Black cohosh has central opioid activity in postmenopausal women

Abstract

Objective-To test whether black cohosh (BC) exhibits an action on the central endogenous opioid system in postmenopausal women.Design-A mechanistic study conducted in the same individuals of LH pulsatility with a saline/ naloxone (NAL) challenge (n=6) and PET imaging with [ 11 C]carfentanil, a selective μ-opioid receptor radioligand (n= 5), before and after 12 weeks of unblinded treatment with a popular black cohosh daily supplement.Results-Black cohosh treatment for 12 weeks at a standard dose (Remifemin, 40 mg/day) had no effect on spontaneous LH pulsatility or estrogen concentrations. With NAL blockade, there was an unexpected suppression of mean LH pulse frequency (saline vs NAL = 9.0+.6 vs 6.0+.7 pulses/ 16 hrs; p= 0.056), especially during sleep when the mean interpulse interval (IPI) was prolonged by approximately 90 minutes (SAL night IPI = 103± 9 mins vs NAL night IPI = 191± 31min, p = 0.03). There were significant increases in μ-opioid receptor binding potential (BP) in the posterior and subgenual cingulate, temporal and orbitofrontal cortex, thalamus and nucleus accumbens ranging from 10% to 61 % across regions -brain regions involved in emotional and cognitive function. In contrast, BP reductions of lesser magnitude were observed in regions known to be involved in the placebo response (anterior cingulate and anterior insular cortex).Conclusion-Using two different challenge paradigms for the examination of central opioid function, a neuropharmacologic action of black cohosh treatment was demonstrated in postmenopausal women.

In Vitro Serotonergic Activity of Black Cohosh and Identification of Nω-Methylserotonin as a Potential Active Constituent

“…Similarities exist between hot flashes experienced as a result of going through menopause or opiate withdrawal (46), which is why opiate-dependent animal models have been used to evaluate hot flashes in vivo (47). It has been reported that black cohosh extracts behave as competitive ligands and partial agonists for opiate receptors (44, 48) similar to serotonin receptors (14). A competitive binding assay using a CHO cell line stably transfected with human μ opioid receptors and the same clinical extract used in this study gave an IC 50 of 170 μg/mL (44) compared to 55 μg/mL for the 5-HT 7 receptor.…”

An ethanolic extract of black cohosh causes hematological changes but not estrogenic effects in female rodents

“…BCE appears to reduce luteinizing hormone secretion in ovariectomized rats but not in perimenopausal women (Chung et al 2007; Jacobson et al 2001; Jarry and Harnischfeger 1985; Nappi et al 2005; Rachon et al 2008; Reame et al 2008; Seidlova-Wuttke et al 2003); demonstrations of estrogenic/anti-estrogenic activity of black cohosh are inconclusive (Jarry and Harnischfeger 1985; Jarry et al 2003). However, neurotransmitter activities that can modify activity of the hypothalamic-pituitary-gonadal (HPG) axis at the CNS level (reviewed by Rivier and Rivest 1991), including dopaminergic, serotonergic, and opioid activity, have been observed in vitro (Jarry et al 2003; Powell et al 2008; Rhyu et al 2006).…”

Role of the ER/NO/cGMP Signaling Pathway in the Promotion of Osteogenic Differentiation of Rat Bone Marrow Mesenchymal Stem Cells by Actaea racemosa Extract

“…It is widely recognized that AR activating the neurotransmitter-based effects [24–27], rather than the estrogen activity [28, 29], is an important mechanism for alleviating menopausal symptoms, such as hot flashes and night sweats. Numerous studies have also confirmed that AR does not have a stimulating effect on the levels of blood estrogen and progestin or estrogen target organs such as the uterus, ovaries, breast, and blood vessels [9, 22, 30].…”