Marijuana (Cannabis)
CBG (Cannabigerol)
The therapeutic benefits from marijuana are derived from the more than 100 pharmacologically active constituents, including many cannabinoids and terpenes. Besides the two best understood and most common of the cannabinoids, Δ-9 THC and CBD (cannabidiol), Cannabigerol (CBG) also appears to provide significant therapeutic benefits explored below.
Although it is proposed that CBG may have therapeutic potential among neurologic, gastrointestinal, and metabolic disorders, more research is required to ensure a lack of unintended cardiovascular side effects. In addition, in the current state of unregulated CBD products, people are making unsubstantiated claims and overselling the benefits and underselling the risks with little documentation of human side effects of CBG.
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CBG (Cannabigerol)
CBG has attracted less attention than Δ-9 THC and CBD, but nowadays is gaining interest among the medical community. Some commercial hemp varieties have CBG and CBGA as their main cannabinoids and, therefore, CBG is developing its place in the therapeutic cannabis market.
Cannabigerol (CBG) is made by the decarboxylation of cannabigerolic acid, CBGA (See Cannabinoids for more information regarding the production of CBG and other cannabinoids from CBGA and other cannabinoid acids). CBG is non-psychoactive and is mostly found in the fresh cannabis plant. It is notable among all other cannabinoids as being the precursor to each one of them, lending to its nickname: “The Mother All Cannabinoids.” In particular, it is converted by the plant to the three most significant and abundant cannabinoids: THC, CBD and CBC. Therefore, the more THC a cannabis plant contains, the less CBG and vice-versa. It should be noted that these conversions only occur in the plant, not in the human body.
Therapeutic Benefits of CBG
Research on CBG is very limited, consisting mostly of preclinical studies in the lab and with animals but few human studies. Early research suggests that CBG may be able to improve the following health conditions:
Anxiety
Preclinical evidence suggests the phytocannabinoid cannabigerol (CBG) could be useful in treating brain disorders, including stress and anxiety-related disorders. CBG is purported to reduce anxiety and symptoms of obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and depression. In a 2021 study in in a mouse model of post-traumatic stress disorder (PTSD), researchers explored whether CBG disrupts various contextually conditioned fear memory processes and trauma-induced anxiety-related behavior.
However, it was concluded that CBG was ineffective in disrupting long-term fear memories, various conditioned fear memory processes, or stress-induced anxiety-related behavior in mice. This preclinical study suggests CBG may have limited benefit if any for PTSD and stress-related anxiety.
Appetite Stimulation
A 2016 study on rats suggested that CBG could stimulate the appetite. CBG has also been shown to increase feeding in rats and to reduce weight loss associated with chemotherapy. Unlike Δ-9 THC and CBD, CBG has not been found to have anti-nausea effects and appears to oppose the anti-nausea effectsof CBD. Taken together, these studies suggest that there may be a role for CBG in chemotherapy-associated weight loss and loss of appetite.
Inflammatory Bowel Disease (IBD)
CBG may reduce the inflammation associated with inflammatory bowel disease, based on a 2013 study conducted on mice. In a 2020 study using a mouse model, orally administered CBG reduced colonic inflammation and adding fish oil enhanced the effect.
Bladder Dysfunction
A 2015 study evaluated how five different cannabinoids affect the bladder, concluding that CBG offers the most promise at treating bladder dysfunctions.
Neurodegenerative Disorders
CBG has previously been reported to have disease-modifying anti-inflammatory effects in mouse models of Huntington’s disease, multiple sclerosis, Parkinson’s disease, and amyotrophic lateral sclerosis. These effects are likely mediated by PPARγ, and not cannabinoid receptors. CBG might have neuroprotective properties, according to a 2015 study that looked at mice with the neurodegenerative condition, Huntington’s disease. The study concluded that CBG might show promise in treating other neurodegenerative conditions.
Neuroinflammation and Oxidative Stress
In laboratory studies CBG pre-treatment reduces inflammation, as by reducing inflammatory agents including IL-1β, TNF-α, IFN-γ and PPARγ protein levels. but also oxidative stress by reducing nitrotyrosine, SOD1 and iNOS protein levels and restoring Nrf-2 levels. Together, these findings suggest neuroprotective benefits of CBG that may offer potential treatment against neuroinflammation and oxidative stress.
