The Science Behind cbd and CBG

CBD is a food supplement; it is not medication and we do not make medical claims. Our The Science page provides an in depth look at the current status of scientific literature as it relates to CBD and CBG.

Cannabinoids are classified into three categories: plant derived cannabinoids (phyto-cannabanoids), cannabinoids produced by the human body (endocannabinoids) and the man-made cannabinoids (synthetic cannabinoids). The CBD in our oils is a phyto-cannabinoid as it is extracted directly from organically grown hemp in Colorado, U.S.A.

The endocannabinoids system is present in our own bodies, it is distributed throughout most of the body and is involved in regulating many different bodily functions. Similar to the endocrine (hormone) or nervous system (NS) it can affect many parts of the bodies vital functions. It relies on a set of receptors that can be activated and or regulated by Cannabinoids. Activation of receptors can lead to varying effects based on where they are located in the body. For example, THC, the psychoactive cannabinoid, activates Cannabinoid receptor 1 in the brain, which causes the psychoactive effects. Whilst CBD and CBG do not cause any psychoactive effects, they do affect hormones, inflammation, the immune system, and oxidative stress. We will look closely at the interactions of CBD and CBG with the endocannabinoid system at a case-by-case basis of potential therapeutic application. There we will go into detail on how therapeutic effect is believed to be achieved based on the molecular targets of CBD and CBG.

Figure 1 showing the distribution of cannabinoid receptors (CB1,2,3R) in the human body. As the graphic shows the endocannabinoid system and its receptors are distributed throughout the body in many different tissues and cell types. This is why cannabinoids can exhibit such a myriad of effects.

Cannabinoids are those compounds which can act on cannabinoid receptors. The best-known cannabinoids are tetrahydrocannabinol (THC), Cannabidiol (CBD) and Cannabigerol (CBG) and there are many other cannabinoids produced by the Cannabis Sativa plant.

Cannabigerol (CBG) and Cannabidiol (CBD) are the two non-psychoactive cannabinoids believed to hold the greatest potential for therapeutic application.

The following applications are mentioned in the current scientific literature:

Cannabidiol – CBDCannabigerol – CBG


CBD has strong anti-epileptic effects as has been demonstrated in various clinical trials. Case examples such as that of Charlotte Figi.

The FDA has approved several anti-epileptics based on CBD.[1-5, 82]


There is not yet significant evidence for CBG action in Epilepsy, due to a lack of research.[6]

Skin Conditions

CBD is in clinical trials for the treatment of acne and psoriasis based on its anti-inflammatory and immunosuppressive effects.[7-9]

Skin Conditions

CBG has been demonstrated to help with some skin conditions, such as psoriasis, by regulating skin cell growth.[10-13]


CBD has been demonstrated to have strong anti-bacterial effects both in vitro and in vivo testing.

The effects have been found comparable to known antibiotics.[14]


CBG has been demonstrated to have strong anti-bacterial effects both in vitro testing and in mouse models. CBG appears to be a stronger antibacterial than some reserve antibiotics.[15-17]

Cancer – Chemotherapy

CBD has been demonstrated to reduce the need to vomit and reduce the pain of those going through chemotherapy.[18]

Cancer – Chemotherapy

CBG has been demonstrated to reduce weight loss when accompanying chemotherapy by increasing appetite.[19]


CBD is believed to help in inflammatory neurological diseases such as Multiple Sclerosis, Alzheimer’s and Parkinson’s as well in acute inflammation due to brain injury.[20]


CBG is believed to function as a neuroprotector by reducing inflammation and oxidative stress.



CBD has been demonstrated to act on a receptor responsible for pain sensation, reducing its activity. This the basis for the pain relieving effects of CBD.[21]


CBG is believed to interact with common analgesic targets that relieve pain, it follows that it might be used for pain relief.


CBD is known for its calming anxiolytic properties. In studies CBD has been demonstrated to reduce stress and relieve anxiousness.[22]


CBG has been demonstrated to have similar molecular action to antidepressants, leading to possible applications as an antidepressant.


