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

Abstract

Nalbuphine, a mixed mu-/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 mu-/kappa-opioids reduce cocaine self-administration by rhesus monkeys. Because cocaine's interactions with the hypothalamicpituitary-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.

Histological and hormonal changes in the European eel (Anguilla anguilla) after exposure to environmental cocaine concentration

“…) and disrupts pituitary–adrenal axis function increasing plasma cortisol levels (Goletiani et al . ). The increase in plasma PRL levels agreed with the increase in PRL levels found in rhesus monkeys after chronic cocaine administration (Mello et al .…”

Substance Abuse and Male Hypogonadism

“…Increase in LH, adrenocorticotropin hormone (ACTH), and cortisol, decrease in prolactin e unchanged testosterone levels have been found in men after intravenous low-dose cocaine injection (0.2-0.4 mg/kg) [93,94]. Conversely, in men who chronically use cocaine, lower free testosterone concentrations have been found, while gonadotropins did not differ compared to nonusers [95].…”

Salvinorin A and Related Compounds as Therapeutic Drugs for Psychostimulant-Related Disorders

“…Acute i.v. doses of the κ-receptor agonist/µreceptor antagonist nalbuphine (5 mg/70 kg) slightly reduce the reinforcing effects of cocaine and significantly decrease diastolic blood pressure in current cocaine abusers [53]. The neuroendocrine alterations produced by cocaine administration to current cocaine abusers on luteinizing hormone, cortisol, and adrenocorticotropic hormone are attenuated by acute i.v.…”

“…In monkeys, κ agonists reduce cocaine intake [19, 26, 33-35, 40, 48]. Although some studies reported that chronic administration of κ agonists increased the motor performance and the dopamine overflow produced by cocaine [21,37], most studies of acute and chronic administration of κ-opiod receptor agonists suggest that these compounds have antiaddictive effects [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54].…”

“…Preclinical and clinical [51][52][53][54] studies suggest that compounds that act as agonists of the κ-opioid receptor produce effects that are potentially beneficial for patients suffering psychostimulant-related disorders. Thus, the objective of the present text is to review data from preclinical and clinical studies suggesting that κ-opioid receptor agonists, including salvinorin A, may produce therapeutic effects in patients with psychostimulant-related disorders.…”