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Disulfiram: New Support for Old Addiction Drug
Disulfiram was the first medication approved for the treatment of alcoholism more than 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 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 ß-hydroxylase (DßH), an enzyme that converts dopamine to norepinephrine. This hypothesis has been supported in a new pharmacogenetic study published in Biological Psychiatry.
The researchers recruited cocaine- and opioid-dependent patients, who were randomly assigned to receive either disulfiram or placebo for 10 weeks. The investigators also genotyped the DBH gene, which alters DßH levels, to determine which variant each patient carried. Prior work has already shown that individuals with the CC genotype have normal DßH levels, whereas those with the T allele have lower DßH levels. This allowed the researchers 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 DßH levels, whereas those with the low-DßH-level T genotype showed no effect of disulfiram. These data support the hypothesis that disulfiram reduces drug consumption, in part, by blocking DßH.
Senior author Dr. David Nielsen said: “We found significantly greater efficacy in cocaine addicts who carried a genetic variant of the dopamine ß-hydroxylase gene that codes for an enzyme with 10 to 100 fold greater enzyme expression and occurs in about 60% of addicts. Thus, pharmacogenetic matching is critical for the optimal efficacy of disulfiram in cocaine addiction, and this matching includes the majority of these patients.”
No medications are currently approved for the treatment of cocaine addiction.
Source: Elsevier; January 31, 2013.