CNR1 gene polymorphisms in addictive disorders: a systematic review and a meta-analysis

Addict Biol. 2011 Jan;16(1):1-6. doi: 10.1111/j.1369-1600.2009.00198.x.


The aim of the present work was to systematically review all association studies of cannabis receptor 1 (CNR1) polymorphisms with dependence syndrome and to perform a meta-analysis. Odds ratios (ORs) were estimated by contrasting the ratio of counts of the 'high risk' versus 'low risk' alleles in cases with dependence versus controls. Studies were analyzed by random-effects meta-analysis using pooled OR. Eleven full text articles met our eligibility criteria and nine meta-analyses were performed on three polymorphisms of CNR1: rs1049353, rs806379 and the AAT repeat. Of these, only the AAT polymorphism showed a significant association with illicit substance dependence but only in the Caucasian population samples and using a risk allele definition of ≥ 16 repeats. Our analysis showed a small effect size (OR = 1.55, P = 0.045), with strong heterogeneity (Q = 19.87, P < 0.01 with I² = 85%). In line with the polygenic model, our meta-analysis supports a minor implication for CNR1 AAT polymorphism in illicit substance dependence vulnerability. Further studies in well-phenotyped samples and using more polymorphisms are needed to conclude on the actual influence of cannabinoid receptor polymorphisms.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Alcoholism / genetics*
  • Alleles*
  • Chromosomes, Human, Pair 6 / genetics
  • Exons / genetics
  • Gene Frequency / genetics
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Illicit Drugs*
  • Introns / genetics
  • Microsatellite Repeats
  • Odds Ratio
  • Polymorphism, Genetic / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Promoter Regions, Genetic / genetics
  • Receptor, Cannabinoid, CB1 / genetics*
  • Risk Assessment
  • Substance-Related Disorders / genetics*


  • Illicit Drugs
  • Receptor, Cannabinoid, CB1