The molecular logic of endocannabinoid signaling by Daniele Piomelli explores the role of endocannabinoids, lipid messengers that interact with cannabinoid receptors, in various brain functions. These endocannabinoids, such as anandamide and 2-arachidonoylglycerol (2-AG), are synthesized on demand from membrane precursors and play a key role in short-range signaling processes. They modulate synaptic efficacy and have therapeutic potential in various neurological functions. The Cannabis plant has a long history of use, with its psychoactive properties recognized in the 19th century. The active compound, Δ9-tetrahydrocannabinol (THC), was identified as the primary psychoactive component of Cannabis. The discovery of cannabinoid receptors, CB1 and CB2, in the brain led to the identification of endocannabinoids as ligands for these receptors. Endocannabinoids are synthesized from arachidonic acid through enzymatic pathways and are released in response to neural activity. Anandamide and 2-AG are the primary endocannabinoids, with anandamide being a fatty acid ethanolamide and 2-AG a monoacylglycerol. These compounds are released from neurons and act on nearby cells, modulating synaptic activity and influencing memory, anxiety, movement, and pain. The release of endocannabinoids is regulated by various mechanisms, including intracellular calcium levels and the activation of G-protein-coupled receptors. Once released, endocannabinoids are deactivated through carrier-mediated transport and intracellular hydrolysis by enzymes such as fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MGL). CB1 receptors are widely distributed in the brain and play a crucial role in various functions, including modulation of GABA and glutamate transmission, regulation of synaptic plasticity, and modulation of emotional and motor behaviors. The endocannabinoid system is also involved in the regulation of pain, with endocannabinoids contributing to central analgesia. The endocannabinoid system has therapeutic potential in various neurological and psychiatric disorders, including anxiety, depression, and obesity. The development of selective agonists and antagonists for CB1 and CB2 receptors has led to the exploration of these compounds as potential treatments for various conditions. However, the exact mechanisms of action and the full therapeutic potential of endocannabinoids are still being investigated.The molecular logic of endocannabinoid signaling by Daniele Piomelli explores the role of endocannabinoids, lipid messengers that interact with cannabinoid receptors, in various brain functions. These endocannabinoids, such as anandamide and 2-arachidonoylglycerol (2-AG), are synthesized on demand from membrane precursors and play a key role in short-range signaling processes. They modulate synaptic efficacy and have therapeutic potential in various neurological functions. The Cannabis plant has a long history of use, with its psychoactive properties recognized in the 19th century. The active compound, Δ9-tetrahydrocannabinol (THC), was identified as the primary psychoactive component of Cannabis. The discovery of cannabinoid receptors, CB1 and CB2, in the brain led to the identification of endocannabinoids as ligands for these receptors. Endocannabinoids are synthesized from arachidonic acid through enzymatic pathways and are released in response to neural activity. Anandamide and 2-AG are the primary endocannabinoids, with anandamide being a fatty acid ethanolamide and 2-AG a monoacylglycerol. These compounds are released from neurons and act on nearby cells, modulating synaptic activity and influencing memory, anxiety, movement, and pain. The release of endocannabinoids is regulated by various mechanisms, including intracellular calcium levels and the activation of G-protein-coupled receptors. Once released, endocannabinoids are deactivated through carrier-mediated transport and intracellular hydrolysis by enzymes such as fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MGL). CB1 receptors are widely distributed in the brain and play a crucial role in various functions, including modulation of GABA and glutamate transmission, regulation of synaptic plasticity, and modulation of emotional and motor behaviors. The endocannabinoid system is also involved in the regulation of pain, with endocannabinoids contributing to central analgesia. The endocannabinoid system has therapeutic potential in various neurological and psychiatric disorders, including anxiety, depression, and obesity. The development of selective agonists and antagonists for CB1 and CB2 receptors has led to the exploration of these compounds as potential treatments for various conditions. However, the exact mechanisms of action and the full therapeutic potential of endocannabinoids are still being investigated.