Cannabinoids as novel anti-inflammatory drugs

[Vince]

It is becoming increasingly clear that cannabinoid receptors and their endogenous ligands play a crucial role in the regulation of the immune system. Exogenous cannabinoids have been shown to suppress T-cell-mediated immune responses by primarily inducing apoptosis and suppressing inflammatory cytokines and chemokines. Such observations indicate that targeting cannabinoid receptor–ligand interactions may constitute a novel window of opportunity to treat inflammatory and autoimmune disorders. As CB2 receptors are primarily expressed on immune cells, targeting CB2 may result in selective immunomodulation without overt toxicity. The future challenges for the use of cannabinoids as anti-inflammatory drugs include synthesis of cannabinoid receptor agonists that are nonpsychoactive with anti-inflammatory activity and then identifying their mode of action. Although current studies suggest that cannabinoids are useful therapeutic agents in the treatment of various inflammatory disorders, further evaluation of the mechanisms that account for their anti-inflammatory properties is necessary. Such studies may involve the use of cannabinoid receptor-knockout mice and use of receptor-specific compounds. While most studies have focused on the effect of cannabinoids on cytokines, apoptosis and Th1 cell functions in the past, additional investigations on their effect on Th17 cells, DCs, NK cells, B cells and Fox-P3[SUP]+[/SUP] regulatory T cells is critical as such cells play an important role in the regulation and mediation of inflammatory or autoimmune disease response. Whether endocannabinoids and cannabinoid receptors play a critical role during normal inflammatory response also requires further consideration. Moreover, cannabinoid receptor signaling and effect of cannabinoids on adhesion molecules, co-stimulatory molecules and chemokines require further study in order to increase our understanding of cannabinoids and their intricate effects on immune system disorders. Overall, cannabinoids have exhibited significant potential to be used as novel anti-inflammatory agents and specific targeting of CB2 receptors holds the promise of mediating immunosuppressive effects without exerting psychotropic side effects.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828614/