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1.
Int J Mol Sci ; 22(4)2021 Feb 17.
Article in English | MEDLINE | ID: covidwho-1110431

ABSTRACT

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.


Subject(s)
Analgesics/therapeutic use , Anticonvulsants/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Cannabidiol/therapeutic use , Analgesics/adverse effects , Analgesics/pharmacology , Animals , Anticonvulsants/adverse effects , Anticonvulsants/pharmacology , Antiviral Agents/adverse effects , Antiviral Agents/pharmacology , Cannabidiol/adverse effects , Cannabidiol/pharmacology , Dronabinol/adverse effects , Dronabinol/pharmacology , Dronabinol/therapeutic use , Humans , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Virus Internalization/drug effects
2.
Sci Rep ; 11(1): 1462, 2021 01 14.
Article in English | MEDLINE | ID: covidwho-1065941

ABSTRACT

Cannabis sativa is widely used for medical purposes and has anti-inflammatory activity. This study intended to examine the anti-inflammatory activity of cannabis on immune response markers associated with coronavirus disease 2019 (COVID-19) inflammation. An extract fraction from C. sativa Arbel strain (FCBD) substantially reduced (dose dependently) interleukin (IL)-6 and -8 levels in an alveolar epithelial (A549) cell line. FCBD contained cannabidiol (CBD), cannabigerol (CBG) and tetrahydrocannabivarin (THCV), and multiple terpenes. Treatments with FCBD and a FCBD formulation using phytocannabinoid standards (FCBD:std) reduced IL-6, IL-8, C-C Motif Chemokine Ligands (CCLs) 2 and 7, and angiotensin I converting enzyme 2 (ACE2) expression in the A549 cell line. Treatment with FCBD induced macrophage (differentiated KG1 cell line) polarization and phagocytosis in vitro, and increased CD36 and type II receptor for the Fc region of IgG (FcγRII) expression. FCBD treatment also substantially increased IL-6 and IL-8 expression in macrophages. FCBD:std, while maintaining anti-inflammatory activity in alveolar epithelial cells, led to reduced phagocytosis and pro-inflammatory IL secretion in macrophages in comparison to FCBD. The phytocannabinoid formulation may show superior activity versus the cannabis-derived fraction for reduction of lung inflammation, yet there is a need of caution proposing cannabis as treatment for COVID-19.


Subject(s)
Anti-Inflammatory Agents/pharmacology , COVID-19/immunology , Cannabinoids/pharmacology , Cannabis/chemistry , Epithelial Cells/immunology , Macrophages/immunology , Plant Extracts/pharmacology , SARS-CoV-2/immunology , A549 Cells , Angiotensin-Converting Enzyme 2/immunology , Anti-Inflammatory Agents/chemistry , COVID-19/drug therapy , COVID-19/pathology , Cannabinoids/chemistry , Cytokines/immunology , Epithelial Cells/pathology , Epithelial Cells/virology , Gene Expression Regulation/drug effects , Gene Expression Regulation/immunology , Humans , Macrophages/pathology , Macrophages/virology , Plant Extracts/chemistry , Receptors, IgG/immunology
3.
Int J Biol Macromol ; 168: 474-485, 2021 Jan 31.
Article in English | MEDLINE | ID: covidwho-1065144

ABSTRACT

Effective treatment choices to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are limited because of the absence of effective target-based therapeutics. The main object of the current research was to estimate the antiviral activity of cannabinoids (CBDs) against the human coronavirus SARS-CoV-2. In the presented research work, we performed in silico and in vitro experiments to aid the sighting of lead CBDs for treating the viral infections of SARS-CoV-2. Virtual screening was carried out for interactions between 32 CBDs and the SARS-CoV-2 Mpro enzyme. Afterward, in vitro antiviral activity was carried out of five CBDs molecules against SARS-CoV-2. Interestingly, among them, two CBDs molecules namely Δ9 -tetrahydrocannabinol (IC50 = 10.25 µM) and cannabidiol (IC50 = 7.91 µM) were observed to be more potent antiviral molecules against SARS-CoV-2 compared to the reference drugs lopinavir, chloroquine, and remdesivir (IC50 ranges of 8.16-13.15 µM). These molecules were found to have stable conformations with the active binding pocket of the SARS-CoV-2 Mpro by molecular dynamic simulation and density functional theory. Our findings suggest cannabidiol and Δ9 -tetrahydrocannabinol are possible drugs against human coronavirus that might be used in combination or with other drug molecules to treat COVID-19 patients.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , COVID-19/virology , Cannabinoids/pharmacology , SARS-CoV-2/drug effects , Antiviral Agents/chemistry , Antiviral Agents/pharmacokinetics , Cannabidiol/chemistry , Cannabidiol/pharmacokinetics , Cannabidiol/pharmacology , Cannabinoids/chemistry , Cannabinoids/pharmacokinetics , Computer Simulation , Coronavirus 3C Proteases/antagonists & inhibitors , Coronavirus 3C Proteases/chemistry , Coronavirus 3C Proteases/drug effects , Dronabinol/chemistry , Dronabinol/pharmacokinetics , Dronabinol/pharmacology , Drug Evaluation, Preclinical , Humans , In Vitro Techniques , Ligands , Models, Biological , Molecular Docking Simulation , Molecular Dynamics Simulation , Pandemics , Protease Inhibitors/chemistry , Protease Inhibitors/pharmacology , SARS-CoV-2/chemistry
4.
Br J Pharmacol ; 177(21): 4967-4970, 2020 11.
Article in English | MEDLINE | ID: covidwho-998830

