In summary, while elevation of CB1 at GABAergic synapses and reduction at glutamatergic synapses likely constitute endogenous adaptations to epilepsy, exogenous CB1 overexpression and activation in principal neurons, possibly via receptors physiologically rarely activated, could effectively protect against seizures (Blair et al., 2006; Guggenhuber et al., 2010; Hofmann and Frazier, 2013). This evidence concerns the gene CNR1 and epilepsy.