molecules Review Endocannabinoid System Dysregulation from Acetaminophen Use May Lead to Autism Spectrum Disorder: Could Cannabinoid Treatment Be Efficacious? Stephen Schultz 1, Georgianna G. Gould 1, Nicola Antonucci 2, Anna Lisa Brigida 3 and Dario Siniscalco 4,* 1 Department of Cellular and Integrative Physiology, Center for Biomedical Neuroscience, University of Texas (UT) Health Science Center San Antonio, San Antonio, TX 78229, USA;
[email protected] (S.S.);
[email protected] (G.G.G.) 2 Biomedical Centre for Autism Research and Therapy, 70126 Bari, Italy;
[email protected] 3 Department of Precision Medicine, University of Campania, 80138 Naples, Italy;
[email protected] 4 Department of Experimental Medicine, University of Campania, 80138 Naples, Italy * Correspondence:
[email protected] Abstract: Persistent deficits in social communication and interaction, and restricted, repetitive pat- terns of behavior, interests or activities, are the core items characterizing autism spectrum disorder (ASD). Strong inflammation states have been reported to be associated with ASD. The endocannabi- noid system (ECS) may be involved in ASD pathophysiology. This complex network of lipid signal- ing pathways comprises arachidonic acid and 2-arachidonoyl glycerol-derived compounds, their G-protein-coupled receptors (cannabinoid receptors CB1 and CB2) and the associated enzymes. Alter- Citation: Schultz, S.; Gould, G.G.; ations of the ECS have been reported in both the brain and the immune system of ASD subjects. ASD Antonucci, N.; Brigida, A.L.; Siniscalco, D. Endocannabinoid children show low EC tone as indicated by low blood levels of endocannabinoids. Acetaminophen System Dysregulation from use has been reported to be associated with an increased risk of ASD.