The article in this issue of the Archives by Anton et al1 is the latest chapter in the story of a treatment translated from animal models to successful clinical trials that, now with genomic evidence, may refine patient selection and improve outcome. A seminal alcoholism discovery was that alcohol significantly activates the endogenous opioid system in some but not all animal and human subjects, so that part of the reward from alcohol ingestion is mediated via opioid peptides. The evidence for this is that pharmacological blockade of opioid receptors reduces alcohol drinking in a dose-related fashion and blocks the increase in dopamine in the ventral striatum associated with alcohol ingestion. Altshuler et al2 reported the dose-related effect of naltrexone on decreasing ethanol drinking in 10 of 21 rhesus monkeys that were willing to self-administer alcohol. This report led to dose-ranging studies in persons with alcoholism beginning in 1983 and then a controlled clinical trial.3,4 Naltrexone was found to reduce alcohol cravings and relapses to heavy drinking, but it did not necessarily produce total abstinence. The finding of an association between alcohol and opiates was met with skepticism (and a rejection of the report by the Archives) in the 1980s, but the treatment results were perfectly replicated by O’Malley et al5 in 1992. In an unusual scenario, study of naltrexone received Food and Drug Administration approval on the basis that 2 academic studies had financial support from the Veterans Administration and later the National Institute on Alcohol Abuse and Alcoholism rather than from the pharmaceutical industry.
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