Striatal cholinergic interneurons (SCIN) are key modulators of cortico-striatal circuits implicated in disorders like obsessive-compulsive disorder and Tourette syndrome (TS). Reduced SCIN density observed in TS patients suggests their involvement, highlighting their relevance for targeted therapeutic strategies. Previous studies in our laboratory showed that SCIN inhibition or ablation in animal models leads to repetitive and perseverative behaviors. Here, we investigated if enhancing endogenous eCB tone could reduce these behaviors, given CB1 receptor abundance and eCB modulation in the striatum. We employed URB597, a fatty acid amide hydrolase inhibitor that elevates endocannabinoid levels and reduces perseverative behaviors in control mice. Additionally, we used viral vectors to selectively express an inhibitory DREADD receptor in SCINs of ChatCre heterozygous mice, enabling reversible SCIN inhibition through CNO administration. Mice were acutely treated with URB597 (0.1 or 1 mg/kg, i.p.) or vehicle 1h before behavioral measurement. SCIN inhibition in control mice increased behaviors indicative of compulsivity, such as grooming, head dipping, nest disruption, and marble burying. Notably, treatment with URB597 reduced these compulsive and perseverative behaviors. In conclusion, our results highlight the involvement of SCINs in ritualistic behavior and support the therapeutic potential of endocannabinoid system modulation in disorders linked to cortico-striatal dysfunction.