Endocannabinoid System (Ecb)

Epilepsy is a chronic neurological disorder associated with recurrent seizures, which influences approximately 50 million individuals worldwide [1-2]. More than 30% of the cases still have uncontrolled seizures even after the administration of antiepileptic drugs [3-4]. This represents a major unmet clinical need for new, well-tolerated antiepileptic drugs able to control pharmacoresistant epilepsies.
Natural cannabis has a long history in medicine [5]. Cannabinoid derivatives have been used as therapeutic for a variety of disorders, including epilepsy disorder and recurrent seizures [6-7]. Recently, non-psychoactive cannabinoid were proposed to be anti-convulsive agent [8-12]. In addition, 2-AG and anandamide (N-arachidonoylethanolamine) are two major endogenous cannabinoid-like compounds, known as endocannabinoids, exist in the nervous system and release on-demanded [13-14]. The endocannabinoid system (eCB) takes an important neuromodulatory role in the peripheral and central nervous system (CNS), modulating a wide range of physiological and pathological processes, including cognition, emotion, mood, appetite, and pain [15-17].
Also, anandamide is mainly produced from N-arachidonyl-phophatidylethanolamine (NAPE) by NAPE-phospholipase D (NAPE-PLD) [18-20]. After release, these endocannabinoids eliminated by a two-step mechanism consisting membrane transport and enzymatic hydrolysis [14]. 2-AG is hydrolyzed and deactivated primarily by monoacylglycerol lipase (MAGL) also through a recently described serine hydrolase a/b-hydrolase domains, ABHD6 [20-21]. Anandamide hydrolyzed and degraded mainly through fatty acid amide hydrolase (FAAH) [19, 22]. It has been shown that FAAH and MAGL inhibitors intensify endogenous eCB activity with temporal and spatial fidelity and should be superior to direct eCB agonists as therapeutic agents