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    Medicinal applications of Cannabinoids extracted from Cannabis sativa (L.): A new Route to Fight against COVID-19?

    DECEMBER 2, 2020

    Published in Current Pharmaceutical Design
    https://www.eurekaselect.com/188617/article

    This review, written by a team of academics from Pakistan, Saudi Arabia, United Arab Emirates and Algeria, focuses on important applications or current utilisation of cannabinoids in the treatment of: Chronic pain, cancer, emesis, anorexia, irritable bowel syndrome, communicative diseases, glaucoma and central nervous system disorders. They conclude that Cannabis has multiple bioactive compounds which have the potential to be approved as cannabinoids suitable for therapy.

    Cannabis, CBD and COVID-19 Research

    Scientists and health specialists around the world are working to understand why the SARS-CoV-2 virus, responsible for the current COVID-19 pandemic, can cause someone to have life-threatening symptoms. They are quite confident that the problem arises from when our bodies respond to a viral infection with an excessive inflammatory response, known as a cytokine storm, and develop acute respiratory distress syndrome (ARDS). Doctors are still trying to figure out the best treatment course for patients with severe COVID-19 symptoms, as traditional anti-inflammatory drugs don’t seem to benefit these patients.  Several research groups that have joined the world-wide efforts in search of therapeutic agents to treat this new threat are currently focusing their attention on the potential of Cannabis.

    Here we list the results of these studies as they become available to the public to provide you with reliable info about the therapeutic use of cannabinoids in treating COVID-19.

    Review

    Published scientific articles that review the currently available evidence

    Opinion

    Opinions, hypotheses and editorials written by professionals in the medical or research field

    NOVEMBER 6, 2020

    Use of Cannabinoids to Treat Acute Respiratory Distress Syndrome and Cytokine Storm Associated with Coronavirus Disease-2019

    Published in Frontiers in Pharmacology
    https://doi.org/10.3389/fphar.2020.589438

    In this opinion article, immunology experts from the University of South Carolina School of Medicine in Columbia (US) start by describing the immune characteristics of COVID-19 and current therapies to treat the cytokine storm. Then, they move on to describe in some detail the biomolecular effects of cannabinoids as anti-inflammatory agents and their potential use for preventing cytokine storm and ARDS.

    The authors conclude:

    “There is a dire need for novel anti-inflammatory agents that exert broad spectrum cytokine suppression associated with ARDS, considering that currently up to 40% of such patients (including those with COVID-19) die because currently there are no FDA-approved drugs that are highly effective against cytokine storm and ARDS. (…) We believe that cannabinoids hold significant promise as potent anti-inflammatory agents.”

    NOVEMBER 5, 2020

    Could Cannabidiol Be a Treatment for Coronavirus Disease-19-Related Anxiety Disorders?

    Published in Cannabis and Cannabinoid Research
    https://doi.org/10.1089/can.2020.0102

    This review, funded by Artelo Biosciences, focuses on the potential of CBD to treat COVID-19-related anxiety disorders. It starts by describing the pharmacological actions of CBD and assesses the documented adverse effects. After explaining the impact of major disasters on the mental health of the general population, the authors describe current evidence and the mechanism of action of CBD in anxiety and sleep disorders. They conclude that in regards to safety and side effect profile, CBD could be a more preferable option if testing through well-designed clinical trials confirms its benefits, while warning prescribers to be aware of potential interaction with other medications.

    OCTOBER 15, 2020

    Cannabidiol (CBD) Modulation of Apelin in Acute Respiratory Distress Syndrome

    Published in the Journal of Cellular and Molecular Medicine
    https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.15883

    Dr. Baban’s research team has published its second study on the use of CBD to treat ARDS. They have discovered that apelin is drastically reduced in the lungs of the animals with ARDS, and treatment with CBD resulted in near-normal apelin levels. Apelin is a natural peptide known to reduce inflammation and is a substrate for ACE2.

    SEPTEMBER 2, 2020

    Cannabidiol Modulates Cytokine Storm in Acute Respiratory Distress Syndrome Induced by Simulated Viral Infection Using Synthetic RNA

    Published in Cannabis and Cannabinoid Research
    https://www.liebertpub.com/doi/pdf/10.1089/can.2020.0043

    This new study has shed some light on whether CBD can help with COVID-19 or not. The team from Augusta University in Georgia (USA), led by Dr. Baban, tested in an animal model if CBD could alleviate severe COVID-19 symptoms by reducing the inflammatory response and by “calming the storm” of cytokines.

