The Endocannabinoid System: Pharmacological Targets and Therapeutic Potential in CNS Disorders

The endocannabinoid system (ECS) influences a wide range of brain functions, including synaptic transmission, neuroplasticity, emotion, and immune regulation within the central nervous system, with CB1 and CB2 receptors mediating various neurophysiological and pathophysiological outcomes. Thus, growing interest in its therapeutic potential has prompted extensive research into how cannabinoid receptors contribute to the pathophysiology of neurological and psychiatric disorders, particularly CB1 and CB2. This review has integrated findings from studies published between 2015 and 2025, covering conditions, like depression, anxiety, pain, multiple sclerosis, and Parkinson's disease. We have also examined recent advances in receptor pharmacology and experimental technologies, including cryo-EM, optogenetics, and chemogenetics. Although ECS-targeted therapeutics hold considerable promise, some key challenges remain in establishing safe and effective dosing protocols and integrating these approaches into clinical frameworks. This review has provided an updated perspective on the system's role in brain health and its potential to inform future therapeutic directions. Thus, ECS-targeted strategies may become increasingly important in managing and treating central nervous system disorders.