Association of a CB1 cannabinoid receptor gene (CNR1) polymorphism with severe alcohol dependence

Due to the involvement of the endogenous cannabinoid system in brain reward mechanisms a silent polymorphism (1359G/A; Thr453Thr) in the single coding exon of the CB1 human cannabinoid receptor gene (CNR1) was analysed in 121 severely affected Caucasian alcoholics and 136 roost likely non-alcoholic controls. The observed frequency of the A allele was 31.2% for controls and 42.1% for alcoholics with severe withdrawal syndromes (P = 0.010). Post-hoc exploration indicated that this allelic association resulted from an excess of the homozygous A/A genotype in patients with a history of alcohol delirium (P = 0.031, DF 2), suggesting an increased risk of delirium (OR = 2.45, 95% CI 1.14-5.25). This finding suggests that the homozygous genotype CNR1 1359A/A confers vulnerability to alcohol withdrawal delirium. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.