Bugbane (Actaea racemosa / Cimicifuga racemosa): A Comprehensive Reference
1. Identity and Botanical Description
Common Names and Synonyms
"Bugbane" is one of several common names for Actaea racemosa (formerly Cimicifuga racemosa), a striking herbaceous perennial plant of the buttercup family (Ranunculaceae). It is also known as black cohosh, black snakeroot, squawroot, and bugbane. The common name "bugbane" specifically arises from the plant's tall tapering racemes of white midsummer flowers borne on wiry black-purple stems, whose mildly unpleasant, medicinal smell at close range gives rise to the name. More precisely, the common name bugbane is in reference to the odoriferous insect-repellant properties of the plant.
Taxonomic History
The plant species has a history of taxonomic uncertainty. Carl Linnaeus, on the basis of morphological characteristics of the inflorescence and seeds, placed the species into the genus Actaea. This designation was later revised by Thomas Nuttall, who reclassified the species to the genus Cimicifuga, based solely on the dry follicles produced by black cohosh, which are typical of species in Cimicifuga. However, recent data from morphological and gene phylogeny analyses demonstrate that black cohosh is more closely related to species of the genus Actaea than to other Cimicifuga species, prompting revision back to Actaea racemosa as originally proposed by Linnaeus.
Former synonyms include Cimicifuga racemosa (L.) Nutt. and Macrotys actaeoides Raf. Additional historical synonyms include Cimicifuga serpentaria Pursh, Macrotrys racemosa (L.) Sweet, and Thalictrodes racemosum (L.) Kuntze.
Botanical Description and Natural Habitat
Actaea racemosa is an upright rhizomatous perennial native to eastern North America, found in a variety of woodland settings from Maine south to Georgia and west to Missouri and Arkansas. It prefers rich moisture-retentive soils in partial to full shade and can be slow to get established.
The leaves of black cohosh are 15–60 cm (~6–23 inches) in length, smooth, and two to three times "ternately" compound, with 20–70 toothed leaflets. The flowering stem can be quite tall, reaching up to 2.5 m (~8 ft) in height. Small, numerous, creamy white, fragrant flowers appear in late summer to early fall in long, terminal racemes resembling fluffy spires (typically 1–2 ft long) rising well above the foliage on wiry stems.
Related Species of Note
A. racemosa can easily be confused with the woodland species A. podocarpa DC. (formerly Cimicifuga americana Michx.), known as mountain bugbane or yellow cohosh. Appalachian bugbane (A. rubifolia Kearney) has the fewest leaflets and the largest terminal leaflet of the group. Asian species of Actaea — including A. cimicifuga, A. dahurica, and A. heracleifolia — are used in Traditional Chinese Medicine for very different complaints such as toothache and diarrhoea, and all are sometimes referred to by the same pharmaceutical name "Cimicifugae Rhizoma" in some medicinal literature, creating potential for confusion.
Parts Used and Common Preparations
Extracts from the underground parts of the plant — the rhizome (Cimicifugae racemosae rhizoma) and the root (Cimicifugae racemosae radix) — are used in herbal medicine. Commercially, pharmaceutical formulations of black cohosh include Remifemin® (sold in Germany since 1956) and Remixin. Preparations of black cohosh available include oral tablets containing 1 to 2 mg of 27-deoxyactein; oral liquid used at a dose of 20 to 40 drops/day containing 1 to 2 mg of 27-deoxyactein; cut and dried rhizome at a dose of 40 to 200 mg/day in several doses by mouth; and powdered root or tea at a dose of 1 to 2 g three times daily.
2. Traditional and Historical Use
Native American Use
The first medicinal use of black cohosh is generally attributed to Native Americans, who used it for the treatment of a variety of disorders, including various conditions unique to women such as amenorrhea and menopause, rheumatism, kidney disorders, malaise, and pain during menses and childbirth.
Black cohosh rhizome was traditionally used by a number of Native American tribes, including the Cherokee and Iroquois, for a broad range of complaints including rheumatism and tuberculosis and as a gynaecological aid.
The herb was introduced to American medicine by Native Americans, who called it "squaw root" because it was predominantly used to treat uterine disorders and female complaints by promoting or restoring healthy menstrual activity; soothing irritation and congestion of the uterus, cervix, and vagina; relieving pregnancy-related pain or distress; and promoting a quick and uncomplicated delivery and uterine involution and recovery.
Cimicifuga rhizome has a long and diverse history of medicinal use in the Eastern United States and Canada. Historically, Native American Indians used it to treat a variety of conditions including malaise, malaria, rheumatism, abnormalities in kidney function, sore throat, menstrual irregularities, and menopause.
Adoption by European Settlers and Eclectic Medicine
European settlers learned the medicinal uses from Native Americans and brought it back to Europe in the 18th and 19th centuries. Early settlers also used it to treat smallpox.
