Autism Spectrum Disorder and the Endocannabinoid system

Autism Spectrum disorders (ASD) are a group of disorders which are characterised by impairments in social communication and interaction with “restrictive or repetitive” motor movements (Zamberletti, Gabaglio and Parolaro, 2017). Autism is also characterized by immune system dysregulation and can be accompanied by depression and Gut disorders. According to The National Autistic Society approximately 700,000 people on the autism spectrum (Brigida et al., 2017).  Globally, the prevalence rates of ASD are feared to be on the rise with numerous theories being provided, however this is partly due to the improvement in our understanding of psychology and identification of behavioural difficulties.

In the UK, the prevalence of ASD has remained steady at approximately 3.8/1000 boys and 0.8/1000 girls (Taylor, Jick and Maclaughlin, 2013). Despite ASD being so prevalent, little is known about the underlying biological basis of ASD and so, no effective treatments currently exist for ASD.  Given this lack of understanding, it is particularly exciting that early animal models of autism have demonstrated that the endocannabinoid system appears to be altered in ASD (Zamberletti, Gabaglio and Parolaro, 2017).We now know the ECS is key neuromodulatory system that regulates emotional, behavioural and social interactions. The medicinal impact of the ECS is commonly seen in other neurological disorders such as epilepsy and anxiety and it appears there may be a greater number of neurological conditions that exhibit ECS alterations.

 

The endocannabinoid, anandamide (AEA), first described in 1992 by the research faculty at the University of Jerusalem, is a signalling molecule used by the ECS to regulate the many millions of communications between cells, throughout the body (Devane et al., 1992). AEA is a naturally occurring molecule that is produced by the body in varying quantities to ensure tissues do not being over or under stimulated. Studies exploring the alterations to this endocannabinoid system have observed that the concentrations of AEA are lower in the blood of children with ASD when compared to children without ASD (Karhson et al., 2018). This trend is such that children with lower AEA concentrations are more likely to have ASD. Not only AEA is known to be disrupted. Other research groups have shown that these systemic alterations also extend to the CB2 receptor as well as the enzymes that produce and digest AEA (Brigida et al., 2017).  

So what does this mean for patients?

With the knowledge that ASD patients are likely to be deficient in AEA, several research groups have set to explore whether treatments that increase the levels of AEA may provide a therapeutic effect. A mouse study exploring exact question, aimed to achieve this through blocking the fatty acid amide hydrolase (FAAH), an enzyme that breaks down a in the body. By inhibiting this enzyme, the research group were able to completely reverse the social impairment of mice two well established models of ASD (Wei et al., 2016).

Although endocannabinoid treatments may some years away from being implemented in humans, phytocannabinoids have been demonstrated to alleviate a variety of the symptoms associated with ASD.

The exploration of non-psychoactive phytocannabinoids, such as Cannabidiol (CBD), for the treatment of neurological conditions is gaining pace. However, a scientific review investigating the use of CBD in ASD was unable to find any research that had directly explored the viability of CBD as an ASD treatment. The review described a great sparsity of research in the field and a necessity for more research to explore the issue directly (Poleg et al., 2019). Our current knowledge of CBD and ASD is based on the indirect exploration of CBD in conditions associated with ASD. By exploring the underlying physiology of the endocannabinoid system there is an opportunity to uncover new methods of managing problematic ASD as well as the biological basis for these disorders.

If you are looking for more information on ASD and cannabis we have attached a PDF portfolio of the latest ASD and cannabis research.

 

References

Brigida, A. L. et al. (2017) ‘EndocannabinodSignal Dysregulation in Autism Spectrum Disorders: A Correlation Link betweenInflammatory State and Neuro-Immune Alterations.’, International journal ofmolecular sciences. Multidisciplinary Digital Publishing Institute  (MDPI), 18(7). doi: 10.3390/ijms18071425.

Devane, W. A. et al. (1992) ‘Isolation and structure of a brainconstituent that binds to the cannabinoid receptor.’, Science (New York,N.Y.). American Association for the Advancement of Science, 258(5090), pp.1946–9. doi: 10.1126/SCIENCE.1470919.

Karhson, D. S. et al. (2018) ‘Plasma anandamide concentrations arelower in children with autism spectrum disorder’, Molecular Autism.BioMed Central, 9(1), p. 18. doi: 10.1186/s13229-018-0203-y.

Poleg, S. et al. (2019) ‘Cannabidiol as a suggested candidate fortreatment of autism spectrum disorder’, Progress in Neuro-Psychopharmacologyand Biological Psychiatry, 89, pp. 90–96. doi: 10.1016/j.pnpbp.2018.08.030.

Taylor, B., Jick, H. and Maclaughlin, D. (2013) ‘Prevalence and incidencerates of autism in the UK: time trend from 2004-2010 in children aged 8years.’, BMJ open. British Medical Journal Publishing Group, 3(10), p.e003219. doi: 10.1136/bmjopen-2013-003219.

Wei, D. et al. (2016) ‘Enhancement of Anandamide-Mediated Endocannabinoid Signaling Corrects Autism-Related Social Impairment’, Cannabisand Cannabinoid Research.  Mary AnnLiebert, Inc.  140 Huguenot Street, 3rdFloor New Rochelle, NY 10801 USA  , 1(1),pp. 81–89. doi: 10.1089/can.2015.0008.

Zamberletti, E., Gabaglio, M. and Parolaro, D. (2017) ‘The EndocannabinoidSystem and Autism Spectrum Disorders: Insights from Animal Models’, InternationalJournal of Molecular Sciences, 18(9), p. 1916. doi: 10.3390/ijms18091916.