IngredientsThe term cohosh β probably derived from an Algonquian word meaning "rough" β refers principally to two botanically unrelated North American plants: black cohosh (Actaea racemosa L., syn. Cimicifuga racemosa) and blue cohosh (Caulophyllum thalictroides). Though they share a common name and a history of use in Native American ethnomedicine, they differ substantially in botanical family, chemical constituents, pharmacology, and safety profile. This article covers both plants in turn, with a substantially larger section dedicated to black cohosh, which is by far the more extensively studied of the two.
Black cohosh is a popular herbal medication derived from a plant of the buttercup family (Ranunculaceae), indigenous to North America (Actaea racemosa, syn. Cimicifuga racemosa), and is a perennial plant indigenous to the eastern United States and Canada. Other, mostly historical, names for this herb include snakeroot, black bugbane, rattleweed, macrotys, and rheumatism weed.
Extracts from the underground parts of the plant β the rhizome (Cimicifugae racemosae rhizoma) and the root (Cimicifugae racemosae radix) β are used in herbal medicine. The part of the black cohosh plant used in herbal preparations is the root or rhizome (underground stem).
Actaea racemosa L. (syn. Cimicifuga racemosa L.) has become increasingly popular as a dietary supplement in the United States for the treatment of symptoms related to menopause. A number of Asian Actaea species β including Cimicifuga dahurica, Cimicifuga foetida, and Cimicifuga hercleifolia β are related but botanically distinct, and product adulteration between these species and genuine North American black cohosh has been documented. Three of 11 commercial products examined in one analytical study were found to contain the Asian marker compound cimifugin rather than the black cohosh marker cimiracemoside C, indicating they contained Asian Actaea instead of black cohosh; one product contained both.
Black cohosh is commercially available in a variety of dosage forms. The most widely used and best-studied commercial formulation available in the United States is Remifemin, an extract of the rhizome produced by a German company; numerous other brands of black cohosh are available, but not all are standardized extracts. Products containing black cohosh extract are frequently standardized to provide at least 1 mg triterpene glycosides per daily dose.
Most studies of black cohosh have used the extract known as Remifemin, standardized to contain 1 mg of terpene glycosides per 20-mg tablet. The most commonly used dosage of Remifemin is two 20-mg tablets twice daily, with maximum effect usually occurring in four to eight weeks. More recent information from the manufacturer suggests that a dosage of 20 mg twice daily may be as effective in the treatment of menopausal symptoms as 40 mg twice daily. Black cohosh extract is also available in tincture form; the reported dosage of the tincture is 2 mL twice daily of a 1:1 tincture in 90 percent alcohol.
When using an aqueous-ethanolic extract of black cohosh root (not Remifemin), doses range from 64β128 mg daily, usually taken in two divided doses, contributing approximately the same amount of triterpenoid glycosides.
Remifemin has changed formulation over time, from a 60% ethanol extract to a 40% isopropanol extract, and the extract preparation is not consistently reported in clinical trials. Variable study outcomes may be due in part to inconsistent triterpene concentrations present in the various preparations used.
Black cohosh was in use by American Indian and Alaska Native people when Europeans arrived in the New World. Among the reported indications for black cohosh in traditional American Indian and Alaska Native medicine were various female conditions, rheumatism, fever (possibly due to malaria), general malaise, sore throat, childbirth, and snakebite.
Native Americans used black cohosh for treatment of a variety of conditions including kidney ailments, malaria, sore throat, and menstrual cramps. It has also been used medicinally in Germany since the late 19th century. Specific tribal use has been documented across multiple nations: the Delaware tribe used black cohosh combined with other herbs such as stoneroot to treat menopausal symptoms, rheumatism, and as a tonic; the Cherokee and Iroquois peoples are believed to have used it for the same conditions. The Algonquins used it to treat kidney ailments.
Early European settlers, and subsequently American eclectic physicians, assimilated the use of black cohosh and began exporting the herb to Europe as early as the 18th century. European settlers used black cohosh as a tonic to support women's reproductive health. The plant appeared in the U.S. Pharmacopoeia under the name "black snakeroot" during the year 1830. In the 19th century, the root was used to treat snakebite, inflamed lungs, and pain from childbirth. Physicians made use of it in the 19th century to treat fever, menstrual cramps, and arthritis. In Europe, black cohosh has been used for over 40 years as a treatment for menstrual pain. Other traditional and folk uses were for treatment of sore throats and bronchitis.
Traditional preparations included decoctions: Native American tribes used it to treat a variety of conditions, including menstrual irregularities, childbirth complications, and rheumatic pains; the herb was often prepared as a decoction or infusion, which allowed its potent compounds to be extracted.
