Opportunities, Challenges and Pitfalls of Using Cannabidiol as an Adjuvant Drug in COVID-19

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may lead to coronavirus disease 2019 (COVID-19) which, in turn, may be associated with multiple organ dysfunction. In this review, we present advantages and disadvantages of cannabidiol (CBD), a non-intoxicating phytocannabinoid from the cannabis plant, as a potential agent for the treatment of COVID-19. CBD has been shown to downregulate proteins responsible for viral entry and to inhibit SARS-CoV-2 replication. Preclinical studies have demonstrated its effectiveness against diseases of the respiratory system as well as its cardioprotective, nephroprotective, hepatoprotective, neuroprotective and anti-convulsant properties, that is, effects that may be beneficial for COVID-19. Only the latter two properties have been demonstrated in clinical studies, which also revealed anxiolytic and antinociceptive effects of CBD (given alone or together with Δ9-tetrahydrocannabinol), which may be important for an adjuvant treatment to improve the quality of life in patients with COVID-19 and to limit post-traumatic stress symptoms. However, one should be aware of side effects of CBD (which are rarely serious), drug interactions (also extending to drugs acting against COVID-19) and the proper route of its administration (vaping may be dangerous). Clearly, further clinical studies are necessary to prove the suitability of CBD for the treatment of COVID-19.

Cannabidiol for COVID-19 Patients with Mild to Moderate Symptoms (CANDIDATE Study): A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

“…Moreover, CBD did not show anxiolytic or antidepressive effects, which also does not confirm previous literature showing anxiolytic properties of this dose. 5,[16][17][18][19][20][21] However, as in the case of inflammation, patients did not have high anxiety and depression levels at baseline (mean GAD-7 and PHQ-9 scores < 10). In addition, all the patients received significant support, with repeated visits of nurses at the residence and remote daily monitoring by the physician.…”

“…Since the beginning of the pandemic, several editorials, reviews, and pre-clinical studies have suggested that cannabidiol (CBD), a nonpsychotomimetic phytocannabinoid, could have potential beneficial effects in the course of COVID-19. [1][2][3][4][5][6] CBD has putative anti-inflammatory properties [7][8][9][10][11][12][13][14] and may attenuate the cytokine storm by reducing the levels of cytokines (such as interleukin-6, IL-6; tumor necrosis factor-a, TNF-a; and interferon-c) and symptoms of acute respiratory distress syndrome in a mouse model, frequent clinical conditions observed in patients with severe COVID-19. 7,8 CBD reduced brain levels of cytokines (such as TNF-a 9 and IL-1b 10 ) and microglia activation, [10][11][12] and decreased the levels of proinflammatory cytokines (IL-5, IL-6, and IL-13) in pre-clinical models of lung inflammation 13 and allergic asthma.…”

“…14 Moreover, CBD has potential antiviral properties. 2,4,5,15 Recently, in vitro and in silico analysis suggested that in VERO cells, CBD reduces intracellular expression of the spike protein S of the SARS-CoV-2. 15 CBD showed anxiolytic and antidepressant effects in pre-clinical [16][17][18] and clinical 19,20 studies.…”

Use of Antioxidants for the Neuro-Therapeutic Management of COVID-19

“…Other antioxidant compounds that have been proposed as potential adjuvants in COVID-19 are zinc [ 260 ], selenium [ 261 ], melatonin [ 262 ], curcumin [ 263 ], N-acetylcystein [ 264 , 265 ], GC4419, a SOD mimetic [ 266 ], colchicine [ 267 ], α-lipoic acid [ 268 ], glutathione [ 269 ], broccoli or glucoraphanin capsules [ 270 ], dypiridamole [ 271 ], cannabidiol [ 272 ], combinations of vitamin D, magnesium, and vitamin B12 [ 273 ], and diammonium glycyrrhizinate with vitamin C [ 274 ].…”

Antimicrobial and Antiviral (SARS-CoV-2) Potential of Cannabinoids and Cannabis sativa: A Comprehensive Review

“…Angiotensin-converting enzyme 2 (ACE2), a SARS-CoV receptor and transmembrane serine protease 2 (TMPRSS2), a cell surface protein, allow entry and S protein priming of SARS-CoV-2, respectively, thereby providing viral gateways ( Figure 4 ) and viral activation in lung tissue, oral and nasal mucosa, and the gastrointestinal tract [ 155 , 156 , 157 , 158 ], and even facilitate mother to fetal transmission of the virus [ 159 ]. ACE2 enzyme binds glycoprotein S1, the characteristic viral spike protein, via a receptor-binding domain, and TMPRSS2 permits entrance of the virus into the cytoplasmic membrane of host cells [ 160 , 161 ]. Investigations also revealed that SARS-CoV-2 M pro (the main protease) has a pivotal role in viral replication and transcription and can be regarded as an attractive drug target [ 162 , 163 ].…”