Through a strong immunosuppressive and anti-inflammatory action CBD exhibits a potent antiarthritic effect.[9]


CBG has been demonstrated to be an antioxidant, preventing damage to cells and DNA, this might reduce the risk of cancer and slow aging.[20]


Several studies have demonstrated antipsychotic effects in human trials.[23]


CBG has been theorized to have similar action to thiazolidinediones which heighten insulin sensitivity and reduce levels of blood sugar.


CBD has been demonstrated to decrease the production of skin oils and thus significantly helps reduce the development of acne.[11]

Dry skin

CBG has been demonstrated to increase the production of skin oils, thereby reducing the dryness of the skin.[10-12]


CBD is believed to reduce the inflammation and excessive skin cell growth associated with psoriatic symptoms.[7-9, 24, 25]


CBG has been demonstrated to decrease skin cell growth and act as an antibiotic reducing itching and probability of bacterial infection.[7, 8, 26, 27]

Due to the lack of large-scale double-blind studies, many of these effects are based on evidence in animals (in vivo) and in vitro testing (laboratory tests) of specific interactions. The data from studies demonstrating interactions between specific receptors and cannabinoids is used to form hypothesis based on the properties and interactions of the receptor. These theoretical effects do not always translate into effects in individual organisms or might vary based on the genetic differences between individual organisms.

Although cannabinoids may interact with medications in Drug-Drug-Interactions, Cannabidiol (CBD) and cannabigerol (CBG) seem to have a low to medium impact, for further detail read the section on DDIs below.

Cannabinoids can also affect human reproduction, both sexes are advised against using any non-medically prescribed medication or supplements without professional consultation, especially during pregnancy. More information about the interaction of cannabinoids with human reproduction can be found below

The Endocannabinoid System, (eCS) CBD and CBG

The Endocannabinoid System

The two major systems governing bodily functions are the nerve system – comprised of the Central Nervous System (CNS) and the Peripheral Nervous System (PNS) – and the “hormone” or Endocrine system (ES). Both systems interact with each other and the endocannabinoid system. The endocannabinoid system is a vital modulator of as many functions as the nervous system and the endocrine system and is heavily involved in the function of both. The endocannabinoid system has been found to play a key role in the regulation of: mood, memory, brain reward systems, drug addiction and metabolic processes such as glycogen and lipid metabolisms, insulin sensitivity, nociception (pain arising from activation of nociceptors) and modulation of inflammatory response. [28]

As explained above; cannabinoids   are classified into three groups: Endocannabinoids, cannabinoids naturally produced by our bodies, Phyto-cannabinoids which are produced by plants, and lastly synthetic cannabinoids, all three are able to interact with the nervous system and the endocannabinoid system.[28] Cannabinoids are mostly classified based on their interaction with the two primary receptors for cannabinoids, therefore there is no molecular feature that constitutes a cannabinoid, the distinction by provenance is mostly arbitrary. [29, 30]

The basis for most of the actions of CBD and CBG is the endocannabinoid system. The endocannabinoid system is present in nearly all animals and all mammals [31]. It consists of mainly two cannabinoid receptors: cannabinoid receptor 1 and 2 (CB1R & CB2R) and their agonists, antagonists and other modulating factors.[30, 32]

Cannabinoid receptors were first identified based on their interaction with the psychoactive phyto-cannabinoid, Δ9-tetrahydrocannabinol (THC) after it was first isolated by Prof. Mechoulam. [29, 33] Now, further interactions are being considered. The endocannabinoid system remains still mostly unexplored, the exact interactions between the many identified endocannabinoids with receptors CB1R and CB2R are not yet well defined.[34] There is a wide array of G-protein coupled receptors and Transient receptors that are likely to interact with endocannabinoids however these interactions are not yet well understood.[34] Additionally there are many other cannabinoid receptors yet to be researched. A putative candidate for receptor CB3R is the transient receptor potential vanilloid 1 (TRPV1), this receptor is involved in pain perception (nociception) and also known as the capsaicin receptor (capsaicinoids are responsible for painfully spicy foods). [35, 36]

