Neural mechanisms underlying cannabinoids’ anxiogenic effects are not fully understood. Here authors show that cannabinoids dose-dependently increased spontaneous activity of central amygdala (CeA) neurons expressing somatostatin (SOM), altered CeA activity patterns during threat processing, and enhanced defensive behavior. Ex vivo studies in brain slices further showed that cannabinoids reduce inhibitory input from neighboring neurons, releasing a “brake” on SOM activity.