Metabolic Syndrome
Metabolic syndrome, with hypertension, hyperlipidemia, and insulin resistance stemming from glucose dysregulation, may be favorably inpacted by CBG. Recent studies indicate CBG may provide promise as part of a multifactorial pharmacotherapy for metabolic syndrome and its components.
Hypertension, one component of metabolic syndrome, can be modestly reduced with a-2 agonist therapy, which reduces synaptic norepinephrine levels to reduce vasoconstriction and improve blood pressure. CBG is the only known cannabinoid that is an agonist at the adrenergic receptor and, additionally, CBG acts on PPARg receptors to reduce neuroinflammation (see below).
Cancer
A 2014 study evaluated colon cancer in rats, concluding that CBG might reduce the growth of cancer cells and other tumors.
Dosing of CBG
Very little is known about optimal dosing of CBG. In the US Pacific Northwest, CBG-predominant cannabis flower and extract have begun to increase in popularity among cannabis users. A 2021 study investigated the reasons for use and self-reported therapeutic effects of 127 cannabis users of CBG-predominant strains (containing >50% CBG). To establish context, none of the marijuana flower strains available at the LA dispensary pharmacies or the hemp flowers available at the CBD stores appear to have more than 2% CBG.
Most people (51.2%) reported use of CBG-predominant products solely for medical purposes, the most common conditions included anxiety (51.2%), chronic pain (40.9%), depression (33.1%), and insomnia/disturbed sleep (30.7%). Effectiveness was highly rated, with the majority reporting their conditions were “very much improved” or “much improved” by CBG.
Furthermore, most subjects reported greater effectiveness of CBG-predominant cannabis over conventional pharmacotherapy, with few side effects. Forty-four percent of CBG-predominant cannabis users reported no side effects, with 16.5% noting dry mouth, 15% sleepiness, 11.8% increased appetite, and 8.7% dry eyes.
Withdrawal symptoms were considered negligible, with 84% reporting no withdrawal symptoms, with sleep difficulties representing the most frequent withdrawal symptom (endorsed by only two respondents).
For some reason, the THC and CBD content of the strains which could significantly impact both benefits and side effects were not reported.
CBG Genetics
CBG, “The Mother All Cannabinoids,” is converted by the plant to the three cannabinoids: THC, CBD and CBC.
CBD and THC chemotype strains are controlled by a gene called B which has two forms (called alleles) BD which leads to the formation of CBD and BT which leads to the formation of THC chemotypes.
Therefore, plants with a high CBD content have dominant BD genes (BD/BD gene – both alleles are BD). Similarly, plants with a majority of THC have a BT/BT gene and plants with a similar ratio between THC and CBD have a BT/BD gene.
Plants with a predominant CBG character, on the other hand, have a defined allele B0 which causes a defect in the synthesis of other cannabinoids. In other words, for a cannabis plant to predominantly produce CBG, it needs to have genetically-based lack of enzymes that convert CBG to the other cannabinoids (CBD, THC, CBC).
Neurobiology of CBG
CBG research has suggested multiple mechanisms by which it may offer therapeutic benefits, but knowledge of CBG is in its infancy with little definitive clinical human research. Thus, much of what is “known” is very speculative.
The proposed mechanisms of CBG activity do not likely involve significant contribution from cannabinoid receptors CB1 or CB2, but possibly include GPR55 and/or modulation of PPARγ. CBG has also been shown to have in vitro activity at the α2 adrenoceptor, 5HT1A, and several transient receptor potential (TRP) channels.
Cannabinoid Receptors
In a 2020 study, CBG was found to be a weak partial agonist of both CB1 receptor (CB1R) and CB2 receptor (CB2R). Previous reports have similarly described CBG as a weak partial agonist of these two receptors, with low affinity for both. In vivo, CBG produced a small analgesic effect and an anxiolytic effect. The authors concluded however, it was possible their in vivo analgesic and anxiolytic effects may have occurred via cannabinoid receptor-independent mechanisms.
