Clinical Characteristics of Naloxone-precipitated Withdrawal in Human Opioid-dependent Subjects

Studies were conducted to investigate the clinical characteristics of naloxone-precipitated withdrawal in human opioid-dependent subjects. Each of 20 male patients stabilized on 24 mg of methadone daily received two i.v. pharmacological challenges: one with naloxone (0.05, 0.10, 0.15 and 0.20 mg; five patients each dose), and one with saline placebo. Measures of opioid withdrawal, affective state, cognitive performance and changes in autonomic parameters were assessed after each pharmacological challenge. Naloxone produced dose-dependent increases in opiate withdrawal scale scores and in symptoms of dysphoria as measured by the Profile of Mood States. Differences within subjects between naloxone and placebo infusions in Profile of Mood States scores were highly correlated with differences in opioid withdrawal as assessed by both subjective and objective rating scales. Naloxone also produced substantial increases in pulse, systolic and diastolic blood pressure and respiratory rate, as well as a small decrease in temperature. However, naloxone-induced changes from base-line values in these autonomic parameters correlated only modestly with other measures of opioid withdrawal. No differences between infusions were observed in two measures of cognitive performance (Stroop Color and Word Test, Digit Span Test). The results indicate that dysphoric mood states reflecting a broad range of affective experience must be considered as integral components of the naloxone-precipitated opioid withdrawal syndrome.