Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disability that demonstrates impaired social interactions, social communication deficits, and restrictive/repetitive behaviors. The endocannabinoid (eCB) system in the brain is a major regulator of synaptic plasticity and neuromodulation. It is reported that the eCB system have been altered in children with ASD and some animal models of ASD. To determine the causal role of the eCB system in the ASD, we have investigated the relationship between declines of the eCB system and the ASD-like symptoms, using the cannabinoid CB₁ receptor knockout (CB1KO) mice. We found that male CB1KO mice demonstrated reduced sociability (3-chambered social approach task), elevated repetitive grooming behaviors (hole-board test) and deficits in short-term memory (Y-maze test). Moreover, the CB1KO mice also showed emotional instabilities (elevated plus-maze test and hole-board test). The serum progranulin, which is lower levels in patients of ASD, was significantly decreased in CB1KO mice. These findings suggested that CB1KO mice showed behavioral phenotypes including social deficits, which have face validity as an animal model of ASD. Therefore, the CB1KO mice will be a valuable tool for the exploration of pathological mechanisms and development of novel therapeutics in the ASD.