Corona Virus: Potential Use of Cannabinoids to Treat Acute Respiratory Distress Syndrome and Cytokine Storm Associated with Coronavirus Disease. HERE

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C.B 2 R.A 30x Cannabinoid Oil is a powerful, non psychoactive, all natural, plant based herbal extract, that targets the C.B 2 Cannabinoid Receptors, & may provide a legal alternative to 'Prescription Only' Cannabidiol (C.B.D) preparations, such as Tilray, Elixinol & Sativex.

There are many commercially available Cannabis preparations rich in β-caryophyllene (BCP), including: Bedrocan®, Sativex®, Marinol®, Bedrobinol®, Namisol®, Arvisol®, Fenoxidol™, Epidiolex® etc. Hebaallah Mamdouh Hashiesh et al, 2021

beta Caryophyllene (BCP) is a major component in Cannabis & some non Cannabis plants, & is classified as a dietary cannabinoid.

BCP, & its status as a dietary Cannabinoid, DOES NOT have the Legal & Licensing restrictions of Cannabis.

At present, the only phytocannabinoid that has been discovered to also exist in plants other than Cannabis is beta Caryophyllene (BCP). Gertsch et al, 2010.

The phytocannabinoid BCP (beta Caryophyllene) has been identified as a fully selective agonist of CB2 cannabinoid receptors, one of the key members of the endocannabinoid system (ECS). Scandiffio et al 2020.

β-caryophyllene (BCP) activity on human CB2 Cannabinoid Receptors, has a binding affinity (pKi) value of 155 nM with a lack of substantial affinity for CB1R. Hashiesh et al 2021.

To compare CB2R binding, β-Caryophyllene has the highest CB2 cannabinoid activity. Cannabinol (CBN) binds to the CB2 receptors as a partial agonist with a binding affinity of CB2 Ki at 126.4 nM^[9] while Delta-9-Tetrahydrocannabinol (THC) binds to the CB2 receptors as a partial agonist with an affinity of Ki at 36nM.^[10]

See Link: Strain Profile White Widow Cannabis (Tilray)
See Link: Terpene Profile Caryophyllene (Tilray)

The phytocannabinoid caryophyllene, also known as beta-caryophyllene or BCP, is crucial to not only the smell and taste of Cannabis, but also the medical benefits and different effects strains provide. There are over 100 known cannabinoids & terpenoids in the cannabis plant, but BCP is one of the most prominent.

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BCP is a major constituent in Cannabis essential oil and shows significant cannabimimetic effects, it may also contribute to the overall effect of Cannabis preparations, including Sativex. Gertsch et al, 2008.

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Cannabinoid type 2 receptor (CB2R)-mediated pharmacological activities and therapeutic potential of β-caryophyllene (BCP):

The Cannabinoid BCP beta Caryophyllene, an attractive compound for chronic pain (both inflammatory and neurogenic)

The Cannabinoid BCP beta Caryophyllene is an attractive compound for chronic pain (both inflammatory and neurogenic) due to its direct action on CB2R without creating a tolerance, as demonstrated in an animal model of neuropathic pain [30].

Remarkably, the researchers concluded that the effect of BCP became stronger during the treatment period.

This is significant considering drug tolerance after prolonged use is observed with other analgesic therapies and may require increased dosage, which may accelerate tolerance and further reduce the effects of a therapeutic substance.

BCP exerts potent anti-inflammatory effects when taken orally, which may be explained by its ability to simultaneously inhibit pathways (toll-like receptor complex CD14/TLR4/MD2) that increase the production of proinflammatory cytokines (IL-1β, IL-6, IL-8, and TNF-⍺), reduce immune-related inflammation, and synergize the µ-opioid receptor pathways.

Preclinical models demonstrate that BCP can reduce inflammation in a variety of bacterial-caused, eosinophil-related, and neuropathic inflammatory conditions [32].

It can also enhance the effects of other pain medications like morphine, making it a promising candidate to reduce effective drug dose and therefore potential drug dependence and tolerance.

In this way, it modulates pain signaling pathways in a manner that may enhance, and not compete with, the benefits of other pain-or inflammation-relieving substances. Scott A. Johnson et al, 2020.

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Research Links:

See: Beta-caryophyllene is a dietary cannabinoid.

" (E)-BCP is the first Cannabis-derived functional CB receptor ligand with a fundamentally different structure from the classical cannabinoids. Thus, it represents a new type of CB2 receptor-selective agonist that is based on an unusual cyclobutane-containing scaffold.

