The earliest studies of opioid antagonists were not satisfactory, because of drawbacks in the then available antagonists. For example, NALOXONE was short-acting and not very effective when taken by mouth. Nalorphine and cyclazocine had some kappa-opioid effects (i.e., were not pure antagonists), which produced unpleasant side effects.

Further work was stimulated by the SPECIAL ACTION Office for Drug Abuse Prevention created by President Richard M. Nixon in June 1971 as part of a ''war on drugs.'' The 1972 funding legislation for this office called for research on ''long-lasting, nonaddictive, blocking and antagonist drugs . . . for the treatment of heroin addiction. ' Eventually twenty-two studies with naltrexone (which had been synthesized by Blumberg and Dayton in 1965) were conducted at various treatment programs in the United States. These studies demonstrated the safety and effectiveness of naltrexone after detoxification as a long-term treatment for opiate dependence, leading to its marketing in North America and Europe. Its effectiveness, however, was defined in terms of blocking the effects of HEROIN, not in the success of changing the behavior of heroin users.

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