studyUse and effects of cannabinoids in military veterans with Post Traumatic Stress Disorder, concluded; "evidence indicates that substantial numbers of military veterans with PTSD use Cannabis or derivative products to control PTSD symptoms, with some patients reporting benefits in terms of reduced anxiety and insomnia and improved coping ability".

♋ Sleep Aid – The sleep-inducing effects of Cannabis are well known and research shows that THC is largely responsible. In fact, trials conducted in the 1970's found oral doses of THC helped both healthy individuals and insomniacs fall asleep faster. More recent studies suggest THC may also improve night-time breathing and reduce sleep interruptions in those who suffer from a common disorder known as Sleep Apnoea.

♋ Tourette Syndrome (TS) – In 2003, the Director of the Tourette Syndrome Clinic at the Medical School of Hannover stated, THC was "effective and safe in the treatment of tics" from Tourette syndrome, following a Double-Blind Study, "Delta 9-Tetrahydrocannabinol (THC) Is Effective in the Treatment of Tics in Tourette Syndrome: A 6-Week Randomized Trial", which was published in the Journal of Clinical Psychiatry. "In this randomised, double-blind, placebo-controlled study, 24 patients with TS (according to DSM-III-R criteria) were treated over a 6-week period with up to 10 mg/day of THC and found a significant difference or a trend toward a significant difference between THC and placebo groups ... at 10 treatment days (between days 16 and 41) there was a significant difference between both groups and no serious adverse effects occurred ... results provide more evidence that THC is effective and safe in the treatment of tics. It, therefore, can be hypothesised that the central cannabinoid receptor system might play a role in TS pathology". Regardless of any personal opinion one may hold on the use of Cannabis, a firm grasp of the facts is necessary to overcome an abundance of misinformation, particularly from mainstream media and those with a vested interest in keeping Cannabis illegal (researchers and government/s reliant on 'donations' from pharmaceutical companies, for example). More research is certainly still necessary to even begin to fully comprehend the seemingly endless applications and benefits of THC and the sometimes extremely subtle ways in which it interacts with a variety of other phyto and endocannabinoids (and that's just for starters). Despite the ability of high-THC strains to cause confusion and anxiety in some patients (easily ameliorated as noted above), THC will continue to be the focus not only of users of Cannabis, but of medical researchers, and as more is learned about its function/s and how it interacts with other cannabinoids, new strains will be bred and natural extracts developed that better target particular illnesses and diseases for the benefit of all humankind.

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).

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