Schizophrenia is one of the most common psychiatric disorders. There is a growing body of evidence associating dysregulation of the endogenous cannabinoid system with the pathogenesis of schizophrenia. In order to test the hypothesis that mutations in the central cannabinoid receptor-1 (CNR1) gene confer susceptibility to the development of schizophrenia, we performed an association study in a group of 104 German patients with schizophrenia and 140 healthy controls, using three polymorphisms within and flanking the coding exon of CNR1 (rs6454674, rs1049353, AL136096). In addition, we analyzed the whole coding region of the CNR1 gene of 50 of the patients by capillary sequencing to detect rare mutations. Our adequately powered study failed to reveal a statistically significant segregation of CNR1 polymorphisms to the diseased or control group. Furthermore, capillary sequencing of CNR1 in a subgroup of study subjects did not show any non-synonymous mutations predicting malfunction of CNR1 in patients with schizophrenia. In conclusion, we could not detect a statistically significant association between mutations in the CNR1 gene and the predisposition to develop schizophrenia. However, further studies are necessary to unravel the relationship between mutations in the CNR1 gene and the genetic susceptibility for the manifestation of certain subtypes or schizophrenia i.e. the predominance of negative or positive symptoms or as predictors of the clinical course.