Endocannabinoid signaling in brain diseases: Emerging relevance of glial cells

• Published in: Glia 2023-01, Vol.71 (1), p.103-126
• Main Authors: Bernal‐Chico, Ana, Tepavcevic, Vanja, Manterola, Andrea, Utrilla, Carmen, Matute, Carlos, Mato, Susana
• Format: Article
• Language: English
• Subjects: Animal models; Animal tissues; Animals; Astrocytes; Brain; Brain Diseases; Brain injury; Cannabinoid receptors; Cannabinoids; Cannabinoids - pharmacology; Cannabis; CB1; CB2; Dronabinol; Endocannabinoids; Glial cells; Head injuries; Human tissues; Humans; Inflammatory diseases; Microglia; Modulators; Neurodegenerative diseases; Neurological diseases; Neuromodulation; Neuronal-glial interactions; Oligodendrocytes; Receptors, Cannabinoid - physiology; Signaling; Special Issue; Tetrahydrocannabinol
• ISSN: 0894-1491; 1098-1136
• DOI: 10.1002/glia.24172

The discovery of cannabinoid receptors as the primary molecular targets of psychotropic cannabinoid Δ9‐tetrahydrocannabinol (Δ9‐THC) in late 1980s paved the way for investigations on the effects of cannabis‐based therapeutics in brain pathology. Ever since, a wealth of results obtained from studies on human tissue samples and animal models have highlighted a promising therapeutic potential of cannabinoids and endocannabinoids in a variety of neurological disorders. However, clinical success has been limited and major questions concerning endocannabinoid signaling need to be satisfactorily addressed, particularly with regard to their role as modulators of glial cells in neurodegenerative diseases. Indeed, recent studies have brought into the limelight diverse, often unexpected functions of astrocytes, oligodendrocytes, and microglia in brain injury and disease, thus providing scientific basis for targeting glial cells to treat brain disorders. This Review summarizes the current knowledge on the molecular and cellular hallmarks of endocannabinoid signaling in glial cells and its clinical relevance in neurodegenerative and chronic inflammatory disorders. Main Points Endocannabinoids modulate glial cells. Targeting glial cells with endocannabinoids is a therapeutic option in neurological disorders. Efficacious endocannabinoid‐based therapies require analysis of cell‐type and disease‐specific mechanisms.