Endocannabinoid system involvement in autism spectrum disorder: An overview with potential therapeutic applications

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Persistent deficits in social communication, restricted-repetitive patterns of behavior, interests, or activities are the core domains characterizing autism spectrum disorder (ASD). In this spectrum are grouped a heterogeneous and complex set of neurodevelopmental conditions. ASD shows pro-inflammatory events and immune system dysfunction. The endocannabinoid (EC) system is an intricate molecular network of lipid signaling pathways. The building-blocks are the arachidonic acid-derived compounds (anandamide, AEA) and 2-arachidonoyl glycerol (2-AG), their G-protein-coupled receptors (cannabinoid receptors CB1 and CB2), and their associated biosynthesizing and degradating enzymes. Recent evidence highlights a strong involvement of the EC system in the pathophysiology of some neuropsychiatric disorders and of ASD. Indeed, the EC system is able to regulate several metabolic and cellular pathways involved in autism, especially regulation of the immune system. ASD-related changes in the immune system involve alterations in monocyte and macrophage responses and pro-inflammatory cytokine up-regulation. It has been demonstrated that these processes are driven by EC system dysfunction, opening the way for targeting this system with novel drugs for ASD. Potentially, pharmacologic treatment with cannabidiol (CBD) is expected to increase endocannabinoid tone by increasing anandamide levels. Additionally, evidence from the literature indicates that CBD may alleviate many conditions co-occurring with ASD, such as seizures, gastro-intestinal problems, anxiety and depression, attention deficit, and sleep problems.