Impulsivity, variation in the cannabinoid receptor (CNR1) and fatty acid amide hydrolase (FAAH) genes, and marijuana-related problems

J Stud Alcohol Drugs. 2013 Nov;74(6):867-78. doi: 10.15288/jsad.2013.74.867.

Abstract

Objective: Impulsivity is associated with increased marijuana use and subsequent marijuana-related problems among marijuana users. In addition, single nucleotide polymorphisms (SNPs) in the cannabinoid receptor 1 (CNR1) and fatty acid amide hydrolase (FAAH) genes have been associated with cannabis-related phenotypes. This exploratory study tested whether the association between different aspects of impulsivity and the number of marijuana-related problems among users is explicated by variation in these putative cannabinoid-related genes.

Method: A total of 151 young adult regular marijuana users (used on M= 41.4% of the prior 60 days, SD = 24.3%) provided DNA and completed measures of trait (Barratt Impulsiveness Scale) and behavioral impulsivity (Stop Signal Task and Delay Discounting Questionnaire), as well as a self-report of marijuana-related problems. Three CNR1 and five FAAH SNPs were genotyped, tested for haplotype blocks, and subsequently examined for association with phenotypes described above.

Results: CNR1 variation significantly moderated the association between trait-level, but not behavioral, impulsivity and marijuana-related problems, such that the combination of higher trait impulsivity and CNR1 variation was associated with a greater number of marijuana-related problems. In contrast, there were no significant FAAH by impulsivity interactions; however, there was a main effect of FAAH on marijuana-related problems.

Conclusions: These findings support an association with CNR1 and FAAH genes and marijuana-related problems among regular marijuana users. CNR1 variation emerged as a moderator of the relationship between trait impulsivity and marijuana problems, thus suggesting that marijuana users with CNR1 risk variants and a higher trait impulsivity are at greater risk for developing marijuana-related problems and supporting a role for CNR1 in a broader impulsivity phenotype.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Amidohydrolases / genetics*
  • Female
  • Genotype
  • Haplotypes
  • Humans
  • Impulsive Behavior / epidemiology*
  • Male
  • Marijuana Abuse / epidemiology*
  • Marijuana Abuse / genetics
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Psychiatric Status Rating Scales
  • Receptor, Cannabinoid, CB1 / genetics*
  • Self Report
  • Surveys and Questionnaires
  • Young Adult

Substances

  • Receptor, Cannabinoid, CB1
  • Amidohydrolases
  • fatty-acid amide hydrolase