A striking feature of the data is its cross-disciplinary concordance so that, for example, CB1R downregulation occurring in cannabis dependence and first demonstrated by autoradiography in brain slices has now been confirmed by super-resolution microscopy and has been shown to be reflected in blunted hedonic drive in the midbrain and ventral tegmental area and in inhibited cortical connectivity from the frontal lobes. Here, CNR1 is linked to cannabis dependence.