Endocannabinoids
Introduction
Endocannabinoids are naturally occurring compounds within the human body that play a crucial role in maintaining internal stability and health by interacting with the endocannabinoid system (ECS). Two of the most researched and significant endocannabinoids are Anandamide (AEA) and 2-Arachidonoylglycerol (2-AG). These molecules are pivotal in various physiological processes, from memory and mood regulation to pain and inflammation management.
Anandamide (AEA)
Anandamide was first identified and named by the eminent scientist Raphael Mechoulam. The name is derived from the Sanskrit word "Ananda," which means "joy, delight, or bliss," reflecting its impact on mood and well-being. Interestingly, it is produced in the human body and found in small quantities in chocolate.
Anandamide is synthesized in cell membranes from arachidonic acid. It is metabolized primarily by the enzyme Fatty Acid Amide Hydrolase (FAAH), which breaks it down and regulates its levels and effects in the body.
Anandamide acts as an agonist at CB1 cannabinoid receptors, located primarily in the brain and throughout the central nervous system, and at TRPV1 receptors, which regulate pain, body temperature, and inflammation.
Anandamide influences several critical physiological processes:
Memory and Learning: It plays a role in modulating memory and learning processes.
Emotional Response and Well-being: Anandamide is known to enhance pleasure and motivation, reduce fear and anxiety, and potentially alleviate symptoms of depression.
Appetite and Feeding Behavior: It regulates feeding patterns and appetite and is linked to the phenomenon known as "runner's high," where elevated mood and pain suppression follow prolonged exercise.
Reproductive Health: Anandamide participates in controlling the pregnancy cycle.
Social Interactions: It influences social behavior and interpersonal interactions.
Hormonal Regulation: Anandamide affects hormone responses, including the release of melatonin and oxytocin, which are crucial for regulating sleep and social bonding, respectively.
2-Arachidonoylglycerol (2-AG)
Mechoulam's group also discovered 2-arachidonoylglycerol. They noted its ability to bind to both CB1 and CB2 receptors, suggesting its broad role in modulating the central nervous and immune systems. 2-AG is present at significantly higher brain concentrations than anandamide—about 170 times higher. Like anandamide, it is synthesized on demand from arachidonic acid in cell membranes.
2-AG is primarily broken down by Monoacylglycerol Lipase (MAGL), an enzyme that regulates its levels and activity within the body.
2-AG is a potent activator of both CB1 and CB2 receptors. Its activity at CB2 receptors influences a broader range of physiological functions than anandamide, mainly in the peripheral organs and cells associated with the immune system.
2-Arachidonoylglycerol influences critical physiological processes:
Neurotransmitter Modulation: 2-AG acts as a retrograde messenger, inhibiting the release of neurotransmitters at synaptic sites. It is crucial in mediating both inhibitory and excitatory synaptic transmission.
Neuroplasticity: It plays a significant role in mediating plasticity, the brain's ability to adapt to new information or injuries
Endocannabinoid-Like
Additionally, the metabolism of acetaminophen, a common pain reliever, produces a metabolite known as N-arachidonoylaminophenol. This derivative acts like an endocannabinoid, inhibiting COX enzymes and activating TRPV1, further illustrating the interconnections between pharmacology and endocannabinoid pathways.