Antiviral Activities of Cannabis

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“Despite the history of scientific evidence regarding plants and their products in prophylactics and therapeutics, their applications in healthcare systems are only now gaining momentum.

Plants contain bioactive compounds that target certain viruses to cure or prevent viral diseases and infections.

They provide a rich resource of antiviral drugs. Identifying the antiviral mechanisms in plants has shed light on where they interact with the life cycle of viruses, such as viral entry, replication, assembly, and release.”

Terpenes and cannabidiol against human corona and influenza viruses-Anti-inflammatory and antiviral in vitro evaluation

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“The activity of the terpenes and Cannabidiol (CBD) against human coronavirus (HCoV) strain OC43 and influenza A (H1N1) was evaluated in human lung fibroblasts (MRC-5 cells). Also, we examined whether these ingredients inhibit pro-inflammatory cytokines in peripheral blood mononuclear cells (PBMC).

The tested preparations exhibited both anti-inflammatory and antiviral effects. The combination of terpenes was effective against both HCoV-OC43 and influenza A (H1N1) virus.

The addition of CBD improved the antiviral activity in some, but not all cases. This variation in activity may suggest an antiviral mechanism. In addition, there was a strong correlation between the quantitative results from a cell-viability assay and the cytopathic effect after 72 h, as observed under a microscope.

The anti-inflammatory properties of terpenes were demonstrated using a pro-inflammatory cytokine-inhibition assay, which revealed significant cytokine inhibition and enhanced by the addition of CBD.”

Cannabinoids and the Endocannabinoid System in Early SARS-CoV-2 Infection and Long COVID-19-A Scoping Review

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“Coronavirus disease-19 (COVID-19) is a highly contagious illness caused by the SARS-CoV-2 virus.

The clinical presentation of COVID-19 is variable, often including symptoms such as fever, cough, headache, fatigue, and an altered sense of smell and taste. Recently, post-acute “long” COVID-19 has emerged as a concern, with symptoms persisting beyond the acute infection. Vaccinations remain one of the most effective preventative methods against severe COVID-19 outcomes and the development of long-term COVID-19. However, individuals with underlying health conditions may not mount an adequate protective response to COVID-19 vaccines, increasing the likelihood of severe symptoms, hospitalization, and the development of long-term COVID-19 in high-risk populations.

This review explores the potential therapeutic role of cannabinoids in limiting the susceptibility and severity of infection, both pre- and post-SARS-CoV-19 infection.

Early in the SARS-CoV-19 infection, cannabinoids have been shown to prevent viral entry, mitigate oxidative stress, and alleviate the associated cytokine storm.

Post-SARS-CoV-2 infection, cannabinoids have shown promise in treating symptoms associated with post-acute long COVID-19, including depression, anxiety, post-traumatic stress injury, insomnia, pain, and decreased appetite.

While current research primarily focuses on potential treatments for the acute phase of COVID-19, there is a gap in research addressing therapeutics for the early and post-infectious phases. This review highlights the potential for future research to bridge this gap by investigating cannabinoids and the endocannabinoid system as a potential treatment strategy for both early and post-SARS-CoV-19 infection.”

Feasibility of a cannabidiol (CBD)-dominant cannabis-based medicinal product (CBMP) for the treatment of Long COVID symptoms: A single arm open-label feasibility trial

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“Aims: To conduct a single arm open-label feasibility trial of the safety and tolerability of a full-spectrum cannabidiol (CBD)-dominant cannabis-based medicinal product (CBMP) for treating the symptoms of Long COVID.

Methods: The treatment phase ran for a total of 21 weeks, followed by ~3 weeks without the study drug. Participants received up to 3 mL of MediCabilis 5% CBD Oil (50 mg CBD/mL, <2 mg delta-9-tetrahydrocannabinol (THC)/mL) per day orally. Monthly patient reported outcome measures (PROMs) of common symptoms and daily self-report of symptoms were collected via a smartphone app. Key measures of heart rate, activity, sleep, and oxygen saturation were assessed using wearable technology.

Results: 12 (1 male, 11 female) individuals diagnosed with Long COVID were recruited into the trial. All patients adhered to the treatment protocol for the duration of the study and there were no serious adverse events. Response rates for the research assessments were high with over 90% completion of PROMs and daily self-report.

Conclusion: The study drug was safe and well tolerated, demonstrating feasibility of CBD-dominant CBMPs in individuals diagnosed with Long COVID. However, there were limitations in research design related to recruitment strategy demonstrating a lack of feasibility in the approach implemented in this study. Future work with larger samples and incorporating a control group are required to test the efficacy of this treatment.”