    They concluded: “Our results suggest a potential protective role for CBD during ARDS that may extend CBD as part of the treatment of COVID-19 by reducing the cytokine storm, protecting pulmonary tissues, and re-establishing inflammatory homeostasis“.

    AUGUST 28, 2020

    Δ9-Tetrahydrocannabinol Prevents Mortality from Acute Respiratory Distress Syndrome through the Induction of Apoptosis in Immune Cells, Leading to Cytokine Storm Suppression

    Published in the International Journal of Molecular Sciences
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503745/pdf/ijms-21-06244.pdf

    In the most severe cases of COVID-19, patients usually develop Acute Respiratory Distress Syndrome (ARDS), a major trigger of mortality associated with SARS-CoV-2 virus-induced disease.

    Using a mouse model of ARDS which triggers 100% mortality (up to 40% of humans with ARDS die) researchers tested if THC would help treat the usual symptoms. Treatment with THC not only reduced mortality to 0%, but it also decreased lung inflammation and suppression of the cytokine storm.

    AUGUST 19, 2020

    Cannabis and COVID-19

    Published in the Medical Cannabis and Cannabinoids
    https://www.karger.com/Article/PDF/510799

    A team of doctors from the Geneva University Hospitals try to address the question on whether the consumption of cannabis or cannabis derivatives/synthetic products could influence the severity of viral or bacterial infections. They list a number of studies that show the involvement of the cannabinoid receptors in the regulation of the immune system and discuss how cannabinoids affect this regulation.

    Their recommendation, based on an internal clinical guideline (available in French), is: “Pre-existing nonmedical consumption of cannabinoids should not be increased, rather decreased, for the duration of the COVID-19 pandemic considering the potential respiratory complications. Sharing a joint should be avoided since this might be a potential way of transmitting the virus. Also, “over-the-counter” CBD cannot be recommended since the impact on immunity in case of SARS-CoV-2 infection is not clear. Continuation or discontinuation of therapeutically prescribed cannabinoids should be discussed on a case by-case basis with the prescribing physician taking each patient’s individual risk-benefit ratio into account.”

    They finish by requesting epidemiological studies and retrospective data on the consumption of cannabinoids by patients with SARS-CoV-2 infection to help with a more accurate assessment of the risk-benefit balance.

    AUGUST 13, 2020

    Cannabis for COVID-19: Can cannabinoids quell the cytokine storm?

    Published in the Future Science OA
    https://dx.doi.org/10.2144%2Ffsoa-2020-0124

    In this editorial letter, Prof. Onaivi and Prof. Sharma from the William Paterson University in New Jersey, US, highlight some of the mechanisms involved in the immune regulation by the endocannabinoid system and the potential of cannabinoids as an anti-inflammatory treatment for COVID-19.

    AUGUST 4, 2020

    Protective Effects of Δ9-Tetrahydrocannabinol Against Enterotoxin-induced Acute Respiratory Distress Syndrome are Mediated by Modulation of Microbiota

    Published in the British Journal of Pharmacology
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436585/pdf/BPH-9999-na.pdf

    After identifying several ways in which treatment with THC prevented death in a mouse model of ARDS and had anti-inflammatory effects, Prof. Nagarkatti and his team looked at changes in the microbiota of the lungs and gut.

    Similar alterations in microbiota found in the lungs and gut in ARDS-induced mice were reversed by THC treatment, and the ability of THC to attenuate ARDS resulted from THC-induced alterations in the microbiota.

    JULY 31, 2020

    The interaction between the endocannabinoid system and the renin angiotensin system and its potential implication for COVID-19 infection

    Published in the Journal of Cannabis Research
    https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-020-00030-4

    Alberto Sainz-Cort and Dr Joost H. Heeroma, who work for the medical cannabis company GH Medical, wrote about the involvement of the angiotensin converting enzyme 2 (ACE-2) in the SARS-CoV-2 infection. They state that they are not aware of any study that links the endocannabinoid system to the ACE-2 receptor. They did find and describe some connections with the renin-angiotensin system (RAS), to which the ACE-2 belongs. 

    They recommend: “If our speculations are right, using cannabinoids like THC might not be advisable in the context of a potential COVID-19 infection.(…) There is actually preclinical evidence suggesting cannabinoids might protect against cytokine storm and they could improve prognosis in the case of sepsis. However, we believe such evidence is not enough to recommend the use of cannabinoids in these cases since there are already other drugs available that have been extensively tested to treat such disorders. In case patients decide to continue using cannabis, it would be advisable to avoid the smoking route of administration and aim for other routes of administration.”

