autism is a neurodevelopmental disorder characterized by impaired social interaction, verbal and non-verbal communication, and restricted and repetitive behavior. There is accumulating evidence for the involvement of the endocannabinoid system in the development of autism and cannabinoids therefore have therapeutic potential. More studies and especially clinical trials should indicate the real potential of cannabinoids in the treatment of autism.
One study in healthy humans linked CB1 polymorphisms (small variations in a gene that are not directly linked to any particular deficit) to variations in the time people spent looking at happy faces (Chakrabarti and Baron-Cohen, 2011). As this ‘gaze duration’ is a measure for autism, the endocannabinoid system may be implicated in autistic behavior.
Similarly, CB2-mediated signaling was significantly upregulated in peripheral blood mononuclear cells obtained from autistic children (Siniscalco et al., 2013).
In addition, the endocannabinoid synthesizing enzyme NAPE-PLD was upregulated and the endocannabinoid degrading enzyme FAAH was downregulated in autistic children (Siniscalco et al., 2014), suggesting raised levels of endocannabinoids.
Interestingly, in another genetic mouse model of mental retardation and autism (FMR1 knockout), blockade of CB1 normalized cognitive defects (Busquets-Garcia et al., 2013), suggesting CB1 may be a therapeutic target for autism treatment.
In another mouse model the human autism-associated R451C mutation of the neuroligin-3 gene was studied.
Neuroligin-3 was found to be specifically required for tonic- but not phasic endocannabinoid signaling (Földy et al., 2013), strengthening the association between autism and the endocannabinoid system.
In a rat model of autism (Valproic Acid model), GPR55, PPARα and PPARγ were reduced in several brain regions involved in higher cognitive functions (frontal cortex and hippocampus). Also, hippocampal Anandamide, OEA and PEA were increased after social exposure (Kerr et al., 2013) once more stipulating the involvement of the endocannabinoid system in autism.
It should be noted however, that no good rodent models exist for autism, and thus that these results should be treated with care.
Some descriptive studies have linked Measles, Mumps and Rubella vaccination with increased risk of developing autism.
Although epidemiological studies do not support this link, acetaminophen/paracetamol which is often given to suppress mild fever after vaccination, might precipitate autism through abnormal activation of the endocannabinoid system.
Busquets-Garcia, A., Gomis-González, M., Guegan, T., Agustín-Pavón, C., Pastor, A., Mato, S., Pérez-Samartín, A., Matute, C., de la Torre, R., Dierssen, M., et al. (2013). Targeting the endocannabinoid system in the treatment of fragile X syndrome. Nat. Med. 19, 603–607.
Onaivi, E.S., Benno, R., Halpern, T., Mehanovic, M., Schanz, N., Sanders, C., Yan, X., Ishiguro, H., Liu, Q.-R., Berzal, A.L., et al. (2011). Consequences of cannabinoid and monoaminergic system disruption in a mouse model of autism spectrum disorders. Curr. Neuropharmacol. 9, 209–214.
Siniscalco, D., Sapone, A., Giordano, C., Cirillo, A., de Magistris, L., Rossi, F., Fasano, A., Bradstreet, J.J., Maione, S., and Antonucci, N. (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 Dev. Disord. 43, 2686–2695.
Siniscalco, D., Bradstreet, J.J., Cirillo, A., and 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.