Endocannabinod Signal Dysregulation in Autism Spectrum Disorders: A Correlation Link between Inflammatory State and Neuro-Immune Alterations

Abstract

Several studies highlight a key involvement of endocannabinoid (EC) system in autism pathophysiology. The EC system is a complex network of lipid signaling pathways comprised of arachidonic acid-derived compounds (anandamide, AEA) and 2-arachidonoyl glycerol (2-AG), their G-protein-coupled receptors (cannabinoid receptors CB1 and CB2) and the associated enzymes. In addition to autism, the EC system is also involved in several other psychiatric disorders (i.e., anxiety, major depression, bipolar disorder and schizophrenia). This system is a key regulator of metabolic and cellular pathways involved in autism, such as food intake, energy metabolism and immune system control. Early studies in autism animal models have demonstrated alterations in the brain’s EC system. Autism is also characterized by immune system dysregulation. This alteration includes differential monocyte and macrophage responses, and abnormal cytokine and T cell levels. EC system dysfunction in a monocyte and macrophagic cellular model of autism has been demonstrated by showing that the mRNA and protein for CB2 receptor and EC enzymes were significantly dysregulated, further indicating the involvement of the EC system in autism-associated immunological disruptions. Taken together, these new findings offer a novel perspective in autism research and indicate that the EC system could represent a novel target option for autism pharmacotherapy.

Clinical Case Report of a Novel Immunotherapeutic Approach to Autism Spectrum Disorders based on an emulsion of Chondroitin Sulfate, Vitamin D₃ and Oleic Acid

“…However, the response to Rerum ® was robust with regard to symptomatic improvements as shown by the CGI-I score and we attribute these remarkable results to the effects of the supplement on the Endocannabinoid (EC) system as it relates to neuroinflammation and neuro-immune alterations. Thus, we recently described the role of the EC system in the pathophysiology of ASD and we highlighted the involvement of the EC system in autism-associated immunological disruptions (Brigida et al, 2017). Preliminary results obtained in our laboratory seem to indicate that Rerum ® acts on the EC system in vitro (manuscript in preparation).…”

Stem cell therapy in autism: recent insights

“… 27 Immune alterations in ASDs are still confirmed by abnormal monocyte and macrophage responses, which overproduce proinflammatory IL-1β cytokine and show several altered molecular systems resulting in long-term immune alterations. 8 , 26 , 28 – 30 The immune modulatory capacity of stem cells could restore these ASD–immune alterations. Stem cells are able to strongly inhibit CD8 + and CD4 + T lymphocytes and NK cell overactivation and proliferation by inhibiting proinflammatory tumor necrosis factor alpha and interferon gamma molecules and increasing anti-inflammatory IL-10 levels.…”

Medical Cannabis for Autism Spectrum Disorder, is it an option?

“…A deficiency in the endocannabinoid system in the body is considered as the reason for many disorders and recent researchers' state that it might help in the treatment of autism [24,25,28,29]. The chronic neuroinflammation can be eased with the help of the antioxidants which are present in the cannabis plant [26,27]. Cannabis helps with mood and behavior of the patients in terms of emotions & aggressive outbursts [28].…”

“…abnormal cytokine and T cell levels, as well as mRNA and protein for CB2 receptor and EC enzymesfurther indicating the involvement of the EC system in autismassociated immunological disruptions. These new findings offer a novel perspective in autism research and indicate that the EC system could represent a novel target option for autism pharmacotherapy[27].• Endocannabinoid signaling in specific circuits of the brain is context dependent and selectively recruited. Therefore, playing a key role in many human health and disease conditions of the central nervous system, thus opening the avenue to the therapeutic exploitation of eCB-oriented drugs for the treatment of psychiatric, neurodegenerative, and neuroinflammatory disorders.…”