Endocannabinoid markers in autism spectrum disorder: A scoping review of human studies

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social communication deficits and patterns of restrictive and repetitive behavior. Although the neurological underpinnings of ASD remain elusive, the endocannabinoid system (ECS) may play a role in modulating social behavior in ASD. Preclinical studies have suggested that alterations in the ECS result in ASD-like phenotypes, but currently no reviews have examined ECS abnormalities in human studies. This scoping review investigated any evidence of ECS alterations in humans with ASD. A comprehensive literature search was conducted and five studies were eligible for review. Three studies reported a significant reduction of anandamide in ASD compared to controls. Other alterations included decreased 2-arachidonoylglycerol, oleoylethanolamide, and palmitoylethanolamide and elevated diacylglycerol lipase and monoacylglycerol lipase. Some discrepant findings were also noted, which included elevated or reduced CB2 receptor in three studies and elevated or reduced N-acyl phosphatidylethanolamine phospholipase D and fatty acid amide hydrolase in two studies. We conclude from this preliminary investigation that the ECS may be altered in humans with ASD. Potential limitations of the reviewed studies include medication use and psychiatric comorbidities. Further research, such as positron emission tomography studies, are necessary to fully understand the relationship between ECS markers and ASD.