" BCP is a major constituent in Cannabis essential oil and shows significant cannabimimetic effects, it may also contribute to the overall effect of Cannabis preparations, including Sativex. "

See: Phytocannabinoids beyond the Cannabis plant.

' At present, the only phytocannabinoid that has been discovered to also exist in plants other than Cannabis is b-caryophyllene (BCP), which is among the most abundant plant essential oil components......

b-caryophyllene, (BCP) which is also one of the most abundant secondary metabolites in Cannabis essential oil, could be considered as a true CB2 receptor-selective Cannabis constituent.'

See: Cannabimimetic phytochemicals in the diet – an evolutionary link to food selection and metabolic stress adaptation?

' The best studied phytochemical is β‐caryophyllene (BCP), which has been independently shown to exert numerous CB₂receptor‐mediated cannabimimetic effects......'

See: β -caryophyllene and β -caryophyllene oxide - natural compounds of anticancer and analgesic properties.

" BCP is a phytocannabinoid with strong affinity to cannabinoid receptor type 2 (CB2 ) but not cannabinoid receptor type 1 (CB1 ). ...the double activity of BCP, anticancer and analgesic, as well as its beneficial influence on the efficacy of classical chemotherapeutics, is particularly valuable in oncology. "

*Full version pdf HERE

See: Cannabinoids Induce Apoptosis of Pancreatic Tumor Cells via Endoplasmic Reticulum Stress–Related Genes.

" Although the pancreatic tumor biopsies and cell lines analyzed expressed both CB₁ and CB₂ cannabinoid receptors, our findings indicate that the CB₂ receptor is the one that plays a major role in the proapoptotic effect of cannabinoids in these cells."

See: Protective Effects of (E)-β-Caryophyllene (BCP) in Chronic Inflammation

" The sesquiterpene hydrocarbon (E)-β-caryophyllene (BCP) is one of the most studied and promising natural compounds In recent years, modulatory and pharmacological effects of BCP have been demonstrated in numerous organs such as liver kidney and brain. BCP has been reported to exert therapeutic effects as antioxidant, anti-inflammatory and anticancer. Importantly, BCP has been identified as a fully selective agonist of CB2 cannabinoid receptors, one of the key members of the endocannabinoid system (ECS)."

See: Beta-caryophyllene a CB2 receptor agonist, produces multiple behavioural changes relevant to anxiety & depression.

" preclinical results suggest that CB2 receptors may provide alternative therapeutic targets for the treatment of anxiety and depression. The possibility that BCP may ameliorate the symptoms of these mood disorders offers exciting prospects for future studies. "

See: β-Caryophyllene, a CB2 Receptor-Selective Phytocannabinoid, Suppresses Motor Paralysis and Neuroinflammation in a Murine Model of Multiple Sclerosis

" (this) study represents significant implications for clinical research and strongly supports the effectiveness of BCP as a novel molecule to target in the development of effective therapeutic agents for MS. "

See: New insights in the antitumor effects of β-caryophyllene in breast cancer cells: The role of cannabinoid and adrenergic systems

" Caryophyllene (CRY) was found able to significantly inhibit the growth of MDA-MB-468 cells..... Data obtained highlight antiproliferative properties of Caryophyllene (CRY) in triple negative breast cancer, with a possible β2-adrenergic system contribution.

CRY acts partly by a CB2- activation, although other CB1/CB2 independent mechanisms appear involved. CRY also interferes with smoking-induced progression and metastatization of breast cancer cells: this effect can be approached as a chemopreventive strategy in breast oncologic patients. Present results encourage further studies on CRY as chemopreventive agent or in targeted supporting therapies for breast cancer.

See: Clinical Endocannabinoid Deficiency

" studies have provided a firmer foundation for the theory, while clinical data have also produced evidence for decreased pain, improved sleep, and other benefits to cannabinoid treatment and adjunctive lifestyle approaches affecting the ECS."

See: Therapeutic Potential of Caryophyllene: A Dietary Cannabinoid in Diabetes & Associated Complications

' Given the safe status, abundant natural occurrence, oral bioavailability, dietary use and pleiotropic properties modulating receptors and enzymes, BCP appears as a promising molecule for diabetes and its complications.'

LINK@ Use of Cannabinoids to Treat Acute Respiratory Distress Syndrome and Cytokine Storm Associated with Coronavirus Disease-2019

" while all attempts are being focused on control of viral replication through development of vaccines, it is also critical to ensure that the vaccines do not trigger hyperactivation of immune response.

It is equally important to develop new anti-inflammatory therapies that can effectively block the cytokine storm seen in patients with severe form of COVID-19.

We believe that cannabinoids hold significant promise as potent anti-inflammatory agents."

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