Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 15 de 15
Filter
1.
Life Sci ; 301: 120624, 2022 Jul 15.
Article in English | MEDLINE | ID: covidwho-2105537

ABSTRACT

AIMS: To study effects on cellular innate immune responses to ORF8, ORF10, and Membrane protein (M protein) from the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes COVID-19, in combination with cannabidiol (CBD). MAIN METHODS: HEK293 cells transfected with plasmids expressing control vector, ORF8, ORF10, or M protein were assayed for cell number and markers of apoptosis at 24 h, and interferon and interferon-stimulated gene expression at 14 h, with or without CBD. Cells transfected with polyinosinic:polycytidylic acid (Poly (I:C)) were also studied as a general model of RNA-type viral infection. KEY FINDINGS: Reduced cell number and increased early and late apoptosis were found when expression of viral genes was combined with 1-2 µM CBD treatment, but not in control-transfected cells treated with CBD, or in cells expressing viral genes but treated only with vehicle. In cells expressing viral genes, CBD augmented expression of IFNγ, IFNλ1 and IFNλ2/3, as well as the 2'-5'-oligoadenylate synthetase (OAS) family members OAS1, OAS2, OAS3, and OASL. CBD also augmented expression of these genes in control cells not expressing viral genes, but without enhancing apoptosis. CBD similarly enhanced the cellular anti-viral response to Poly (I:C). SIGNIFICANCE: Our results demonstrate a poor ability of HEK293 cells to respond to SARS-CoV-2 genes alone, but an augmented innate anti-viral response to these genes in the presence of CBD. Thus, CBD may prime components of the innate immune system, increasing readiness to respond to RNA-type viral infection without activating apoptosis, and could be studied for potential in prophylaxis.


Subject(s)
COVID-19 , Cannabidiol , Antiviral Agents , Apoptosis , Cannabidiol/pharmacology , HEK293 Cells , Humans , Immunity, Innate/genetics , Interferons/pharmacology , Membrane Proteins , Poly I-C/pharmacology , RNA , SARS-CoV-2
2.
Cells ; 11(9)2022 04 20.
Article in English | MEDLINE | ID: covidwho-1792800

ABSTRACT

Cannabinoids, mainly cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), are the most studied group of compounds obtained from Cannabis sativa because of their several pharmaceutical properties. Current evidence suggests a crucial role of cannabinoids as potent anti-inflammatory agents for the treatment of chronic inflammatory diseases; however, the mechanisms remain largely unclear. Cytokine storm, a dysregulated severe inflammatory response by our immune system, is involved in the pathogenesis of numerous chronic inflammatory disorders, including coronavirus disease 2019 (COVID-19), which results in the accumulation of pro-inflammatory cytokines. Therefore, we hypothesized that CBD and THC reduce the levels of pro-inflammatory cytokines by inhibiting key inflammatory signaling pathways. The nucleotide-binding and oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome signaling has been implicated in a variety of chronic inflammatory diseases, which results in the release of pyroptotic cytokines, interleukin-1ß (IL-1ß) and IL-18. Likewise, the activation of the signal transducer and activator of transcription-3 (STAT3) causes increased expression of pro-inflammatory cytokines. We studied the effects of CBD and THC on lipopolysaccharide (LPS)-induced inflammatory response in human THP-1 macrophages and primary human bronchial epithelial cells (HBECs). Our results revealed that CBD and, for the first time, THC significantly inhibited NLRP3 inflammasome activation following LPS + ATP stimulation, leading to a reduction in the levels of IL-1ß in THP-1 macrophages and HBECs. CBD attenuated the phosphorylation of nuclear factor-κB (NF-κB), and both cannabinoids inhibited the generation of oxidative stress post-LPS. Our multiplex ELISA data revealed that CBD and THC significantly diminished the levels of IL-6, IL-8, and tumor necrosis factor-α (TNF-α) after LPS treatment in THP-1 macrophages and HBECs. In addition, the phosphorylation of STAT3 was significantly downregulated by CBD and THC in THP-1 macrophages and HBECs, which was in turn attributed to the reduced phosphorylation of tyrosine kinase-2 (TYK2) by CBD and THC after LPS stimulation in these cells. Overall, CBD and THC were found to be effective in alleviating the LPS-induced cytokine storm in human macrophages and primary HBECs, at least via modulation of NLRP3 inflammasome and STAT3 signaling pathways. The encouraging results from this study warrant further investigation of these cannabinoids in vivo.


