ArticlePDF Available

The potential of cannabidiol in the COVID‐19 pandemic: a hypothesis letter


Identifying candidate 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: 1) High‐CBD Cannabis Sativa extracts are able to downregulate the expression of the two key receptors for SARS‐CoV2 in several models of human epithelia 2) CBD exerts a wide range of immunomodulatory and anti‐inflammatory effects and it can mitigate the uncontrolled cytokine production featuring Acute Lung Injury 3) Being a PPARγ agonist, it can display a direct antiviral activity 4) 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 several preclinical evidence, will inspire further targeted studies to test CBD as a support drug against the COVID‐19 pandemic.
This article has been accepted for publication and undergone full peer review but has not
been through the copyediting, typesetting, pagination and proofreading process which may
lead to differences between this version and the Version of Record. Please cite this article as
doi: 10.1111/bph.15157
This article is protected by copyright. All rights reserved.
Esposito Giuseppe (Orcid ID: 0000-0001-8080-8218)
The potential of cannabidiol in the COVID-19 pandemic: a hypothesis letter
Giuseppe Esposito1, Marcella Pesce2, Luisa Seguella1, Walter Sanseverino3, Jie Lu4, Chiara
Corpetti1, and Giovanni Sarnelli2*
1 Department of Physiology and Pharmacology “V. Erspamer”, Sapienza University of
Rome, Italy
2 Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples,
3 Sequentia Biotech SL, Carrer Comte D’Urgell 240 3D, Barcelona, Spain
4 Department of Human Anatomy, College of Basic Medical Sciences, China Medical
University, Shenyang City, Liaoning, China
Identifying candidate 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: 1) High-CBD Cannabis Sativa extracts are able
to downregulate the expression of the two key receptors for SARS-CoV2 in several models of
human epithelia 2) CBD exerts a wide range of immunomodulatory and anti-inflammatory
effects and it can mitigate the uncontrolled cytokine production featuring Acute Lung Injury
3) Being a PPAR agonist, it can display a direct antiviral activity 4) PPAR 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 several preclinical evidence, will inspire further targeted studies
to test CBD as a support drug against the COVID-19 pandemic.
ABBREVIATIONS: Corona Virus Disease 2019 (COVID-19), Severe Acute Respiratory
Syndrome - Coronavirus 2 (SARS-CoV2), interleukin (IL), monocyte chemoattractant
protein (MCP)-1, cannabidiol (CBD), Angiotensin-converting enzyme 2 (ACE2),
Transmembrane Serine Protease 2 (TMPRSS2), peroxisome proliferator-activated receptor
gamma (PPAR), 5-hydroxytryptamine (5HT)-1A, transient receptor potential (TRP), Acute
Lung injury (ALI), Tumor Necrosis Factor (TNF), Macrophage Inflammatory Protein 2
(MIP-2), Food and Drug Administration (FDA), Human Immunodeficiency Virus (HIV),
This article is protected by copyright. All rights reserved.
Respiratory syncytial virus (RSV), Hepatitis B virus (HBV), Hepatitis C Virus (HCV),
Cytochromes P450 (CYP450), half inhibitory concentration (IC50).
Dear editor,
An aberrant release of cytokines and proinflammatory molecules is closely related to lung
injury, multiorgan failure and ultimately poor prognosis in the new Severe Acute Respiratory
Syndrome - Coronavirus 2 (SARS-CoV2) pandemic [Huang et al. 2020].
Such uncontrolled release of cytokines, namely interleukin (IL)-1ß, IL-6, monocyte
chemoattractant protein (MCP)-1, paralleled with the decreased natural killer cells may result
in the so-called cytokine storm. Immune dysregulation, rather than viremia levels per se,
has been related to the massive proinflammatory cytokine secretion by alveolar macrophages,
and subsequent CD4+ and CD8+ T cell dysfunction observed in SARS-CoV infection
[Channappanavar et al. 2016]. Hence, until specific vaccines become available, the use of
antiviral agents alone may not be sufficient to stop the cytokine storm and respiratory distress
in severely-ill patients. In the attempt of reducing their overall mortality, it is therefore
essential to identify new therapeutics able of mitigating the cytokine storm [Huang et al.
2020]. Nonetheless, redundancies within the complex cytokine network still represent a
major obstacle to monoclonal antibodies therapies. The ideal drug candidate should be
already in use for other indications, have a favorable safety profile and a multitargeted action,
able to synergistically mitigate the cytokine storm, acting as an immunomodulatory rather
than an immunosuppressant drug.
In a recent paper, high-cannabidiol (CBD) Cannabis Sativa extracts have been reported to
downregulate Angiotensin-converting enzyme 2 (ACE2) and Transmembrane Serine Protease
2 (TMPRSS2) receptors, crucial viral gateways in oral, lung and intestinal epithelia
constituting important routes of SARS-CoV2 invasion [Wang et al 2020]. By downregulating
This article is protected by copyright. All rights reserved.
ACE2 and TMPRSS2 receptors, the authors suggested high-CBD products, such as mouth
washes, as a preventative strategy in COVID-19 infection to limit SARS-CoV2 entry into
susceptible hosts. While this article puts forward the concept that cannabinoids-containing
products may serve as a preventative treatment for topical use, there is evidence suggesting
that CBD immunomodulatory activities may play a role in later stages of the disease.
We herein explore the hypothesis that systemic administration of CBD could have the
potential to limit COVID-19 disease progression and post-infectious sequelae.
Non-psychotropic phytocannabinoid CBD is considered one of the most interesting emerging
molecules in the field of pharmacology, since it exerts a wide range of therapeutic effects,
ranging from anticonvulsive, sedative, hypnotic, antipsychotic, anti-cancer, anti-
inflammatory and neuroprotective activities [Iffland and Grotenhermen, 2017]. Lacking of
the unwanted psychotropic effects of marijuana derivatives, CBD has little binding affinity to
cannabinoid receptors (acting as allosteric modulator of cannabinoid CB1 receptors) and a
favorable safety profile in humans [Iffland and Grotenhermen, 2017]. CBD acts as a powerful
antioxidant acting at various receptor sites, including peroxisome proliferator-activated
receptor gamma (PPAR), 5-hydroxytryptamine (5HT)-1A, Adenosine A2, transient receptor
potential (TRP) channels receptors to directly or indirectly display a wide range of anti-
inflammatory and immunomodulatory effects. A complete review of CBD receptor targets is
beyond the purpose of the present article and the readers are invited refer to more extensive
review on this subject [Iffland and Grotenhermen, 2017].