    JULY 1, 2020

    Therapeutic Cannabis and COVID-19: Between opportunism and infoxication

    Published in Adicciones
    https://doi.org/10.20882/adicciones.1603

    Academics and health professionals from the Grupo Ibero Ciência wrote about how the growing proliferation of fake news about alleged healing properties of cannabis can be dangerous, especially in times of COVID-19. They warn about the risks of smoking cannabis and vaping THC or CBD concentrates, and recommend that those doing so should stop or at least replace it with edible forms. Given the lack of studies on the use of THC/CBD for COVID-19 treatment and seeing that cannabinoids can decrease the capacity of fighting infections, the authors recommend against the use of CBD or other cannabinoids during the pandemic, unless it is by medical prescription.

    JUNE 30, 2020

    Opioids/cannabinoids as a potential therapeutic approach in COVID-19 patients

    Published in Expert Review of Respiratory Medicine
    https://doi.org/10.1080/17476348.2020.1787836

    A team of academics from Iran suggest the use of compounds that activate the opioid/cannabinoid receptors, considering that currently there are no effective treatments for COVID-19. They discuss evidence showing the specific involvement of opioids/cannabinoids systems in the outcome of viral infections and in modulating inflammation. 

    They conclude that “the biocompatibility, availability, and cheapness are considerable privileges of opioids/cannabinoids-based drugs” and that more research is needed to determine the right compounds or mixtures effective in treating COVID-19 as well as the correct concentrations.

    JUNE 26, 2020

    Cannabis in the Time of Coronavirus Disease 2019: The Yin and Yang of the Endocannabinoid System in Immunocompetence

    Published in The Journal of Alternative and Complementary Medicine
    https://doi.org/10.1089/acm.2020.0144

    Dr Michelle Sexton, a naturopathic doctor and Adjunct Assistant Professor at the University of California, San Diego describes the multiple immune modulating effects associated with cannabis.

    She warns that people smoking cannabis and vaping concentrates should substitute these with “orally administered products at low doses (<5 mg THC suggested) or using vaporized dried flower material (to avoid byproducts of combustion)” because smoking/vaping concentrates may reduce the efficiency in which the respiratory system responds to infection. Based on existing clinical data, Dr Sexton predicts that the low-dose oral products are far from containing a concentration of cannabinoids that would create a clinically significant immunosuppression. She stresses that effective anti-inflammatory doses for CBD are unknown until we have high-quality evidence in humans and that to date no data suggests THC or CBD to be a proven therapeutic intervention for COVID-19.

    JUNE 17, 2020

    Debunking Cannabidiol as a Treatment for COVID-19: Time for the FDA to Adopt a Focused Deterrence Model?

    Published in Cureus
    https://pdfs.semanticscholar.org/364b/52521b5cac6945807abb21ec781747da252d.pdf

    The authors look at the response from CBD retailers to FDA issued warning letters and express concern in the increase of unsupported medical claims by many of them. Given the fact that after receiving FDA letters regarding COVID-19 related claims, more companies addressed this issue, the authors suggest that “significant public health benefit at marginal cost could be garnered if FDA letters sent in response to COVID-19 claims were amended to encompass all unsupported therapeutic claims made by recipients.”

    JUNE 16, 2020

    Administration of Δ9-Tetrahydrocannabinol (THC) Post-Staphylococcal Enterotoxin B Exposure Protects Mice From Acute Respiratory Distress Syndrome and Toxicity

    Published in Frontiers in Pharmacology
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308536/

    In this study, a team of researchers led by Prof. Nagarkatti looked to see if THC could prevent the onset of symptoms developed in severe COVID-19 cases, using a mouse model of ARSD.

    THC led to 100% survival of mice and significantly suppressed inflammatory cytokines. This study goes deep into the molecular and gene regulation mechanisms that brought about this striking result.

    JUNE 10, 2020

    The potential of cannabidiol in the COVID-19 pandemic

    Published in British Journal of Pharmacology
    https://bpspubs.onlinelibrary.wiley.com/doi/epdf/10.1111/bph.15157

    This publication explores the hypothesis that administration of CBD could have the potential to limit COVID-19 disease progression and post-infectious outcome. The authors consider that there is still data missing regarding the adverse effects if co-administered with other drugs used for COVID-19, but do not anticipate any serious side effects. Importantly, the authors address the concern about the possible immunosuppression during acute infections by pointing out that CBD did not cause an increase in mortality in acutely infected animals, rather in pneumococcal meningitis animal survival was increased with CBD doses ranging from 2.5 to 10 mg/kg.

