Study supports hypothesis that disulfiram reduces drug consumption by blocking DβH

Published on February 1, 2013 at 7:48 AM · No Comments

Disulfiram was the first medication approved for the treatment of alcoholism over 50 years ago. It works, at least in part, by preventing the metabolism of an alcohol by-product, acetaldehyde. High levels of acetaldehyde in the body quickly cause unpleasant symptoms, including nausea, vomiting, headache, and accelerated heart rate. Thus, disulfiram provides a very strong incentive to avoid drinking.

Beginning in the late 1990s, a series of studies conducted at Yale University found that disulfiram reduced the consumption of cocaine, particularly in the context of alcohol or opiate dependence. One mechanism introduced to explain this phenomenon was the ability of disulfiram to inhibit dopamine β-hydroxylase, or DβH, an enzyme that converts dopamine to norepinephrine. This hypothesis was supported in a new pharmacogenetic study by Thomas Kosten and colleagues, published in Biological Psychiatry.

The researchers recruited cocaine- and opioid-dependent patients who were randomized to receive either disulfiram or placebo for ten weeks. They also genotyped the DBH gene, which alters DβH levels, to determine which variant that each patient carried. Prior work has already shown that individuals with the CC genotype have normal DβH levels, whereas those carrying the T allele have lower DβH levels. This allowed them to determine whether the functional DBH variant influences the success of disulfiram treatment.

Disulfiram was effective in reducing cocaine use in patients with the CC genotype and normal DβH levels, whereas those with the low DβH level T genotype showed no disulfiram effect. These data support the hypothesis that disulfiram reduces drug consumption, in part, by blocking DβH.

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