Most of the phytochemical and biological research has focused on two abundant classes of compounds in black cohosh: the triterpene glycosides and phenolic acids. Thirty-nine constituents covering three major classes β triterpene glycosides, phenolic acids, and alkaloids β have been identified in characterized extracts.
The rhizomes and roots contain various saponins (triterpene saponins and triterpene glycosides, such as actein) as well as cimifugic acids and other phenol carboxylic acids. Some studies suggest that several biologically active substances are responsible for the plant's action. A partial list of active compounds includes the isoflavone formononetin, isoferulic, caffeic, salicylic, and fukinolic acids; miscellaneous fatty acids, tannins, and sugars; phytosterin and resins that include Cimicifuga and triterpene glycosides.
It is currently common practice to standardize the content of commercially available black cohosh supplements to certain triterpene compounds related to actein, such as 23-epi-26-deoxyactein. Among constituents quantified in a well-characterized extract, triterpene glycosides made up approximately 4.7% (w/w), with total quantified constituents making up 5.8% (w/w) of the extract.
The first report on the isolation and full structural characterization of an alkaloid in black cohosh was published in 2005 by Fabricant et al., who identified a new cyclic guanidine-type alkaloid named cimipronidine, reflecting its source, a (homo)proline base structure, and the occurrence of a guanidine group. This was notable both for the novelty of the structure β a new chemical entity with seven carbon atoms β and because guanidine alkaloids are relatively rare in higher plants; cimipronidine was the first reported guanidine alkaloid from the Ranunculaceae family.
The nitrogen-containing fraction of black cohosh also includes a serotonin-related compound. Since serotonergic receptors and transporters are involved with thermoregulation, black cohosh and its phytoconstituents were evaluated for serotonergic activity; crude extracts displayed 5-HT7 receptor binding activity and induced cAMP production. Fractionation led to the identification of NΟ-methylserotonin by LC/MS-MS. In contrast to triterpenoids and phenolic acids, NΟ-methylserotonin showed 5-HT7 receptor binding (IC50 23 pM), induced cAMP (EC50 22 nM), and blocked serotonin reuptake (IC50 490 nM).
The mechanism by which black cohosh exerts its effects remains incompletely understood and is an active area of research. Several hypotheses have been proposed: that it acts (1) as a selective estrogen receptor modulator, (2) through serotonergic pathways, (3) as an antioxidant, or (4) on inflammatory pathways.
The mechanism of action of black cohosh is still a matter of intense research. Several in vitro and in vivo studies have established that black cohosh extracts are not estrogenic. Ovariectomized SpragueβDawley rats administered a 40% 2-propanol extract of black cohosh at doses of 4, 40, and 400 mg/kg/day for 2 weeks showed no effects on uterine weight or vaginal cellular cornification, with or without estradiol co-treatment, indicating that this black cohosh extract had no estrogenic or antiestrogenic properties in the ovariectomized rat model.
Extracts of the rhizome of black cohosh did not bind to estrogen receptors and were shown to be devoid of estrogenic effects on mammary cancer cells in vitro and on mammary gland and uterine histology in ovariectomized rats; in addition, the special extract CR BNO 1055 inhibited the occurrence of hot flushes and development of osteoporosis in this rat model.
Nevertheless, some tissue-specific estrogenic effects have been observed. The most consistent evidence of an estrogenic-like effect of black cohosh extract in preclinical studies is on bone. Like estrogen, black cohosh extract induces osteoprotegerin (OPG, a bone marker), progesterone receptor, and ERΞ± in human osteoblast cells, and BCE upregulation of OPG is inhibited by the estrogen receptor antagonist ICI 182,780, implying an estrogenic mechanism in bone tissue.
Black cohosh has dopaminergic, serotonergic, and gamma-aminobutyric acid (GABAergic) actions but no direct effects on hormone receptors. While black cohosh extract does not inhibit the serotonin transporter, it binds eight serotonin receptor subtypes, acting most strongly on serotonin receptors 5-HT7 and 5-HT1A as a mixed competitive ligand, with partial agonist activity on 5-HT7. Both 5-HT7 and 5-HT1A are found in the hypothalamus and are involved in thermoregulation. Since black cohosh exhibited no estrogenic or antiestrogenic activity in vivo, an alternative serotonergic mechanism linked to thermoregulation was examined.
A further mechanism involves central opioid pathways. Over a period of 12 weeks, black cohosh appears to increase binding activity for mu-opioid receptors in a variety of brain regions after ingestion of 40 mg isopropanolic extract (Remifemin) daily, ranging from 10% in the nucleus accumbens to a 61% increase in the posterior cingulate. This finding from neuroimaging research adds a third plausible neurobiological pathway distinct from estrogen receptor engagement.
