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The association of a functional polymorphism in CNR1 with alcohol withdrawal in a treatment-seeking alcoholic sample

Friday, November 08, 2013 — Poster Session III

10:00 a.m. – 12:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • J. Yan
  • M.L. Schwandt
  • H. Sun
  • D.W. Hommer
  • D.T. George
  • M. Heilig
  • V.A. Ramchandani


The single nucleotide polymorphism (SNP), rs2023239, in CNR1, the gene encoding cannabinoid receptor 1 (CB1), has been implicated in substance use disorders, response to alcohol, and CB1 receptor density in both postmortem and human brain studies. We assessed the effect of this SNP on alcohol-related traits in 551 treatment-seeking alcoholics and 405 non-treatment-seeking controls using regression models, with sex and ancestry as covariates. The rs2023239 C allele was associated with alcohol withdrawal severity, measured by the Clinical Institute Withdrawal Assessment-Alcohol-Revised (CIWA-Ar) at treatment start in the treatment-seeking sample (p=0.039). The SNP had a nominal effect on the Addiction Severity Index withdrawal subcomponent (p=0.086) and peak overall CIWA-Ar score (p=0.061). It was not significantly associated with other clinical phenotypes or drinking history. This study suggests a potential involvement of rs2023239 in alcohol withdrawal. This pattern is consistent with prior studies reporting a lack of alcohol withdrawal responses in CB1 knockout mice, and studies showing a gain of function for the C allele in CB1 ligand binding. Because an increase in number of CB1 receptors may provide a neuroprotective effect against excitotoxic cell death during alcohol withdrawal, the C allele of rs2023239 may confer a downstream protective effect against alcohol withdrawal severity.

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