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Experimental data suggest that the endogenous cannabinoid system is involved in mood regulation, but no study has been performed so far to investigate the role of endocannabinoid genes in the susceptibility to major depression (MD) and/or bipolar disorder (BD). We assessed the CB1 receptor gene (CNR1) single nucleotide polymorphism (SNP) rs1049353 (1359 G/A) and the fatty acid amide hydrolase (FAAH) gene rs324420 SNP (cDNA 385C to A) for their associations with MD and/or BD in 83 Caucasian patients with recurrent MD, 134 Caucasian individuals with BD, and 117 Caucasian healthy subjects. The distribution of the CNR1 1359 G/A genotypes and alleles significantly differed among the groups (χ²=12.595; df=4, P=0.01 for genotypes; χ²=13.773; df=2, P=0.001 for alleles) with MD patients showing a higher frequency of both AG, GG genotypes and A allele as compared to healthy controls. The …