Epigenetic Regulation of Cannabinoid-Mediated Attenuation of Inflammation and Its Impact on the Use of Cannabinoids to Treat Autoimmune Diseases

Abstract

Chronic inflammation is considered to be a silent killer because it is the underlying cause of a wide range of clinical disorders, from cardiovascular to neurological diseases, and from cancer to obesity. In addition, there are over 80 different types of debilitating autoimmune diseases for which there are no cure. Currently, the drugs that are available to suppress chronic inflammation are either ineffective or overtly suppress the inflammation, thereby causing increased susceptibility to infections and cancer. Thus, the development of a new class of drugs that can suppress chronic inflammation is imperative. Cannabinoids are a group of compounds produced in the body (endocannabinoids) or found in cannabis (phytocannabinoids) that act through cannabinoid receptors and various other receptors expressed widely in the brain and immune system. In the last decade, cannabinoids have been well established experimentally to mediate anti-inflammatory properties. Research has shown that they suppress inflammation through multiple pathways, including apoptosis and inducing immunosuppressive T regulatory cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Interestingly, cannabinoids also mediate epigenetic alterations in genes that regulate inflammation. In the current review, we highlight how the epigenetic modulations caused by cannabinoids lead to the suppression of inflammation and help identify novel pathways that can be used to target autoimmune diseases.

The Expanded Endocannabinoid System Contributes to Metabolic and Body Mass Shifts in First-Episode Schizophrenia: A 5-Year Follow-Up Study

“…In addition, it is widely documented that eCBs and eCB-like NAEs have a major role in the suppression of low-grade chronic inflammation through multiple pathways [ 84 ]. Similar to a previous report [ 78 ], we speculate that increased levels of PEA and AEA and a decreased level of 2-AG found in the AP-naïve group, as well as the considerably elevated level of 2-AG during the 5-year follow-up in our study, might be a consequence or the causative factors of the immunomodulatory effect of the eECS.…”

Epigenetic modifications in the accumulation and function of myeloid-derived suppressor cells

“…For example, the CBD treatment of MDSCs reduce neuroinflammation in experimental autoimmune encephalomyelitis (EAE) mice. Thus, Cannabinoids treatment may play a key role in regulating inflammation through epigenetic pathways (78). Immune-checkpoint inhibition (ICI) therapy is a revolutionary treatment for cancer.…”

Role of Gut Microbiota in Cannabinoid-Mediated Suppression of Inflammation

“…Epigenetic modulations are additional mechanisms of immunosuppression triggered by cannabinoids ( 43 ). The eCB system undergoes epigenetic modifications and such variations are observed in pathological disorders such as Diabetes, Parkinson’s, Alzheimer’s, and colorectal cancer.…”