The Potential of Salivary Lipid-Based Cannabis-Responsive Biomarkers to Evaluate Medical Cannabis Treatment in Children with Autism Spectrum Disorder

Introduction: Autism spectrum disorder (ASD) is a group of heterogeneous neurodevelopmental conditions affecting social communication and social interaction. Medical cannabis (MC) treatment shows promising results as an approach to reduce behavioral difficulties, as determined mainly by subjective observations. We have recently shown the potential of cannabis-responsive biomarkers detected in saliva of children with ASD to objectively quantify the impact of successful MC treatment using a metabolomics approach. Since the pathology of ASD is associated with abnormal lipid metabolism, we used lipidomics on the same samples to (1) expand the repertoire of cannabis-responsive biomarkers and (2) provide preliminary insight into the role of MC on lipid metabolism.

Materials and Methods: Saliva samples collected from children with ASD (n=15) treated with MC (both before and at the time of maximal impact of treatment) and an age-matched group of typically developing (TD) children (n=9) were subjected to untargeted lipidomics. The study was observational. Each child from the ASD group was receiving a unique individualized MC treatment regimen using off-the-shelf products as permitted by California law under physician supervision for at least 1 year. Doses of tetrahydrocannabinol (THC) ranged from 0.05 to 50 mg and cannabidiol (CBD) from 7.5 to 200 mg per treatment. The ASD group was evaluated for signs of improvement using parental brief Likert scale surveys.

Results: Twenty-two potential lipid-based cannabis-responsive biomarkers exhibiting a shift toward the TD physiological levels in children with ASD after MC treatment were identified. Members from all five lipid subclasses known to be present in saliva were characterized. Preliminary lipid association network analysis suggests involvement of two subnetworks previously linked to (1) inflammation and/or redox regulation and (2) oxidative stress. The significant changes in sphingomyelin in this study and in N-acetyl-aspartate (NAA) previously detected in the metabolomics analysis of the same saliva samples may indicate a role of MC in neuron function.

Conclusions: Our findings suggest that lipid metabolites in saliva can potentially serve as cannabis-responsive biomarkers and objectively quantify the impact of MC treatment, and indicate a possible mechanism of action for MC. This preliminary study requires further investigation with a larger population and appropriate clinical trial monitoring.