Black cohosh has central opioid activity in postmenopausal women: evidence from naloxone blockade and positron emission tomography neuroimaging.
OBJECTIVE
To test whether black cohosh (BC) exhibits an action on the central endogenous opioid system in postmenopausal women.


METHODS
This was a mechanistic study conducted in the same individuals of luteinizing hormone pulsatility with a saline/naloxone challenge (n = 6) and positron emission tomography with [C]carfentanil, a selective micro-opioid receptor radioligand (n = 5), before and after 12 weeks of unblinded treatment with a popular BC daily supplement.


RESULTS
BC treatment for 12 weeks at a standard dose (Remifemin, 40 mg/day) had no effect on spontaneous luteinizing hormone pulsatility or estrogen concentrations. With naloxone blockade, there was an unexpected suppression of mean luteinizing hormone pulse frequency (saline vs naloxone = 9.0 +/- 0.6 vs 6.0 +/- 0.7 pulses/16 h; P = 0.056), especially during sleep when the mean interpulse interval was prolonged by approximately 90 minutes (saline night interpulse interval = 103 +/- 9 min vs naloxone night interpulse interval = 191 +/- 31 min, P = 0.03). There were significant increases in mu-opioid receptor binding potential in the posterior and subgenual cingulate, temporal and orbitofrontal cortex, thalamus, and nucleus accumbens ranging from 10% to 61% across brain regions involved in emotional and cognitive function. In contrast, binding potential reductions of lesser magnitude were observed in regions known to be involved in the placebo response (anterior cingulate and anterior insular cortex).


CONCLUSIONS
Using two different challenge paradigms for the examination of central opioid function, a neuropharmacologic action of BC treatment was demonstrated in postmenopausal women.
School of Nursing, Columbia University, New York, NY 10032, USA. nr2188@columbia.edu
Nancy E
NE
Reame
Jane L
JL
Lukacs
Vasantha
V
Padmanabhan
Aimee D
AD
Eyvazzadeh
Yolanda R
YR
Smith
Jon-Kar
JK
Zubieta
D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects*; D031885:Cimicifuga; D005260:Female; D006801:Humans; D007986:Luteinizing Hormone / Q000378:metabolism*; D008875:Middle Aged; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology*; D008517:Phytotherapy / Q000379:methods; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D017698:Postmenopause / Q000187:drug effects*; D011673:Pulsatile Flow / Q000187:drug effects; D011957:Receptors, Opioid / Q000378:metabolism*; D014055:Tomography, Emission-Computed / Q000379:methods; D016896:Treatment Outcome
D010936:Plant Extracts; D011957:Receptors, Opioid; C073419:Remifemin; D009270:Naloxone; D007986:Luteinizing Hormone