The present study concerns the characterization of the potential interaction between CB1R and lipid rafts/caveolae in neuronal and glial cells. In particular, in a glioma cell line we could demonstrate the colocalization of CB1R with caveolin-1, by using subfractionation and confocal microscopy techniques. Moreover, we found that CB1R completely co-immunoprecipitates with caveolin-1, suggesting that these two proteins are part of a macromolecular complex. Finally, we also investigated the trafficking of CB1R and caveolin-1 in response to methyl-beta-cyclodextrin treatment, finding that the acute cholesterol depletion causes a CB1R trafficking that is superimposable on that of caveolin-1, and that it enhances the accessibility of receptor binding sites to specific anti-CB1R antibodies. These observations suggest a strong link between CB1R and caveolin-1, that seems interesting because caveolae play a role in neurodegenerative diseases, like Parkinson’s disease, Alzheimer’s disease and dementia with Lewy’s bodies, as well as in other neurological abnormalities.[...]