In March 2020, the World Health Organization (WHO) announced that COVID-19 is a global pandemic. At the time of writing this article, the number of patients suffering from COVID-19 reached 100 million individuals, with over 2 million deaths worldwide. The highest burden of this disease and the reason why it was declared pandemic is because of the high spread potential of the virus and the high death rate associated with it.
COVID-19 has been known to primarily target the lungs of humans and rendering them dysfunctional. The lungs become inflamed, scarred, and unable to work properly. This is caused by the release of various cytokines and pro-inflammatory molecules that target the lung, causing lung damage. Unfortunately, the current treatment recommendations for COVID-19 are diverse from country to country, and some people may respond to them while others might not. Therefore, researchers have been putting much effort into investigating various drugs that could alleviate the inflammation of the lungs and prevent the cytokine storm (the rapid increase in inflammatory cytokines) from occurring. And based on its potent anti-inflammatory properties, cannabidiol (CBD) was studied to determine if it is a potent option for relieving the severity of COVID-19.
Recent research indicates that the use of high CBD-containing extracts leads to the down-regulation of angiotensin-converting enzyme (2) and transmembrane serine protease 2 (TMPRSS2), which are the major routes for the novel coronavirus to invade the lungs. Therefore, it was suggested that high CBD-containing products, such as CBD mouthwashes or CBD oil, might be effective in preventing COVID-19 infection by preventing it from invading the human lungs. Despite the fact that this research highlights the importance of CBD as a preventative approach for COVID-19, there is an increasing body of evidence suggesting that CBD may modulate the immune system and its response to COVID-19 infection and eventually prevent severe COVID-19 from occurring.
Herein, we will discuss all of the recent researches that hypothesized that the use of CBD could potentially limit COVID-19 progression and prevent post-infection complications.
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CBD and COVID-19-Associated Inflammation
CBD is a phytocannabinoid found in marijuana, along with many other cannabinoids. Although it is not the most abundant compound in marijuana, its therapeutic potential has been remarkable over the past few decades. It has been used in clinical practice in many conditions, including drug-resistant epilepsy, pain, certain inflammatory conditions, and many others. It also has a very good safety and tolerability profile. Unlike tetrahydrocannabinol (THC), which is the major cannabinoid in marijuana, CBD does not have any psychoactive properties, making it desirable for medicinal uses.
Various cannabinoids, including CBD, can suppress the immune system response towards certain pathogens and the production of inflammatory cytokines. This highlights their potential in modulating excessive inflammation. These cannabinoids exert their actions by interacting with certain receptors known as cannabinoid receptors type 1 (CB1) and type 2 (CB2). CB1 receptors are predominantly found in the central nervous system (the brain and the spinal cord); however, they are also found in peripheral tissues, such as the lungs, but to a lesser extent. Meanwhile, CB2 receptors are predominantly found on the various types of immune cells, including lymphocytes, monocytes, and mast cells.
Preclinical studies indicate that the epithelial cells that cover the airways of the lungs readily respond to cannabinoids through the activation of CB2 receptors. The activation of these receptors has been shown to prevent or suppress the release of various inflammatory cytokines, including interleukins (ILs) and tumor necrotic factor (TNF)-alpha. Under normal conditions, cannabinoids are also produced inside our bodies in the form of endocannabinoids. Recent research indicates that the lung macrophages (inflammatory cells) produce various endocannabinoids, causing protection against acute and chronic inflammation, mostly via CB2 receptor activation.
CB2 receptor agonists have been shown to alleviate the inflammatory response by inhibiting TNF-alpha and other inflammatory cytokines. These agents have also been shown to induce anti-inflammatory effects through the differentiation of a certain type of immune cells named regulatory T-cells (Tregs). Of note, recent studies highlight that CBD can induce the differentiation of these “Tregs”, and thus, preventing excessive cytokine production and further inflammation.
There, as COVID-19 induces substantial damage via pro-inflammatory cytokine storms mediated by various immune cells and according to the fact that CBD has potent anti-inflammatory properties, CBD could be a potential therapeutic drug against COVID-19-induced inflammation.
Are There Concerns with CBD Use in COVID-19-Positive Individuals?
Despite the above-mentioned hypotheses of CBD’s efficacy in improving the inflammatory condition associated with COVID-19, CBD has not been clinically studied in patients with COVID-19, and its interaction with other COVID-19 drugs is not yet studied. Therefore, more studies are still needed in this context to study the effectiveness of CBD during the early stage of COVID-19 to observe whether or not CBD will prevent the cytokine storm from occurring.
Noteworthy, CBD has been shown to be therapeutically effective in controlling the immune system activation in patients with human immunodeficiency virus (HIV) and post-Ebola syndrome. Based on this fact, a group of researchers recommended the use of oral CBD in patients with COVID-19, starting at a dose of 100 mg/day and titrating up to 300 mg/day. Based on a number of human clinical trials, this dose is known to be safe with no serious adverse events, even with the prolonged use of CBD (up to 18 weeks). However, it is worth mentioning that CBD has not yet been studied in properly-conducted human clinical trials.
Recent Clinical Trials on CBD and COVID-19
Based on the previous research on CBD’s potential in preventing excessive inflammation and cytokine storm from occurring, a group of researchers in the University of Maryland School of Medicine conducted a research study to further investigate CBD’s role in COVID-19. The researchers highlighted that CBD could block the molecule through which COVID-19 invades a person’s cells to spread throughout the human body. However, it should be noted that these results are not yet published in a medical journal and are not peer-reviewed by experts in the field.
In conclusion, despite the fact that CBD shows great promise as a preventative and a therapeutic agent against COVID-19, its use should not be initiated without consulting a physician first, particularly if you are COVID-19-positive. The interaction between CBD and the drugs that are recommended in the COVID-19 treatment protocols is not yet known. Therefore, you should always consult your physician prior to using CBD along with other drugs.
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