Black cohosh (Cimicifuga racemosa) is a perennial dicot plant from the buttercup family (Ranunculaceae), and is native to North America, spanning from Canada to Georgia. Its roots and rhizomes (underground stems) are utilized in supplements. Black cohosh extracts can vary considerably depending on factors such as cultivation, harvesting, extraction techniques, solvent used, and standardization methods.^[1][2]

The rhizomes of black cohosh are typically harvested during early autumn once the flowers have turned to fruit and the leaves have withered. The harvested rhizomes are cut into segments, dried, and propagated in spring to create new plants.^[3]

The main active compounds in black cohosh, sometimes referred to as triterpene glycosides, include cycloartanol compounds (e.g., acteol, actein), cimigenol, and cimicifugoside. Other bioactives include flavonoids, (E)-isoferulic acid, dopargine (a derivative of dopamine), cimipronidine, salsolinol, and N(omega)-methylserotonin.

Research on black cohosh primarily focuses on its potential benefits for perimenopause and postmenopause symptoms.

One meta-analysis revealed that the isopropanolic extract of black cohosh (iCR) was found to be more effective than placebo in alleviating neurovegetative symptoms (e.g., hot flashes, night sweats, palpitations) and psychological symptoms (e.g., depression) in women with natural perimenopausal and postmenopausal symptoms.^[1] One of the studies within this meta-analysis also found that black cohosh improved sleep efficiency and decreased wake after sleep onset (WASO) compared to placebo.^[4]

For women undergoing iatrogenic menopause (i.e., menopause brought about by medical interventions such as hysterectomy), the effects of black cohosh are inconsistent. In one placebo double-blind RCT menopausal women with breast cancer (many undergoing tamoxifen treatment) who received iCR for 2 months did not exhibit a significant reduction in the intensity and count of hot flashes compared to placebo. However, they reported notably-reduced night sweating.^[5] It’s important to note that this study suffered from a small sample size and a high dropout rate, with hot flashes being self-reported by the participants. That said, longer-duration open studies (12–24 weeks) also have demonstrated significant reductions in induced hot flashes, sweating, and psychological symptoms in participants taking iCR.^[1]

To validate these findings, more extended RCTs that assess climacteric symptoms (i.e., symptoms of perimenopause, menopause and/or postmenopause) using objective measurements^[6] (e.g., increases in heart rate, finger blood flow, respiratory exchange ratio, skin temperature, and core body temperature) instead of self-reported questionnaires are essential.

Black cohosh is generally considered safe, and clinical studies did not report significant side effects.

The administration of standard or high doses of black cohosh over 3–6 months does not appear to impact liver function. Likewise, black cohosh shows no significant effects on blood pressure, heart rate, body weight, or body mass index (BMI). Studies have also explored its impact on kidney function, total cholesterol, and triglycerides, revealing no overall effects except for a few studies reporting instances of increased high-density lipoprotein (HDL) cholesterol and decreased low-density lipoprotein (LDL) cholesterol.^[1] Furthermore, trials comparing black cohosh to tibolone (a medication used to treat menopausal symptoms) found that people taking black cohosh exhibited fewer side effects (e.g., vaginal bleeding, spotting) than those taking tibolone.^[1][7]

One meta-analysis indicated that 0.5% to 15% of menopausal women taking black cohosh experienced gastrointestinal discomfort.^[8]

One animal study, coupled with in vitro testing on human cells, found that both in rats and in vivo black cohosh induced micronuclei (MN), which are biomarkers of genetic alterations, while also disrupting the folate pathway. This disruption led to non-regenerative macrocytic anemia in rats, characterized by enlarged red blood cells and inadequate bone marrow red blood cell replacement. Although these results indicate a potential risk associated with taking black cohosh, clinical studies are required to examine the impact on the human body.^[9]

Initially, the presumed mechanism of black cohosh involved the activation of estrogen receptors. However, both in vitro and in vivo studies on black cohosh extracts yielded no evidence of estrogenic activity. Instead, it appears that black cohosh binds to receptors in the central nervous system responsible for functions like thermoregulation, mood, and sleep (e.g., mu-opioid,^[10] serotonin, dopamine, c-aminobutyric acid). This mode of action clarifies why black cohosh does not influence estrogen levels, breast tissue density or proliferation, endometrial thickness, or vaginal cytology.^[11][1]

Additionally, black cohosh showed anti-estrogenic properties in breast cancer studies. This anti-estrogenic effect was observed in vitro as a reduction in the growth of estrogen-responsive breast cancer cells.^[12]

Another in vitro study found a potential nonestrogenic thermoregulatory mechanism of black cohosh, which may modulate the immune system by promoting nitric oxide (NO) production in cells treated with interferon gamma (INF-gamma).^[11]