Cannabinoid receptor type 2 gene is associated with comorbidity of schizophrenia and cannabis dependence and fatty acid amide hydrolase gene is associated with cannabis dependence in the Spanish population.

The endocannabinoid system has been associated with various psychiatric disorders, such as schizophrenia or addictive disorders. Recent studies have found that some polymorphisms in the cannabinoid receptor type 2 (CNR2), cannabinoid receptor type 1 (CNR1) and fatty acid amide hydrolase (FAAH) genes could play an important role as risk factors in the etiology of these diseases. We analysed different cannabinoid gene polimorphisms from non-substance using patients diagnosed with schizophrenia (n = 379), schizophrenic patients with cannabis use disorders (n = 124), cannabis users who did not have psychoses (n = 71), and 316 controls from various Spanish hospitals and health centres. We found a statistical association between polymorphisms rs35761398 and rs12744386 in the CNR2 gene and comorbidity of schizophrenia and cannabis dependence, as well as an association between loss of heterozygosity (overdominance) for polymorphism rs324420 in the FAAH gene and cannabis dependence in a Spanish population sample. The rs35761398 and rs12744386 polymorphisms in the CNR2 gene are genetic risk factors for schizophrenia in cannabis-dependent subjects. Loss of heterozygosity for polymorphism rs324420 in the FAAH gene is a genetic risk factor for cannabis dependence in this population.