Such pleiotropic pharmacological activity has been tested in various pathological conditions,
including respiratory diseases resembling COVID19-induced respiratory distress. Acute Lung
injury (ALI) refers to a characteristic form of parenchymal lung disease, featured by bilateral
pulmonary infiltrates, alveolar-capillary vasculitis with neutrophil infiltration and
This article is protected by copyright. All rights reserved.
proinflammatory cytokines release, comparable to COVID19. By acting at adenosine A2
receptor site, CBD caused a marked amelioration of the pulmonary function [Ribeiro et al.
2015, Ribeiro et al. 2012] as a consequence of the significantly decreased lung resistance and
elastance due to the reduction of leukocyte migration into the lung, accompanied to a marked
inhibition of both pro-inflammatory cytokines (TNF and IL-6) and chemokines (MCP-1 and
MIP-2) released [Ribeiro et al. 2015, Ribeiro et al. 2012].
Although limited to interesting preclinical studies, scattered evidence also points towards a
possible use of CBD in viral infections. Indeed, several plant-derived compounds have
evolved to display antiviral activity, including many phenol-based compounds, such as
CBD and other cannabinoids exert their activity through the interaction with the nuclear
peroxisome proliferator-activated receptors (PPARs) [O’Sullivan and Kendall, 2010]. The
PPARs belong to the family of nuclear hormone receptors and their activity is regulated by
steroids and lipid metabolites. Three different PPAR isoforms (PPARα, PPARβ, also called δ,
and PPAR) have been identified and they have been described to regulate the expression of
genes related to lipid and glucose homeostasis and inflammatory responses.
PPAR agonism in resident alveolar macrophages significantly limits pulmonary
inflammation and promotes host recovery following respiratory viral infections [Huang et al.,
2019]. As it has been demonstrated during acute pneumonia, alveolar macrophage largely
express PPAR. PPAR activation is also responsible for the control of cytokine over-
secretion with consequent amelioration of the tissue damage. It is therefore likely that in
addition to directly determining an improvement in lung dynamics, CBD could significantly
counteract the onset of the cytokine storm from resident macrophages. Interestingly,
prophylactic or therapeutic administration of PPAR agonists led to reduction of morbidity
This article is protected by copyright. All rights reserved.
and mortality during influenza A virus infection [Bassaganya-Riera et al. 2010]. Not
coincidentally, the opportunity of thiazolidinediones repurposing for the treatment of
COVID-19 patients has been recently suggested, based on their activity on PPAR receptors
[Carboni et al. 2020]. Nonetheless, full PPARγ agonists bear several unwanted side effects
that could limit their clinical applicability in COVID-19 infection. The use of
thiazolidinediones indeed suffered a back-box warning from the FDA given the risk of
cardiovascular complications, such as acute myocardial infarction, heart failure and stroke.
Conversely, being a weak PPARγ agonist, CBD may overcome these limitations and be
voided of these side effects [Graham et al. 2010].
Moreover, PPAR agonists may directly inhibit viral replication by different human viruses
such as Human Immunodeficiency Virus, Respiratory syncytial virus, Hepatitis B Virus and
Hepatitis C Virus. Noteworthy, these experimental evidences are corroborated by recent
study showing a direct antiviral against HCV in vitro [Lowe et al. 2017].
Recent reports show that a subset of COVID-19 survivors can develop post-infectious
sequelae with persistently impaired lung function and pulmonary fibrosis [Ng et al. 2020].
PPAR-γ receptors represent a potential therapeutic target in fibrotic lung diseases, given their
ability of regulating fibroblast/myofibroblast activation and collagen secretion in murine
models [Milam et al. 2008]. Notably, CBD has been shown to reduce pulmonary
inflammation and fibrosis in animal models of asthma [Vuolo et al. 2018]. It is therefore
conceivable to speculate that, being a PPAR-γ receptor agonist, CBD can potentially limit the
onset of late-onset pulmonary fibrosis in COVID19-recovered patients.
Although CBD is a relatively safe molecule for humans and different trials have been
conducted [Millar et al. 2019] or are ongoing, especially in the field of neurological disorders
This article is protected by copyright. All rights reserved.
therapy; there are currently no evidences about the efficacy and relative toxicity of CBD in
Even if CBD was (incorrectly in our opinion) considered as a mere therapeutic supplement,
there is still lack of data regarding the relative toxicity profile in co-administration with other
drugs in the current anti-COVID19 protocols. According to a precautionary principle, a
possible strategy would be testing CBD therapeutic potential in COVID-19 patients (aged 18
years or older) either at an early stage of the disease to stop the cytokine storm and
development of respiratory distress, or alternatively, to evaluate its effectiveness in COVID-
19 recovered patients to prevent pulmonary fibrosis. CBD effects in vivo largely depend on
its doses and the bioavailability of its receptor targets in various pathological conditions.
Different plasmatic concentrations of CBD may be required in order to activate the distinct
pathways responsible for its multifaceted activity; indeed, subtherapeutic dosing (0.3
mg/kg/die) has been suggested to account for CBD lack of effectiveness in Crohn’s disease
[Millar et al. 2019]. In humans, CBD has been tested across a wide dosage range, varying
from <1 up to 50 mg pro kg/die depending on the trials and on the explored pathological
condition, with both in vitro and in vivo studies suggesting an immunosuppressive action at
higher concentrations or doses. Both in HIV and in post-Ebola syndrome, CBD has been
proposed as a therapeutic agent to control immune activation at the doses of 10-20 mg/kg/die
and 1.710 mg/kg/d (100 mg/die titrating up to 600 mg/die), respectively [Costiniuk et al,
2019; Reznik et al. 2016]. We suggest that CBD should be given orally starting at 100
mg/day titrating up to 300 mg/day (2.5 mg/kg/die), since this dosage did not produce relevant
adverse effects even for prolonged administrations (up to 18 weeks) in clinical trials in
humans. However, it is worth mentioning that most of the published clinical trials lack of the
effective plasmatic concentrations reached by orally-administered CBD in vivo. This has also
implications for its safety profile, since CBD acts as an in vitro inhibitor of several CYP450
This article is protected by copyright. All rights reserved.
