Autism-Open Access

Autism-Open Access
Open Access

ISSN: 2165-7890

Editorial - (2014) Volume 4, Issue 2

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Endocannabinoid System as Novel Therapeutic Target for Autism Treatment

Dario Siniscalco1,2,3*
1Department of Experimental Medicine, Second University of Naples, Italy
2Centre for Autism – La Forza del Silenzio, Caserta, Italy
3Cancellautismo – No Profit Association for Autism Care, Florence, Italy
*Corresponding Author: Dario Siniscalco, Department of Experimental Medicine-Division of Pharmacology, Second University of Naples, Via S. Maria Di Costantinopoli, 16 - 80138 Napoli, Italy, Tel: +39 (0)81 5665880, Fax: +39 (0)81 5667503 Email:

Editorial

The newest dramatic increased prevalence rates of autism and autism spectrum disorders (ASDs) [1] recall the urgent needed for finding a definitive cure, as well as the finding for a specific biomarker for early diagnosis. Recently, several studies highlight a key involvement of endocannabinoid (EC) system in autism pathophysiology [2].

Endocannabinoids are arachidonic acid derived compounds and together with their receptors and the associated enzymes, they the EC system, an intricate network of lipid signalling pathways [3]. The EC “building blocks” are the N-arachidonoylethanolamine (anandamide, AEA) and 2-arachidonoyl glycerol (2-AG), that exerts their effects through the G-protein-coupled cannabinoid receptors CB1 and CB2, which, in turn, are negatively coupled to adenylate cyclase enzyme [4].

Beyond autism, EC system is also involved in several other psychiatric disorders (i.e. anxiety, major depression, bipolar disorder and schizophrenia) [2]. This system is also a key regulator of other metabolic and cellular pathways involved in ASDs, such as food intake, energy metabolism, immune system controlling.

Early studies in animal models demonstrated that BTBR mice show an abnormal regulation of dopamine levels functioning with an up-regulated CB2A gene expression [5]. In addition, in the valproic acid induced model of autism, alterations in the brain's endocannabinoid system have been reported in a newest research [6].

Autism is a human pathology: the possibility of autism activation by EC system has been reviewed [7]. Accordingly, sulfation deficits in acetaminophen (paracetamol) metabolism with the autism population could indirectly increase the endocannabinoids levels, which in turn are able to activate CB1/2 receptors triggering autism. Endocannabinoid-CB2 signalling dysregulation has been reported in monocytic cells extracted from autistic children [2]. More interesting, blood monocyte-derived macrophagic cells from autistic patients also reveal EC system dysregulation, further indicating the involvement of the EC system in autism associated immunological disruptions and pointed to a potential nexus between endocannabinoids, vitamin D and the immune dysregulations observed with autism [8].

Taken together, all these new findings are offering novel perspectives in autism research and indicate that the EC system could represent a novel target option for autism pharmacotherapy. Potential future drugs could target CB2 receptor activation, in order to design new personalized strategies in the pharmacotherapeutical management of autism.

References

  1. Developmental Disabilities Monitoring Network Surveillance Year 2010 Principal Investigators; Centers for Disease Control and Prevention (CDC) (2014) Prevalence of autism spectrum disorder among children aged 8 years - autism and developmental disabilities monitoring network, 11 sites, United States, 2010. MMWR SurveillSumm 63: 1-21.
  2. Siniscalco D, Sapone A, Giordano C, Cirillo A, de Magistris L, et al. (2013) Cannabinoid receptor type 2, but not type 1, is up-regulated in peripheral blood mononuclear cells of children affected by autistic disorders. J Autism DevDisord 43: 2686-2695.
  3. Li C, Jones PM, Persaud SJ (2011) Role of the endocannabinoid system in food intake, energy homeostasis and regulation of the endocrine pancreas. PharmacolTher 129: 307-320.
  4. Pertwee RG, Howlett AC, Abood ME, Alexander SP, Di Marzo V, et al. (2010) International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CBâ‚ and CBâ‚‚. Pharmacol Rev 62: 588-631.
  5. Onaivi ES, Benno R, Halpern T, Mehanovic M, Schanz N, et al. (2011) Consequences of cannabinoid and monoaminergic system disruption in a mouse model of autism spectrum disorders. CurrNeuropharmacol 9: 209-214.
  6. Kerr DM, Downey L, Conboy M, Finn DP, Roche M (2013) Alterations in the endocannabinoid system in the rat valproic acid model of autism. Behav Brain Res 249: 124-132.
  7. Schultz ST (2010) Can autism be triggered by acetaminophen activation of the endocannabinoid system? ActaNeurobiolExp (Wars) 70: 227-231.
  8. Siniscalco D, Bradstreet JJ, Cirillo A, Antonucci N (2014) The in vitro GcMAF effects on endocannabinoid system transcriptionomics, receptor formation, and cell activity of autism-derived macrophages. J Neuroinflammation 11: 78.
Citation: Siniscalco D (2014) Endocannabinoid System as Novel Therapeutic Target for Autism Treatment. Autism Open Access 4:e122.

Copyright: © 2014 Siniscalco D. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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