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Randomized Controlled Trial
. 2009 Feb;91(4):526-36.
doi: 10.1016/j.pbb.2008.09.007. Epub 2008 Sep 18.

Opioid and cocaine combined effect on cocaine-induced changes in HPA and HPG axes hormones in men

Nathalie V Goletiani  1 , Jack H Mendelson, Michelle B Sholar, Arthur J Siegel, Nancy K Mello
Affiliations
Randomized Controlled Trial

Opioid and cocaine combined effect on cocaine-induced changes in HPA and HPG axes hormones in men

Nathalie V Goletiani et al. Pharmacol Biochem Behav. 2009 Feb.

Abstract

Nalbuphine, a mixed micro-/kappa-opioid analgesic, may have potential as a new medication for the treatment of cocaine abuse. Kappa-opioid agonists functionally antagonize some abuse-related and locomotor effects of cocaine, and both kappa-selective and mixed micro-/kappa-opioids reduce cocaine self-administration by rhesus monkeys. Because cocaine's interactions with the hypothalamic-pituitary-adrenal and (HPA) hypothalamic-pituitary-gonadal (HPG) axes may contribute to its reinforcing properties, we examined the effects of cocaine alone and in combination with nalbuphine. Neuroendocrine effects of a single dose of cocaine alone (0.2 mg/kg, IV), with nalbuphine (5 mg/70 kg, IV)+cocaine (0.2 mg/kg, IV) in combination were compared in seven adult men (ages 18-35) who met DSM-IV criteria for current cocaine abuse. Cocaine alone, and in combination with nalbuphine was administered on separate test days under placebo-controlled, double blind conditions. Cocaine stimulated ACTH, cortisol, and LH, whereas cocaine+nalbuphine in combination produced a smaller increase in ACTH, and decreased cortisol and LH. Thus it appears that nalbuphine attenuated cocaine's effects on ACTH, cortisol, and LH. These data are consistent with our earlier report that nalbuphine modestly attenuated cocaine's positive subjective effects, and that the subjective and cardiovascular effects of cocaine+nalbuphine in combination were not additive.

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Figures

Fig. 1
Fig. 1
Plasma cocaine levels after i.v. administration of 5 mg /70 kg and 0.2 mg/kg cocaine. Significant changes from baseline are indicated by daggers (†, P=0.005).
Fig. 2
Fig. 2
Plasma ACTH levels after i.v. administration of 5 mg/70kg nalbuphine and of 0.2 mg/kg cocaine. Significant changes from the baseline are indicated by daggers (†, P=0.001-0.02). Asterisks (*, P<0.05) indicate points at which ACTH levels differed between subjects who received 0.2 mg/kg cocaine or a combination of 5 mg/70 kg nalbuphine and 0.2 mg/kg cocaine.
Fig. 3
Fig. 3
Plasma Cortisol levels after i.v. administration of 5 mg/70kg nalbuphine and of 0.2 mg/kg cocaine. Significant changes from the baseline are indicated by daggers (†, P P=0.001-0.02). Asterisks (*, P<0.05) indicate points at which cortisol levels differed between subjects who received 0.2 mg/kg cocaine or a combination of 5 mg/70 kg nalbuphine and 0.2 mg/kg cocaine.
Fig. 4
Fig. 4
Serum LH levels after i.v. administration of 5mg /70 kg nalbuphine and 0.2 mg/kg cocaine. Significant changes from the baseline are indicated by daggers (†, P<0.05). Asterisks (*, P<0.05) indicate points at which LH levels differed between subjects who received 0.2 mg/kg cocaine or a combination of 5 mg/70 kg nalbuphine and 0.2 mg/kg cocaine.
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