The two most discussed endocannabinoids are (N-arachidonoylethanolamine) named Anandamide by Prof. Dr. Mechoulam et al. and 2-Arachidonylgylcerol (2-AG) the latter being the most abundant endocannabinoid in the brain. [37-40]

The Endocannabinoid System

CB1R and CB2R are  G-protein coupled receptors (GPCRs).[32] This means that the cannabinoid receptors are presented on the surface of the cell membrane and they mostly pass on their signal to inhibitory G-proteins ( Gi/o). Generally these pathways inhibit adenylyl cyclase and some voltage-gated calcium channels as well as stimulate mitogen-activated protein Kinases(collective term for a group of enzymes that can attach a phosphate group to another protein or molecule), inwardly rectifying potassium channels and recruit β-arrestins.[41] Cannabinoid receptors display functional selectivity based on different ligands, activating different signalling pathways based on the specific interactions with that ligand.[42, 43]  Cannabinoid receptors are also able to heterodimerize with other G-protein coupled receptors such as dopamine D2, hypocretin and opioid receptors.[43]

These are just some of the reasons the endocannabinoids can have such a variety of effects, another is that there are many unaccounted-for interactions of endocannabinoids with other receptors that may increase or decrease their activities in a concentration dependent or independent manner.

CB1Rs are the most abundant G-protein receptors in the mammalian brain, present predominantly in the hippocampus and associational cortical regions, the cerebellum and the basal ganglia.[44] In contrast they are only present at very low levels in the brain stem, medulla and thalamus. This distribution accounts for the lack of mortality at high doses of cannabinoids, as they do not depress vital functions such as breathing, literature speaks of “unlimited” therapeutic dose potential. [36] CB1Rs mediate the psychedelic and mood altering affects often experienced by those consuming THC. They dose dependently  and stereoselectivity inhibit the adenylate cyclase affecting memory, perception and motor control and can regulate neurotransmission through retrograde signalling.[34] CB1Rs are mainly expressed on the axonal terminals of GABAergic neurons which facilitates their retrograde anti-inhibitory action.[45]

CB2R is structurally similar to CB1Rs but is different in function and distribution of expression throughout the body. CB2Rs are mostly found on immune cells, neurons, peripheral tissues, hematopoietic cells and recently in also in the brain stem.[45] CB2Rs are found to have an opposing effect to CB1Rs, reducing post synaptic excitability, being more highly expressed on the post synaptic cell body.[45] CB2Rs are highly inducible, which means that their low level of expression in the brain can quickly be upregulated in cases of addiction, anxiety or inflammation.


Figure 1 showing Cannabidiol (CBD) on the left and Cannabigerol (CBG) on the right.

CBD and CBG  are the two non-psychoactive phyto-cannabanoids (plant derived) naturally produced in the cannabis sativa plant which have shown the highest potential for therapeutic effect in recent scientific literature. CBD, CBG and other cannabinoids are synthesized by plants in their carboxylic acid forms CBDa and CBGa, which are then decarboxylated in the extraction and refinement process. For a detailed review of the production process of CBD and CBG see our production page. The CBGa and CBDa have significantly different properties from their decarboxylated states.[46] Taking a short overview over the properties of CBD and CBG in the human body we can generalize the effects as follows:
  • CBD is primarily associated with anti-inflammatory, anxiolytianti-epileptic and neuroprotective effects.
  • CBG is primarily associated with anti-inflammatory, anti-bacterial, oxidative stress reducing effects.

The Entourage Effect

The Entourage effect is the stipulation that the efficacy of cannabinoid action can be enhanced by other accompanying cannabinoids and other molecules. This effect might relate to allosteric modulation of the receptors of the endocannabinoid system and interaction with various synthesis and expression control pathways affecting the endocannabinoid system.

