Disruption of an enhancer associated with addictive behaviour within the cannabinoid receptor-1 gene suggests a possible role in alcohol intake, cannabinoid response and anxiety-related behaviour.

•We identified a highly conserved enhancer in the CB1 gene that contains a SNP associated with substance abuse in humans.•CRISPR genome editing to delete this enhancer caused a reduction of CB1 gene expression in hippocampus.•Deletion of this enhancer reduced alcohol intake, cannabinoid response and altered anxiety-like behaviour.•These studies provide an important platform for the future exploration of cannabinoid pharmacogenetics.