Tag: treatment

STERO Biotechs, headquartered in Israel, provides insight into the use of cannabis and CBD as potential treatment for COVID-19 and other conditions

Source: Health Europa | Author: Dr Sari Prutchi Sagiv, Chief Science Officer | Jan 29, 2021

Thanks to universal access to a well-organised healthcare system and constant scientific advances, Israel has had relatively fewer severe cases and deaths in the COVID-19 pandemic.

For decades, Israel has also been a pioneer in investigating the potential mechanisms of action and uses of cannabis and its derivatives for a wide range of medical conditions. STERO Biotechs, a research and development start-up, is committed to the research and development of novel cannabidiol (CBD)-based treatment solutions which will potentially benefit millions of patients. STERO works to achieve further knowhow in its quest for more effective treatments for COVID-19 patients, among other conditions.

Cannabis and COVID-19: friends or foes?

An array of literature has been written on CBD and cannabis as potential treatments for COVID-19. It is important to understand that, depending on the stage of the disease, cannabinoids could either help or harm a patient; as each phase of the disease is likely to require very different treatments. In the early stages, patients must mount an immune response to combat the virus so their immune system must be at its best. In the later stages, however, if a patient with a severe case of COVID-19 develops a cytokine storm, the immunosuppressive function of cannabinoids might be used to fight off its harmful, often fatal effects. Evaluating the safety and efficacy of isolated cannabinoids or Cannabis in general, at various stages of COVID-19 infection in clinical settings, is key.

STERO Biotechs is supporting a clinical study to evaluate the safety and efficacy of STERO’s CBD solution for treating patient cytokine storms in severe stages of COVID-19. STERO has extensive experience working with CBD-based drug development from previous trials performed in over 150 patients with Graft Versus Host Disease (GVHD), Steroid-Dependent Crohn’s Disease, Chronic Urticaria, and more; searching for effective ways of reducing or eliminating patients’ dependence on steroids, as well as helping patients who are refractory to steroids to respond to them.

Cannabis in the early stages of COVID-19

Under normal circumstances, whenever 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 which mediate and regulate immunity, inflammation, and haematopoiesis – by rushing to the site and communicating to white blood cells which virus or cell to attack. Once the infected or damaged cell is destroyed, the cytokines disperse; and the destroyed cells are carried away as waste.

As cytokines play a crucial role in fighting off infections, reducing them as a preventative measure or in early stages of the infection may be a bad idea. Many authorities caution against using cannabis agents in early stages of infection because cannabis and specific cannabinoids such as CBD and THC suppress immune responses.

Patients with weakened immune systems are at higher risk of getting gravely sick or remaining infectious for a longer period of time than others with COVID-19. There are many reasons a person may be immunocompromised or have a weakened immune system, including a solid organ, blood, or bone marrow transplant; immune deficiencies; and prolonged use of corticosteroids or treatments with other immune weakening medicines.¹

However, some evidence does indicate that several high-CBD extracts can inhibit viral cell entry and spread by decreasing angiotensin-converting enzyme 2 (ACE2) receptor levels, a receptor expressed in lung tissue and the oral and nasal mucosa that SARS-CoV-2 uses for entry into a human host.² As this data is from in vitro studies only, it is not conclusive and requires further large-scale validation and clinical studies.

Furthermore, observation in patients being treated with other immunosuppressants or anti-tumour necrosis factor (TNF) alpha biologics for inflammatory bowel disease (IBD) or rheumatoid arthritis, indicates they seem to fare better than the general population, needing less hospitalisation, and not reaching the most severe stages of COVID-19.³ Trials are still ongoing using various anti-TNF alpha treatments.

Cannabinoids and cytokine storms in patients with severe COVID-19 infection

Various studies have shown that cytokine storms, resulting in acute respiratory distress syndrome (ARDS), are a leading cause of death in severe COVID-19 cases. In some cases where cytokine release is necessary, the immune system overreacts, releasing too many proinflammatory cytokines like interleukins IL-6 and IL-1β, as well as immune cells like neutrophils and monocytes. This hyperinflammation 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 hypercytokinaemia, a cytokine storm can become life-threatening and even cause organ failure.

In these cases, the lungs fail to remove harmful gases like carbon dioxide and are unable to efficiently provide oxygen to the body. This helps the virus multiply rapidly in the lungs, resulting in respiratory conditions such as ARDS.

Endocannabinoids produced in the respiratory system and cannabinoid-induced bronchial dilation suggest a significant therapeutic potential for cannabinoids in the treatment of respiratory diseases, including COVID-19-induced ARDS. Several studies mimicking lung damage caused by ARDS in mice show that CBD improved clinical symptoms, significantly improved the levels of oxygen, and reduced the levels of inflammation-promoting cytokines caused by COVID-19 induced ARDS.⁴ Detailed examination showed that CBD partially or totally reversed the damage caused to the lungs, such as tissue overgrowth, scarring and swelling. A study showed the reason for this is a significant increase in the levels of apelin, a peptide made by cells of the heart, lung, brain, fat tissue and blood that works in reducing inflammation. In the ARDS model, apelin levels dropped close to zero in the lungs and blood, but when scientists gave the mice CBD, apelin levels increased by 20 times.⁵

Whole plant cannabis extracts have also been shown to reduce blood coagulation in animal models.⁶ It is known that many of the negative systemic effects of COVID-19 appear to be related to altered coagulation, so it is possible that cannabis may be useful in managing these sequelae too.