We label our products full spectrum to indicate that there is not only a range of phyto-cannabanoids present in the hemp oil which is extracted from the seeds of the cannabis sativa plant but also many other aromatics, terpenes, terpenoids, ketones, ketides, isoprenoids, polyunsaturated fatty acids, vitamins, and proteins which support the action of the main component CBD and CBG.

As described by Citti, Linciano [47] there are over 32 cannabinoids present in industrial hemp oil, as verified by High Resolution Mass Spectrometry coupled with a liquid chromatography method.

The composition of hemp oil has been characterized in the Journal of Nutraceuticals [48], finding the following compositions in the various industrial hemp oils they tested:

Fatty acids % content w/w
Linoleic Acid (18:2ω6) 52-62
α-Linolenic Acid (18:3ω3) 12-23
Oleic Acid (18:1ω9) 8-13
Palmitic Acid (16:0) 5-7
Stearic Acid (18:0) 1-2
γ-Linolenic Acid (18:3ω6) 2-4
Eicosanoic Acid (20:0) 0.39-0.79
Eicosanoic Acid (20:1) 0.51
Natural Products w/w or w/L
Cannabidiol 10 mg/kg
Δ9-tetrahydrocannabinol nd
Myrcene 160 mg/L
β -Caryophyllene 740 mg/L
β-Sitosterol 100-148 g/L
γ-Tocopherol 468 mg/L

Even though many cannabinoids are present in very low quantities they impact the effect of any other cannabinoids they are combined with because the receptors and other interaction cellular proteins for these compounds show very high affinities and are affected even by the smallest amounts.

Pharmacological basis of possible therapeutic applications:

Recognizing that not enough research has been conducted to map the full range of effects induced by CBD and CBG, we present the current therapeutic applications which are often referred to within the field of cannabinoid research. We will present on which mechanism or empirical findings the therapeutic potential is based.


Epilepsy encompasses a range of neurological disorders which lead to recurring spontaneous epileptic seizures. These seizures can be severely detrimental to the quality of life of the affected person. Epilepsy is either present since birth or acquired through inflammation, trauma, or infection. Such seizures can be devastating in children. As such assessing the efficacy of cannabinoids in the treatment of these disorders has a high priority.

The popularization of the treatment of epilepsy with CBD followed the case of Charlotte Figi a young girl with Dravet syndrome. She did not respond to traditional anti-epileptics, but treatment with high doses of CBD resulted in a reduction from 300 seizures per week to just 2 or 3 per month.

In two forms of epilepsy, Dravet Syndrome and Lennox Gastaut, CBD has been proven to significantly reduced the frequency of seizures. A 2017 and a 2018 double blind study found that treatment with CBD at 20 mg/kg decreased the frequency of seizures by a factor of 2.1.

Cannabidiol (sold as Epidiolex) is currently approved and indicated for Lennox-Gastaut and Dravet syndrome by the FDA and multiple clinical trials have proven its effectiveness.[3-5]

Due to a lacking body of evidence the efficacy of cannabigerol (CBG) as a potential Therapeutic in Epilepsy is unknown.[6]


Both in vitro and in vivo studies have examined the effects of cannabinoids on bacteria. Promising results have been attained in testing CBD and CBG against antibiotic resistant strains. This opens up the possibility of clinical CBD and CBG application in the field of novel antibiotics.

CBD was found to have significant bactericide action in four dangerous pathogens Neisseria gonorrhoeae (MIC 1–2 μg mL−1) responsible for the sexually transmitted disease gonorrhoea, Neisseria meningitides (MIC 0.25 μg mL−1) responsible for meningitis, Moraxella catarrhalis (MIC 1 μg mL−1) responsible for airway infections and Legionella pneumophila (MIC 1 μg mL−1) responsible for legionnaires disease.[14] However the in vivo activity of CBD could be much lower than the in vitro case as CBD exhibits a very high degree of protein binding in serum assays ( >94%). This might limit the applicability in vivo, as mentioned in the FDA filings for Epidiolex a 100 mg/ml CBD.