isoforms [Millar et al. 2019]. As previously underlined, drugdrug interaction studies
between CBD and anti-COVID-19 treatments are lacking; therefore, monitoring of patients
for potential drug interactions would be required. Similarly, CYP inhibitors are predicted to
increase CBD plasma concentrations and patients should be carefully monitored for adverse
effects. Nonetheless, we do not anticipate serious adverse side effects, since the proposed
dose of CBD is generally well tolerated in humans and the half inhibitory concentration
(IC50) required to inhibit the CYP450 is significantly higher to the plasmatic concentration
of CBD achieved following oral administration. Finally, regarding the possible concerns
about immunosuppression during acute infections, we believe it is important to underline that
CBD did not determine an increased mortality in acutely infected animals; rather, in
pneumococcal meningitis, animal survival was increased and TNFα concentrations decreased
at the doses of 2.5, 5 and 10 mg/kg [Barichello et al. 2012].
The COVID19 pandemic is testing the planet. The off-label use of readily available
therapeutics able to limit the severity of the disease must be scrupulously scrutinized, pending
a vaccine against SARS- CoV2. In keeping with this, we consider CBD a promise candidate
drug to bet on, based on the encouraging preclinical studies and its relative safety profile in
humans (figure 1). Further evidence will be needed to confirm its beneficial activities and
turn CBD into a useful addition to the treatment of COVID-19.
This article is protected by copyright. All rights reserved.
Barichello T, Cerreta RA, Generoso JS, Moreira AP, Simo˜es LR, Comim CM, et al.
Cannabidiol reduces host immune response and prevents cognitive impairments in Wistar rats
submitted to pneumococcal meningitis. Eur J Pharmacol 2012; 697:15864.
Bassaganya-Riera J, Song R, Roberts PC, Hontecillas R. PPAR-gamma activation as an anti-
inflammatory therapy for respiratory virus infections. Viral Immunol. 2010;23:343352. doi:
Carboni E, Carta AR, Carboni E. Can pioglitazone be potentially useful therapeutically in
treating patients with covid-19? Med Hypotheses. 2020 Apr 22 : 109776. doi:
10.1016/j.mehy.2020.109776 [Epub ahead of print]
Channappanavar R, Fehr AR, Vijay R., Mack M., Zhao J., Meyerholz DK. et al.
Dysregulated type I interferon and inflammatory monocyte-macrophage responses cause
lethal pneumonia in SARS-CoV-infected mice. Cell Host Microbe. 2016;19(2):181193. doi:
Costiniuk CT, Saneei Z, Routy J, Margolese S., Mandarino E., Singer J., et al Oral
cannabinoids in people living with HIV on effective antiretroviral therapy: CTN PT028
study protocol for a pilot randomised trial to assess safety, tolerability and effect on immune
activation. BMJ Open. 2019 Jan 17;9(1):e024793. doi: 10.1136/bmjopen-2018-024793.
Graham DJ, Ouellet-Hellstrom R, MaCurdy TE, Ali F, Sholley C, Worrall C, et al. Risk of
acute myocardial infarction, stroke,heart failure,and death in elderly Medicare patients treated
with rosiglitazone or pioglitazone. JAMA. 2010 Jul 28;304(4):411-8. doi:
10.1001/jama.2010.920. Epub 2010 Jun 28.
Huang S, Goplen NP, Zhu B, Cheon IS, Son Y, Wang Z, et al. Macrophage PPAR-γ
suppresses long-term lung fibrotic sequelae following acute influenza infection. PLoS One.
2019 Oct 4;14(10):e0223430. doi: 10.1371/journal.pone.0223430. PMID: 31584978;
PMCID: PMC6777801.
Huang C, Wang Y, Li X, Ren L., Zhao J., Hu Y. et al. Clinical features of patients infected
with 2019 novel coronavirus in Wuhan, China Lancet. 2020;395(10223):497506.
Iffland K., Grotenhermen F. An Update on Safety and Side Effects of Cannabidiol: A Review
of Clinical Data and Relevant Animal Studies. Cannabis Cannabinoid Res. 2017;2:139154.
doi: 10.1089/can.2016.0034.
Lowe HI, Toyang NJ, McLaughlin W. Potential of Cannabidiol for the Treatment of Viral
Hepatitis. Pharmacognosy Res. 2017 Jan-Mar;9(1):116-118. doi: 10.4103/0974-8490.199780.
PMID: 28250664; PMCID: PMC5330095.
This article is protected by copyright. All rights reserved.
Milam JE, Keshamouni VG, Phan SH, Hu B, Gangireddy SR, Hogaboam CM et al. PPAR‐γ
agonists inhibit profibrotic phenotypes in human lung fibroblasts and bleomycin‐induced
pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 2008 May;294(5):L891-901. doi:
10.1152/ajplung.00333.2007. Epub 2007 Dec 27.
Millar SA, Stone NL, Bellman ZD, Yates AS, England, TJ O'Sullivan SE. A systematic
review of cannabidiol dosing in clinical populations. Br J Clin Pharmacol. 2019
Sep;85(9):1888-1900. doi: 10.1111/bcp.14038. Epub 2019 Jul 19.
Ng FH, Li SK, Lee YC, Ma JKF. Temporal changes in computed tomography of COVID-19
pneumonia with perilobular fibrosis. Hong Kong Med J. 2020 Apr 29. doi:
O’Sullivan SE, Kendall D. Cannabinoid activation of peroxisome proliferator-activated
receptors: Potential for modulation of inflammatory disease. Immunobiology 2010; 215:
Ribeiro A, Almeida VI, Costola-de-Souza C, Ferraz-de-Paula V, Pinheiro ML, Vitoretti LB,
et al. Cannabidiol improves lung function and inflammation in mice submitted to LPS-
induced acute lung injury. Immunopharmacol Immunotoxicol. 2015 Feb;37(1):35-41. doi:
10.3109/08923973.2014.976794. Epub 2014 Oct 30.
Ribeiro A, Ferraz-de-Paula V, Pinheiro ML, Vitoretti LB, Mariano-Souza DP, Quinteiro-
Filho WM, et al. Cannabidiol, a non-psychotropic plant-derived cannabinoid, decreases
inflammation in a murine model of acute lung injury: role for the adenosine A(2A) receptor .
