What Is Dexamethasone?

Dexamethasone has recently emerged as the best drug to treat severe life-threatening cases of Coronavirus Disease 2019 (COVID-19).  The World Health Organization (WHO) is in the process (as of June 29, 2020) of updating their treatment guidelines to include Dexamethasone or other steroids in the treatment of COVID-19. Dexamethasone is a synthetic corticosteroid that is used as an anti-inflammatory or immunosuppressant agent.  It is primarily used to treat short-term inflammation (swelling, heat, redness, and pain), but it is also used to treat autoimmune diseases, such as arthritis and colitis, and certain types of cancer.  Dexamethasone, like other anti-inflammatory agents, acts by suppressing the cytokine storm which occurs when the immune system is highly induced.  To fully appreciate and understand dexamethasone and its use to treat severe cases of COVID-19, one has to understand the immune system, cytokine storms, and corticosteroids, which are a subcategory of steroids.

Understanding the Immune System

The immune system is a complex network of cells, effector proteins, and chemical compounds that defend the body against invading agents.  Usually, the immune system responds to foreign antigens, such as bacteria, fungi, and viruses, or to tissue damage caused by contusions or abrasions.  These responses are typically referred to as inflammatory since they induce or turn on the immune system.  Unfortunately, the immune system can also respond to antigens produced by the body as well, the result of which is the development of autoimmune diseases.  The prevalence of autoimmune diseases is rapidly increasing with Addison’s disease, autoimmune hepatitis, Celiac disease, Crohn’s disease, Grave’s disease, idiopathic thrombocytopenic purpura, multiple sclerosis, primary biliary cirrhosis, psoriatic disease, rheumatoid arthritis, scleroderma, Sjogren’s syndrome, systemic lupus erythematosus, type I diabetes and ulcerative colitis all being recognized as autoimmune diseases.

There are a number of cellular indicators that can be used to identify elevated immune responses.  These include increased amounts of histamine, nitric oxide (NO), reactive oxygen species (ROS), such as H2O2, and secreted cytokine proteins.  The cytokine proteins are receiving more and more attention as it has become clear that they are one of the major regulators of the immune response.  There are over 100 cytokines that are involved in regulating the immune system and they are becoming increasingly important as a key indicator of elevated immune responses.

What Are Cytokines?

The immune system is stringently regulated via a counterbalance between inflammatory (proinflammatory) and anti-inflammatory cytokines.  Inflammatory cytokines induce the immune system while anti-inflammatory cytokines repress the immune system.  Normally this counterbalance keeps the immune system in check and ready to act when necessary.  When an inflammatory response occurs due to inflammation or autoimmune diseases, the levels of inflammatory cytokines drastically increase.  The term “cytokine storm” is generally used to describe the increase in inflammatory cytokine levels that occur in people suffering from inflammatory conditions or autoimmune diseases.  The repression of inflammatory cytokines that are involved in cytokine storms by pharmaceutical agents is gaining attention as a treatment regimen for severe inflammatory conditions.  There is no universal agreement as to which inflammatory cytokines are the most important, however, inflammatory cytokines such as interleukin-1𝛽, interleukin -6, interleukin -17 and tumor necrosis factor alpha (TNFa or TNF) appear to figure prominently in regulating the immune response and being the key causative agents of cytokine storms.

The heightened response of the immune system to various inflammatory conditions was first recognized by Dr. William Nelson in 1983 who defined the phenomenon as the systemic inflammatory response syndrome (SIRS).  A key component of SIRS is elevated cytokine levels and the term “cytokine storm” to define this occurrence was suggested by Dr. James Ferrara and co-workers in 1993.  Now the fact that elevated cytokine levels occur in any situation where there is a heightened immune response is widely accepted in the medical and scientific literature. 

What Is Dexamethasone and How Do Corticosteroids Work?