However, despite all the observations above together with less grounded rumours and promises, there remains little clear evidence regarding the effect of cannabis on the course of COVID-19.

Exercising caution

A survey of over 1,500 cannabis users in the Netherlands ⁷ showed that during the lockdown, habitual users increased rather than decreased cannabis consumption regarding both frequency and quantity: 41.3% of all respondents reported they had increased their cannabis use since the lockdown measures and 49.4% used it as often as before. Only 2.8% stopped temporarily. One third of those who were not daily users before the lockdown began to use cannabis daily or close to daily.

In the US, cannabis use increased among seniors between 2015 and 2018.⁸ This is of concern because the most serious complications and highest mortality rates from COVID-19 infection occur in older people.⁹ Weakly or unsupported claims on the internet that cannabis use can prevent COVID-19 may have encouraged its use.

Risk may become heightened for regular cannabis smokers: as COVID-19 predominantly kills people by harming their lungs, it seems logical to think that patients whose lungs are irritated and inflamed have a higher risk of lung damage and complications from COVID-19.

Both the FDA and the WHO advise against smoking cannabis to treat COVID-19

Several CBD producers and vendors claiming their products can be used to mitigate the symptoms of or treat COVID-19 have been issued warnings by the US Food and Drug Administration (FDA), which considers the sale and promotion of products with unsubstantiated claims of treating COVID-19 to be a threat to public health. Dubious products promising to cure, treat, or prevent COVID-19 have not been properly evaluated for safety and effectiveness. The main concern is that people may be given the false perception that they are protected from contracting the virus, in the best case; or in the worst, cause them to delay or avoid appropriate medical treatment altogether, leading to serious and potentially fatal outcomes.

The STERO Biotechs contribution to COVID-19 research

STERO Biotechs will supply and support a clinical trial, covered by its IP for Cannabidiol Treatment of Severe and Critical COVID-19 Pulmonary Infection, at Rabin Medical Center (RMC) in Israel, as part of the global effort to fight COVID-19.

The investigator-initiated clinical study running in cooperation with STERO and Mor Research Applications, the TTO arm of Clalit, commenced with the onset of the ‘second wave’ rise in the number of COVID-19 patients in Israel. The trial has already received Helsinki Committee approval and plans to include 20 patients as a Proof of Concept (POC), using STERO’s CBD-based treatment. It will be conducted by Dr Ilya Kagan from the Intensive Care department at RMC.

The study aims to help severely affected COVID-19 patients with respiratory failure stemming from ARDS. The treatment cycle will be 14 to 28 days with a subsequent follow-up period of the same length. Pending the success of this POC, STERO plans to expand and scale to a Phase 2a multicentre study with 40 additional patients, under FDA clinical trial guidelines and regulations.

Founded in 2017 and headquartered in Israel, STERO Biotechs is a clinical-stage company committed to research and development of novel cannabidiol (CBD)-based treatment solutions that will potentially benefit millions of patients by enhancing the therapeutic effect of steroid treatments; lowering the dosage of steroids needed in such treatments, thus reducing their terrible side effects; and allowing refractory patients to begin responding to the steroid treatments they need, all by using STERO’s CBD-based treatment. STERO’s patent was issued in the US and covers over 130 indications by name, CBD from any source (botanical or synthetic), any dosage, in any combination and any delivery system. The company currently has two ongoing Phase 2a clinical trials and is planning to commence more clinical trials in 2020-2021 for various indications.

One of STERO’s main partners and shareholders is MOR Research Applications, the technology-transfer arm of the Clalit Health Services, a 360° HMO, the largest in Israel and second largest in the world. Clalit owns 14 hospitals and around 2,000 clinics, employs 9,000 physicians who provide care for over five million patients. MOR manages the process of finding new indications and commercialising the ideas and inventions conceived at Clalit, so everybody wins: researchers, industry partners, and the public at large.

The concepts of Talent Biotechs and STERO were conceived by one of these physicians and all resources of this gigantic, well-oiled HMO mechanism are available for the continuation of our research and trial work.

References

1. https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html#immunocompromised-state
2. Wang, B et al. Aging (Albany NY); 2020 Nov 22;12(22):22425-22444.
3. Robinson et al. The Lancet, Vol. 2, Issue 11, E653-E655, November 01, 2020
4. Khodadadi, H et al. Cannabis Cannabinoid Res. 2020; 5(3): 197–201
5. Salles, E et al. Journal of Cellular and Molecular Medicine. 15 October, 2020
6. Coetzee, C et al. Phytomedicine 2007 May;14(5):333-7
7. Van Laar, M et al. Front. Psychiatry, 21 December 2020
8. Han, BH et al. JAMA Intern Med. (2020) 180:609–11
9. Onder, G et al. JAMA. (2020) 323:1775–6