Use of black cohosh was accepted and popularized by eclectic medical practitioners in the late 19th and early 20th centuries. Dr. John King made a significant contribution by publicizing the use of black cohosh, or as he referred to it, "Macrotys." King claimed that Macrotys was a remedy of "abnormal conditions of the principal organs of reproduction in the female," and that the roots were "very efficacious in the treatment of chronic ovaritis, endometriosis, and menstrual derangements, such as amenorrhea, dysmenorrhea."
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. Black cohosh root was listed in the U.S. Pharmacopeia as an official drug from 1820 to 1926.
Asian Relatives in Traditional Chinese Medicine
In Asian countries including China, Japan, and Korea, Cimicifuga racemosa and its counterparts Cimicifuga heracleifolia, Cimicifuga foetida, and Cimicifuga dahurica have been used as traditional medicinal herbs to treat fever, pain, and inflammation.
Regulatory and Modern Traditional Status
Black cohosh root has been approved by the German Commission E as a nonprescription drug to treat premenstrual discomfort, dysmenorrhea, and neurovegetative menopausal symptoms such as hot flashes, heart palpitations, nervousness, irritability, vertigo, sleep disturbances, perspiration, and depression. In Germany, an extract of Cimicifuga (Remifemin) has been used to treat postmenopausal symptoms for more than 40 years. In modern Western herbal medicine, use of black cohosh is generally limited to treating the symptoms of menopause and other complaints of the female reproductive system, but application across a much broader range of disorders, including arthritis and tinnitus, is still supported by many.
3. Key Constituents and Active Compounds
Overview of Phytochemistry
There are more than 100 chemical constituents in black cohosh products, including triterpene glycosides (more than 40 chemicals), polyphenols (more than 20 chemicals), and nitrogenous compounds (more than 70 chemicals).
The constituents of black cohosh include triterpene glycosides and polyphenols. 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.
Triterpene Glycosides
The naturally occurring triterpene constituents of Cimicifuga include actein, cimicifugoside, acetylacteol, 27-deoxyactein, cimigenol, and deoxyacetylacteol. Triterpene glycosides have structures similar to steroids, but have no apparent direct binding to the estrogen receptor. One of the most abundant of such glycosides, 23-epi-26-deoxyactein, is specific for black cohosh and is the constituent usually chosen for standardization of commercial preparations.
Phenolic and Other Acids
A partial list of active compounds includes the isoflavone formononetin, isoferulic, caffeic, salicylic, and fukinolic acids. There are also miscellaneous fatty acids, tannins, and sugars. Phytosterin and resins that include Cimicifuga and triterpene glycosides are also present.
Standardization Challenges
There is not a universally accepted method to standardize the dose of black cohosh triterpenes, the presumed active ingredients in the extract. Commercially available BCE products can differ markedly in composition, leading to the potential for variable bioactivities among complex commercial products. Variable study outcomes may be due in part to inconsistent triterpene concentrations present in the various preparations used.
4. Mechanisms of Action
Summary of Proposed Mechanisms
The exact mechanism of action for black cohosh is not known. Some studies suggest that several biologically active substances are responsible for their action. Several hypotheses have been proposed: it acts (1) as a selective estrogen receptor modulator, (2) through serotonergic pathways, (3) as an antioxidant, or (4) on inflammatory pathways.
Estrogenic Hypothesis
Black cohosh was initially believed to have estrogen-like activity and to modulate tissue-specific subtypes of the estrogen receptor; more recent investigations suggest that it may have serotonergic activity. 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. Some researchers have demonstrated its ability to act as a selective estrogen receptor modulator similarly to tamoxifen.
Serotonergic Hypothesis
The black cohosh 40% 2-propanol extract inhibited radioligand binding to the human 5-HT7 receptor. Analysis of ligand binding data indicated that components of a black cohosh methanol extract functioned as a mixed competitive ligand of the 5-HT7 receptor. In addition, a black cohosh methanol extract elevated cAMP levels in 5-HT7-transfected HEK cells, suggesting the extract acted as a partial agonist at the receptor. The elevation in cAMP mediated by the black cohosh extract could be reversed in the presence of the antagonist methiothepin, indicating a receptor-mediated process. These data suggest that reductions in hot flashes in some women taking black cohosh may not be due to estrogenic properties.
The alleviation of menopausal symptoms by BCE suggests an estrogenic mechanism, but menopausal symptoms can also be alleviated by selective serotonin reuptake inhibitors (SSRIs), suggesting that BCE may work through a serotonergic mechanism. Many menopausal symptoms — hot flashes, mood swings and anxiety, insomnia — are mediated through the central nervous system (CNS) and may be alleviated through a variety of mechanisms.
Nitric Oxide and Neuroinflammatory Pathways
Research has found that while the most prominent triterpene in BCE, 23-epi-26-deoxyactein, suppresses cytokine-induced nitric oxide production in brain microglial cells, the whole BCE extract actually enhanced this pathway. It is possible that BCE can act via multiple tissue-dependent mechanisms, including estrogenic (or antiestrogenic), serotonergic, antioxidative, and inflammatory or antiinflammatory.
