Endocrine Effects of Opioid Antagonists

Mendelson, Jack H.; Mello, Nancy K.

doi:10.1007/978-1-59745-197-0_31

Cited by 4 publications

(4 citation statements)

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“…Naltrexone is an approved pharmacotherapy for heroin and alcohol dependence and is under investigation for the treatment other addictions (Comer et al, 2013; King et al, 2012). Along with nalmefene and naloxone, naltrexone is also commonly used to probe endogenous opioid, dopamine, HPA axis, and HPG axis functioning (Bart et al, 2005; Mendelson and Mello, 2009; Wand et al, 2011). Therefore, the current study’s finding that women display altered acute sensitivity to naltrexone based on their respective MC phase may have several clinical and experimental implications.…”

Section: 0 Discussionmentioning

confidence: 99%

“…Anatomical and functional data suggests the HPA and HPG axes are tonically inhibited by endogenous opioids at the level of the hypothalamus (Baker and Herkenham, 1995; Dudas and Merchenthaler, 2004). Accordingly, opioid receptor antagonists acutely disinhibit these axes and increase the secretion of cortisol from the adrenal cortices and LH from the anterior pituitary (Mendelson and Mello, 2009). Opioids directly regulate the hypothalamic TIDA neurons that tonically inhibit prolactin secretion from the anterior pituitary (Durham et al, 1996; Fitzsimmons et al, 1992).…”

Section: 0 Introductionmentioning

confidence: 99%

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Sex differences in acute hormonal and subjective response to naltrexone: The impact of menstrual cycle phase

Roche

King

2015

Psychoneuroendocrinology

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Women often exhibit larger hormonal and subjective responses to opioid receptor antagonists than men, but the biological mechanisms mediating this effect remain unclear. Among women, fluctuations in estradiol (E2) and progesterone (P4) across the menstrual cycle (MC) affect the endogenous opioid system. Therefore, the goal of the current study was to compare acute naltrexone response between women in the early follicular phase of the MC (low E2 and P4), women in the luteal phase of the MC (high E2 and P4), and men. Seventy healthy controls (n = 46 women) participated in two morning sessions in which they received 50 mg naltrexone or placebo in a randomized, counterbalanced order. Women were randomized to complete both sessions in either the early follicular (n = 23) or luteal phase of the MC. Serum cortisol, prolactin, and luteinizing hormone (LH), salivary cortisol, and subjective response were assessed upon arrival to the laboratory and at regular intervals after pill administration. In luteal and early follicular women but not men, naltrexone (vs. placebo) increased serum cortisol and prolactin levels from baseline; however, the naltrexone-induced increases in these hormones were significantly greater in luteal women than early follicular women. Additionally, only luteal women demonstrated an increase from baseline in salivary cortisol levels and the severity of adverse drug effects in response to naltrexone. In sum, the results indicate that luteal phase women are more sensitive to acute hormonal and subjective effects of naltrexone than early follicular women and men. These findings may have important implications for the use of naltrexone in women.

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Section: 0 Discussionmentioning

confidence: 99%

Section: 0 Introductionmentioning

confidence: 99%

Sex differences in acute hormonal and subjective response to naltrexone: The impact of menstrual cycle phase

Roche

King

2015

Psychoneuroendocrinology

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“…Psychosocial stressors and mu -opioid receptor antagonists reliability activate the hypothalamic-pituitary-adrenal axis (HPA) and increase circulating cortisol levels, but do so through separate mechanisms. For example, mu -opioid receptor antagonists, such as naltrexone and naloxone, are thought to disinhibit tonic endogenous opioid-mediated suppression of CRF neurons of the paraventricular nucleus of the hypothalamus (Baker and Herkenham 1995; Mendelson and Mello 2009). In contrast, psychosocial stressors, such as public speaking and mental arithmetic, activate diffuse corticolimbic circuitry that can relieve GABAergic inhibition or provide catecholaminergic stimulation of paraventricular CRF neurons (Herman and Cullinan 1997; Radley and Sawchenko 2011; Radley 2012).…”

Section: Introductionmentioning

confidence: 99%

Hormonal contraceptive use diminishes salivary cortisol response to psychosocial stress and naltrexone in healthy women