It is possible that black cohosh extract can act via multiple tissue-dependent mechanisms, including estrogenic (or antiestrogenic), serotonergic, antioxidative, and inflammatory or antiinflammatory pathways. Given that the clinically utilized hydrophilic extracts of black cohosh roots and rhizomes are not estrogenic, alternative mechanisms of menopausal symptom relief have been proposed, one of which suggests serotonergic activity by triterpenes to minimize episodes of hot flashes and bone loss.
This is the area of most concentrated clinical research. A substantial number of studies in people have evaluated black cohosh for menopause symptoms; much less research has been done on other conditions.
A 2017 systematic review and meta-analysis of 47 randomized controlled trials involving a total of 8,326 women with menopausal symptoms found that black cohosh was more effective than placebo in reducing vasomotor symptoms, but not significantly better than transdermal estradiol and progestogen.
A 2023 review of 22 studies of products containing black cohosh extracts, alone or in combination with other herbs, found that they were potentially beneficial for overall menopause symptoms. Data on specific symptoms showed improvements in hot flashes but not anxiety or depressive symptoms. It remains uncertain whether black cohosh can reduce hot flashes related to breast cancer treatment.
A 2016 review found that there is no high-quality, consistent evidence that black cohosh benefits patients with menopausal symptoms more than placebo.
One representative clinical trial: a randomized, double-blind, placebo-controlled trial was conducted on 84 early post-menopausal participants; participants were randomly allocated into a treatment group receiving 6.5 mg of dried extract of black cohosh roots daily and a control (placebo) group and took one tablet per day for 8 weeks.
The American College of Obstetricians and Gynecologists, in its 2015 clinical guidelines for managing menopausal symptoms, concluded that "data do not show that" herbal dietary supplements like black cohosh "are efficacious for the treatment of vasomotor symptoms." The North American Menopause Society advises clinicians against recommending herbal therapies such as black cohosh because "they are unlikely to be beneficial" in alleviating vasomotor symptoms.
The Cochrane Review found adequate justification for conducting further studies on black cohosh's use to treat menopausal symptoms and recommended that researchers conduct higher quality trials with larger samples and provide more details about their experimental protocols.
Evidence strength: Mixed. Multiple RCTs and meta-analyses exist, but heterogeneity across preparations, doses, and outcomes makes definitive conclusions difficult. Major medical organizations regard evidence as insufficient to recommend clinical use, while some meta-analyses support a modest benefit over placebo for vasomotor symptoms.
Since black cohosh is believed to have a serotonergic rather than estrogenic impact, it has been recommended to treat vasomotor symptoms associated with tamoxifen-taking breast cancer patients.
Observational and open-label studies have demonstrated reductions in the number and severity of hot flashes among breast cancer patients undergoing adjuvant endocrine therapy complemented with black cohosh; however, randomized, double-blind, placebo-controlled clinical trials have failed to demonstrate reductions greater than that seen with placebo. Significant declines in hot flash frequency and severity are reported in a review of observational studies of breast cancer patients and survivors taking Remifemin (20β40 mg/day), with or without tamoxifen or raloxifene; prospective trials indicated reductions as high as 56% (95% CI = 40%β71%) in hot flash scores.
Given conflicting results between observational and randomized clinical trials, a large placebo effect is presumably at play, especially considering the subjective nature of many endpoint measures. Furthermore, given the unlikely negative impact on breast cancer risk or recurrence, along with evidence of relative safety, more research is warranted.
Evidence strength: Preliminary and mixed. Controlled trials do not confirm the benefit seen in observational data; the placebo effect appears to be a substantial confound.
Evidence regarding the benefit of black cohosh for treating or preventing osteoporosis is conflicting. One study found that taking a product containing 40 mg of black cohosh (Remifemin) for 3 months improves bone formation and reduces the breakdown of bone. Another study found that taking 40 mg of black cohosh extract (CR BNO 1055) for 3 months increases markers of bone formation in postmenopausal women.
Black cohosh does appear to have an osteoprotective effect in postmenopausal women, though the mechanism may differ from that of conjugated estrogens. Potential benefits on bone metabolism are further supported in an uncontrolled trial by increases in osteocalcin levels in women receiving the supplement.
Physicians should be clear that although black cohosh may be useful in treating some menopausal symptoms, there is currently no established evidence regarding any protective effect of black cohosh against the development of osteoporosis.
Evidence strength: Preliminary. Animal and biomarker data suggest a possible osteoprotective effect, but there are no large, long-term clinical trials demonstrating fracture reduction or clinically meaningful improvements in bone density.