Eur J Pharmacol. 2012 Mar 5;678(1-3):78-85. doi: 10.1016/j.ejphar.2011.12.043. Epub 2012
Jan 12.
Reznik SE, Gardner EL, Ashby Jr CR. Cannabidiol: a potential treatment for post Ebola
syndrome? Int. J Inf. Dis. 2016 (52) 74-76 DOI:
Vuolo, F., Abreu, S. C., Michels, M., Xisto DG, Blanco NG, Hallak JE. et al. Cannabidiol
reduces airway inflammation and fibrosis in experimental allergic asthma. Eur J Pharmacol.
2019 Jan 15;843:251-259. doi: 10.1016/j.ejphar.2018.11.029. Epub 2018 Nov 24.
Wang B, Kovalchuk A, Dongping L, Ilnytskyy Y, Kovalchuk I, Kovalchuk O. al. In Search
of Preventative Strategies: Novel AntiInflammatory High-CBD Cannabis Sativa Extracts
Modulate ACE2 Expression in COVID-19 Gateway Tissues. Preprints 2020, 2020040315
(doi: 10.20944/preprints202004.0315.v1)
This article is protected by copyright. All rights reserved.
Figure 1. The potential of cannabidiol in SARS-CoV2 infection.
... More generally, given the hastiness with which drugs are required during sudden pandemics, it would be highly desirable to repurpose drugs already used for clinical treatments that do not require further toxicity studies. Endocannabinoid-related compounds are endogenous bioactive lipid amides with pleiotropic homeostatic properties, including immune response regulation, control of food intake, neuroprotection, and inhibition of pain and inflammation [39][40][41][42][43][44][45]. These well-known multifaceted properties, readily translatable to clinics, and the lack of unwanted side effects have already attracted the attention of the scientific community toward the repurposing of these compounds during the COVID-19 pandemic [43,[46][47][48]. ...
... Endocannabinoid-related compounds are endogenous bioactive lipid amides with pleiotropic homeostatic properties, including immune response regulation, control of food intake, neuroprotection, and inhibition of pain and inflammation [39][40][41][42][43][44][45]. These well-known multifaceted properties, readily translatable to clinics, and the lack of unwanted side effects have already attracted the attention of the scientific community toward the repurposing of these compounds during the COVID-19 pandemic [43,[46][47][48]. In particular, Oleoylethanolamide (OEA), cannabidiol, PEA, and other unsaturated fatty acids have been selected as drug candidates for potential novel strategies against COVID-19 [47,49,50]. ...
... More generally, given the hastiness with which drugs are required during sudden pandemics, it would be highly desirable to repurpose drugs already used for clinical treatments that do not require further toxicity studies. Endocannabinoidrelated compounds are endogenous bioactive lipid amides with pleiotropic homeostatic properties, including immune response regulation, control of food intake, neuroprotection, and inhibition of pain and inflammation [39][40][41][42][43][44][45]. These well-known multifaceted properties, readily translatable to clinics, and the lack of unwanted side effects have already attracted the attention of the scientific community toward the repurposing of these compounds during the COVID-19 pandemic [43,[46][47][48]. ...
Full-text available
Lipids play a crucial role in the entry and egress of viruses, regardless of whether they are naked or enveloped. Recent evidence shows that lipid involvement in viral infection goes much further. During replication, many viruses rearrange internal lipid membranes to create niches where they replicate and assemble. Because of the close connection between lipids and inflammation, the derangement of lipid metabolism also results in the production of inflammatory stimuli. Due to its pivotal function in the viral life cycle, lipid metabolism has become an area of intense research to understand how viruses seize lipids and to design antiviral drugs targeting lipid pathways. Palmitoylethanolamide (PEA) is a lipid-derived peroxisome proliferator-activated receptor-α (PPAR-α) agonist that also counteracts SARS-CoV-2 entry and its replication. Our work highlights for the first time the antiviral potency of PEA against SARS-CoV-2, exerting its activity by two different mechanisms. First, its binding to the SARS-CoV-2 S protein causes a drop in viral infection of ~70%. We show that this activity is specific for SARS-CoV-2, as it does not prevent infection by VSV or HSV-2, other enveloped viruses that use different glycoproteins and entry receptors to mediate their entry. Second, we show that in infected Huh-7 cells, treatment with PEA dismantles lipid droplets, preventing the usage of these vesicular bodies by SARS-CoV-2 as a source of energy and protection against innate cellular defenses. This is not surprising since PEA activates PPAR-α, a transcription factor that, once activated, generates a cascade of events that leads to the disruption of fatty acid droplets, thereby bringing about lipid droplet degradation through β-oxidation. In conclusion, the present work demonstrates a novel mechanism of action for PEA as a direct and indirect antiviral agent against SARS-CoV-2. This evidence reinforces the notion that treatment with this compound might significantly impact the course of COVID-19. Indeed, considering that the protective effects of PEA in COVID-19 are the current objectives of two clinical trials (NCT04619706 and NCT04568876) and given the relative lack of toxicity of PEA in humans, further preclinical and clinical tests will be needed to fully consider PEA as a promising adjuvant therapy in the current COVID-19 pandemic or against emerging RNA viruses that share the same route of replication as coronaviruses.
... There is evidence, albeit limited, that cannabidiol (CBD) may have potential as an anti-SARS-CoV-2 agent [48,[67][68][69][70][71] presented concomitantly with important warnings against prescription of cannabinoid products for COVID-related symptoms at present [50,72]. For example, CBD has been suggested to be an efficient inhibitor of SARS-CoV-2 (strain 229E) replication in human lung fibroblasts (MRC-5) through enhancement of antiviral terpene efficacy [68]. ...
... Both THC and CBD have been reported to interact with the Mpro protein of SARS-CoV-2 and to exhibit anti-SARS-CoV-2 activities with an IC50 of 10.25 µM and 7.91 µM, respectively [48]. Moreover, Esposito et al. [69] have hypothesized that CBD may have some adjunctive anti-COVID efficacy, as CBD administration can down-regulate the expression of SARS-CoV2 receptors (ACE2, transmembrane proteinase 2 [TMPRSS2]) in 3D human epithelial tissue models, as initially reported by Wang et al. [70]. ...
