Abstract
This study investigated diurnal variations in the affective and endocrine response to opioid blockade in man and whether there were effects related either to the dose of naloxone or the time of day at which it was given. Normal male subjects were given an intravenous bolus of either 0.2 mg/kg (study 1) or 1 mg/kg naloxone (study 2) or control infusions at two time points (0900 or 1800 hours) in a single-blind crossover design. Before and following each infusion, mood was measured by the Profile of Mood States (POMS) and a visual analogue scale (VAS), and blood samples taken at 15-min intervals. Cortisol, LH ACTH and vasopressin (study 2 only) were measured. Blood pressure and heart rate were also monitored. The lower dose of naloxone had no effect on overall mood (POMS), though tension and confusion were increased in the afternoon. The VAS showed increased depression in the afternoon, and heightened tension, sleepiness and reduced ability to concentrate at both times of day. The higher dose increased overall dysphoria at both time points, though the tension and depression subscales were not altered. VAS depression and tension were increased, and there were changes in sleepiness. Subjective reports showed that 45% of the subjects correctly identified the drug treatment at the lower dose compared with 89% at the higher one. ACTH increased after both doses of naloxone irrespective of time of day. Cortisol was also raised by naloxone; the effect was greater in the afternoon for the lower dose, but not the higher. LH also increased after either dose, but in this case the effect was greater in the afternoon only for the higher dose. Vasopressin was not altered by 1 mg/kg naloxone. Systolic blood pressure increased after both doses, irrespective of the time of day. There were no effects on diastolic pressure or heart rate. There were no consistent relations between personality dimensions (EPI) and changes in either mood or endocrine levels after naloxone. Comparisons across the two studies showed that there were dose-related effects on both mood (dysphoria) and hormone levels (ACTH, cortisol and LH). These studies show that naloxone has pervasive effects on both mood and endocrine function in man, that these effects are dose-responsive, and that there are diurnal changes in sensitivity that differ according to the parameter being measured or the dose of drug administered.
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Martin del Campo, A.F., Dowson, J.H., Herbert, J. et al. Effects of naloxone on diurnal rhythms in mood and endocrine function: a dose-response study in man. Psychopharmacology 114, 583–590 (1994). https://doi.org/10.1007/BF02244988
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DOI: https://doi.org/10.1007/BF02244988