Abstract

Nalorphine was administered chronically to 7 subjects, using progressively increasing dose levels, to determine if tolerance and physical dependence would develop. Both physiologic and subjective responses were studied. During the course of chronic intoxication with nalorphine, it became apparent that subjects became tolerant to the effects of nalorphine and were cross tolerant to the subjective effects of the narcotic antagonist cyclazocine. When abruptly withdrawn from nalorphine all subjects exhibited an abstinence syndrome which was qualitatively different from the morphine abstinence syndrome but closely resembled the abstinence syndrome seen in patients who had received large doses of cyclazocine. The studies provide additional support for the hypothesis (Martin et al., 1965) that the narcotic antagonists produce a type of physical dependence that is qualitatively different from that produced by the narcotic analgesics. The abstinence syndrome seen following withdrawal from large doses of narcotic antagonists causes only mild discomfort and does not seem to give rise to compulsive drug-seeking behavior.