Full-text available
Cannabinoid receptor 2 (CB2) is of interest as a much-needed target for the treatment or prevention of several neurogenerative diseases. However, CB2 agonists, particularly phytocannabinoids, have been ascribed antimicrobial properties and are associated with the induction of microbiome compositional fluxes. When developing novel CB2 therapeutics, CB2 engagement and antimicrobial functions should both be considered. This review summarizes those cannabinoids and cannabis-informed molecules and preparations (CIMPs) that show promise as microbicidal agents, with a particular focus on the most recent developments. CIMP–microbe interactions and anti-microbial mechanisms are discussed, while the major knowledge gaps and barriers to translation are presented. Further research into CIMPs may proffer novel direct or adjunctive strategies to augment the currently available antimicrobial armory. The clinical promise of CIMPs as antimicrobials, however, remains unrealized. Nevertheless, the microbicidal effects ascribed to several CB2 receptor-agonists should be considered when designing therapeutic approaches for neurocognitive and other disorders, particularly in cases where such regimens are to be long-term. To this end, the potential development of CB2 agonists lacking antimicrobial properties is also discussed.
... Furthermore, PPARγ activation is also responsible for the control of cytokine over-production with consequent amelioration of the tissue damage (Esposito et al., 2020). Several studies have indicated that genistein increases upregulating PPARγ expression (Hall et al., 2019;Valles et al., 2010;Wang et al., 2014). ...
Full-text available
The Coronavirus Disease 2019 (COVID‐19) pandemic has been caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). It is a global problem that humanity has not yet found a definitive solution for it. In this regard, a global effort has been done to find effective or potential adjuvant therapies in order to fight this infection. Genistein is a small, biologically active phytoestrogen flavonoid that is found in high amounts in soy and plants of the Fabaceae family. This important compound is known due to its anti‐cancer, anti‐inflammatory, and antioxidant effects. Additionally, protective effects of genistein have been reported in different pathological conditions through modulating intracellular pathways such as PI3K, Akt, mTOR, NF‐κB, PPARγ, AMPK, and Nrf2. Scientific evidence suggests that genistein could have a potential role to treat COVID‐19 through its anti‐inflammatory and anti‐oxidant effects. Furthermore, it appears to interfere with intracellular pathways involved in viral entry into the cell. This review provides a basis for further research and development of clinical applications of genistein as a potential alternative therapy to decrease inflammation and oxidative stress in COVID‐19 patients. Practical applications The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the etiological agent for the Coronavirus Disease 2019 (COVID‐19), has brought unprecedented untold hardship to both developing and developed countries. The inflammation, cytokine storm, and oxidative stress have an important role in the pathogenesis of this infection. In this regard, finding plant‐derived compounds with anti‐inflammatory and anti‐oxidative effects would be very beneficial in reducing the mortality induced by this infection. Genistein an isoflavone derived from soy‐rich products possesses versatile biological activities. It has potent anti‐inflammatory and anti‐oxidative and immunomodulatory effects. Furthermore, this compound may prevent viral entry to host cells and reduce SARS‐CoV2‐induced lung injury. Therefore, we suggest further studies on the effects of genistein on SARS‐Cov‐2 infection.
... Cannabis and Cannabidiol: Cannabidiol, one of the Cannabis constituents, can block SARS-CoV-2 virus entry to the cell by downregulating ACE2 enzymes [3]. NCT03944447 is inquiring about the ability of Cannabis in inhibiting the virus entry, for the prevention of COVID-19. ...
Full-text available
In this study, we addressed the alternative medications that have been targeted in the clinical trials (CTs) to be evidenced as an adjuvant treatment against COVID-19. Based on the outcomes from CTs, we found that dietary supplements such as Lactoferrin, and Probiotics (as SivoMixx) can play a role enhancing the immunity thus can be used as prophylactics against COVID-19 infection. Vitamin D was proven as an effective adjuvant treatment against COVID-19, while Vitamin C role is uncertain and needs more investigation. Herbals such as Guduchi Ghan Vati can be used as prophylactic, while Resveratrol can be used to reduce the hospitalization risk of COVID-19 patients. On the contrary, there were no clinical improvements demonstrated when using Cannabidiol. This study is a part of a two-phase research study. In the first phase, we gathered evidence-based information on alternative therapeutics for COVID-19 that are under CT. In the second phase, we plan to build a mobile health application that will provide evidence based alternative therapy information to health consumers.
... Besides, activation of Nrf2 following Crocin treatment leads to down-regulation of ACE2 receptors, thereby inhibiting viral entry to cells. Also, PPAR-γ inhibits over-production of cytokines and NF-κB pathway and Crocin has a potential immune-modulatory role by increasing the expression of PPAR-γ, preventing cytokine storm, and protecting against severe clinical symptoms of COVID-19 [222,224,232]. Also, bleomycin-induced pulmonary fibrosis in rat was improved after treatment with Crocin owing to its antioxidant, anti-inflammatory, and immuno-modulatory properties [233]. ...
Full-text available
Crocin, an active ingredient derived from saffron, is one of the herbal components that has recently been considered by researchers. Crocin has been shown to have many anti-inflammatory and antioxidant properties, and therefore can be used to treat various diseases. It has been shown that Crocin has a positive effect on the prevention and treatment of cardiovascular disease, cancer, diabetes, and kidney disease. In addition, the role of this substance in COVID-19 pandemic has been identified. In this review article, we tried to have a compre- hensive review of the antioxidant and anti-inflammatory effects of Crocin in different diseases and different tissues. In conclusion, Crocin may be helpful in pathological conditions that are associated with inflammation and oxidative stress.
... Cannabinoids have been proposed as potential therapies or adjuvant drugs against the SARS-CoV-2 infection from the beginning of the COVID-19 pandemic because of their anti-inflammatory and immunomodulatory activities [4,90,97,98]. ...