Dexamethasone is a synthetic corticosteroid and corticosteroids are a subcategory of steroids.  The steroids are an important group of hormones, which are chemical compounds produced by the body that regulate cellular function by interacting with hormone receptor proteins.  The steroid hormones act by regulating the gene expression of the enzymes that they effect. Steroids are chemically defined by their four-carbon ring structure, which consists of three six-carbon cyclohexane rings and one five-carbon cyclopentane ring.  Most steroids contain additional carbon-based organic moieties that are linked to the cyclopentane ring.  Steroids are routinely used in medicine and the best examples are estradiol, which is used to treat menopause and prevent osteoporosis in women, progesterone, which is used to regulate ovulation and menstruation in women and testosterone, which is used for testosterone sex hormone replacement therapy in men.

Corticosteroids are divided into two groups, the glucocorticoids, which regulate many aspects of metabolism and immune function and the mineralocorticoids, which help maintain blood volume and control the renal excretion of electrolytes.  The most prescribed corticosteroids are the glucocorticoids, which are used primarily as anti-inflammatory or immunosuppressant agents and include cortisol or hydrocortisone, cortisone, dexamethasone, hydrocortisone and prednisone, that are used at daily doses ranging from 20 – 240 mg, 5 – 20 mg, 1 – 10 mg, and 5 – 60 mg, respectively.  Years of research have shown that corticosteroids can reduce the cytokine storms associated with heightened inflammatory conditions.  Dexamethasone was created by Dr. Glen E. Arth and co-workers in 1958 at Merck, Sharp & Dohme Laboratories.  Numerous studies have shown that dexamethasone is clearly the most potent of the anti-inflammatory corticosteroids that are used in medicine.

COVID-19 and Dexamethasone

COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).  As per its name, SARS-CoV-2 is a coronavirus, which is a family of viruses that can cause mild to lethal respiratory tract infections.  The milder variants of coronaviruses are one of the viruses that can cause common colds.  SARS-CoV-2, however, can result in fatal infections.  Part of the problem that has caused the COVID-19 pandemic is a great percentage of the people that are infected with SARS-CoV-2 are asymptomatic, have few or no symptoms, don’t know that they are sick, yet can infect other people.  In patients with severe life-threatening cases of COVID-19, the immune system becomes highly induced and cytokine storms occur.

In the United Kingdom RECOVERY Trial, led by Dr. Peter Horby at the University of Oxford to evaluate different potential treatment regimens for patients infected with SARS-CoV-2, dexamethasone was one of the treatment options chosen, because it is a potent anti-inflammatory agent and a heightened inflammatory response with elevated cytokine levels is one of the hallmarks of patients who have severe potentially lethal COVID-19.  In the clinical trials, dexamethasone has shown great promise in reducing the inflammatory response in these patients and preventing their death. 

What Are the Anti-Inflammatory Effects of Cannabinoids?

It is interesting to note that other anti-inflammatory products are available as nutritional supplements for consumers who wish to explore a more natural approach to treating inflammatory issues, such as muscle or joint aches, whether they are associated with arthritis or not, and persistent skin conditions, such as dry or itchy skin, dermatitis or psoriasis, without resorting to prescription drugs.  GreenWay Tanasi, LLC, and its brand, Tanasi, a subsidiary of GreenWay Herbal Products, LLC, sells a number of cannabidiol (CBD) products that feature a unique patent-pending blend of cannabinoids (CBD and Cannabidiolic-acid (CBDA)) extracted from Cannabis Sativa L. hemp plants.  GreenWay Herbal Products, LLC developed this patent-pending technology with a university partner, which has demonstrated that cannabinoids are natural anti-inflammatory agents that can suppress cytokine storms.  In direct comparison studies, the unique formulation of cannabinoids used in the Tanasi CBD product line was as effective as dexamethasone in reducing cytokine storms.  Thus it is not surprising that customers using the Tanasi CBD/CBDA products report that they are very effective at reducing a number of inflammatory conditions.  See the customer reviews at www.tanasi.com.

Tanasi is not recommending using its CBD/CBDA patent-pending formula as a treatment for COVID-19. Hemp extracts are not approved for medical treatments, and the only FDA approved CBD formula recommended for use in medical treatments is Epidiolex for the intended use of treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients 2 years of age and older.