Subject(s)
COVID-19 , Cannabidiol , Cannabinoids , Cannabidiol/pharmacology , Cannabinoids/pharmacology , Cytokine Release Syndrome , Cytokines/metabolism , Dronabinol/pharmacology , Humans , Inflammasomes/metabolism , Lipopolysaccharides/pharmacology , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , STAT3 Transcription Factor/metabolism , Signal Transduction , TYK2 Kinase/metabolism , TYK2 Kinase/pharmacology
3.
Front Immunol ; 13: 870787, 2022.
Article in English | MEDLINE | ID: covidwho-1785352

ABSTRACT

Cannabidiol (CBD) can prevent the inflammatory response of SARS-CoV-2 spike protein in Caco-2-cells. This action is coupled with the inhibition of IL-1beta, IL-6, IL-18, and TNF-alpha, responsible for the inflammatory process during SARS-CoV-2 infection. CBD can act on the different proteins encoded by SARS-CoV-2 and as an antiviral agent to prevent the viral infection. Furthermore, recent studies have shown the possible action of CBD as an antagonist of cytokine release syndromes. In the SARS-CoV-2 pathophysiology, the angiotensin-converting enzyme 2 (ACE2) seems to be the key cell receptor for SARS-CoV-2 infection. The WNT/ß-catenin pathway and PPARγ interact in an opposite manner in many diseases, including SARS-CoV-2 infection. CBD exerts its activity through the interaction with PPARγ in SARS-CoV-2 infection. Thus, we can hypothesize that CBD may counteract the inflammatory process of SARS-CoV-2 by its interactions with both ACE2 and the interplay between the WNT/ß-catenin pathway and PPARγ. Vaccines are the only way to prevent COVID-19, but it appears important to find therapeutic complements to treat patients already affected by SARS-CoV-2 infection. The possible role of CBD should be investigated by clinical trials to show its effectiveness.


Subject(s)
COVID-19 , Cannabidiol , Angiotensin-Converting Enzyme 2 , COVID-19/drug therapy , Caco-2 Cells , Cannabidiol/pharmacology , Cannabidiol/therapeutic use , Humans , PPAR gamma , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , beta Catenin
4.
Front Immunol ; 13: 841459, 2022.
Article in English | MEDLINE | ID: covidwho-1731786

ABSTRACT

In late 2019, COVID-19 emerged in Wuhan, China. Currently, it is an ongoing global health threat stressing the need for therapeutic compounds. Linking the virus life cycle and its interaction with cell receptors and internal cellular machinery is key to developing therapies based on the control of infectivity and inflammation. In this framework, we evaluate the combination of cannabidiol (CBD), as an anti-inflammatory molecule, and terpenes, by their anti-microbiological properties, in reducing SARS-CoV-2 infectivity. Our group settled six formulations combining CBD and terpenes purified from Cannabis sativa L, Origanum vulgare, and Thymus mastichina. The formulations were analyzed by HPLC and GC-MS and evaluated for virucide and antiviral potential by in vitro studies in alveolar basal epithelial, colon, kidney, and keratinocyte human cell lines. Conclusions and Impact: We demonstrate the virucide effectiveness of CBD and terpene-based formulations. F2TC reduces the infectivity by 17%, 24%, and 99% for CaCo-2, HaCat, and A549, respectively, and F1TC by 43%, 37%, and 29% for Hek293T, HaCaT, and Caco-2, respectively. To the best of our knowledge, this is the first approach that tackles the combination of CBD with a specific group of terpenes against SARS-CoV-2 in different cell lines. The differential effectiveness of formulations according to the cell line can be relevant to understanding the pattern of virus infectivity and the host inflammation response, and lead to new therapeutic strategies.