Full-text available
This review is dedicated to the cross-talk between the (endo)cannabinoid and renin angiotensin systems (RAS). Activation of AT1 receptors (AT1Rs) by angiotensin II (Ang II) can release endocannabinoids that, by acting at cannabinoid CB1 receptors (CB1Rs), modify the response to AT1R stimulation. CB1R blockade may enhance AT1R-mediated responses (mainly vasoconstrictor effects) or reduce them (mainly central nervous system-mediated effects). The final effects depend on whether stimulation of CB1Rs and AT1Rs induces opposite or the same effects. Second, CB1R blockade may diminish AT1R levels. Third, phytocannabinoids modulate angiotensin-converting enzyme-2. Additional studies are required to clarify (1) the existence of a cross-talk between the protective axis of the RAS (Ang II—AT2 receptor system or angiotensin 1-7—Mas receptor system) with components of the endocannabinoid system, (2) the influence of Ang II on constituents of the endocannabinoid system and (3) the (patho)physiological significance of AT1R-CB1R heteromerization. As a therapeutic consequence, CB1R antagonists may influence effects elicited by the activation or blockade of the RAS; phytocannabinoids may be useful as adjuvant therapy against COVID-19; single drugs acting on the (endo)cannabinoid system (cannabidiol) and the RAS (telmisartan) may show pharmacokinetic interactions since they are substrates of the same metabolizing enzyme of the transport mechanism.
... Even with optimal viral suppression, YWH will have chronic inflammation across their life span with its associated comorbidities. If it can be demonstrated that marijuana attenuates pro-inflammatory cytokines in chronic infections such as HIV, or even COVID-19 [81], our results may have implications for management of other inflammatory conditions. ...
Full-text available
Background Marijuana’s putative anti-inflammatory properties may benefit HIV-associated comorbidities. How recreational marijuana use affects gene expression in peripheral blood cells (PBC) among youth with HIV-1 (YWH) is unknown. Approach YWH with defined substance use (n = 54) receiving similar antiretroviral therapy (ART) were assigned to one of four analysis groups: YWH with detectable plasma HIV-1 (> 50 RNA copies/ml) who did not use substances (H+V+S−), and YWH with undetectable plasma HIV-1 who did not use substances (H+V−S−), or used marijuana alone (H+V−S+[M]), or marijuana in combination with tobacco (H+V−S+[M/T]). Non-substance using youth without HIV infection (H−S−, n = 25) provided a reference group. PBC mRNA was profiled by Affymetrix GeneChip Human Genome U133 Plus 2.0 Array. Differentially expressed genes (DEG) within outcome groups were identified by Significance Analysis of Microarrays and used for Hierarchical Clustering, Principal Component Analysis, and Ingenuity Pathways Analysis. Results HIV-1 replication resulted in > 3000 DEG involving 27 perturbed pathways. Viral suppression reduced DEG to 313, normalized all 27 pathways, and down-regulated two additional pathways, while marijuana use among virally suppressed YWH resulted in 434 DEG and no perturbed pathways. Relative to H+V−S−, multiple DEG normalized in H+V−S+[M]. In contrast, H+V−S+[M/T] had 1140 DEG and 10 dysregulated pathways, including multiple proinflammatory genes and six pathways shared by H+V+S−. Conclusions YWH receiving ART display unique transcriptome bioprofiles based on viral replication and substance use. In the context of HIV suppression, marijuana use, alone or combined with tobacco, has opposing effects on inflammatory gene expression.
Full-text available
Currently, the number of cases and deaths of SARS-CoV2, especially among the chronic disease groups, due to aggressive SARS-CoV2 infection is increasing day by day. Various infections, particularly viral ones, cause a cytokine storm resulting in shortness of breath, bleeding, hypotension, and ultimately multi-organ failure due to over-expression of certain cytokines and necrosis factors. The most prominent clinical feature of SARS-CoV2 is the presence of elevated proinflammatory cytokines in the serum of patients with SARS-CoV2. Severe cases exhibit higher levels of cytokines, leading to a “cytokine storm” that further increases disease severity and causes acute respiratory distress syndrome, multiple organ failure, and death. Therefore, targeted cytokine production could be a potential therapeutic option for patients severely infected with SARS-CoV2. Given the current scenario, great scientific progress has been made in understanding the disease and its forms of treatment. Because of natural ingredients properties, they have the potential to be used as potential agents with the ability to modulate immune responses. Moreover, they can be used safely because they have no toxic effects, are biodegradable and biocompatible. However, these natural substances can continue to be used in the development of new therapies and vaccines. Finally, the aim and approach of this review article is to highlight current research on the possible use of natural products with promising potential as immune response activators. Moreover, consider the expected use of natural products when developing potential therapies and vaccines.
The recent legalization of cannabidiol (CBD) to treat neurological conditions such as epilepsy has sparked rising interest across global pharmaceuticals and synthetic biology industries to engineer microbes for sustainable synthetic production of medicinal CBD. Since the process involves screening large amounts of samples, the main challenge is often associated with the conventional screening platform that is time consuming, and laborious with high operating costs. Here, a portable, high‐throughput Aptamer‐based BioSenSing System (ABS3) is introduced for label‐free, low‐cost, fully automated, and highly accurate CBD concentrations’ classification in a complex biological environment. The ABS3 comprises an array of interdigitated microelectrode sensors, each functionalized with different engineered aptamers. To further empower the functionality of the ABS3, unique electrochemical features from each sensor are synergized using physics‐guided multidimensional analysis. The capabilities of this ABS3 are demonstrated by achieving excellent CBD concentrations’ classification with a high prediction accuracy of 99.98% and a fast testing time of 22 µs per testing sample using the optimized random forest (RF) model. It is foreseen that this approach will be the key to the realistic transformation from fundamental research to system miniaturization for diagnostics of disease biomarkers and drug development in the field of chemical/bioanalytics. An Aptamer‐based BioSenSing System (ABS3) comprising an array of aptamer‐functionalized interdigitated microelectrodes for accurate identification and concentration classification of cannabidiol is developed. Unique electrochemical features from each sensor are synergized using physics‐guided multidimensional analysis, and the ABS3 achieves excellent cannabidiol concentration classification with a high prediction accuracy of 99.98% using the random forest model.
The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory distress syndrome coronavirus 2 (SARS-Cov-2), was identified for the first time in late 2019 in China, resulting in a global pandemic of massive impact. Despite a fast development and implementation of vaccination strategies, and the scouting of several pharmacological treatments, alternative effective treatments are still needed. In this regard, cannabinoids represent a promising approach because they have been proven to exhibit several immunomodulatory, anti-inflammatory, and antiviral properties in COVID-19 disease models and related pathological conditions. This mini-review aims at providing a practical brief overview of the potential applications of cannabinoids so far identified for the treatment and prevention of COVID-19, finally considering key aspects related to their technological and clinical implementation.
