Substance abuse is the most prevalent comorbid psychiatric condition associated with schizophrenia. Cannabis is a drug frequently used for schizophrenic patients. In the last decades the endocannabinoid system and their endogenous ligands have been discovered. Endogenous cannabinoids act in the brain on cannabinoid CB1 receptor. On the other hand this system may be involved in several brain functions through neuromodulation dopaminergic and other neurotransmitter system involved in schizophrenic and substance abuse disorders. Advances of genetic research have addressed the focus on the search of candidate genes for both disorders. In this review we have summarized the studies published about the CNR1 gene on schizophrenia and substance abuse disorders.