The cytokine storm, an extreme inflammatory response by the body, causes some of the most severe complications of coronavirus disease, COVID-19. Many current therapeutic strategies are designed to suppress the inflammation by modulating the immune system.
My laboratory has demonstrated that stimulation of endogenous cannabinoid receptors can reduce numerous biomarkers of inflammation. Specifically, stimulation of cannabinoid type 2 (CB2) receptors induces anti-inflammatory actions by modulating numerous signaling pathways. Recently, some attention has been given to targeting the endocannabinoid system using compounds found in the cannabis plant.
The benefits of beta-caryophyllene:
CB2 receptors can be activated by a naturally occurring cannabinoid molecule called beta-caryophyllene (BCP). BCP is actually a constituent of many different essential oils derived from cloves, rosemary, and hops. BCP demonstrates potent anti-inflammatory, antiviral, and immunomodulatory properties most likely by activating CB2 receptors. The action of BCP at CB2 receptors leads to the inhibition of a significant number of inflammatory mediators, including cytokines, chemokines, prostanoids, and eicosanoids (chemicals that are frequently mentioned in hay fever treatment commercials). Due to these actions, a recent publication suggested that BCP might be a promising therapy to target the triad of infection, immunity, and inflammation in COVID-19 long-haulers. In addition, because BCP targets only the CB2 receptor, it does not possess psychoactive properties.
COVID alters the function of specific proteins in long-haulers:
Some patients develop complications long after the initial symptoms of COVID infection have dissipated. These so-called “long-haulers” may experience physical fatigue, mental abnormalities, and multiple organ damage. No treatment strategies currently exist for these patients.
Four proteins are known to be altered by COVID. The first protein is called ACE2. ACE2 is actually the principal target of the COVID virus. The virus finds the ACE2 protein floating on the surface of a cell and binds to it in order to gain entry into the cell. Once inside, the virus starts replicating itself using the cell’s own genetic machinery.
The second protein affected by COVID is the cytokine Interleukin-6 (IL-6). IL-6 is a powerful pro-inflammatory cytokine that is essential during the initial inflammatory response by the body following invasion by the virus. A third protein, called transmembrane serine protease (TSP), can actually activate COVID; its level is elevated in long-haulers. The fourth protein affected in COVID long-haulers is called NRP1. NRP1 plays an important role in COVID infection in humans by assisting the virus’ actions. Blocking the NRP1 interaction with the virus reduces its infectivity.
The benefits of CBD and CVN for COVID long-haulers:
A recent investigation targeted the proteins ACE2, IL-6, TSP, and NRP1 that are known to be damaged or upregulated by COVID. Two different molecules found in the cannabis plant, cannabidiol (CBD) and cannabivarin (CVN), were investigated for potential use in long-hauler COVID patients.
Using a series of sophisticated molecular docking and simulation studies, scientists discovered that CBD and CVN can effectively bind to these proteins and downregulate them. Taken together, these studies suggest that some components of the cannabis plant might be beneficial as a post-covid treatment strategy. Obviously, much more research is required in order to prove the effectiveness of these cannabinoids.