Isolation and in silico investigation of cannflavins from Cannabis sativa leaves as potential anti-SARS-CoV-2 agents targeting the Papain-Like Protease

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“This study aimed to isolate and identify three prenylflavonoids (cannflavin A, B, and C) from Cannabis sativa leaves using different chromatographic techniques. The potential of the isolated compounds against SARS-CoV-2 was suggested through several in silico analysis. Structural similarity studies against nine co-crystallized ligands of SARS-CoV-2’s proteins indicated the similarities of the isolated cannflavins with the SARS-CoV-2 Papain-Like Protease (PLP) ligand, Y95. Then, flexible allignment study confirmed this similarity. Docking experiments showed successful binding of all cannflavins within the active pocket of PLP, with energies comparable to Y95. Among them, cannflavin A demonstrated the most similar binding mode, while cannflavin C exhibited the best energy. Molecular dynamics (MD) simulations and MM-GPSA confirmed the accurate binding of cannflavin A to the PLP. In silico ADMET studies indicated favourable drug-like properties for all three compounds, suggesting their potential as anti-SARS-CoV-2 agents. Further In vitro and In vivo investigations are necessary to validate these findings and establish their efficacy and safety profiles.”


“PURPOSE: Marijuana use is becoming increasingly prevalent worldwide, yet the full spectrum of its effects largely remains unknown. Although cannabinoids have immunomodulatory properties, there remains a significant gap in our understanding of the potential impact of marijuana use on COVID-19 outcomes. The purpose of the study is to compare the outcomes of COVID-19 infection on individuals who use marijuana and those who do not.

METHODS: National Inpatient Sample Database was used to sample individuals admitted with the diagnosis of COVID-19. Patients were divided into two groups based on marijuana use. Baseline demographics and comorbidities were collected using ICD-10 codes. Patients with missing data or age under 18 were excluded. Greedy propensity matching using R was performed to match marijuana users to non-users 1:1 on age, race, gender, and 17 other comorbidities including chronic lung disease. Univariate analysis pre- and post-match were performed. Binary logistic regression was performed post-match. A p-value of <0.05 was considered statistically significant.

RESULTS: Out of 322,214 patients included in the study, 2,603 were marijuana users. Marijuana users were younger and had higher prevalence of tobacco use. However, other comorbidities including obstructive sleep apnea, obesity, hypertension, and diabetes mellitus were more prevalent in marijuana non-users. On univariate analysis, marijuana users had significantly lower rates of intubation (6.8% vs 12%), acute respiratory distress syndrome (ARDS) (2.1% vs 6%), acute respiratory failure (25% vs 52.9%) and severe sepsis with multiorgan failure (5.8% vs 12%). They also had lower in-hospital cardiac arrest (1.2% vs 2.7%) and mortality (2.9% vs 13.5%). After 1:1 matching, marijuana users had lower rates of intubation (OR: 0.64 [0.51-0.81]; p<0.01), ARDS (OR: 0.39 [0.26-0.58]; p<0.01), acute respiratory failure (OR: 0.53 [0.47-0.61]; p<0.01), severe sepsis with multiorgan failure (OR: 0.68 [0.52-0.89]; p<0.01) and lower mortality (OR: 0.48 [0.33-0.69]; p<0.01)

CONCLUSIONS: Marijuana smokers had better outcomes and mortality compared to non-users. The beneficial effect of marijuana use may be attributed to its potential to inhibit viral entry into cells and prevent the release of proinflammatory cytokines, thus mitigating cytokine release syndrome.

CLINICAL IMPLICATIONS: The significant decrease in mortality and complications warrants further investigation of the association between marijuana use and COVID-19. Our study highlights a topic of future research for larger trials especially considering the widespread use of marijuana.”

“Study Finds Cannabis Users Had Better Covid-19 Outcomes”

The Potential of Cannabidiol for Acute Respiratory Distress Syndrome in COVID-19

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“COVID-19 disease manifests itself in a wide range of signs and symptoms, beginning with mild symptoms, such as fever, cough, and dyspnea, progressing to acute respiratory distress syndrome (ARDS) and death in some cases. The cytokine storm, or an excess of cytokines released locally, is assumed to be the primary cause of ARDS and mortality in COVID-19 patients. To enhance the survival rate of COVID-19 patients, early management of the cytokine storm with immunomodulators is crucial. Although the effectiveness of some immunosuppressants, such as corticosteroids and tocilizumab, has been studied in clinical trials, the administration of these drugs should be exercised cautiously. Cannabidiol (CBD) is a non-psychotropic phytocannabinoid from Cannabis sativa extracts with anti-inflammatory properties. This review is intended to discuss the possible utility of CBD for the management of COVID-19 patients, particularly those with ARDS.”

Cannabidiol Reduces Systemic Immune Activation in Experimental Acute Lung Injury

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“Background: The underlying pathomechanism of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is the immune response to inflammation or infection within the pulmonary microcirculation. Systemic spread of pathogens, activated immune cells, and inflammatory mediators contributes significantly to mortality in patients with ARDS. 

Objective: The endogenous cannabinoid system is a major modulator of the immune response during inflammation and infection. Phytocannabinoids, such as cannabidiol (CBD), have shown promising anti-inflammatory effects in several pathologies. The overall objective of this study was to evaluate the effects of CBD on local and systemic inflammation in endotoxin-induced ALI in mice. 

Materials and Methods: ALI was induced by pulmonary endotoxin challenge. Four groups of male C57BL/6 mice were randomized in this study: control, ALI, ALI with CBD treatment, and control with CBD treatment. Analyses of local and systemic cytokine levels, lung histology, and leukocyte activation as visualized by intravital microscopy of the intestinal and pulmonary microcirculation were performed 6 h following intranasal endotoxin administration. 