    JUNE 5, 2020

    Cannabinoids and the Coronavirus

    Published in Cannabis and Cannabinoid Research
    https://doi.org/10.1089/can.2020.0035

    Dr Kevin P. Hill, Director of the Division of Addiction Psychiatry and Associate Professor of Psychiatry at BIDMC/Harvard Medical School, recognises that patients have started asking about the benefits and risks of cannabinoids related to COVID-19. After briefly discussing the current therapeutic use of cannabinoids (some FDA approved, some still lacking concrete evidence) he focuses on the available limited data showing a possible role in viral illnesses. Dr Hill sees the current pandemic as an opportunity to drive new preclinical and clinical studies in this field to reach the level of evidence required to consider using cannabinoids as pharmacotherapy for viral illnesses.

    MAY 27, 2020

    Cannabinoid Receptor Type 2: A Possible Target in SARS-CoV-2 (CoV-19) Infection?

    Published in International Journal of Molecular Sciences
    https://doi.org/10.3390/ijms21113809

    A research team from the University of Campania “Luigi Vanvitelli” in Naples, Italy, describes the extensive scientific evidence that demonstrates the involvement of the CB2 receptor in modulating our immune response. The authors describe the clinical traits of SARS-CoV-2 infection and the severe acute inflammation that causes cytokine storm in COVID-19 patients and suggest that the selective stimulation of CB2 could reduce the inflammatory response in SARS-CoV-2 patients, improving the outcome.

    MAY 20, 2020

    Acute inflammation and pathogenesis of SARS-CoV-2 infection: Cannabidiol as a potential anti-inflammatory treatment?

    Published in Cytokine and Growth Factor Reviews 
    https://dx.doi.org/10.1016%2Fj.cytogfr.2020.05.008

    This review shortly describes the mechanism of SARS-CoV-2 infection and known immune responses. It then continues to give a concise description of how cannabinoids can suppress immune activation and inflammatory cytokine production seen in COVID-19 patients. Since CBD is already a therapeutic agent used for other conditions and it is accepted to be generally safe, the authors encourage further studies on animals/cells to provide proof-of-concept before embarking on clinical trials.

    MAY 7, 2020

    COVID-19 Related Lung Inflammation and Oxidative Stress – A Role for Cannabidiol?

    Published in Journal of Pharmacology & Pharmaceutical Research
    https://researchopenworld.com/wp-content/uploads/2020/05/JPPR-3-1-306.pdf

    The authors review current SARS-CoV-2 treatment approaches, their effectiveness and safety. They question if a well-known mutation (Q63R) in the CB2 receptors known to be less functional and associated with increased risk of severe respiratory infection in children can contribute to an increased risk for COVID-19. They shortly describe several demonstrated mechanisms of action of CBD and its potential benefit in reducing infection and symptoms when the need for an anti-inflammatory and immunosuppressive intervention arises.

    APRIL 28, 2020

    SARS-CoV2 induced respiratory distress: Can cannabinoids be added to anti-viral therapies to reduce lung inflammation?

    Published in Brain, Behaviour and Immunity
    https://dx.doi.org/10.1016%2Fj.bbi.2020.04.079

    This article, written by two academic experts in immunology and viral infections, first exposes how a drug that blocks the IL-6 receptor (Tocilizumab) had improved the condition of 90% of the test subjects who then recovered from COVID-19. However the drug also gave rise to serious adverse effects. After a short description of the immune modulatory effects of THC and CBD, the authors point out that  unlike THC, CBD has a high margin of safety and is well tolerated. This makes CBD a feasible treatment compound to reduce SARS-CoV2 induced lung inflammation and disease severity. In addition, the authors suggest CBD can also help fight anxiety.

    MARCH 31, 2020

    Cannabidiol as prophylaxis for SARS-CoV-2 and COVID-19? Unfounded claims versus potential risks of medications during the pandemic

    Published in British Journal of Pharmacology
    https://doi.org/10.1016/j.sapharm.2020.03.020

    Dr. Joshua Brown, an Assistant Professor at the Department of Pharmaceutical Outcomes and Policy from the University of Florida, US, expresses his opinion on the use of CBD to combat SARS-CoV-2. He claims that CBD and its impacts on the immune system suggest a potentially detrimental effect. Dr. Brown recommends that patients and clinicians should be encouraged to avoid the use of CBD and other cannabinoids during this pandemic and that false marketing claims (such as “immune booster” or “anti-viral effects”) should be reported to regulatory bodies.

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