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1 National Institute of Mental Health, Addiction Research Center, Lexington, Kentucky
The narcotic antagonist naloxone was studied in man to determine if it produced behavioral effects and physical dependence and if it substituted for morphine in morphine-dependent subjects. When compared to placebo in 12 subjects in a cross-over design, no or little activity was demonstrated for naloxone while, in contrast, the narcotic antagonists, nalorphine and levallorphan, constricted pupils, produced responses on the subject's and observer's single-dose opiate questionnaires and produced psychotomimetic and sedative-like responses in a "subjective drug effect" questionnaire. In 10 subjects, naloxone administered 1, 2 and 4 hr before a test dose of morphine antagonized the effects of morphine. In morphine-dependent subjects, naloxone was 7 times as potent as nalorphine in precipiting abstinence. In three subjects, no behavioral or physiologic changes were observed during chronic administration and withdrawal of naloxone; however, the ability of naioxone to antagonize the effects of a test dose of morphine persisted. It is concluded that naloxone does not have abuse potential of the morphine type since it does not produce subjective effects or physical dependence and precipitates abstinence in morphine-dependent subjects. Further, naloxone is distinguished from the narcotic antagonists, nalorphine, levallorphan and cyclazocine, in that it does not constrict pupils or produce subjective effects, physical dependence or tolerance.
Submitted on January 23, 1967
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