Lower circulating endocannabinoid levels in children with autism spectrum disorder

Abstract

BackgroundThe endocannabinoid system (ECS) is a major regulator of synaptic plasticity and neuromodulation. Alterations of the ECS have been demonstrated in several animal models of autism spectrum disorder (ASD). In some of these models, activating the ECS rescued the social deficits. Evidence for dysregulations of the ECS in human ASD are emerging, but comprehensive assessments and correlations with disease characteristics have not been reported yet.MethodsSerum levels of the main endocannabinoids, N-arachidonoylethanolamine (AEA or anandamide) and 2-arachidonoylglycerol (2-AG), and their related endogenous compounds, arachidonic acid (AA), N-palmitoylethanolamine (PEA), and N-oleoylethanolamine (OEA), were analyzed by liquid chromatography/tandem mass spectrometry in 93 children with ASD (age = 13.1 ± 4.1, range 6–21; 79% boys) and 93 age- and gender-matched neurotypical children (age = 11.8 ± 4.3, range 5.5–21; 79% boys). Results were associated with gender and use of medications, and were correlated with age, BMI, and adaptive functioning of ASD participants as reflected by scores of Autism Diagnostic Observation Schedule (ADOS-2), Vineland Adaptive Behavior Scale-II (VABS-II), and Social Responsiveness Scale-II (SRS-2).ResultsChildren with ASD had lower levels (pmol/mL, mean ± SEM) of AEA (0.722 ± 0.045 vs. 1.252 ± 0.072, P < 0.0001, effect size 0.91), OEA (17.3 ± 0.80 vs. 27.8 ± 1.44, P < 0.0001, effect size 0.94), and PEA (4.93 ± 0.32 vs. 7.15 ± 0.37, P < 0.0001, effect size 0.65), but not AA and 2-AG. Serum levels of AEA, OEA, and PEA were not significantly associated or correlated with age, gender, BMI, medications, and adaptive functioning of ASD participants. In children with ASD, but not in the control group, younger age and lower BMI tended to correlate with lower AEA levels. However, these correlations were not statistically significant after a correction for multiple comparisons.ConclusionsWe found lower serum levels of AEA, PEA, and OEA in children with ASD. Further studies are needed to determine whether circulating endocannabinoid levels can be used as stratification biomarkers that identify clinically significant subgroups within the autism spectrum and if they reflect lower endocannabinoid “tone” in the brain, as found in animal models of ASD.Electronic supplementary materialThe online version of this article (10.1186/s13229-019-0256-6) contains supplementary material, which is available to authorized users.

The Alternations of Endocannabinoid System and its Therapeutic Potential in Autism Spectrum Disorder

“…To date, there were only two human evidence about the eCBs levels in ASD children's blood sample [11,12], and their ndings that lower concentrations of AEA, PEA and OEA in autistic children were consistent with ours. Noteworthily, this is the rst time that we found circulating 2-AG levels were reduced in autistic children.…”

“…Indeed, the dysregulation of eCB system has been documented in several neuropsychological and neurodevelopmental diseases, including ASD. Two case-control studies found decreased circulating levels of AEA, PEA and OEA in ASD children compared with their matched healthy children [11,12].…”

Phytocannabinoids in Neurological Diseases: Could They Restore a Physiological GABAergic Transmission?

“…Furthermore, a recent study pointed out that children afflicted by ASD have significantly reduced circulating levels of the main ECs [81], suggesting an important role of these compounds in the early stages of the disease.…”

Medical Cannabis in Children

“…109 Additionally, children with ASD have been found to have lower peripheral endocannabinoid levels. 110,111 Therefore, dysregulation of the endocannabinoid system may play an important role in ASD pathophysiology and may represent a target for pharmacological intervention. 112 Four uncontrolled case-series, including 60, 188, 53, and 18 children with ASD and severe behavioral problems, reported high tolerability and efficacy of artisanal CBD-rich cannabis strains.…”