The endogenous cannabinoid system has been implicated in drug addiction in animal models.23,27,54,55 The CNR1 gene is an essential component of the endogenous cannabinoid system. It has been shown that CNR1 is widely expressed in various regions of the brain.38-40 Zhang and colleagues37 reported that CNR1 is associated with polysubstance abuse. Associations with cannabis dependence,56 alcohol dependence,31,36 and other drug dependence32,33,57 and with psychiatric disorders58-60 were also reported. In this study, we tested the association of CNR1 with SI and ND or FTND score in 2 independent samples drawn from 2 large epidemiologic studies of Virginia twins. In both samples, we found nominally significant associations in individual markers and multimarker haplotypes: rs2023239 showed sex-specific associations with SI in the same allele in the 2 samples and rs6928499 was significantly associated with SI in the VAND sample but only showed a trend in the VAANX sample. Two multimarker haplotypes showed the same sex-specific associations with ND in both samples. Haplotype 1-1-2 for combination 7-9-10 just met the cutoff of multiple testing correction (0.00909 vs 0.00909) for a 1-tailed test. Because the
