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Marijuana and COVID-19 Patients: New Insights from Israel

Publication from: Medical Cannabis Network
Marijuana and COVID-19 Patients: New Insights from Israel
January 29, 2021
STERO Biotechs, based in Israel, provides insight into the use of cannabis and CBD as a potential treatment for COVID-19 and other conditions
Thanks to universal access to a well-organized healthcare system and continuous scientific advances, Israel has had relatively fewer severe cases and deaths from the COVID-19 pandemic.
For decades, Israel has also pioneered research into the potential mechanisms of action and uses of cannabis and its derivatives in a wide range of medical conditions. STERO Biotechs, a research and development start-up, is committed to research and development of new cannabidiol (CBD) -based treatments that will potentially benefit millions of patients. STERO is working to gain further know-how in the search for more effective treatments for patients with COVID-19, including other conditions.
Cannabis and COVID-19: Friends or Foes?
Many publications have already been written about CBD and marijuana as potential COVID-19 treatments. It is important to understand that, depending on the stage of the disease, cannabinoids can help or harm the patient; because each phase of the disease is likely to require completely different treatment. In the early stages of the disease, patients need to build up an immune response to fight the virus, so their immune system needs to be at its best. However, in the later stages, if a patient with a severe case of COVID-19 develops a cytokine storm, the immunosuppressive function of the cannabinoids can be used to combat the harmful, often fatal, effects of the disease. It is crucial to evaluate the safety and efficacy of the isolated cannabinoids, or Cannabis in general, at different stages of COVID-19 infection in a clinical setting.
STERO Biotechs is supporting a clinical trial to evaluate the safety and efficacy of STERO’s CBD solution in treating cytokine storms in patients with severe stages of COVID-19 disease. STERO has extensive experience working on CBD drug development from previous studies on more than 150 patients with graft versus host disease (GVHD), steroid-dependent Crohn’s disease, chronic urticaria and others; by looking for effective ways to reduce or eliminate patients’ dependence on steroids, as well as helping patients who are resistant to steroids to respond to them.
Cannabis in the early stages of COVID-19 disease
Normally, when the immune system senses an infection or inflammation, the body releases cytokines into the bloodstream. Cytokines are – proteins, peptides, or glycoproteins secreted by specific cells of the immune system that mediate and regulate immunity, inflammation, and hematopoiesis – rushing around and communicating to white blood cells which virus or cell is to be attacked. When an infected or damaged cell is destroyed, the cytokines diffuse and the damaged cells are removed as waste
Since cytokines play a key role in fighting infection, reducing them as a preventative measure or in the early stages of an infection may be a bad idea. Many authorities caution against the use of cannabis remedies in the early stages of an infection, as cannabis and specific cannabinoids such as CBD and THC suppress immune responses.
Patients with a weakened immune system are at a higher risk of developing severe disease or remaining contagious for a longer period of time than others with COVID-19. There are many reasons why a person may be immunocompromised or a weakened immune system, including solid organ, blood or bone marrow transplantation, immunodeficiency, and long-term use of corticosteroids or treatment with other medications that suppress the immune system.1
However, some evidence suggests that several CBD-rich extracts can inhibit viral cell entry and spread by lowering the levels of Angiotensin Converting Enzyme 2 (ACE2), a receptor found in lung tissue and the oral and nasal mucosa that is used by SARS- CoV-2 for entry into the human host.2 As these data are only derived from in vitro studies, they are not conclusive and require further large-scale validation and clinical trials.
In addition, observations of patients treated with other immunosuppressants or biological anti-tumor necrosis factor (TNF) alpha drugs for inflammatory bowel disease (IBD) or rheumatoid arthritis indicate that they are doing better than the general population, requiring fewer hospitalizations and not reaching the most severe stages COVID-19.3 Research is ongoing with various anti-TNF alpha drugs.
Cannabinoids and cytokine storm in patients with severe COVID-19 infection

Various studies have shown that cytokine storms, resulting in acute respiratory distress syndrome (ARDS), are the leading cause of death in severe COVID-19 cases. In some cases where cytokine release is necessary, the immune system overreacts, releasing too many pro-inflammatory cytokines such as the interleukins IL-6 and IL-1β, as well as immune cells such as neutrophils and monocytes. This inflammation is called a cytokine storm and can become dangerous to patients’ health as the immune system attacks the body’s own cells instead of the virus, meaning patients may experience high fever, inflammation, severe fatigue and nausea. In extreme cases known as hypercytokineemia, a cytokine storm can be life-threatening and even cause organ failure.
In these cases, the lungs are unable to remove harmful gases, such as carbon dioxide, and are unable to efficiently deliver oxygen to the body. This helps the virus to multiply rapidly in the lungs, leading to respiratory conditions such as ARDS.
Respiratory-produced endocannabinoids and cannabinoid-induced bronchodilation suggest a significant therapeutic potential of cannabinoids in the treatment of respiratory diseases, including ARDS induced by COVID-19. Several studies mimicking ARDS lung damage in mice have shown that CBD improved clinical symptoms, significantly improved oxygen levels, and reduced cytokines that promote inflammation induced by COVID-19.4 ARDS. Detailed studies have shown that CBD partially or completely reversed lung damage such as like tissue overgrowth, scarring and swelling. The study found that the reason for this is a significant increase in apelin, a peptide produced by cells in the heart, lung, brain, fat and blood that works to reduce inflammation. In the ARDS model, apelin levels in the lungs and blood dropped to almost zero, but when the scientists gave mice CBD, the apelin levels increased 20-fold.5
Cannabis whole plant extracts have also been shown to reduce blood clotting in animal models. these aftermaths.

