Cannabidiol as an emergent therapeutic strategy for lessening the impact of inflammation on oxidative stress

Abstract

Oxidative stress with reactive oxygen species generation is a key weapon in the arsenal of the immune system for fighting invading pathogens and initiating tissue repair. If excessive or unresolved, however, immune-related oxidative stress can initiate further increasing levels of oxidative stress that cause organ damage and dysfunction. Targeting oxidative stress in various diseases therapeutically has proven more problematic than first anticipated given the complexities and perversity of both the underlying disease and the immune response. However, growing evidence suggests that the endocannabinoid system, which includes the CB₁ and CB₂ G-protein-coupled receptors and their endogenous lipid ligands, may be an area that is ripe for therapeutic exploitation. In this context, the related nonpsychotropic cannabinoid cannabidiol, which may interact with the endocannabinoid system but has actions that are distinct, offers promise as a prototype for anti-inflammatory drug development. This review discusses recent studies suggesting that cannabidiol may have utility in treating a number of human diseases and disorders now known to involve activation of the immune system and associated oxidative stress, as a contributor to their etiology and progression. These include rheumatoid arthritis, types 1 and 2 diabetes, atherosclerosis, Alzheimer disease, hypertension, the metabolic syndrome, ischemia-reperfusion injury, depression, and neuropathic pain.

Figure 1

Chemical structure of cannabidiol (CBD).

Figure 2

Inflammation and oxidative stress in atherosclerotic plaque formation. Endothelial dysfunction causes monocyte activation and their binding to endothelial cells, via the production of MCP-1, its binding to CCR2 receptors, and the upregulation of adhesion molecules on endothelial cells (1). Monocytes cross the endothelium and differentiate into macrophages (2). Due to ROS, LDL that traverses the endothelium is converted to mmLDL and oxLDL. Macrophages accumulate oxLDL through scavenger receptors and are turned into foam cells (3). Along with T cells, foam cells produce inflammatory mediators that stimulate migration of smooth muscle and endothelial cells into the intima (4). Figure taken with permission from Reference .