CBG is found to be one of the most potent cannabinoids tested against antibiotic resistant strains of staphylococcus aureus. CBG has a lower minimum inhibitory dose than norfloxacin and is more potent than several conventional antibiotics (tetracycline, erythromycin and oxacillin). [15] CBG was found to be more effective at reducing colony forming units (CFUs) than the very potent reserve antibiotic vancomycin, in a systemic S. aureus infection model in mice. However it also showed that CBG was only effective against gram-negative bacteria when their outer membrane was permeabilized. [16] According to in silico modelling (a computer simulated experiment) of interactions, CBG acts as a micromolar inhibitor of the enoyl acyl carrier protein reductase, leading to the inhibition of a vital metabolic pathway.[17]

Skin diseases

Cannabinoids such as CBD and CBG are being examined at an increasing rate for their potential use as a treatment for various skin diseases. Since CBD and CBG modulate inflammation and immune infiltration researchers see significant potential in using CBD and CBG to treat inflammation-based diseases. Several CBD containing formulations are currently in clinical trials for the application on psoriasis and acne.

Acne can have different causes ranging from psychological stress and diet to genetic predisposition. One of the core issues in acne is the overproduction of sebaceous fluid by sebaceous cells. Thus, the effects of CBD and CBG were examined in vitro and ex vivo in a skin model. CBG was excluded as a viable candidate for acne therapy because it increased sebaceous fluid (sebum) production and lipid synthesis. CBD on the other hand proved promising as it reduced lipid synthesis and the production of sebum.[11]

This leads to the Conclusion that CBD might be useful in cases of acne, and CBG in cases of dry skin as it increases oil production.

Psoriasis is an immune mediated inflammatory disease usually presenting as irregular, itchy, discoloured and inflamed patches of skin. [24] Psoriasis affects (1-3%) of the population and is distributed equally amongst the sexes.[25]

Psoriasis is a complex disease with many factors, two of which, keratinocyte hyperproliferation and dysfunctional differentiation, and chronic inflammation, are modulated by cannabinoids.[8, 26]

Keratinocyte proliferation has been shown to be inhibited by CBD and CBG.[7, 27]

CBD has been shown to have anti-inflammatory and immune modulating effects, leading to a decrease in chronic inflammation in the psoriatic plaques, possibly reducing the irritation and discomfort. CBD inhibits several cytokines which are implicated in the T-cell path mechanism of psoriasis.[7, 8] CBD has also been shown to reduce oxidative stress and NETosis in psoriasis patients.[49] Arthritic inflammation has also been shown to be decreased by CBD trans dermally in animal models. This might be relevant since up to a third of psoriasis patients can develop psoriatic arthritis.[9]

Another factor of psoriasis are patches of dry skin with increased sensitivity and reduced protection from infections. As discussed above CBG increases sebum production. This might make CBG suitable for decreasing the dryness of said skin patches.[10, 11] The decrease in dryness and increase in oils might help to restore some of the skins barrier function, increase moisturization and decrease the risk of infection.[12, 13]

Additionally there is evidence that an increase in bacteria in the microbiome of the psoriatic plaque is implicated in irregular inflammatory response, reducing the number of bacteria on the plaque may be a further additional avenue to eliminate a mediator of inflammation.[8] Since CBG and CBD have  shown strong antibacterial effects they might mediate the reduction of bacteria in the microbiome.[14, 16, 17]

To summarize, there are several ways in which CBD and CBG might be used in therapeutic applications in acne and psoriasis amongst other skin diseases.