Subject(s)
Antiviral Agents/pharmacology , Cannabidiol/pharmacology , SARS-CoV-2/drug effects , Terpenes/pharmacology , Anti-Inflammatory Agents/pharmacology , Antiviral Agents/chemistry , Cannabidiol/chemistry , Cell Line , Cell Survival/drug effects , Drug Synergism , Humans , Plants, Medicinal/chemistry , Terpenes/chemistry , Virus Internalization/drug effects , Virus Replication/drug effects
5.
Sci Adv ; 8(8): eabi6110, 2022 Feb 25.
Article in English | MEDLINE | ID: covidwho-1714330

ABSTRACT

The spread of SARS-CoV-2 and ongoing COVID-19 pandemic underscores the need for new treatments. Here we report that cannabidiol (CBD) inhibits infection of SARS-CoV-2 in cells and mice. CBD and its metabolite 7-OH-CBD, but not THC or other congeneric cannabinoids tested, potently block SARS-CoV-2 replication in lung epithelial cells. CBD acts after viral entry, inhibiting viral gene expression and reversing many effects of SARS-CoV-2 on host gene transcription. CBD inhibits SARS-CoV-2 replication in part by up-regulating the host IRE1α RNase endoplasmic reticulum (ER) stress response and interferon signaling pathways. In matched groups of human patients from the National COVID Cohort Collaborative, CBD (100 mg/ml oral solution per medical records) had a significant negative association with positive SARS-CoV-2 tests. This study highlights CBD as a potential preventative agent for early-stage SARS-CoV-2 infection and merits future clinical trials. We caution against use of non-medical formulations including edibles, inhalants or topicals as a preventative or treatment therapy at the present time.


Subject(s)
Antiviral Agents/pharmacology , Cannabidiol/pharmacology , Host-Pathogen Interactions/drug effects , Immunity, Innate/drug effects , SARS-CoV-2/drug effects , A549 Cells , Animals , Antiviral Agents/chemistry , COVID-19/drug therapy , COVID-19/virology , Cannabidiol/chemistry , Cannabidiol/metabolism , Chlorocebus aethiops , Endoplasmic Reticulum Stress/drug effects , Endoribonucleases/genetics , Endoribonucleases/metabolism , Epithelial Cells/virology , Female , Gene Expression Regulation, Viral/drug effects , Host-Pathogen Interactions/physiology , Humans , Interferons/metabolism , Mice , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , SARS-CoV-2/physiology , Vero Cells , Virus Internalization/drug effects , Virus Replication/drug effects
6.
Phytother Res ; 35(12): 6893-6903, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1568309

ABSTRACT

Given the abundancy of angiotensin converting enzyme 2 (ACE-2) receptors density, beyond the lung, the intestine is considered as an alternative site of infection and replication for severe acute respiratory syndrome by coronavirus type 2 (SARS-CoV-2). Cannabidiol (CBD) has recently been proposed in the management of coronavirus disease 2019 (COVID-19) respiratory symptoms because of its anti-inflammatory and immunomodulatory activity exerted in the lung. In this study, we demonstrated the in vitro PPAR-γ-dependent efficacy of CBD (10-9 -10-7  M) in preventing epithelial damage and hyperinflammatory response triggered by SARS-CoV-2 spike protein (SP) in a Caco-2 cells. Immunoblot analysis revealed that CBD was able to reduce all the analyzed proinflammatory markers triggered by SP incubation, such as tool-like receptor 4 (TLR-4), ACE-2, family members of Ras homologues A-GTPase (RhoA-GTPase), inflammasome complex (NLRP3), and Caspase-1. CBD caused a parallel inhibition of interleukin 1 beta (IL-1ß), IL-6, tumor necrosis factor alpha (TNF-α), and IL-18 by enzyme-linked immunosorbent assay (ELISA) assay. By immunofluorescence analysis, we observed increased expression of tight-junction proteins and restoration of transepithelial electrical resistance (TEER) following CBD treatment, as well as the rescue of fluorescein isothiocyanate (FITC)-dextran permeability induced by SP. Our data indicate, in conclusion, that CBD is a powerful inhibitor of SP protein enterotoxicity in vitro.