CBG has previously been reported to have disease-modifying anti-inflammatory effects in mouse models of Huntington’s disease, multiple sclerosis, Parkinson’s disease, and amyotrophic lateral sclerosis. These effects are likely mediated by PPARγ, and not cannabinoid receptors.
CBG is a highly potent agonist for α2-adrenoceptor which has significant implications for potential therapeutic uses and adverse side effects. The catecholamines neurotransmitters (dopamine, norepinephrine, and epinephrine) use different receptors to exert different physiologic effects. The main receptor families that mediate these effects are the adrenergic receptors [alpha (a-1 and a-2) and beta (b-1, b-2, and b-3) families] and the dopamine receptors (D1 through D5 receptors).
Current therapeutic applications of α2 agonists include sedative, analgesic and blood pressure reduction benefits. The prescription α2 agonist medications clonidine (Catapres) and lofexidine (Lucemyra) work by blocking the release of norepinephrine, a hormone/neurotransmitter similar to adrenaline that contributes to opioid withdrawal symptoms.
These α2 agonists are used in pain managament to reduce nerve pain, help insomnia and reduce opioid withdrawal symptoms. Because CBG is a potent α2 agonist it suggests that it may also be helpful for management of these conditions.
α2 agonists are also commonly prescribed for neuropsychiatric conditions because of their effects on a-2 receptors in the prefrontal cortex (PFC) of the brain. Modulating and improving impaired PFC functioning may benefit attention-deficit disorder (ADD), tic disorders, post-traumatic stress disorder and dementia.
The a-2 receptors, specifically 2A, are highly involved in norepinephrine signaling in the PFC, and α2 agonists are used to improve memory and planning abilities in ADD. In treating ADD, α2 agonists offer effective alternatives or adjuncts to the use of stimulant amphetamine medications. Use of a-2 agonists in conjunction with stimulant medications can reduce stimulant-induced tics and high blood pressure, along with allowing lower doses of the stimulants. As such, it has been suggested that CBG may be helpful for ADD.
Caution should be used with CBG since its a-2 agonist activity may unpredictably change blood pressure, cause sedation, or interact with other cardiovascular medications.
Serotonin 5-HT1A receptor Blocker
CBG acts as a blocker of the serotonin 5-HT1A receptor, which can result in decreased anxiety and muscle tension.
Serotonin, or 5-hydroxytryptamine (5-HT), is a neurotransmitter produced throughout the body with many physiologic and neurologic functions. It provides a balancing role in maintaining gastrointestinal functions (in the enteric gastrointestinal nervous system). In the central nervous system, serotonin plays an important role in anxiety and depression and is targeted by many anti-anxiety and antidepressant medications. Serotonin binds to different receptors but especially the 5-HT1A receptor, which interacts with CBG and other cannabinoids.
As a potent 5-HT1A antagonist, CBG may have significant but as yet unpredictable potentiating effects on concurrent use of selective serotonin reuptake inhibitors (SSRIs), including Paxil and Lexapro, commonly used to treat anxiety and depression.
Peroxisome Proliferator–Activated Receptors (PPAR)
The PPAR family consisting of three PPAR isoforms: PPARa, PPARb, and PPARg, a collection of nuclear receptor transcription factors. Transcription factors are proteins involved in the process of converting, or transcribing, DNA (genes) into RNA that in turn drives the cell’s manufacturing of proteins and other compounds that regulate fat metabolism, hepatic functions, insulin sensitivity and inflammation.
Many cannabinoids are reported to interact with the various PPAR isoforms and CBG exhibits stronger affinity to the PPARg receptor than THC and CBD. CBG and these receptors are being studied in the regulation of inflammation and metabolic functioning.
When associated with CBD, it has anti-inflammatory activity by reducing tumor necrosis factor (TNF) expression and upregulating Interleukin–10 (IL-10) and Interleukin–37 (IL-37) levels.
CBG also shows activity on TRP channels and CB1 receptors, as well as inhibiting AEA reuptake, suggesting possible benefits for pain
Additionally, CBG has shown anti-tumor activity in the colon by inhibiting transient receptor potential melastatin 8 (TRPM8) channels.
