Cannabis for COVID-19: Can Cannabinoids Quell the Cytokine Storm?

Onaivi, Emmanuel S.; Sharma, Vaishali

doi:10.2144/fsoa-2020-0124

Cited by 36 publications

(44 citation statements)

References 26 publications

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“…Cell-type-specific cKO mice of CB1R, CB2R, or both will promote understanding of CBRs not only in the high baseline but also low baseline CB1R and CB2R expressing cell types in vivo and in real time. In the current COVID-19 pandemic period, the application of CB2R agonists for therapeutic treatment of COVID-19 could be explored for their anti-inflammation effects [ 88 ] and potential interaction to SARS-CoV-2 spike glycoprotein receptor-binding domains (RBDs) where linoleic acid binds and exerts allosteric inhibition [ 89 ].…”

Section: Discussionmentioning

confidence: 99%

Low Basal CB2R in Dopamine Neurons and Microglia Influences Cannabinoid Tetrad Effects

Liu

Canseco-Alba

Liang

et al. 2020

IJMS

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There are two well-characterized cannabinoid receptors (CB1R and CB2R and other candidates): the central nervous system (CNS) enriched CB1R and peripheral tissue enriched CB2R with a wide dynamic range of expression levels in different cell types of human tissues. Hepatocytes and neurons express low baseline CB1R and CB2R, respectively, and their cell-type-specific functions are not well defined. Here we report inducible expression of CB1R in the liver by high-fat and high sugar diet and CB2R in cortical neurons by methamphetamine. While there is less controversy about hepatocyte CB1R, the presence of functional neuronal CB2R is still debated to date. We found that neuron CB2R basal expression was higher than that of hepatocyte CB1R by measuring mRNA levels of specific isoform CB2A in neurons isolated by fluorescence-activated cell sorting (FACS) and CB1A in hepatocytes isolated by collagenase perfusion of liver. For in vivo studies, we generated hepatocyte, dopaminergic neuron, and microglia-specific conditional knockout mice (Abl-Cnr1Δ, Dat-Cnr2Δ, and Cx3cr1-Cnr2Δ) of CB1R and CB2R by crossing Cnr1f/f and Cnr2f/f strains to Abl-Cre, Dat-Cre, and Cx3cr1-Cre deleter mouse strains, respectively. Our data reveals that neuron and microglia CB2Rs are involved in the “tetrad” effects of the mixed agonist WIN 55212-2, CB1R selective agonist arachidonyl-2′-chloroethylamide (ACEA), and CB2R selective agonist JWH133. Dat-Cnr2Δ and Cx3cr1-Cnr2Δ mice showed genotypic differences in hypomobility, hypothermia, analgesia, and catalepsy induced by the synthetic cannabinoids. Alcohol conditioned place preference was abolished in DAT-Cnr2Δ mice and remained intact in Cx3cr1-Cnr2Δ mice in comparison to WT mice. These Cre-loxP recombinant mouse lines provide unique approaches in cannabinoid research for dissecting the complex endocannabinoid system that is implicated in many chronic disorders.

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Section: Discussionmentioning

confidence: 99%

Low Basal CB2R in Dopamine Neurons and Microglia Influences Cannabinoid Tetrad Effects

Liu

Canseco-Alba

Liang

et al. 2020

IJMS

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“…During treatment, already known drugs are being used. Neither a vaccine nor a specific cure has been developed yet [ 139 ].…”

