Cannabinoid receptor 1 gene association with nicotine dependence. Academic Article uri icon


  • CONTEXT: The endogenous cannabinoid system has been implicated in drug addiction in animal models. The cannabinoid receptor 1 (CNR1) gene is 1 of the 2 receptors expressed in the brain. It has been reported to be associated with alcoholism and multiple drug abuse and dependence. OBJECTIVE: To test the hypothesis that the CNR1 gene is associated with nicotine dependence. DESIGN: Genotype-phenotype association study. Ten single-nucleotide polymorphisms were genotyped in the CNR1 gene in 2 independent samples. For the first sample (n = 688), a 3-group case-control design was used to test allele association with smoking initiation and nicotine dependence. For the second sample (n = 961), association was assessed with scores from the Fagerstrm Test for Nicotine Dependence (FTND). Settings Population samples selected from the Mid-Atlantic Twin Registry. PARTICIPANTS: White patients aged 18 to 65 years who met the criteria of inclusion. MAIN OUTCOME MEASURES: Fagerstrm Tolerance Questionnaire and FTND scores. RESULTS: Significant single-marker and haplotype associations were found in both samples, and the associations were female specific. Haplotype 1-1-2 of markers rs2023239-rs12720071-rs806368 was associated with nicotine dependence and FTND score in the 2 samples (P < .001 and P = .009, respectively). CONCLUSION: Variants and haplotypes in the CNR1 gene may alter the risk for nicotine dependence, and the associations are likely sex specific.

published proceedings

  • Arch Gen Psychiatry

altmetric score

  • 3

author list (cited authors)

  • Chen, X., Williamson, V. S., An, S., Hettema, J. M., Aggen, S. H., Neale, M. C., & Kendler, K. S.

citation count

  • 74

complete list of authors

  • Chen, Xiangning||Williamson, Vernell S||An, Seon-Sook||Hettema, John M||Aggen, Steven H||Neale, Michael C||Kendler, Kenneth S

publication date

  • July 2008