【】? Objective? To investigate the regulation of synaptic plasticity by CB1R and its effects on ASD-like behavior. ?Methods ?CB1R knockout (knockout,KO) mice and valproic acid (VPA)-induced ASD model mice (VPA mice) were used as study subjects. Behavioral experiments assessed the effects of CB1R on ASD-like behavior in mice; neuronal structural integrity and dendritic density were detected by passaging MAP2 staining experiments, and Western Blot experiments detected the expression of synapse-associated proteins to assess the effects of CB1R on synaptic plasticity. Results ?Behavioral results showed that VPA mice had significant ASD-like behavior; CB1R-/- mice had a significantly lower ratio of residence time in the central region of the open field, a significant increase in the number of buried beads and self-combing time, a significant decrease in the time spent socialising with unfamiliar mice2 and exploring unfamiliar objects, and a significant increase in the time spent exploring old objects (P <0.05); CB1R+/- mice had a significantly lower ratio of The ratio of dwell time was significantly reduced, and the number of buried beads and self-combing time were significantly increased (P <0.05). The results of synaptic plasticity assay showed that there was significant synaptic plasticity impairment in VPA mice; the hippocampal MAP2-positive neuron densities were significantly reduced in CB1R-/- and CB1R+/- mice, and the expression levels of SYN1 were significantly increased (P <0.05).? Conclusion ?CB1R knockdown causes mice to exhibit significant ASD-like behavior such as anxiety and repetitive stereotyped behavior, social and cognitive impairments, as well as neuronal damage, dendritic dysplasia and disrupted synaptic protein expression, suggesting that CB1R is involved in regulating abnormal synaptic plasticity as a pathological mechanism for the development of ASD-like behavior.