Lower circulating endocannabinoid levels in children with autism spectrum disorder

Adi Aran*, Maya Eylon, Moria Harel, Lola Polianski, Alina Nemirovski, Sigal Tepper, Aviad Schnapp, Hanoch Cassuto, Nadia Wattad, Joseph Tam

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


Background: The 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. Methods: Serum 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). Results: Children 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. Conclusions: We 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.

Original languageAmerican English
Article number2
JournalMolecular Autism
Issue number1
StatePublished - 30 Jan 2019

Bibliographical note

Funding Information:
This research was supported by the National Institute for Psychobiology in Israel (#203–17-18), BOL pharma, Revadim, Israel, and the Israel Science Foundation (ISF grant #617/14). The funding bodies were not involved in any way in the study design, collection, analysis and interpretation of data or in the writing of the manuscript.

Publisher Copyright:
© 2019 The Author(s).


  • 2-arachidonoylglycerol
  • Anandamide
  • Arachidonic acid
  • Autism spectrum disorder
  • Biomarkers
  • Cannabinoids
  • Endocannabinoid system
  • N-arachidonoylethanolamine
  • N-oleoylethanolamine
  • N-palmitoylethanolamine


Dive into the research topics of 'Lower circulating endocannabinoid levels in children with autism spectrum disorder'. Together they form a unique fingerprint.

Cite this