Alcohol binge worsened cognitive impairment, accelerated AD pathology, and increased Aβ42 levels. Alcohol lowered CB2 RNA levels and increased the expressions of MAGL, with no change in DAGLα.Conclusion: Binge alcohol drinking during adolescence alters hippocampal ECS activity in adult mice. These altered ECS conditions could contribute to memory impairment. Binge alcohol also accelerates hippocampal Aβ in AD mice. Here, CNR2 is linked to Alzheimer disease.