The coronavirus disease 2019 (COVID-19) pandemic, caused by the sudden outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has claimed more than 6.39 million lives worldwide. Scientists have worked extensively to develop pharmaceutical and non-pharmaceutical measures to protect individuals from COVID-19 infection. All the available COVID-19 vaccines have been designed against the spike protein of the original SARS-CoV-2 strain. Owing to this reason, some of the newly emerged variants, such as the Delta and Omicron, have exhibited reduced efficacy.
About the study
Recently, researchers reviewed the effectiveness of cannabidiol (CBD) in treating COVID-19 inflammatory-related symptoms. This review article is available in Cannabis and Cannabinoid Research. In this study, the authors analyzed research documents from several sources, including the Cochrane COVID-19 study register, CINAHL, PubMed, ClinicalTrials.gov, Embase, and the WHO's International Clinical Trials Registry Platform, between September and December 2020. This study included all preclinical, clinical, and pharmacological outcomes.
COVID-19 disease and therapeutics
Some of the common mild symptoms associated with the disease are fever, cough, muscle soreness, fatigue, sore throat, headache, and diarrhea. In the case of severe COVID-19 infection, multiorgan dysfunction and acute respiratory distress syndrome can occur.
Previous studies have reported the induction of proinflammatory cytokine storms in severely infected COVID-19 patients, which cause acute lung injury. This extreme immune response occurs due to the very high production of interleukin (IL-6, IL-1b, IL-18) and immune cells. Inflammation caused during severe SARS-CoV-2 infection also affects other organs and the central nervous system.
Several drugs with anti-inflammatory, immune suppressive, and immune-modulatory (e.g., dexamethasone) properties and antiviral activities (e.g., remdesivir) have been used to treat severely infected COVID-19 patients. Other strategies used to treat patients are monoclonal antibodies and convalescent plasma therapy.
Patients who required hospitalization due to severe COVID-19 infection significantly responded to dexamethasone and remdesivir treatment. However, the effectiveness of this dexamethasone, if administered during the early phase of COVID-19 infection, has not been determined. Additionally, remdesivir is not recommended for ambulatory use but for severely infected hospitalized patients.
Besides remdesivir, dexamethasone, and viral antibody therapies, two new drugs, namely, paxlovid and molnupiravir, have received emergency use authorization (EUA) to treat COVID-19 patients who are susceptible to developing severe infection. Scientists stated that more effective and safe drugs are required to treat COVID-19 patients.
Cannabidiol (CBD) for COVID-19 treatment
CBD, a metabolite isolated from Cannabis sativa, has been approved by the U.S Food and Drug Administration (FDA) and the European Union (EU) to treat a rare form of severe pediatric and adult epilepsy. CBD contains anti-inflammatory and immunosuppressive properties, so it has been considered for COVID-19 treatment, particularly for lung inflammation. The authors found eighteen articles related to the application of CBD, among which nine were included in this study. All the human and animal-based studies considered in this review showed that CBD had no adverse effects or drug interaction.
Pharmacological studies have reported that the endocannabinoid receptors 1 (CB1) and 2 (CB2) are associated with anti-inflammatory properties. These receptors are present in the human nervous system as well as other tissues. Studies have shown that activation of these receptors causes a reduction in the production of proinflammatory cytokines.
The lung injury models in murine demonstrated the anti-inflammatory effects of CBD. Several studies have indicated that CBD can inhibit the production of IL-6. Two in vivo animal studies analyzed the treated serum and reported that CBD was able to decrease IL-4, IL-5, IL-13, IL-6, proinflammatory cytokines, and ARDS. However, these studies revealed that CBD failed to reduce the levels of IL-10 levels.
The authors found that CBD can effectively lower leukocyte migration into the lungs, production of proinflammatory cytokines (TNF and IL-6), albumin concentration in the bronchoalveolar lavage fluid, chemokines (MCP-1 and MIP-2), and myeloperoxidase activity in the lung tissue.
One of the studies reported that CBD increased the monocytes after 6 and 25 hours of postlipopolysaccharide (LPS)-induced pulmonary inflammation. This study indicated an inverse correlation between CB1 and lung function. Only one human-related study reported that CBD treatment was not effective for patients with mild COVID-19 symptoms.
The majority of the studies reported that CBD reduced inflammatory response in COVID-19-infected Caco-2 cells and human colon epithelial tissues. Researchers compared inflammatory responses in human airway epithelial cells when treated with CBD and dexamethasone. This study reported that CBD significantly decreased LPS-induced NF-κB activity, MCP-1, and IL-8 release from macrophages.
Scientists reported that treatment of COVID-19 patients with 300 mg CBD for fourteen days prevented the development of severe infection, reduction in the parenchymal lung damage, change in proinflammatory cytokine concentration, and, subsequently, decreased chances of hospitalization.
The authors strongly suggested that CBD is a promising anti-inflammatory agent for treating severely infected COVID-19 patients. However, more clinical studies are required to evaluate the clinical benefits and adverse effects of CBD.