Section: Pharmacological Applicationmentioning

confidence: 99%

Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment

Stasiłowicz

Tomala

Podolak

et al. 2021

IJMS

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Cannabis sativa L. turned out to be a valuable source of chemical compounds of various structures, showing pharmacological activity. The most important groups of compounds include phytocannabinoids and terpenes. The pharmacological activity of Cannabis (in epilepsy, sclerosis multiplex (SM), vomiting and nausea, pain, appetite loss, inflammatory bowel diseases (IBDs), Parkinson’s disease, Tourette’s syndrome, schizophrenia, glaucoma, and coronavirus disease 2019 (COVID-19)), which has been proven so far, results from the affinity of these compounds predominantly for the receptors of the endocannabinoid system (the cannabinoid receptor type 1 (CB1), type two (CB2), and the G protein-coupled receptor 55 (GPR55)) but, also, for peroxisome proliferator-activated receptor (PPAR), glycine receptors, serotonin receptors (5-HT), transient receptor potential channels (TRP), and GPR, opioid receptors. The synergism of action of phytochemicals present in Cannabis sp. raw material is also expressed in their increased bioavailability and penetration through the blood–brain barrier. This review provides an overview of phytochemistry and pharmacology of compounds present in Cannabis extracts in the context of the current knowledge about their synergistic actions and the implications of clinical use in the treatment of selected diseases.

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“…Within the group of papers dealing with the literature, seven publications consider the potential use of CBD for the treatment of COVID-19 mainly due to its potent anti-inflammatory activity [ 14 , 15 , 56 , 57 , 58 , 59 , 60 ]. However, as suggested by another three authors, there is a lack of high-quality studies dedicated to the anti-inflammatory effects of CBD [ 61 , 62 ] or to its effects on the central nervous system (e.g., anxiety or neurological complications) [ 63 ].…”

Section: Cannabidiol—pharmacological Potential and Mechanism Of Acmentioning

confidence: 99%

“…Nonetheless, the antiviral drug remdesivir shortens hospitalization time and the glucocorticoid dexamethasone even reduces mortality [ 10 , 11 ]. In addition, it is suggested that alternative compounds, including phytochemicals and natural agents targeting coronavirus development directly or as a result of their immunomodulatory effects, could be applied as potential therapies and for the prevention of COVID-19 [ 12 , 13 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Opportunities, Challenges and Pitfalls of Using Cannabidiol as an Adjuvant Drug in COVID-19

Malinowska

Baranowska-Kuczko

Kicman

et al. 2021

IJMS

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may lead to coronavirus disease 2019 (COVID-19) which, in turn, may be associated with multiple organ dysfunction. In this review, we present advantages and disadvantages of cannabidiol (CBD), a non-intoxicating phytocannabinoid from the cannabis plant, as a potential agent for the treatment of COVID-19. CBD has been shown to downregulate proteins responsible for viral entry and to inhibit SARS-CoV-2 replication. Preclinical studies have demonstrated its effectiveness against diseases of the respiratory system as well as its cardioprotective, nephroprotective, hepatoprotective, neuroprotective and anti-convulsant properties, that is, effects that may be beneficial for COVID-19. Only the latter two properties have been demonstrated in clinical studies, which also revealed anxiolytic and antinociceptive effects of CBD (given alone or together with Δ9-tetrahydrocannabinol), which may be important for an adjuvant treatment to improve the quality of life in patients with COVID-19 and to limit post-traumatic stress symptoms. However, one should be aware of side effects of CBD (which are rarely serious), drug interactions (also extending to drugs acting against COVID-19) and the proper route of its administration (vaping may be dangerous). Clearly, further clinical studies are necessary to prove the suitability of CBD for the treatment of COVID-19.

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Cannabis for COVID-19: Can Cannabinoids Quell the Cytokine Storm?

Abstract: Along with many ongoing studies and clinical trials, cannabis and cannabinoid adjunctive treatment in COVID-19 could be of use in countering SARS-CoV-2 infections by quelling the cytokine storm, but require more studies and trials. "

Cited by 36 publications

References 26 publications

Low Basal CB2R in Dopamine Neurons and Microglia Influences Cannabinoid Tetrad Effects

Low Basal CB2R in Dopamine Neurons and Microglia Influences Cannabinoid Tetrad Effects

Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment

Opportunities, Challenges and Pitfalls of Using Cannabidiol as an Adjuvant Drug in COVID-19

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