Results: Pulmonary endotoxin challenge induced significant inflammation evidenced by local and systemic cytokine and chemokine release, lung histopathology, and leukocyte adhesion. Intraperitoneal CBD treatment resulted in a significant decrease in systemic inflammation as shown by reduced leukocyte adhesion in the intestinal microcirculation and reduced plasma cytokine and chemokine levels. Pulmonary chemokine levels were decreased, while pulmonary cytokine levels were unchanged. Surprisingly, the ALI score was slightly increased by CBD treatment in a manner driven by enhanced neutrophil infiltration of the alveoli. 

Conclusion: In this model of experimental ALI, CBD administration was associated with reduced systemic inflammation and heterogeneous effects on pulmonary inflammation. Future studies should explore the mechanisms involved as they relate to neutrophil infiltration and proinflammatory mediator production within the lungs.”

Broad-Spectrum Antiviral Effect of Cannabidiol Against Enveloped and Nonenveloped Viruses

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“Introduction: Cannabidiol (CBD), the main non-psychoactive cannabinoid of the Cannabis sativa plant, is a powerful antioxidant compound that in recent years has increased interest due to causes effects in a wide range of biological functions. Zika virus (ZIKV) is a virus transmitted mainly by the Aedes aegypti mosquitoes, which causes neurological diseases, such as microcephaly and Guillain-Barre syndrome. Although the frequency of viral outbreaks has increased recently, no vaccinations or particular chemotherapeutic treatments are available for ZIKV infection. 

Objectives: The major aim of this study was to explore the in vitro antiviral activity of CBD against ZIKV, expanding also to other dissimilar viruses. 

Materials and Methods: Cell cultures were infected with enveloped and nonenveloped viruses and treated with non-cytotoxic concentrations of CBD and then, viral titers were determined. Additionally, the mechanism of action of the compound during ZIKV in vitro infections was studied. To study the possible immunomodulatory role of CBD, infected and uninfected Huh-7 cells were exposed to 10 μM CBD during 48 h and levels of interleukins 6 and 8 and interferon-beta (IFN-β) expression levels were measured. On the other hand, the effect of CBD on cellular membranes was studied. For this, an immunofluorescence assay was performed, in which cell membranes were labeled with wheat germ agglutinin. Finally, intracellular cholesterol levels were measured. 

Results: CBD exhibited a potent antiviral activity against all the tested viruses in different cell lines with half maximal effective concentration values (CE50) ranging from 0.87 to 8.55 μM. Regarding the immunomodulatory effect of CBD during ZIKV in vitro infections, CBD-treated cells exhibited significantly IFN-β increased levels, meanwhile, interleukins 6 and 8 were not induced. Furthermore, it was determined that CBD affects cellular membranes due to the higher fluorescence intensity that was observed in CBD-treated cells and lowers intracellular cholesterol levels, thus affecting the multiplication of ZIKV and other viruses. 

Conclusions: It was demonstrated that CBD inhibits structurally dissimilar viruses, suggesting that this phytochemical has broad-spectrum antiviral effect, representing a valuable alternative in emergency situations during viral outbreaks, like the one caused by severe acute respiratory syndrome coronavirus 2 in 2020.”

High-CBD cannabis extracts inhibit the expression of proinflammatory factors via miRNA-mediated silencing in human small intestinal epithelial cells

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“The incidence of chronic inflammatory disorders and autoimmune diseases is rapidly growing. To date, the COVID-19 pandemic caused by SARS-CoV-2 has killed over 6,209,000 people globally, while no drug has been proven effective for the disease. Screening natural anti-inflammatory compounds for clinical application has drawn much attention.

In this study, we showed that high-CBD cannabis extracts #1, #5, #7, #169, and #317 suppressed the levels of expression of proinflammatory cyclooxygenase 2 (COX2) and increased the expression of the anti-inflammatory suppressor of cytokine signaling 3 (SOCS3) in human small intestinal epithelial cells (HSIEC) in TNFα/IFNγ-triggered inflammation.

We revealed that these extracts, with the exception of extract #169, also profoundly attenuated induction of proinflammatory cytokines interleukin-6 (IL-6) and/or IL-8 proteins through miR-760- and miR-302c-3p-mediated silencing. The prevalent components in extracts #1 and #7 influenced the levels of IL-8 both individually as well as in combination with each other. However, the high-dose cannabis extracts displayed an inhibitory effect in the growth of HSIEC cells.

These results show that our high-CBD cannabis extracts decrease the levels of proinflammatory molecules COX2, IL-6, and IL-8 via transcriptional suppression or miRNA-mediated silencing, highlighting their potential against COVID-19-associated cytokine storm syndrome.”

“Growing evidence has demonstrated that cannabinoids can reduce the production of pro-inflammatory cytokines and inhibit tumor growth in humans and/or animal models.”

“Our findings reveal certain anti-inflammatory and anti-cytokine properties of the several studied cannabis extracts, confirming the anti-COVID-19 potential of these extracts.”