Doron Michaeli, Reem Smoum, Raphael Meschoulam, Haitham Amal

Cannabis-related therapeutic research is steadily rising. Several studies have been exploring the potential of plant-derived compounds as ASD treatments, but evidence for benefits on the core ASD symptoms from these studies is inconclusive and mixed. As a novel approach, we employed synthetic endocannabinoids (AEA and 2-AG) and an endocannabinoid-like compound (ARA-S) as a treatment. All three compounds were tested on the SHANK3Δex4-22 ASD mouse model, and 2-AG only was tested on the CASPR2 model. Mice behaviors were analyzed via video software while eCBs and eCB-like compounds brain concentrations were analyzed via mass spectrometry. We report rescue effects of 2-AG on both mouse models, as measured by behavioral tests, and significant changes in brain tissue concentrations of several eCB and eCB-like compounds shown by MS. Of all three compounds, only 2-AG showed significant effects in behavioral tests of SHANK3Δex4-22 groups.