It may possess reinforcing effects of its own, and it is implicated in the reinforcing and addictive effects of various drugs of abuse, including non-cannabinoids. Indeed, several studies indicate that AEA exerts an overall modulatory effect on the reward circuitry. With regard to its involvement in the mechanisms of reward, AEA has been the most studied among the endocannabinoids. It modulates the rewarding and pharmacological responses induced by cannabinoids, as well as those induced by other drugs of abuse. Furthermore, the endocannabinoid system is an important constituent of the neuronal substrates involved in the reinforcement and reward processes of the brain. In mammals, it has been recently recognized as a modulator of a large variety of physiological processes, including inflammation and pain, appetite, mood, and pre-and postnatal development. The endocannabinoid system is an important lipid signaling system that emerged before the evolution of vertebrates and it is well preserved across species. The discovery of CBRs and endocannabinoids led to the identification of other components of what was then called the “endocannabinoid system”, which also includes the enzymes that are responsible for both the biosynthesis and the metabolism of endocannabinoids. Since the discovery of these first two endogenous cannabinoids, numerous studies have been carried out demonstrating that their behavioral and molecular effects only partially overlap between compounds, as well as between each compound and the most studied CB1 agonist, THC. 2-Arachidonoylglycerol (2-AG) was the second endocannabinoid to be identified it was isolated from the rat brain and the canine gut. Its name comes from the Sanskrit word “ananda” ( internal bliss), which emphasizes the interesting role of AEA as an endogenous marijuana-like substance self-delivered by the brain. The first endocannabinoid to be discovered was anandamide (AEA), which was isolated from the pig brain by William Devane and co-workers in 1992. The discovery of CB1 receptors, the primary pharmacological target of THC, prompted research to find the endogenous ligands for these receptors. Nevertheless, until the discovery of CB1 receptors in 1988, the mechanisms involved in the action of THC on the brain were elusive and were suggested to consist of non-specific activity on the neuronal cell membrane. Since then, THC has been synthesized, and many studies have been conducted on its activity. The major psychoactive component of marijuana, Δ9-tetrahydrocannabinol (THC), was isolated and its chemical structure clarified by Gaoni and Mechoulam in 1964.
We will also discuss how modulation of anandamide levels through inhibition of enzymatic metabolic pathways could provide a basis for developing new pharmaco-therapeutic tools for the treatment of substance use disorders.Ĭannabis sativa and its derivatives, i.e., marijuana, are among the best-known mind-altering substances used by man in ancient times and are still among the most abused substances worldwide. In this review, we will provide an overview from a preclinical perspective of the current state of knowledge regarding the behavioral pharmacology of anandamide, with a particular emphasis on its motivational/reinforcing properties. Enhanced brain levels of anandamide after treatment with inhibitors of fatty acid amide hydrolase, the main enzyme responsible for its degradation, seem to affect the rewarding and reinforcing actions of many drugs of abuse. Importantly, all these effects of anandamide appear to be potentiated by pharmacological inhibition of its metabolic degradation. Several reports suggest its involvement in the addiction-producing actions of other abused drugs, and it can also act as a behavioral reinforcer in animal models of drug abuse. Several studies demonstrate that anandamide exerts an overall modulatory effect on the brain reward circuitry. These receptors are also the primary molecular target responsible for the pharmacological effects of Δ9-tetrahydrocannabinol, the psychoactive ingredient in Cannabis sativa. Anandamide is a lipid mediator that acts as an endogenous ligand of CB1 receptors.
0 kommentar(er)