Chronic Pain management

Chronic pain as opposed to acute pain often serves no real function and causes many detrimental effects in physical and psychological wellbeing as well as in socio-economic status. The effect of pain reduction is referred to as analgesic. CBD as it interacts with several nociception related receptors like TRPV-1, CB1R and CB2R the latter two are however disputed, which is the basis for its analgesic effects. In a multitude of small trials CBD was found to be moderately effective at reducing or eliminating chronic pain in individuals. [50, 51]

A very convincing model for testing the effect CBD has on chronic pain is the mouse model with partial sciatic nerve ligation employed by Abraham et al. They showed that the analgesic effect of CBD at a near constant dose is comparable, although lower, to the effect of morphine in first application, and even outperforms morphine in analgesic effect after 7 days.[21] This suggests that there is little increase in drug tolerance for CBD in comparison to morphine, which shows a significant reduction of efficacy after 7 days.[21]

Most interestingly it was found that long term regular intake of CBD lowered the levels of hepatic cytochrome P450 by 40% and intestinal P-glycoprotein by 49%, which may lead to increased bioavailability of CBD, suggesting that long term application of CBD is more efficacious than short acute exposures. This coincides with the data from Abraham et al..[21, 52]

Furthermore, in a recent review of the literature surrounding cannabinoid application as a therapeutic for chronic pain the administration in patients with back pain was examined. The review found that several studies reported a significant reduction of pain. [53]

To conclude, it is clear from the literature that there is therapeutic potential for CBD in chronic pain.


An anxiousness reducing effect has been reported in several studies, the application of which could provide a great benefit to those suffering from anxiety. The ability to relief emotional distress without the significant side effects that most psychopharmaceutics have would be of great benefit.

In a double-blind placebo controlled study on the effect of CBD on anxiety in the Test of Public Speaking in a Real Situation (TPSRS) it was found that CBD significantly reduced anxiety.[22] The anxiolytic effect was dose dependant reaching its maximum at 300 mg and falling off rapidly with dose increase or decrease.[22, 54]

These studies indicate that through further research the therapeutic effect can be more rigorously defined and translated into clinical application.


Attention-deficit/hyperactivity disorder (ADHD) is first recognized in children. The disorder continues to affect most of the afflicted throughout their lives presenting them with challenges in their daily life. These challenges range from emotional, to educational and professional aspects. ADHD is also associated with a range of comorbidities and patients are likely to have other psychological disorders.[55]

A recent study on CBD in Autism Spectrum Disorder (ASD), which shares symptoms such as inability to concentrate, emotional instability and hyperactivity with ADHD, demonstrated a significant improvement in the subjects.[56]

Sleep deprivation

Sleep deprivation is a serious issue leading to many secondary outcomes that are detrimental to the health of the afflicted and has further reaching consequences in terms of economic productivity and quality of life.

CBD has been shown to significantly increase the duration of sleep in patients with insomnia at an oral dose of 160 mg/day.[57] Recently a study examining CBD application in Parkinson’s patients showed that CBD was able to help in sleep disorders with a high response rate.[58]


Psychosis is a disorder that results in a alienation from reality, where patients can no longer distinguish what is real and what is not.[59] This results in heavy impairments to the patients ability to lead a normal and healthy life.

In a double blind placebo controlled trial of CBD in artificially (NMDA-R antagonist ketamine) induced psychosis, it was found that CBD (600 mg) induced  a modest trend towards the reduction of depersonalization..[23] However it might be the case that this high dose of CBD is responsible for a lack of significant effect, as noted in papers on the anxiolytic effect, the efficacy of CBD is severely reduced at high and low doses peaking between (250 mg – 350 mg).[22]

In psychosis in Parkinson’s disease it was found that CBD significantly reduced psychosis and was safe and well tolerated by patients.[60] The same study found that there was a small improvement in motor activity and no negative effects on cognition.[60]

Appetite promotion (CBG) and reduction (CBD)

Many diseases and therapies such as cis-platin chemotherapy or AIDS have strong effects on the appetite of the patients. Making sure that the patients consume adequate amounts of nutrition is vital to the clinical outcome. The modulation of appetite might also be relevant outside of clinical application in those wishing to change body composition.