However, despite all of the above observations, as well as less substantiated rumors and promises, there is still little conclusive evidence regarding the effects of cannabis on the course of COVID-19.
Be careful
A survey of more than 1,500 cannabis users in the Netherlands 7 found that, during blockade, cannabis users increased rather than decreased their use, both in frequency and quantity: 41.3% of all respondents reported that they had since the introduction of blocking agents increased cannabis use, and 49.4% used it as often as before. Only 2.8% stopped temporarily. One-third of people who had not used cannabis daily before the blockage began using it daily or almost daily.
In the US, marijuana use increased among seniors between 2015 and 2018.8 This is worrying as the most serious complications and the highest mortality from COVID-19 infection occur in the elderly.9 Weak or unsubstantiated claims on the Internet that marijuana use may prevent COVID-19, could encourage its use.
The risk may be greater in regular cannabis smokers: Since COVID-19 mainly kills people by damaging the lungs, it seems logical that patients whose lungs are irritated and inflamed have a higher risk of lung damage and complications from COVID-19.
Both the FDA and WHO advise against smoking marijuana to treat COVID-19.

Several CBD manufacturers and vendors claiming their products can be used to relieve symptoms or treat COVID-19 have received warnings from the U.S. Food and Drug Administration (FDA), which considers selling and promoting products with unsubstantiated claims about COVID-19 treatment as a threat to public health. Questionable products that promise to cure, treat, or prevent COVID-19 have not been adequately evaluated for safety and efficacy. The main cause for concern is that people may have the false belief that they are protected from being infected with the virus, at best; or at worst, delay or avoid appropriate medical treatment, leading to serious and potentially fatal consequences.
STERO Biotechs contribution to COVID-19 research
STERO Biotechs will provide and support a clinical trial under its intellectual property on cannabidiol treatment for severe and critical COVID-19 pulmonary infection at Rabin Medical Center (RMC) in Israel as part of a global effort to combat COVID-19.
An investigator-initiated clinical trial conducted in collaboration with STERO and Mor Research Applications, an arm of Clalit’s TTO, began with the start of a “second wave” of COVID-19 patient growth in Israel. The study has already obtained approval from the Helsinki Committee and is planned to include 20 patients as proof of concept (POC) using STERO’s CBD-based treatment. It will be led by Dr. Ilya Kagan from the intensive care unit at RMC.
The study is designed to help critically ill COVID-19 patients with ARDS-related respiratory failure. A treatment cycle will be 14 to 28 days followed by an observation period of the same duration. In anticipation of the success of this POC, STERO plans to expand and scale to a multi-center phase 2a trial with 40 additional patients, in line with FDA clinical trial guidelines and regulations.
Established in 2017 and headquartered in Israel, STERO Biotechs is a company in the clinical phase committed to research and development of innovative cannabidiol (CBD) -based therapeutic solutions that will potentially benefit millions of patients by enhancing the therapeutic effect of steroid therapies; lowering the doses of steroids needed for such therapies, thereby reducing their terrible side effects; and enabling treatment-resistant patients to begin responding to the steroid therapies they need, all through the use of CBD-based STERO therapy. STERO’s patent was issued in the USA and covers more than 130 indications by name, CBD from any source (botanical or synthetic), any dosage, in any combination and in any delivery system. The company is currently conducting two phase 2a clinical trials and plans to start further clinical trials in 2020-2021 for a variety of indications.
One of the main partners and shareholders of STERO is MOR Research Applications, a unit dedicated to technology transfer to Clalit Health Services, 360 ° HMO, the largest in Israel and the second largest in the world. Clalit owns 14 hospitals and approximately 2,000 clinics, employs 9,000 doctors who care for over five million patients. MOR manages the process of finding new indications and commercializing ideas and inventions created in Clalit, thanks to which everyone wins: scientists, industrial partners and society.
The concepts of Talent Biotechs and STERO were invented by one of these physicians, and all the resources of this gigantic, well-oiled HMO mechanism are available for the continuation of our research and testing work.
Wang, B et al. Aging (Albany NY); 2020 Nov 22; 12 (22): 22425-22444.
Robinson et al. The Lancet, Vol. 2, Issue 11, E653-E655, November 01, 2020
Khodadadi, H et al. Cannabis Cannabinoid Res. 2020; 5 (3): 197-201
Salles, E et al. Journal of Cellular and Molecular Medicine. October 15, 2020
Coetzee, C et al. Phytomedicine 2007 May; 14 (5): 333-7
Van Laar, M et al. Front. Psychiatry, December 21, 2020
Han, BH et al. JAMA Intern Med. (2020) 180: 609-11
Onder, G et al. CAVITY. (2020) 323: 1775-6
Dr. Sari Prutchi Sagiv
Scientific Director
STERO Biotechs
This article is from issue 16 of Health Europa.

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