Resources:
National Academy of Sciences
This website appears to be good resource for exploring medical marijuana.
References:
Cannabinoids: CBG
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- Beneficial effect of the non-psychotropic plant cannabinoid cannabigerol on experimental inflammatory bowel disease – ScienceDirect -2013
- In vitro and in vivo pharmacological activity of minor cannabinoids isolated from Cannabis sativa – 2020
- Pharmacological data of cannabidiol- and cannabigerol-type phytocannabinoids acting on cannabinoid CB 1, CB 2 and CB 1_CB 2 heteromer receptors – PubMed – 2020
- Cannabigerol is a novel, well-tolerated appetite stimulant in pre-satiated rats – 2016
- Survey of Patients Employing Cannabigerol-Predominant Cannabis Preparations Perceived Medical Effects, Adverse Events, and Withdrawal Symptoms – PubMed – 2021
- Survey of Patients Employing Cannabigerol- Predominant Cannabis Preparations – Perceived Medical Effects, Adverse Events, and Withdrawal Symptoms – flyer
- Cannabigerol Is a Potential Therapeutic Agent in a Novel Combined Therapy for Glioblastoma – 2021
- In Vitro and Clinical Evaluation of Cannabigerol (CBG) Produced via Yeast Biosynthesis – A Cannabinoid with a Broad Range of Anti-Inflammatory and Skin Health-Boosting Properties – 2022
- The Pharmacological Case for Cannabigerol – 2021 Cannabigerol Action at Cannabinoid CB1 and CB2 Receptors and at CB1–CB2 Heteroreceptor Complexes – 2018
- Effect of Non-psychotropic Plant-derived Cannabinoids on Bladder Contractility: Focus on Cannabigerol. – PubMed – NCBI
- In Vitro Model of Neuroinflammation – Efficacy of Cannabigerol, a Non-Psychoactive Cannabinoid – 2018
CBG – Anxiety
Cannabinoids – Pain
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- Effects of Cannabinoid Administration for Pain – A Meta-Analysis and Meta-Regression – 2019
- Cannabis-based medicines and the perioperative physician – 2019
- Cannabis‐based medicines for chronic neuropathic pain in adults – 2018
- Cannabinoids in the Descending Pain Modulatory Circuit- Role in Inflammation – 2020
- Current Evidence of Cannabinoid-Based Analgesia Obtained in Preclinical and Human Experimental Settings – PubMed – 2018
- Role of Cannabinoids and Terpenes in Cannabis-Mediated Analgesia in Rats – PubMed – 2019
- Medicinal Properties of Cannabinoids, Terpenes, and Flavonoids in Cannabis, and Benefits in Migraine, Headache, and Pain – An Update on Current Evidence and Cannabis Science – 2018
- The Molecular Mechanisms That Underpin the Biological Benefits of Full-Spectrum Cannabis Extract in the Treatment of Neuropathic Pain and Inflammation – PubMed – 2020
- Cannabis sativa L. an
d Nonpsychoactive Cannabinoids – Their Chemistry and Role against Oxidative Stress, Inflammation, and Cancer – 2018 - Cannabinoid Delivery Systems for Pain and Inflammation Treatment – 2018
- Cannabinoid Formulations and Delivery Systems – Current and Future Options to Treat Pain – 2021
Cannabinoids: Tetrahydrocannabivarin (THCV):
Medical Marijuana – Misc Cannabinoids
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- Pharmacology of Cannabinoids
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- Myorelaxant Effect of Transdermal Cannabidiol Application in Patients with TMD – A Randomized, Double-Blind Trial – 2019
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- Practical Strategies Using Medical Cannabis to Reduce Harms Associated With Long Term Opioid Use in Chronic Pain – 2021
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Medical Marijuana – Product Evaluation
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- Quality Control of Traditional Cannabis Tinctures – Pattern, Markers, and Stability – 2016
- Cannabinoid, Terpene, and Heavy Metal Analysis of 29 Over-the-Counter Commercial Veterinary Hemp Supplements – 2020
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