Full-text available
Background: A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods: All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings: By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0-58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0-13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation: The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding: Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
Full-text available
Influenza virus causes a heterogeneous respiratory infectious disease ranging from self-limiting symptoms to non-resolving pathology in the lungs. Worldwide, seasonal influenza infections claim ~500,000 lives annually. Recent reports describe pathologic pulmonary sequelae that result in remodeling the architecture of lung parenchyma following respiratory infections. These dysfunctional recovery processes that disproportionately impact the elderly have been understudied. Macrophages are involved in tissue remodeling and are critical for survival of severe influenza infection. Here, we found intrinsic deficiency of the nuclear receptor PPAR-γ in myeloid cells delayed the resolution of pulmonary inflammation following influenza infection. Mice with myeloid cell-specific PPAR-γ deficiency subsequently presented with increased influenza-induced deposition of pulmonary collagen compared to control mice. This dysfunctional lung remodeling was progressive and sustained for at least 3 months following infection of mice with myeloid PPAR-γ deficiency. These progressive changes were accompanied by a pro-fibrotic gene signature from lung macrophages and preceded by deficiencies in activation of genes involved with damage repair. Importantly similar aberrant gene expression patterns were also found in a secondary analysis of a study where macrophages were isolated from patients with fibrotic interstitial lung disease. Quite unexpectedly, mice with PPAR-γ deficient macrophages were more resistant to bleomycin-induced weight loss whereas extracellular matrix deposition was unaffected compared to controls. Therefore PPAR-γ expression in macrophages may be a pathogen-specific limiter of organ recovery rather than a ubiquitous effector pathway in response to generic damage.
Full-text available
Aims: Cannabidiol is a cannabis-derived medicinal product with potential application in a wide-variety of contexts, however its effective dose in different disease states remains unclear. This review aimed to investigate what doses have been applied in clinical populations, in order to understand the active range of cannabidiol in a variety of medical contexts. Methods: Publications involving administration of cannabidiol alone were collected by searching PubMed, EMBASE and Results: A total of 1038 articles were retrieved, of which 35 studies met inclusion criteria covering 13 medical contexts. 23 studies reported a significant improvement in primary outcomes (e.g. psychotic symptoms, anxiety, seizures), with doses ranging between <1 - 50 mg/Kg/day. Plasma concentrations were not provided in any publication. Cannabidiol was reported as well tolerated and epilepsy was the most frequently studied medical condition, with all 11 studies demonstrating positive effects of cannabidiol on reducing seizure frequency or severity (average 15 mg/Kg/day within randomised controlled trials). There was no signal of positive activity of CBD in small randomised controlled trials (range n=6-62) assessing diabetes, Crohn's disease, ocular hypertension, fatty liver disease or chronic pain. However, low doses (average 2.4 mg/Kg/day) were used in these studies. Conclusion: This review highlights cannabidiol has a potential wide range of activity in several pathologies. Pharmacokinetic studies as well as conclusive phase III trials to elucidate effective plasma concentrations within medical contexts are severely lacking and highly encouraged.
Full-text available
Introduction Despite antiretroviral therapy (ART), people living with HIV have higher rates of non-infectious chronic diseases. These conditions are driven by relatively high levels of inflammation persisting on ART compared with uninfected individuals. Chronic inflammation also contributes to HIV persistence during ART. Cannabis when taken orally may represent a way to reduce inflammation and strengthen immune responses. Before planning large interventional studies, it is important to ensure that cannabis taken orally is safe and well tolerated in people living with HIV. We propose to conduct a pilot randomised trial to examine the safety and tolerability of cannabis oils containing tetrahydrocannabinol (THC) and cannabidiol (CBD) consumed orally in people living with HIV. We will also measure inflammatory markers, markers of HIV persistence in peripheral blood cells and changes in the gastrointestinal microbiome. Methods and analysis Twenty-six people living with HIV having undetectable viral load for at least 3 years will be randomised to receive TN-TC11LM (THC:CBD in 1:1 ratio) or TN-TC19LM (THC:CBD in 1:9 ratio) capsules daily for 12 weeks. Safety and tolerability of these capsules will be assessed through haematological, hepatic and renal blood tests, face-to-face interviews and questionnaires. Proportions of participants without any signs of significant toxicity (grades 0–2 scores on the WHO toxicity scale) and who complete the study, as well as scores on quality of life and mood will be examined using descriptive statistics. The effects on inflammatory markers, markers of peripheral blood reservoir size and effect on the composition of the gastrointestinal microbiome will be assessed before and after study completion. Ethics and dissemination This study has been approved by the Research Institute of the McGill University Health Centre. A Data Safety Monitor will review safety information at regular intervals. The final manuscript will be submitted to an open-access journal within 6 months of study completion. Trial registration number NCT03550352 .