The administration of CBG was shown to slightly increase the amount of food consumed in mice at a dose of (17.6 mg/kg).[19] A later study with higher dosing (120 mg – 240 mg) found that CBG intake was responsible for a doubling in food consumption in pre-satiated rats, with increases in meal frequency, reduced latency to feed and no changes in duration or volume of individual meals.[61] These effects on feeding were found without detrimental side-effects on muscular health, cognition or alertness.[61]

In contrast to CBG, CBD has been shown to significantly decrease feeding in mice at a dose of (4.4 mg/kg). [19] Thus CBD and CBG are opposite in their effects on feeding patterns. This finding indicates that both can be applied for a modulating effect on feeding.


Post-Traumatic Stress Disorder (PTSD) is a serious disorder with a large impact on the patients’ lives. Given the prevalence of PTSD through war, accidents, crimes, and psychological abuse, a widely available therapeutic with minimal side effects is very desirable.

PTSD has no well-defined pathophysiology, however the application of CBD in PTSD patients is believed to interact with the dysregulated memory retrieval.[62, 63] Based on rat models where the effect on CBD on fear extinction was examined with inhibitors of CB1R it was found that CB1R is involved in the fear extinction effect.[64]

 A recent study suggests that CBD might be an effective therapeutic for PTSD, reducing recall of traumatic memories and reducing response to triggers.[65]

Studies in a fear conditioned model have shown better data towards the fear conditioning extinction. These Studies showed varying levels of fear extinction more traumatic conditioning seemed to be more affected by CBD, seemingly stronger trauma was more successfully extinguished than weaker trauma.[64, 66, 67] Fear extinction is defined as a lessening of conditioned fear responses following extinction training, during which subjects are exposed to repetitive presentations of conditioned stimuli (CS) alone.[68-70]


The potential use of CBD as a neuroprotectant lies in its anti-inflammatory and anti-oxidative properties. Many neurodegenerative disorders such as Multiple Sclerosis (MS), Alzheimer’s and Parkinson’s Disease are at least in part mediated by neuroinflammation. [71]

In vitro neuronal cell models on H2O2 and rotenone (mitochondrial dysfunction) have shown that CBD and CBG are effective at protecting the neurons from peroxide and rotenone neurotoxicity.[20] In the rotenone model of neurotoxicity CBG was found to implicate the 5-HT1A receptor in its mechanism of action.[20] The same authors found in yet unpublished data that CBG and CBD exhibited a mechanism of neuroprotection which was not directly based on their role as an anti-oxidant, because a strong antioxidant, quercetin, could not replicate the neuroprotection from the rotenone model which CBD and CBG achieved. [20]They claim that CBD and CBG interfere with the mechanisms of cell death associated with rotenone damage.[20]

CBD and CBG have been shown to readily cross the blood brain barrier. This explains anti-inflammatory effects on cells within the brain, such as downregulating the release of cytokines, reducing activity of microglia, and thereby reducing the cytotoxic effects of hyperactive microglia as seen in neuroinflammation. This coincides with the observed protective effect on the blood brain barrier following inflammation and injury. [72-74] The reduction of immune response in the brain causes less degradation of the blood brain barrier so that Natural Killer cells, dendritic cells, CD8+/CD4+ T-cells and antibody producing B-cells do not cross the blood brain barrier and cause additional damage to the inflamed area and do not perpetuate a vicious inflammatory cycle.

There exists a large body of evidence for the neuroprotective effects of CBD and CBG.

Cannabinoids and Reproduction

It is unadvisable to consume any cannabinoids before the period of conception and during breastfeeding.

CB1R and CB2R as well as endocannabinoids have been found to be present in oocytes, uterus, oviduct, follicular fluids, ovarian medulla and cortex with studies suggesting effects on hormone regulation and follicle maturation. [75] The presence and interplay between the male reproductive system and cannabinoids has also been noted.[15, 76, 77]It is therefore clear that there is significant interaction between the endocannabinoid system and the reproductive system, the exact interaction of cannabinoids have not yet been clearly defined and more research is needed to define the exact role of the endocannabinoid system in the female and male reproductive system.[75]