Many menopausal symptoms β hot flashes, mood swings and anxiety, insomnia β are mediated through the central nervous system and may be alleviated through a variety of mechanisms. Some trials have included psychological endpoints, but data on specific symptoms showed improvements in hot flashes but not anxiety or depressive symptoms in the most recent meta-analytic review. Black cohosh may be a viable option for women seeking relief from menopausal symptoms, particularly those experiencing mood disturbances, though this conclusion is based on limited and heterogeneous evidence.
Evidence strength: Weak. Current meta-analyses do not support clinically meaningful improvements in anxiety or depression specifically attributable to black cohosh.
The following dosage information is drawn directly from published studies and authoritative sources:
In clinical trials, people have taken black cohosh for as long as 12 months with no serious harmful effects. A safety review found that adverse events associated with black cohosh when administered under trial conditions in doses ranging from 6.5 mg to 160 mg for a period lasting from one to 12 months were rare, mild and reversible. The most common side effects were gastrointestinal, musculoskeletal, and connective tissue complaints.
In recent years, products labeled as black cohosh have been implicated in many instances of clinically apparent, acute liver injury, some cases of which have been severe and led to emergency liver transplantation or death.
Black cohosh does not appear to be inherently hepatotoxic, and the clinical features of cases suggest that the liver injury is an idiosyncratic reaction which may be immunologically mediated. The specific component of black cohosh responsible for hepatic injury is not known. As with many herbal and dietary supplement products, unknown adulterants or herbals mislabeled as black cohosh may be the actual cause of hepatic injury.
An analysis of 69 cases of reported black cohosh toxicity by Teschke et al. identified only one case with possible black cohosh-induced hepatotoxicity, with the remaining cases labeled as having confounding variables such as pre-existing liver diseases, lack of temporal association, and use of herbal mixtures with multiple ingredients; it was concluded there was not enough evidence to substantiate a causal relationship.
Common reported side effects include weight gain, headache, heart arrhythmia, difficult breathing, nausea, vomiting, breast pain/enlargement, muscle pain, and skin rashes. BCE-induced hepatotoxicity can range from mild, self-limited liver injury to acute liver damage, fulminant hepatic failure, and even death. Consequently, health agencies in the U.K., U.S., Australia, Canada, and the European Agency have issued warning labels on BCE products, advising caution due to potential hepatotoxicity.
Histological and immunohistochemical analysis of two liver biopsies from patients following consumption of black cohosh showed a pattern of pathological injury identical to troxis necrosis, seen during autoimmune hepatitis.
It is possible but not proven that product contaminants might be responsible for cases of liver damage linked to black cohosh products.
The botanical authenticity of most products containing black cohosh has not been evaluated, nor is manufacturing highly regulated in the United States. Available preparations vary considerably in their chemical composition, in part because the compounds in black cohosh that may be responsible for any relief of menopausal symptoms are not known.
As with other herbal medicines believed to have potential estrogenic effects, there has been concern about the safety of black cohosh in women with a personal history or strong family history of breast cancer. At least one tissue-culture study showed no stimulation of estrogen receptorβpositive breast cancer cell lines by black cohosh extract; this study found that black cohosh extract increased the inhibitory effect of tamoxifen on breast cancer cell lines.
Purported estrogenic actions of black cohosh are refuted by current laboratory and clinical studies of commercially available hydroalcoholic extracts. Suggestions of serotonergic activity are well supported. Recent findings show that black cohosh contains a large variety of constituents chemically related to central nervous systemβactive molecules, which have not been studied in detail yet. Commercially available hydroalcoholic extracts of black cohosh have been well tolerated, with very rare serious adverse effects reported.
Blue cohosh (Caulophyllum thalictroides) is a species of flowering plant in the Berberidaceae (barberry) family. It is a medium-tall perennial with blue berry-like fruits and bluish-green foliage. A member of the Berberidaceae family, blue cohosh is a long-lived herbaceous perennial native to the moist woodlands of the upper Appalachian Mountain Range.
Dietary supplements containing dried roots or extracts of the roots and/or rhizomes of blue cohosh are widely available. The plant is also known as papoose root. Black cohosh and blue cohosh are different herbs β a distinction of clinical importance given their divergent safety profiles.
Black cohosh should not be confused with the blue cohosh herb (Caulophyllum thalictroides), which is used for different indications and has a greater potential for toxicity.
Blue cohosh has a long history of use by Native Americans and its use continues to the present day. Blue cohosh naturally grows throughout North America, and extracts from the roots have been sold as a tincture. It has been traditionally used as an emmenagogue and uterotonic.
