To evaluate the pharmacogenetic evidence relating to the use of opioid antagonists (in particular naltrexone) in treating patients with alcohol abuse problems.
Narrative review of pre-clinical and clinical published research regarding genetic modulation of psychotropic effects produced by alcohol and the therapeutic effects of opioid antagonists.
Alcohol activates brain reward pathways, leading to positive reinforcement of alcohol seeking and consumption. Thus, the underlying biological mechanisms may be targets for treatment, particularly in the early stages of addiction development. Alcohol reward is in part mediated by endogenous opioids. A single-nucleotide polymorphism (SNP) within the OPRM1 gene, A118G, leading to an amino acid change (Asn40Asp) in the extracellular portion of the receptor, has been implicated in alcoholism as well as in drug addiction, pain sensitivity and stress response, and in animal and human studies relates to the alcohol-dependent phenotype as well as to the treatment response to the µ-opioid antagonist naltrexone.
The effect size reported in naltrexone clinical studies is often small, which may be due to heterogeneity among patients. Pharmacogenetic approaches may help guide us in the search for the appropriate treatment optimal for one patient's need.
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