ABSTRACT

Identifying drugs effective in the new coronavirus disease 2019 (COVID-19) is crucial, pending a vaccine against SARS-CoV2. We suggest the hypothesis that cannabidiol (CBD), a non-psychotropic phytocannabinoid, has the potential to limit the severity and progression of the disease for several reasons:- (a) High-cannabidiol Cannabis sativa extracts are able to down-regulate the expression of the two key receptors for SARS-CoV2 in several models of human epithelia, (b) cannabidiol exerts a wide range of immunomodulatory and anti-inflammatory effects and it can mitigate the uncontrolled cytokine production responsible for acute lung injury, (c) being a PPARγ agonist, it can display a direct antiviral activity and (d) PPARγ agonists are regulators of fibroblast/myofibroblast activation and can inhibit the development of pulmonary fibrosis, thus ameliorating lung function in recovered patients. We hope our hypothesis, corroborated by preclinical evidence, will inspire further targeted studies to test cannabidiol as a support drug against the COVID-19 pandemic. LINKED ARTICLES: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc.


Subject(s)
Cannabidiol/administration & dosage , Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Animals , Betacoronavirus/drug effects , Betacoronavirus/isolation & purification , COVID-19 , Cannabidiol/isolation & purification , Cannabidiol/pharmacology , Cannabis/chemistry , Coronavirus Infections/virology , Disease Progression , Humans , Pandemics , Plant Extracts/chemistry , Plant Extracts/pharmacology , Pneumonia, Viral/virology , SARS-CoV-2 , Severity of Illness Index
5.
J Addict Med ; 15(5): 355-356, 2021.
Article in English | MEDLINE | ID: covidwho-978613

ABSTRACT

COVID-19 pandemic has resulted in devastating mortality and morbidity consisting of socioeconomic and health effects that have included respiratory/pulmonary, cardiovascular, mental health and neurological consequences such as anxiety, depression, and substance use. Extensive efforts are underway to develop preventive vaccines and therapeutics such as remdesivir, dexamethasone, convalescent plasma, and others to treat COVID-19 but many report residual mental health problems after recovery. Cannabis products such as cannabidiol (CBD) are being advertised for the treatment of COVID-19 associated mental health problems and substance use disorders. This commentary will briefly clear the myth that CBD can ameliorate a wide range of COVID-19 associated health effects including anxiety, depression, or any substance use disorder, and show that there is a clear lack of sufficient unbiased clinical evidence from well-designed double-blind, placebo-controlled clinical trials to prove the antianxiety or antidepression therapeutic properties of CBD and support its wide use as medicine to treat COVID-19- associated mental health conditions or substance use disorders. Finally, we suggest that addiction physicians must play an important role in dealing with their patients requesting CBD prescription for treating any of these conditions.


Subject(s)
COVID-19 , Cannabidiol , COVID-19/therapy , Cannabidiol/therapeutic use , Humans , Immunization, Passive , Pandemics , SARS-CoV-2
6.
Aging (Albany NY) ; 12(22): 22425-22444, 2020 11 22.
Article in English | MEDLINE | ID: covidwho-969889

ABSTRACT

With the current COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is an urgent need for new therapies and prevention strategies that can help curtail disease spread and reduce mortality. The inhibition of viral entry and thus spread is a plausible therapeutic avenue. SARS-CoV-2 uses receptor-mediated entry into a human host via the angiotensin-converting enzyme 2 (ACE2), which is expressed in lung tissue as well as the oral and nasal mucosa, kidney, testes and gastrointestinal tract. The modulation of ACE2 levels in these gateway tissues may be an effective strategy for decreasing disease susceptibility. Cannabis sativa, especially those high in the anti-inflammatory cannabinoid cannabidiol (CBD), has been found to alter gene expression and inflammation and harbour anti-cancer and anti-inflammatory properties. However, its effects on ACE2 expression remain unknown. Working under a Health Canada research license, we developed over 800 new C. sativa cultivars and hypothesized that high-CBD C. sativa extracts may be used to down-regulate ACE2 expression in target COVID-19 tissues. Using artificial 3D human models of oral, airway and intestinal tissues, we identified 13 high-CBD C. sativa extracts that decrease ACE2 protein levels. Some C. sativa extracts down-regulate serine protease TMPRSS2, another critical protein required for SARS-CoV-2 entry into host cells. While our most effective extracts require further large-scale validation, our study is important for future analyses of the effects of medical cannabis on COVID-19. The extracts of our most successful novel high-CBD C. sativa lines, pending further investigation, may become a useful and safe addition to the prevention/treatment of COVID-19 as an adjunct therapy.