As a dietary supplement, blue cohosh is used as an antispasmodic, emmenagogue (menstrual flow stimulator), parturifacient (labor inducer), and abortifacient. In 1999, it was estimated that 64% of American midwives used blue cohosh to induce labor.
The primary constituents of blue cohosh are its alkaloids and saponins. The structures of the alkaloids magnoflorine, baptifoline, anagyrine, and N-methylcytisine have been known for many years. The last decade has seen a great increase in isolation and identification of the large number of saponins present in blue cohosh.
The root contains essential fatty acids, glucosides, phytosterols, saponins, and resinous essential oil. Blue cohosh contains the plant alkaloid N-methylcytisine, which is a nicotinic acetylcholine receptor agonist, with structural similarity to nicotine found in the tobacco plant (Nicotiana tabacum).
Blue cohosh root contains N-methylcytisine, which has nicotine-like effects, and caulosaponin, a glycoside that constricts coronary vessels and may have oxytocic activity.
Alkaloid and glycoside components in blue cohosh suggest possible mechanisms for uterine effects, as well as teratogenicity and mutagenicity, however, case reports involving neonatal adverse events are considered inconclusive. Toxic effects of the plant's constituents include coronary vasoconstriction, tachycardia, hypotension, and respiratory distress.
Blue cohosh methanol extract has exhibited mitochondriotoxic activity in laboratory testing. The alkaloids magnoflorine, baptifoline, anagyrine, and N-methylcytisine, as well as certain saponins, are constituents with established toxicological relevance.
Blue cohosh has been used to induce uterine contractions in labor; however, there are no quality clinical trials to support any therapeutic application for blue cohosh, and concerns of toxicity outweigh any potential clinical benefit. Despite widespread knowledge and use, there are no clinical trials on which to base dosing recommendations.
According to a survey of midwives in the United States, approximately 64% of midwives reported using blue cohosh as a labor-inducing aid. There are three case reports in the scientific literature that blue cohosh taken at the time of delivery may cause: (1) perinatal stroke, (2) acute myocardial infarction, profound congestive heart failure and shock, and (3) severe multi-organ hypoxic injury. There is one case report that blue cohosh possesses abortifacient properties. There is in vitro evidence that blue cohosh may have teratogenic, embryotoxic, and oxytoxic effects.
Evidence strength: No controlled human clinical trials exist. The evidence base consists entirely of observational reports, case series, and in vitro/animal data. Multiple authoritative sources classify the potential for toxicity as outweighing any potential clinical benefit.
When ingested as a labor induction agent, blue cohosh has been shown to have transplacental toxicity through case reports of neonatal congestive heart failure and stroke following maternal exposure. Use of blue cohosh during pregnancy to "prepare" the uterus for parturition is a widespread practice among midwives and pregnant women. Although this practice is rarely associated with significant adverse outcomes, maternal ingestion has been associated with a range of fetal and neonatal side effects, including fetal tachycardia and increased meconium, as well as several case reports of profound neonatal congestive heart failure and perinatal stroke. There is one case report of a neonate born with complications including myocardial infarction and profound congestive heart failure whose mother had ingested blue cohosh capsules as a labor preparatory; the newborn remained critically ill for several months and at 2 years of age required continued digoxin therapy for poor ventricular function.
The alkaloid anagyrine, found in the root of blue cohosh, has been held responsible for the congenital deformity "crooked calf disease" in bovine stock. There is also a case report of a similar human congenital malformation (marked anaemia, skeletal dysplasia, and vascular anomaly) in an infant, which could have been due to maternal exposure to anagyrine. The alkaloid methylcytisine was shown to be teratogenic in rats.
When used in high doses as an abortifacient, symptoms similar to nicotine poisoning can occur, including nausea and emesis, headache, dizziness, muscle fasciculations, tachycardia, tachypnea, hypertension, seizure, and respiratory failure.
No data exist on the safety and efficacy of blue cohosh in nursing mothers or infants; however, it can cause severe gastrointestinal and cardiovascular toxicity, including in neonates whose mothers used it to stimulate labor. Most sources recommend strongly against its use during breastfeeding because of lack of safety data and potential toxicity.
Based on available scientific information, blue cohosh should be used with extreme caution during pregnancy, only under medical professional supervision, and arguably not be available to the public as an over-the-counter product. There is an urgent need to conduct retrospective or prospective cohort studies of midwives using blue cohosh to determine its safety.
The following table-style summary compares the two cohosh plants across major parameters discussed in this article:
Health conditions that Cohosh may help support.
Body systems that Cohosh may help support.
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