Roche

King

Cohoon

et al. 2013

Pharmacology Biochemistry and Behavior

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The use of hormonal contraception (HC) may affect salivary cortisol levels at rest and in response to a pharmacological or stress challenge. Therefore, the current study used a secondary data analysis to investigate the effect of HC on salivary cortisol levels in response to the mu-opioid receptor antagonist naltrexone and a psychosocial stressor, and also across the diurnal curve. Two hundred and nine women (n = 72 using hormonal contraception; HC+) completed a two-session stress response study that consisted of a stress day, in which they were exposed to public speaking and mental arithmetic, and a rest day, in which unstimulated cortisol levels were measured to assess the diurnal rhythm. A subset of seventy women (n = 24 HC+) also completed a second study in which they were administered oral naltrexone (50 mg) or placebo in a randomized, placebo-controlled, double blind fashion. Women who were HC+ had a significantly reduced salivary cortisol response to both the psychosocial stressor (p < 0.001) and naltrexone (p < 0.05) compared to HC− women. Additionally, HC+ women had a significantly altered morning diurnal cortisol rhythm (p < 0.01), with a delayed peak and higher overall levels. The results of the current study confirm that HC attenuates salivary cortisol response to a psychosocial stressor and mu-opioid receptor antagonism, and also alters the morning diurnal cortisol curve.

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“…Accordingly, blockade of endogenous opioid peptides by acute administration of an opioid antagonist such as naltrexone, nalmefene or naloxone produces a dramatic increase in LH in premenopausal women but not in postmenopausal women 18-20…”

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Commentary on black cohosh for the treatment of menopausal symptoms

Mello

2008

Menopause

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Black cohosh as a possible treatment for menopausal symptoms reflects an increasing interest in the use of non-conventional or "alternative" medicines for amelioration of many disorders. However, it has often been difficult to distinguish between the purported benefits of herbal medicines and vitamins from the effects associated with a variety of placebos. To promote research in this area, an Office of Alternative Medicine was established at the National Institutes of Health in 1992. The Institute of Medicine (IOM) published a report on Complementary and Alternative Medicine in 2005 1 . Given the popularity of alternative medicines, objective examination of the effectiveness of these remedies as well as the possible interactions with conventional prescription medications is very important. The IOM recommended that "the same principles and standards of evidence of treatment effectiveness apply to all treatments, whether currently labeled as conventional medicine or complementary and alternative medicines. Implementing this recommendation requires that investigators use and develop as necessary, common methods, measures, and standards for the generation and interpretation of evidence necessary for making decisions about the use of complementary and alternative medicines and conventional therapies".In this context, the report by Reame et al 2 in this issue of Menopause on the effects of black cohosh on LH pulse frequency, estradiol levels, hot flashes and brain activation patterns measured by Positron Emission Tomography (PET) is a potentially valuable contribution to an often contradictory and inconclusive literature on alternative medicines for treatment of menopausal symptoms 3 . The rhizome of the black cohosh (Cimicifuga racemosa) is thought to contain estrogen-like compounds and to offer a natural alternative to estrogen therapy. One major finding was that 12 weeks of treatment with a commercial preparation of black cohosh (Remifemin, 40 mg/day) in 6 menopausal women did not change the pulse frequency of luteinizing hormone (LH) or levels of estrogen from pre-treatment baseline levels. No significant changes in the average number of hot flashes were detected. This was an open trial in a small sample of menopausal women and there was no placebo control treatment. However, this finding is consistent with previous reports that black cohosh had no discernable effect on the vaginal epithelium, endometrium, LH, FSH or estradiol during one year of treatment in a double-blind, placebo-controlled trial in women with vasomotor symptoms 4 . Similarly, a double-blind, cross-over trial comparing 4 weeks of black cohosh treatment with placebo did not detect any effect on the incidence of hot flashes 5 . A one year, double-blind, placebocontrolled trial reached similar conclusions 6 . There are several reports of liver toxicity associated with black cohosh treatment 7-10 as well as transient gastrointestinal disturbances and headache 11 . Given the apparent lack of efficacy of black cohosh as an estrogen substitute for the ...

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Endocrine Effects of Opioid Antagonists

Cited by 4 publications

References 110 publications

Sex differences in acute hormonal and subjective response to naltrexone: The impact of menstrual cycle phase

Sex differences in acute hormonal and subjective response to naltrexone: The impact of menstrual cycle phase

Hormonal contraceptive use diminishes salivary cortisol response to psychosocial stress and naltrexone in healthy women

Commentary on black cohosh for the treatment of menopausal symptoms

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