Immunomodulation via the Endocannabinoid System: Mechanisms and Therapeutic Potentials

Abstract

The endocannabinoid system (ECS) plays a crucial role in regulating immune responses, influencing both innate and adaptive immunity through its interaction with cannabinoid receptors, particularly CB2, which is predominantly expressed on immune cells. This review explores the mechanisms of ECS-mediated immunomodulation, focusing on its ability to balance pro-inflammatory and anti-inflammatory processes, thereby contributing to immune homeostasis. Endocannabinoids, such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG), modulate immune cell activity, cytokine production, and migration. These actions make the ECS a promising therapeutic target for chronic inflammatory and autoimmune diseases, including rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease. Additionally, the ECS has potential applications in cancer immunotherapy by modulating the tumor microenvironment and enhancing anti-tumor immune responses. Non-psychoactive cannabinoids like cannabidiol (CBD) have emerged as attractive candidates for therapeutic use, offering anti-inflammatory benefits without the adverse psychoactive effects associated with tetrahydrocannabinol (THC). However, challenges remain in understanding the ECS’s complex interactions within the immune system and optimizing cannabinoid-based therapies for clinical use. As research progresses, the ECS may provide novel therapeutic avenues for immune regulation and disease management, contributing to improved outcomes in a variety of immune-related disorders. Keywords: Endocannabinoid system, Immunomodulation, CB2 receptors, Inflammation, Autoimmune diseases