Subject(s)
Angiotensin-Converting Enzyme 2/antagonists & inhibitors , COVID-19/prevention & control , Cannabis/chemistry , Plant Extracts/pharmacology , SARS-CoV-2/drug effects , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/drug therapy , COVID-19/epidemiology , COVID-19/virology , Cannabidiol/pharmacology , Cannabidiol/therapeutic use , Computer Simulation , Gene Expression Regulation/drug effects , Humans , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Intestinal Mucosa/virology , Models, Anatomic , Mouth Mucosa/drug effects , Mouth Mucosa/metabolism , Mouth Mucosa/virology , Pandemics/prevention & control , Plant Extracts/chemistry , Plant Extracts/therapeutic use , Respiratory Mucosa/drug effects , Respiratory Mucosa/metabolism , Respiratory Mucosa/virology , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Virus Internalization/drug effects
7.
J Cell Mol Med ; 24(21): 12869-12872, 2020 11.
Article in English | MEDLINE | ID: covidwho-863121

ABSTRACT

Considering lack of target-specific antiviral treatment and vaccination for COVID-19, it is absolutely exigent to have an effective therapeutic modality to reduce hospitalization and mortality rate as well as to improve COVID-19-infected patient outcomes. In a follow-up study to our recent findings indicating the potential of Cannabidiol (CBD) in the treatment of acute respiratory distress syndrome (ARDS), here we show for the first time that CBD may ameliorate the symptoms of ARDS through up-regulation of apelin, a peptide with significant role in the central and peripheral regulation of immunity, CNS, metabolic and cardiovascular system. By administering intranasal Poly (I:C), a synthetic viral dsRNA, while we were able to mimic the symptoms of ARDS in a murine model, interestingly, there was a significant decrease in the expression of apelin in both blood and lung tissues. CBD treatment was able to reverse the symptoms of ARDS towards a normal level. Importantly, CBD treatment increased the apelin expression significantly, suggesting a potential crosstalk between apelinergic system and CBD may be the therapeutic target in the treatment of inflammatory diseases such as COVID-19 and many other pathologic conditions.


Subject(s)
Apelin/metabolism , Cannabidiol/pharmacology , Respiratory Distress Syndrome/drug therapy , Administration, Intranasal , Animals , Lung/drug effects , Lung/pathology , Male , Mice, Inbred C57BL , Poly I-C/toxicity , Respiratory Distress Syndrome/chemically induced , Respiratory Distress Syndrome/metabolism , Respiratory Distress Syndrome/pathology
8.
Cannabis Cannabinoid Res ; 5(3): 197-201, 2020.
Article in English | MEDLINE | ID: covidwho-638503

ABSTRACT

Introduction: In the absence of effective antivirals and vaccination, the pandemic of COVID-19 remains the most significant challenge to our health care system in decades. There is an urgent need for definitive therapeutic intervention. Clinical reports indicate that the cytokine storm associated with acute respiratory distress syndrome (ARDS) is the leading cause of mortality in severe cases of some respiratory viral infections, including COVID-19. In recent years, cannabinoids have been investigated extensively due to their potential effects on the human body. Among all cannabinoids, cannabidiol (CBD) has demonstrated potent anti-inflammatory effects in a variety of pathological conditions. Therefore, it is logical to explore whether CBD can reduce the cytokine storm and treat ARDS. Materials and Methods: In this study, we show that intranasal application of Poly(I:C), a synthetic analogue of viral double-stranded RNA, simulated symptoms of severe viral infections inducing signs of ARDS and cytokine storm. Discussion: The administration of CBD downregulated the level of proinflammatory cytokines and ameliorated the clinical symptoms of Poly I:C-induced ARDS. Conclusion: Our results suggest a potential protective role for CBD during ARDS that may extend CBD as part of the treatment of COVID-19 by reducing the cytokine storm, protecting pulmonary tissues, and re-establishing inflammatory homeostasis.

9.
Cureus ; 12(6): e8671, 2020 Jun 17.
Article in English | MEDLINE | ID: covidwho-620848

ABSTRACT

Many cannabidiol (CBD) retailers make unsupported medical claims about their product. In recent years, the U.S. Food and Drug Administration (FDA) has sent warning letters to CBD retailers who promoted CBD to treat Alzheimer's disease, cancer, diabetes, and other serious conditions for which there is no evidence of its efficacy as a treatment or preventive. Compliance with these warning letters has been low. During the novel coronavirus disease 2019 (COVID-19) pandemic, the FDA has begun sending more strongly worded warning letters that appear to have better compliance in that most of these companies have removed COVID-19-related claims. However, many continue to present other unsupported medical claims on other serious medical conditions like cancer, depression, addiction, and bone fractures, among many others. We argue that adopting a strategy of focused deterrence where the FDA prioritizes enforcement related to COVID-19 claims - but when COVID-19-related claims are found, pursues all other violations by that company - would present an opportunity to efficiently cut down on harmful claims overstating CBD's benefits.

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