The endocannabinoid system: an overview

Abstract

Upon the identification of anandamide (AEA) in the porcine brain, numerous studies contributed to the current state of knowledge regarding all elements that form the “endocannabinoid system (ECS).”How this complex system of receptors, ligands, and enzymes is integrated in helping to regulate fundamental processes at level of central nervous and peripheral systems and how its regulation and dysregulation might counteract disturbances of such functions, is nowadays still under investigation. However, the most recent advances on the physiological distribution and functional role of ECS allowed the progress of various research tools aimed at the therapeutic exploitation of endocannabinoid (eCB) signaling, as well as the development of novel drugs with pharmacological advantages. Here, we shall briefly overview the metabolic and signal transduction pathways of the main eCBs representatives, AEA, and 2-arachidonoylglycerol (2-AG), and we will discuss the therapeutic potential of new ECS-oriented drugs.

Cannabidiol as a Potential Treatment for Anxiety Disorders

“…The primary mechanism by which eCBs regulate synaptic function is retrograde signaling, wherein eCBs produced by depolarization of the postsynaptic neuron activate presynaptic CB 1 Rs, leading to inhibition of neurotransmitter release [23]. The BeCB systemî ncludes AEA and 2-arachidonoylglycerol; their respective degradative enzymes fatty acid amide hydroxylase (FAAH) and monoacylglycerol lipase; the CB 1 R and related CB 2 receptor (the latter expressed mainly in the periphery); as well as several other receptors activated by eCBs, including the TRPV1 receptor, peroxisome proliferator-activated receptor-γ, and G protein-coupled 55 receptor, which functionally interact with CB 1 R signaling (reviewed in [21,24]). Interactions with the TRPV1 receptor, in particular, appear to be critical in regulating the extent to which eCB release leads to inhibition or facilitation of presynaptic neurotransmitter release [25].…”

A quantitiative LC-MS/MS method for the measurement of arachidonic acid, prostanoids, endocannabinoids, N-acylethanolamines and steroids in human plasma

“…The highest variability is observed in QC 4 . This could be explained by the fact that the amounts of analytes spiked are low as compared to the endogenous levels of the analytes (the variability is less noticeable when spiking samples with higher concentrations of analytes, such as QC 7 ). This can be better appreciated when comparing the concentration spiked in QC 4 (Table 4) with the values reported in Table 5 (i.e., dynamic range and average of the analytical concentration obtained from the analysis of 32 plasma samples from healthy male volunteers (see section 2.4).…”

“…The endocannabinoid system is involved in different physiological and pathophysiological processes that occur mainly in the central nervous system (CNS) and immune system, but also exerts regulatory effects on metabolic processes and vascular tone [7]. ECs are produced "on demand" in the body from precursor phospholipids containing arachidonyl moieties derived from arachidonic acid including N-acylphosphatidylethanolamine (NAPE) and diacylglycerol (DAG) [8,9].…”

Evidence for Bidirectional Endocannabinoid Transport across Cell Membranes

“…The endocannabinoid system is a lipid signaling system comprising arachidonic acid-derived ligands, such as arachidonoylethanolamide (AEA) 2 and 2-arachidonoylglycerol (2-AG), which interact with the G protein-coupled cannabinoid receptors CB 1 and CB 2 in different cell types (1,2). The diverse roles of the endocannabinoid system (ECS) in physiological and pathological processes have been elucidated both in the central nervous system and in the periphery.…”