Endocannabinoid signaling in the central nervous system. Glia 2023 Jan;71(1):5-35
Date
10/30/2022Pubmed ID
36308424Pubmed Central ID
PMC10167744DOI
10.1002/glia.24280Scopus ID
2-s2.0-85141398970 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
It is hard to overestimate the influence of the endocannabinoid signaling (ECS) system on central nervous system (CNS) function. In the 40 years since cannabinoids were found to trigger specific cell signaling cascades, studies of the ECS system continue to cause amazement, surprise, and confusion! CB1 cannabinoid receptors are expressed widely in the CNS and regulate cell-cell communication via effects on the release of both neurotransmitters and gliotransmitters. CB2 cannabinoid receptors are difficult to detect in the CNS but seem to "punch above their weight" as compounds targeting these receptors have significant effects on inflammatory state and behavior. Positive and negative allosteric modulators for both receptors have been identified and examined in preclinical studies. Concentrations of the endocannabinoid ligands, N-arachidonoylethanolamine and 2-arachidonoylglycerol (2-AG), are regulated by a combination of enzymatic synthesis and degradation and inhibitors of these processes are available and making their way into clinical trials. Importantly, ECS regulates many essential brain functions, including regulation of reward, anxiety, inflammation, motor control, and cellular development. While the field is on the cusp of preclinical discoveries providing impactful clinical and therapeutic insights into many CNS disorders, there is still much to be learned about this remarkable and versatile modulatory system.
Author List
Martinez Ramirez CE, Ruiz-Pérez G, Stollenwerk TM, Behlke C, Doherty A, Hillard CJAuthor
Cecilia J. Hillard PhD Associate Dean, Center Director, Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
CannabinoidsCentral Nervous System
Endocannabinoids
Receptor, Cannabinoid, CB1
Receptors, Cannabinoid
Signal Transduction