Subject(s)
Cannabidiol , SARS-CoV-2/drug effects , Signal Transduction/drug effects , Spike Glycoprotein, Coronavirus/immunology , COVID-19 , Caco-2 Cells , Cannabidiol/pharmacology , Caspase 1 , Cytokines , Humans , Inflammation , NLR Family, Pyrin Domain-Containing 3 Protein , PPAR gamma , Toll-Like Receptor 4
7.
Biomed Pharmacother ; 142: 111956, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1330661

ABSTRACT

Novel coronavirus 2019 (COVID-19) is a zoonosis that revised the global economic and societal progress since early 2020. The SARS-CoV-2 has been recognized as the responsible pathogen for COVID-19 with high infection and mortality rate potential. It has spread in 192 countries and infected about 1.5% of the world population, and still, a proper therapeutic approach is not unveiled. COVID-19 indication starts with fever to shortness of breathing, leading to ICU admission with the ventilation support in severe conditions. Besides the symptomatic mainstay clinical therapeutic approach, only Remdesivir has been approved by the FDA. Several pharmaceutical companies claimed different vaccines with exceptionally high efficacy (90-95%) against COVID-19; how long these vaccines can protect and long-term safety with the new variants are unpredictable. After the worldwide spread of the COVID-19 pandemic, numerous clinical trials with different phases are being performed to find the most appropriate solution to this condition. Some of these trials with old FDA-approved drugs showed promising results. In this review, we have precisely compiled the efforts to curb the disease and discussed the clinical findings of Ivermectin, Doxycycline, Vitamin-D, Vitamin-C, Zinc, and cannabidiol and their combinations. Additionally, the correlation of these molecules on the prophylactic and diseased ministration against COVID-19 has been explored.


Subject(s)
COVID-19/drug therapy , Cannabidiol/pharmacology , SARS-CoV-2 , Antiviral Agents/pharmacology , Ascorbic Acid/pharmacology , COVID-19/epidemiology , COVID-19/prevention & control , Dietary Supplements , Doxycycline/pharmacology , Drug Repositioning/methods , Drug Therapy, Combination/methods , Humans , Ivermectin , SARS-CoV-2/drug effects , SARS-CoV-2/isolation & purification , Treatment Outcome , Vitamin D/pharmacology , Zinc/pharmacology
8.
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
9.
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
10.
J Med Chem ; 63(21): 12137-12155, 2020 11 12.
Article in English | MEDLINE | ID: covidwho-1023817

ABSTRACT

This Perspective of the published essential medicinal chemistry of cannabidiol (CBD) provides evidence that the popularization of CBD-fortified or CBD-labeled health products and CBD-associated health claims lacks a rigorous scientific foundation. CBD's reputation as a cure-all puts it in the same class as other "natural" panaceas, where valid ethnobotanicals are reduced to single, purportedly active ingredients. Such reductionist approaches oversimplify useful, chemically complex mixtures in an attempt to rationalize the commercial utility of natural compounds and exploit the "natural" label. Literature evidence associates CBD with certain semiubiquitous, broadly screened, primarily plant-based substances of undocumented purity that interfere with bioassays and have a low likelihood of becoming therapeutic agents. Widespread health challenges and pandemic crises such as SARS-CoV-2 create circumstances under which scientists must be particularly vigilant about healing claims that lack solid foundational data. Herein, we offer a critical review of the published medicinal chemistry properties of CBD, as well as precise definitions of CBD-containing substances and products, distilled to reveal the essential factors that impact its development as a therapeutic agent.


Subject(s)
Cannabidiol/pharmacology , Animals , Cannabidiol/pharmacokinetics , Cannabidiol/therapeutic use , Cannabidiol/toxicity , Chemistry, Pharmaceutical , Clinical Trials as Topic , Humans , Placebo Effect
11.
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
12.
J Med Internet Res ; 22(10): e21743, 2020 10 30.
Article in English | MEDLINE | ID: covidwho-982837

