Related Experiment Video
Updated: Oct 4, 2026

The Motivation for Alcohol Reward: Predictors of Progressive-Ratio Intravenous Alcohol Self-Administration in Humans
Published on: April 28, 2022
Variation in alcohol pharmacokinetics as a risk factor for alcohol dependence
J B Whitfield1, G Zhu, D L Duffy
1Department of Clinical Biochemistry, Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia. johnwhit@bioc.rpa.cs.nsw.gov.au
Background:
The significant association between alcohol dehydrogenase (ADH)-2 genotype and alcohol-dependence risk, demonstrated in both Asian and non-Asian populations, suggests a link between the metabolism of alcohol (ethanol) and individual differences in susceptibility to dependence.
Methods:
We tested this hypothesis by following up on subjects who took part in the Alcohol Challenge Twin Study conducted in 1979-1981 and comparing the blood and breath alcohol results in that study between subjects who subsequently did or did not meet diagnostic criteria for lifetime alcohol dependence in 1992-1993.
Results:
Subjects who met DSM-III-R criteria for lifetime alcohol dependence at follow-up had higher blood and breath alcohol values after alcohol challenge than never-dependent subjects. Multivariate analysis showed independent effects of susceptibility to alcohol dependence and smoking status on blood alcohol concentrations, whereas habitual alcohol intake at the time of the initial study had marginally significant effects. The risk of alcohol dependence was 2-fold higher in men and 3-fold higher in women with blood or breath alcohol concentrations in the highest quartile than in the lowest quartile.
Conclusions:
In view of this association and the known genetic influences on both alcohol pharmacokinetics and alcohol dependence, it is probable that part of the heritability of dependence is mediated by genes (other than the known ADH2 and ADH3 polymorphisms) affecting alcohol metabolism.
More Related Videos
Related Concept Videos
Drug toxicity: Idiosyncratic Reactions
Dosage Regimen: Individualization
Drug Toxicity: Risk factors
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Pharmacogenetics of Drug Metabolism: Overview
Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment

