Previous schizophrenia-CNR1 genetic association studies, restricted mostly to two CNR1 variants, have found mixed results. Several studies report no significant associations between schizophrenia and a synonymous SNP (rs1049353) within the CNR1 coding region on Exon 4 (Leroy et al., 2001; Seifert et al., 2007; Ujike et al., 2002). The (AAT)n trinucleotide repeat located 18kb downstream from the Exon 4 translational start site (Zhang et al., 2004) has been associated with schizophrenia and with hebephrenic schizophrenia subtype in several (Chavarría-Siles et al., 2008; Martinez-Gras et al., 2006; Ujike et al., 2002) but not all studies (Tsai, Wang, & Hong, 2000). Few prior schizophrenia-CNR1 genetic association studies have included schizophrenia patients with comorbid substance misuse. Martinez-Gras and colleagues did not find significant differences in (AAT)n trinucleotide variant allele frequencies between patients with and without substance abuse (Martinez-Gras et al., 2006). Leroy et al (Leroy et al., 2001) reported preponderance of rs1049353-G-allele among substance abusing schizophrenia patients. Similarly, patients with marijuana abuse/dependence in our study were also more likely to have the rs1049353-G-allele although this difference did not achieve statistical significance.
