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Association study of cannabinoid receptor gene (CNR1) alleles and drug dependence

Molecular Psychiatry volume 6, pages 501–502 (2001)Cite this article

SIR – The endogenous cannabinoid system is thought to be an important neuromodulator in motivation, reward and motor control systems.1 Observations using animal models suggest that modulation of endogenous central cannabinoid signaling in mesolimbic pathways may be one component of the addiction process, particularly via interaction with opioid and dopaminergic systems.2,3,4 Loss of central cannabinoid signaling in CB1 knockout mice reduces the addictive properties of opiates.5 Based on a case-control study of the cannabinoid receptor gene (CNR1, 6q14–15), in which they observed an increased frequency of long (AAT)n repeats in a group of drug-dependent non-Hispanic Caucasians from Southern California, Comings et al6 hypothesized that changes in the level of expression of the central cannabinoid receptor (CB1) may contribute to drug but not alcohol dependence. We report here an attempt to replicate those findings in a case-control study of 399 European-American (EA) and 130 African-American (AA) subjects recruited in southern New England. No significant differences in the frequencies of CNR1 (AAT)n repeats were observed in either population for drug- or alcohol-dependent subjects compared with controls. Significant differences in allele frequencies were observed between EA and AA control groups.

PCR amplification of the (AAT)n repeat7 was carried out using 50 ng of DNA with primers 32P-GCTGCTTCTGTTAACCCTGC and TACATCTCCGTGT GATGTTCC, 1.5 mM MgCl2, and 48°C as annealing temperature. Nine allele types were identified from autoradiographs of polyacrylamide gels. Allele numbering is as described by Comings et al.6 Chi-square statistical testing for comparison of allele distributions was carried out using the CLUMP program.8 Substance use disorders were confirmed using the Structured Clinical Interview9 for DSM-III-R or for DSM-IV. Written informed consent was obtained from all subjects prior to diagnostic interview and phlebotomy.

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Acknowledgements

The study was supported by NIH Grants M01-RR06192 (General Clinical Research Center at UCHC), P50-AA03510, R01-AA11330, K02-AA00239 (HRK), and K02-MH01387 (JG).

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  1. Department of Psychiatry, University of Conneticut School of Medicine, Farmington, 06030, CT, USA

    J Covault & H Kranzler

  2. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA

    J Gelernter

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  1. J Covault
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Correspondence to J Covault.

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Covault, J., Gelernter, J. & Kranzler, H. Association study of cannabinoid receptor gene (CNR1) alleles and drug dependence. Mol Psychiatry 6, 501–502 (2001). https://doi.org/10.1038/sj.mp.4000925

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