Interaction of Cannabinoids with Medications

Cannabinoids are metabolized through the liver as are most medications. Many medications rely on the transformation in the liver by various enzymes for activation. Medications may also need to be broken down and deactivated in the liver to prevent toxic effects or ensure correct dosing. The oxidation based metabolic prosses are mediated by a group of enzymes called Cytochrome P450 superfamily (CYPs) containing a Haem group that acts as a oxidation catalyst with its complexed iron (III). Interaction with CYPs account for 70-80% of Drug Drug Interactions (DDIs) which is why inhibition of these enzymes needs to be taken into account when taking medications with narrow therapeutic ranges (little margin between therapeutic and toxic effect).[78, 79]

Each molecule will interact differently with the different isoforms of the CYP family, with some CYPs more significant in drug metabolisms than others the exact isoforms affected by CBD and CBG are important to considerations about DDIs. Predominant isoforms relevant in drug metabolism are: CYP3A4 (30%), CYP2D6 (20%), CYP2C9 (13%), CYP1A2 ( 9%), CYP2B6 ( 7%), CYP2C19 ( 7%), CYP2C8 (5%), CYP2A6 ( 4%), CYP2E1 ( 3%) CYP2J2 ( 3%).

% of Drug Metabolism CYP isoform Action of CBD Action of CBG
30.2 CYP3A4 Partial inhibition of Triazolam metabolism non
12.8 CYP2C9 non Inhibition of tolbutamide metabolism similar to positive control sulfaphenazole
8.9 CYP1A2 non Minimal inhibition of caffeine metabolism
7.2 CYP2B6 Partial inhibition of bupropion metabolism non
6.8 CYP2C19 Partial inhibition of (S)-mephenytoin Minimal inhibition of (S)-mephenytoin

The pharmacokinetics of opioids are mostly unaffected by CBD and CBG as the main metabolizers of opioids (CYP3A4/5 ,CYP2D6, CYP2B6 and CYPC19) are not significantly impaired by CBD and CBG.[79] Although some alteration of pharmacodynamics has been noted and additional research is needed to define the exact interactions between opioids and cannabinoids.[80]

Some antidepressants may be affected by their metabolism’s inhibition by cannabinoids, however the most prevalent isoforms (CYP3A4, CYP1A2, CYP2D6 and CYPC19) in antidepressant metabolisms are not significantly inhibited by CBD and CBG.[80] Both Fluoxetine and CBD affect serotonin, one by inhibiting reuptake, leaving more in nerve synapses, the other (CBD) by producing serotonin at higher concentrations. Theoretically, both agents enhance each other’s effect, and the combined use is only recommended under the supervision of a specialized physician or pharmacist.

For a table overview of potential interactions regarding pain and anti-depressant medications see:

The strong inhibition of CYP2C9 by CBG could affect a wide range of important drugs, because CYP2C9 is responsible for metabolizing 15-20% of drugs undergoing phase I metabolization. DDIs can be expected with the anticoagulant warfarin, the diabetic drugs based on sulfonylurea (K+-Blockers), NSAIDs for pain, statins for blood cholesterol, arbs for blood pressure, and specific antiepileptic and chemotherapeutic agents.[81] Further research needs to be conducted and the array of affects that CYP2C9 inhibition has on the pharmacokinetics and pharmacodynamics of the various drugs that it metabolizes physiologically.

Concluding the short overview of relevant CBD and CBG DDIs, it has been shown that CBD and CBG can have a significant effect on specific drug metabolisms affecting up to 65.9% of enzymes involved in drug metabolisms. However, the most important inhibitions might be partial CYP2C19 inhibition by CBD and CBG, and significant CYP2C9 inhibition by CBG which only account for 19.6% of drug metabolizations.

This is not a complete list of interactions, merely an indication that there are potential DDIs with respect to CBD and CBG and that they need to be studied in further detail. It is unlikely that there will be any very severe DDIs with regard to CBD and CBG. In the meantime, if you are taking any of the mentioned classes of drugs consult your pharmacist or physician before taking supplements.


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