Immunomodulation by cannabinoids and the endocannabinoid system

The endocannabinoid system, which is composed of endocannabinoids and cannabinoid receptors (CBRs), plays roles in neurological and psychological functions, as well as in regulating vascular tone and blood pressure. Cannabis and cannabinoid products are increasingly being used to manage symptoms associated with inflammation, but the understanding of how the endocannabinoid system is involved in inflammation is limited. Emerging evidence suggests that cannabinoids can affect inflammation, and that CBRs play substantial immunomodulatory roles in sepsis and injury. We reported that Δ-9-tetrahydrocannbinol (THC) strongly induces the anti-inflammatory cytokine IL-10, while reducing multiple pro-inflammatory cytokines in LPS-treated mice. We also found that THC improves functional outcomes and lung inflammation at 24 hours in LPS-treated mice. We identified CB1R as the receptor responsible for the anti-inflammatory and improved functional outcomes in THC-treated endotoxemic mice. In recent studies we have found that another cannabinoid, Cannabinol (CBN) also has CB1R-dependent anti-inflammatory effects in LPS-treated mice.

Current Projects on Cannabinoids and the Endocannabinoid System

1. Determining the immunomodulatory effects and mechanisms of action of cannabinoids, including THC, CBN, and several other minor cannabinoids in sepsis and inflammation, and in acute and chronic pain. 
2. Elucidating the mechanisms by which THC CBN and other minor cannabinoids upregulate systemic IL-10 in mice with endotoxemia or with bacterial sepsis. Studies are also focused on understanding the role of IL-10 upregulation in determining functional outcomes of sepsis, acute inflammation and pain.
3. Defining the effects of bacterial sepsis on endocannabinoid levels in the circulation and in neuronal tissues.  
4. Defining the role of IL-10 upregulation induced by THC and CBN in directing functional outcomes of sepsis and, acute inflammation.