ABSTRACT

BACKGROUND: The COVID-19 outbreak was designated a global pandemic on March 11, 2020. The relationship between vaping and contracting COVID-19 is unclear, and information on the internet is conflicting. There is some scientific evidence that vaping cannabidiol (CBD), an active ingredient in cannabis that is obtained from the hemp plant, or other substances is associated with more severe manifestations of COVID-19. However, there is also inaccurate information that vaping can aid COVID-19 treatment, as well as expert opinion that CBD, possibly administered through vaping, can mitigate COVID-19 symptoms. Thus, it is necessary to study the spread of inaccurate information to better understand how to promote scientific knowledge and curb inaccurate information, which is critical to the health of vapers. Inaccurate information about vaping and COVID-19 may affect COVID-19 treatment outcomes. OBJECTIVE: Using structural topic modeling, we aimed to map temporal trends in the web-based vaping narrative (a large data set comprising web-based vaping chatter from several sources) to indicate how the narrative changed from before to during the COVID-19 pandemic. METHODS: We obtained data using a textual query that scanned a data pool of approximately 200,000 different domains (4,027,172 documents and 361,100,284 words) such as public internet forums, blogs, and social media, from August 1, 2019, to April 21, 2020. We then used structural topic modeling to understand changes in word prevalence and semantic structures within topics around vaping before and after December 31, 2019, when COVID-19 was reported to the World Health Organization. RESULTS: Broadly, the web-based vaping narrative can be organized into the following groups or archetypes: harms from vaping; Vaping Regulation; Vaping as Harm Reduction or Treatment; and Vaping Lifestyle. Three archetypes were observed prior to the emergence of COVID-19; however, four archetypes were identified post-COVID-19 (Vaping as Harm Reduction or Treatment was the additional archetype). A topic related to CBD product preference emerged after COVID-19 was first reported, which may be related to the use of CBD by vapers as a COVID-19 treatment. CONCLUSIONS: Our main finding is the emergence of a vape-administered CBD treatment narrative around COVID-19 when comparing the web-based vaping narratives before and during the COVID-19 pandemic. These results are key to understanding how vapers respond to inaccurate information about COVID-19, optimizing treatment of vapers who contract COVID-19, and possibly minimizing instances of inaccurate information. The findings have implications for the management of COVID-19 among vapers and the monitoring of web-based content pertinent to tobacco to develop targeted interventions to manage COVID-19 among vapers.


Subject(s)
Cannabidiol/administration & dosage , Coronavirus Infections/epidemiology , Coronavirus Infections/etiology , Internet/statistics & numerical data , Pneumonia, Viral/epidemiology , Pneumonia, Viral/etiology , Vaping/adverse effects , Vaping/epidemiology , COVID-19 , Cannabidiol/adverse effects , Cannabidiol/pharmacology , Cannabidiol/therapeutic use , Coronavirus Infections/drug therapy , Coronavirus Infections/therapy , Humans , Pandemics , Pneumonia, Viral/therapy , Smokers/psychology , Smokers/statistics & numerical data , Social Media , Tobacco Products
13.
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
14.
Cannabis Cannabinoid Res ; 6(1): 7-18, 2021.
Article in English | MEDLINE | ID: covidwho-955809

ABSTRACT

Coronavirus disease-19 (COVID-19)-related anxiety and post-traumatic stress symptoms (PTSS) or post-traumatic stress disorder (PTSD) are likely to be a significant long-term issue emerging from the current pandemic. We hypothesize that cannabidiol (CBD), a chemical isolated from Cannabis sativa with reported anxiolytic properties, could be a therapeutic option for the treatment of COVID-19-related anxiety disorders. In the global over-the-counter CBD market, anxiety, stress, depression, and sleep disorders are consistently the top reasons people use CBD. In small randomized controlled clinical trials, CBD (300-800 mg) reduces anxiety in healthy volunteers, patients with social anxiety disorder, those at clinical high risk of psychosis, in patients with Parkinson's disease, and in individuals with heroin use disorder. Observational studies and case reports support these findings, extending to patients with anxiety and sleep disorders, Crohn's disease, depression, and in PTSD. Larger ongoing trials in this area continue to add to this evidence base with relevant patient cohorts, sample sizes, and clinical end-points. Pre-clinical studies reveal the molecular targets of CBD in these indications as the cannabinoid receptor type 1 and cannabinoid receptor type 2 (mainly in fear memory processing), serotonin 1A receptor (mainly in anxiolysis) and peroxisome proliferator-activated receptor gamma (mainly in the underpinning anti-inflammatory/antioxidant effects). Observational and pre-clinical data also support CBD's therapeutic value in improving sleep (increased sleep duration/quality and reduction in nightmares) and depression, which are often comorbid with anxiety. Together these features of CBD make it an attractive novel therapeutic option in COVID-related PTSS that merits investigation and testing through appropriately designed randomized controlled trials.


Subject(s)
Anxiety Disorders/drug therapy , Anxiety Disorders/etiology , COVID-19 , Cannabidiol/pharmacology , Cannabinoid Receptor Modulators/pharmacology , Humans
15.
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
SELECTION OF CITATIONS
SEARCH DETAIL