Endocannabinoid-metabolizing enzymes and related transport processes

The endocannabinoid-metabolizing enzymes and related transport processes represent the biochemical machinery responsible for terminating the signaling of endogenous cannabinoids, primarily anandamide (AEA) and 2-arachidonoylglycerol (2-AG) (Piomelli, 2003, Nature Reviews Neuroscience). The system's primary enzymes include Fatty Acid Amide Hydrolase (FAAH), which degrades AEA, and Monoacylglycerol Lipase (MAGL), which is responsible for the majority of 2-AG hydrolysis (Di Marzo, 2018, Nature Reviews Drug Discovery). Transport processes involve proteins such as Fatty Acid Binding Proteins (FABPs) and the FAAH-like anandamide transporter (FLAT), which facilitate the movement of these lipophilic ligands from the plasma membrane to intracellular sites for degradation (Fowler, 2013, British Journal of Pharmacology). Dysregulation of these metabolic and transport pathways is associated with various conditions, including chronic pain, inflammation, anxiety, and neurodegenerative diseases (Ligresti et al., 2016, Physiological Reviews). Pharmacological inhibition of these enzymes or transporters aims to increase the endocannabinoid tone, providing therapeutic benefits by prolonging the activity of endogenous ligands at CB1 and CB2 receptors. This strategy is considered a promising alternative to direct cannabinoid receptor agonists, as it may offer a more localized effect with fewer central nervous system side effects (Maccarrone et al., 2015, Nature Reviews Neuroscience).

Other names

Endocannabinoid turnover systemEndocannabinoid metabolic enzymesEndocannabinoid transport systemEndocannabinoid degradation and transport

Inhibition of endocannabinoid degradation enzymes (e.g., FAAH, MAGL) or transport proteins (e.g., FABPs) to increase the local concentration and signaling duration of endogenous cannabinoids like anandamide and 2-arachidonoylglycerol at cannabinoid receptors.