Full-text available
Asthma is characterized by chronic lung inflammation and airway hyperresponsiveness. Asthma remains a major public health problem and, at present, there are no effective interventions capable of reversing airway remodelling. Cannabidiol (CBD) is known to exert immunomodulatory effects through the activation of cannabinoid-1 and − 2 (CB1 and CB2) receptors located in the central nervous system and immune cells, respectively. However, as the role of CBD on airway remodelling and the mechanisms of CB1 and CB2 aren’t fully elucidated, this study was designed to evaluate the effects of cannabidiol in this scenario. Allergic asthma was induced in Balb/c mice exposed to ovalbumin, and respiratory mechanics, collagen fibre content in airway and alveolar septa, cytokine levels, and CB1 and CB2 expression were determined. Moreover, expressions of CB1 and CB2 in induced sputum of asthmatic individuals and their correlation with airway inflammation and lung function were also evaluated. CBD treatment, regardless of dosage, decreased airway hyperresponsiveness, whereas static lung elastance only reduced with high dose. These outcomes were accompanied by decreases in collagen fibre content in both airway and alveolar septa and the expression of markers associated with inflammation in the bronchoalveolar lavage fluid and lung homogenate. There was a significant and inverse correlation between CB¹ levels and lung function in asthmatic patients. CBD treatment decreased the inflammatory and remodelling processes in the model of allergic asthma. The mechanisms of action appear to be mediated by CB1/CB2 signalling, but these receptors may act differently on lung inflammation and remodelling.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic disease (COVID-19) that has spread globally causing more than 30,000 deaths. Despite the immense and ongoing global effort, no efficacious drugs to fight this plague have been identified and patients admitted to the intensive care units (ICU), for respiratory distress, are managed mostly by means of supportive care based on oxygen maintenance. Several authors have reported that the prevalence of hypertension, diabetes, cardiovascular and cerebrovascular diseases comorbidities were indeed frequent among patients with COVID-19, which suggests that these conditions are likely to aggravate and complicate the prognosis. What the aforementioned diseases have in common is a latent chronic inflammatory state that may be associated with the alteration of laboratory parameters that are typical of the metabolic syndrome and insulin resistance. In severe COVID-19 patients laboratory markers of inflammation such as C-reactive protein, IL-6, D-dimer, serum ferritin and lactate dehydrogenase are elevated in many patients; assessed since the 4th-6th day of illness onset, such increases seem to be predictive of an adverse prognosis. Our hypothesis is that drugs belonging to the family of thiazolidinediones (TZD) such as pioglitazone or rosiglitazone, approved for treating the condition of insulin resistance and the accompanying inflammation, could ameliorate the prognosis of those COVID-19 patients with diabetes, hypertension and cardiovascular disorders comorbidities. TZD are PPARγ agonists that act on nuclear receptors, thereby triggering certain transcription factors. TZD were widely used for type-2 diabetes in the first decade of this century and although concerns have been raised for possible side effects associated with long-term treatment, their use has been recently revaluated for their anti-inflammatory properties in numerous medical conditions.
With the rapidly growing pandemic of COVID-19 caused by the new and challenging to treat zoonotic SARS-CoV2 coronavirus, there is an urgent need for new therapies and prevention strategies that can help curtail disease spread and reduce mortality. Inhibition of viral entry and thereby spread constitute plausible therapeutic avenues. Similar to other respiratory pathogens, SARS-CoV2 is transmitted through respiratory droplets, with potential for aerosol and contact spread. It uses receptor-mediated entry into the human host via angiotensin-converting enzyme II (ACE2) that is expressed in lung tissue, as well as oral and nasal mucosa, kidney, testes, and the gastrointestinal tract. Modulation of ACE2 levels in these gateway tissues may prove a plausible strategy for decreasing disease susceptibility. Cannabis sativa, especially one high in the anti-inflammatory cannabinoid cannabidiol (CBD), has been proposed to modulate gene expression and inflammation and harbour anti-cancer and anti-inflammatory properties. Working under the Health Canada research license, we have developed over 800 new Cannabis sativa lines and extracts and hypothesized that high-CBD C. sativa extracts may be used to modulate ACE2 expression in COVID-19 target tissues. Screening C. sativa extracts using artificial human 3D models of oral, airway, and intestinal tissues, we identified 13 high CBD C. sativa extracts that modulate ACE2 gene expression and ACE2 protein levels. Our initial data suggest that some C. sativa extract down-regulate serine protease TMPRSS2, another critical protein required for SARS-CoV2 entry into host cells. While our most effective extracts require further large-scale validation, our study is crucial for the future analysis of the effects of medical cannabis on COVID-19. The extracts of our most successful and novel high CBD C. sativa lines, pending further investigation, may become a useful and safe addition to the treatment of COVID-19 as an adjunct therapy. They can be used to develop easy-to-use preventative treatments in the form of mouthwash and throat gargle products for both clinical and at-home use. Such products ought to be tested for their potential to decrease viral entry via the oral mucosa. Given the current dire and rapidly evolving epidemiological situation, every possible therapeutic opportunity and avenue must be considered.
Introduction: This literature survey aims to extend the comprehensive survey performed by Bergamaschi et al. in 2011 on cannabidiol (CBD) safety and side effects. Apart from updating the literature, this article focuses on clinical studies and CBD potential interactions with other drugs. Results: In general, the often described favorable safety profile of CBD in humans was confirmed and extended by the reviewed research. The majority of studies were performed for treatment of epilepsy and psychotic disorders. Here, the most commonly reported side effects were tiredness, diarrhea, and changes of appetite/weight. In comparison with other drugs, used for the treatment of these medical conditions, CBD has a better side effect profile. This could improve patients' compliance and adherence to treatment. CBD is often used as adjunct therapy. Therefore, more clinical research is warranted on CBD action on hepatic enzymes, drug transporters, and interactions with other drugs and to see if this mainly leads to positive or negative effects, for example, reducing the needed clobazam doses in epilepsy and therefore clobazam's side effects. Conclusion: This review also illustrates that some important toxicological parameters are yet to be studied, for example, if CBD has an effect on hormones. Additionally, more clinical trials with a greater number of participants and longer chronic CBD administration are still lacking.
Viral hepatitis B (HBV) and hepatitis C (HCV) pose a major health problem globally and if untreated, both viruses lead to severe liver damage resulting in liver cirrhosis and cancer. While HBV has a vaccine, HCV has none at the moment. The risk of drug resistance, combined with the high cost of current therapies, makes it a necessity for cost-effective therapeutics to be discovered and developed. The recent surge in interest in Medical Cannabis has led to interest in evaluating and validating the therapeutic potentials of Cannabis and its metabolites against various diseases including viruses. Preliminary screening of cannabidiol (CBD) revealed that CBD is active against HCV but not against HBV in vitro. CBD inhibited HCV replication by 86.4% at a single concentration of 10 μM with EC50 of 3.163 μM in a dose-response assay. These findings suggest that CBD could be further developed and used therapeutically against HCV. Summary: Cannabidiol exhibited in vitro activity against viral hepatitis C. Abbreviations Used: CB2: Cannabis receptor 2, CBD: Cannabidiol, DNA: Deoxyribonucleic acid, HBV: Hepatitis B virus, HCV: Hepatitis C virus, HIV/AIDS: Human immunodeficiency virus/acquired immune deficiency syndrome, HSC: Hepatic stellate cells, MTS: 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2Htetrazolium, PCR: Polymerase chain reaction.