Mechanism proposed for black cohosh menopause benefits

Black cohosh (referred to by the European Medicines Agency, or EMEA, as Cimicifugae racemosae rhizome​) is a member of the buttercup family, and is a perennial plant native to North America. It has a long history of use for by women to reduce menopausal symptoms such as hot flushes.

Historically it has been a popular alternative to hormone replacement therapy (HRT) in many countries including the UK, where it is estimated that 9 million days worth of black cohosh supplements were purchased in 2004.

Despite this popularity, how exactly the herb could benefit women with hot flushes has eluded clarification until now. The new research, from scientists at the University of Illinois in Chicago and the National Institutes of Health (UIC/NIH) Center for Botanical Dietary Supplements Research, reports that the herb may act on human opiate receptors which play a role in body temperature regulation.

Opiate receptors are chemical sensors that are associated with activation by opiates like morphine and heroin. However, other chemical substances may also bind to the opiate receptors and activate the appropriate response including pain control, an immune response, or other body functions including core temperature regulation.

The new study used an ethanol extract of black cohosh and found that constituent(s) of the herb could bind to the human mu-opiate receptor (hMOR) associated with mood, body temperature and sex hormone levels.

"The opiate receptor system affects several aspects of female reproductive neuroendocrinology, such as the control of sex hormones,"​ wrote lead author Mee-Ra Rhyu.

Hot flushes are suggested to be the result of flawed body core temperature settings, controlled by the central nervous system (CNS), which in turn is regulated by the opiate system, said the researchers.

"Opiates can therefore alter core temperature setting directly or indirectly,"​ they said. "Striking similarities exist between opiate withdrawal and menopausal hot flushes."

This is the first time that scientists have linked constituents of black cohosh to human opiate receptors.

Significantly, the extract used in this in vitro​ study is the same that is being used in a phase II clinical trial currently underway and being conducted by researchers from the UIC/NIH Center for Botanical Dietary Supplements Research.

"Therefore, botanical dietary supplements containing opiate activity are expected to have beneficial effects in relieving menopausal symptoms, including hot flushes,"​ concluded the researchers.

"The opiate agonistic activity of black cohosh may explain at least in part its efficacy in alleviating menopausal symptoms."​

The research may be good news for the herbal industry, but this year black cohosh has been in the news for new labelling requirements in some markets.

Fears over a rare causal link between black cohosh and liver damage have this year led to Australia's Therapeutics Goods Administration and the UK's Medicines and Healthcare Products Regulatory Agency to require warning statements to appear on product packaging, and the European Medicines Agency and Health Canada to issue public safety statements.

The mechanism behind these potential problems has not been elucidated however and a recent court case in the US (Grant and Beck v Pharmavite and Nutraceutical Corp) ruled that research has consistently held that black cohosh is non-hepatoxic.

According to the American Herbal Products Association's (AHPA) most recent Tonnage Survey of Select North American Wild-Harvested Plants, the herb was the second most harvested plant, with 159 tons from wild sources and 0.2 tons from cultivated sources.

Source: Journal of Agricultural and Food Chemistry​ Published on-line ahead of print, doi: 10.1021/jf062808u "Black cohosh (Actaea racemosa, Cimicifuga racemosa) behaves as a mixed competitive ligand and partial agonist at the human mu-opiate receptor"​ Authors: M-E. Rhyu, J. Lu, D.E. Webster, D.S. Fabricant, N.R. Farnsworth, Z.J. Wang