In summary, the mechanism of action of black cohosh has not been fully understood. It is likely involved with the nervous system through central nervous activity, serotonergic, or dopaminergic pathways. The only thing that can be said with certainty is that it is not completely understood and appears to have multiple potential mechanisms of action.
5. Scientific Evidence by Area of Use
5.1 Menopausal Vasomotor Symptoms (Hot Flashes, Night Sweats)
This is the area with the most substantial human clinical trial data for black cohosh/bugbane.
Evidence from Clinical Trials and Meta-Analyses
A substantial number of studies in people have evaluated black cohosh for menopause symptoms; much less research has been done on black cohosh for other conditions. 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 is uncertain whether black cohosh can reduce hot flashes related to breast cancer treatment.
A 2012 Cochrane Review evaluated 16 randomized clinical trials on the effectiveness of black cohosh in reducing menopausal symptoms, including hot flushes, night sweats, vaginal dryness, and combinations of symptoms measured by validated rating scales. The 16 included trials randomized a total of 2,027 women (mean age 50.5 to 56.4 years), and their samples ranged from 23 to 351 participants. Study durations were 8 to 54 weeks, with a mean duration of 22.8 weeks. Participants received a daily dose of various formulations of 8 to 160 mg/day black cohosh extract, with a median dose of 40 mg/day. There were no significant associations between supplementation with black cohosh and reduction in the number of vasomotor symptoms, such as hot flashes.
There is a growing literature on the efficacy of black cohosh for several menopausal symptoms, but when viewed in aggregate, the literature is equivocal. Some studies have reported a positive effect on specific symptoms while others have not. In one double-blind randomized study that compared placebo, conjugated estrogens, and black cohosh (preparation BNO 1055), the therapeutic effects of black cohosh were equally potent to conjugated estrogens in diminishing vasomotor symptoms.
A meta-analysis involving four randomized clinical trials on black cohosh indicated that three of the four trials found black cohosh helpful in treating menopausal symptoms. Black cohosh reduces hot flashes and night sweats most effectively. The fourth trial did not show a significant improvement with black cohosh treatment.
Guideline Positions
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 its authors recommended that researchers conduct higher quality trials with larger samples and provide more details about their experimental protocols.
Evidence Strength
Overall, the evidence for black cohosh in menopausal vasomotor symptoms is mixed and of variable quality. Some randomized controlled trials show benefit over placebo, while others do not, and major clinical guideline bodies do not recommend it as an established treatment. Heterogeneity in preparations, doses, and outcome measures makes definitive conclusions difficult.
5.2 Menstrual Dysfunction and Premenstrual Syndrome
Black cohosh is promoted as a dietary supplement for menopause symptoms. It has also been promoted for other conditions, including menstrual cramps and premenstrual syndrome, and to induce labor. Much less research has been done on black cohosh for these other conditions. The evidence for PMS, dysmenorrhea, and labor induction remains insufficiently investigated in rigorous human trials.
5.3 Bone Health / Osteoporosis
Evidence regarding the benefit of black cohosh for treating or preventing osteoporosis is conflicting. One study shows 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 shows that taking a different product containing 40 mg of black cohosh extract (CR BNO 1055) for 3 months increases markers of bone formation in postmenopausal women. However, other research shows that taking this black cohosh product does not improve bone mineral density.
Research has found that 25-acetylcimigenol xylopyranoside (ACCX), a component isolated from black cohosh, inhibited receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclast differentiation of mouse bone marrow macrophages. Black cohosh extract has also been associated with decreased bone loss in the ovariectomized (OVX) rat model, as well as increased bone mineral density (BMD) and enhanced callus formation in an OVX rat tibia fracture healing model.
Under the experimental conditions of one study, black cohosh extract alone had no effect on bone mineral density. Physicians should be quite clear in explaining to patients that although black cohosh may be useful in treating some menopausal symptoms, there is currently no evidence regarding any protective effect of black cohosh against the development of osteoporosis.
Evidence strength: preliminary and inconsistent. Animal and in vitro data suggest plausible mechanisms, but human clinical evidence is conflicting and insufficient to support a clinical recommendation.
5.4 Musculoskeletal Pain and Arthritis
Early research suggests that taking a specific product containing black cohosh and other ingredients (Reumalex) daily for 2 months improves pain, but not joint function, in people with osteoarthritis. This evidence is very preliminary and the multi-ingredient nature of the studied product makes attribution to black cohosh alone impossible.
5.5 Mood and Anxiety
Data on specific menopausal symptoms in the 2023 review showed improvements in hot flashes but not anxiety or depressive symptoms. Black cohosh acts on serotonin receptors, which can reduce menopausal symptoms and raise mood, but the current clinical evidence does not conclusively demonstrate an effect on anxiety or depression as discrete conditions. Evidence remains insufficient and preliminary.
5.6 Hot Flashes in Breast Cancer Patients
Black cohosh has shown the potential to reduce the frequency and intensity of vasomotor symptoms in breast cancer patients undergoing tamoxifen treatment. However, it is uncertain whether black cohosh can reduce hot flashes related to breast cancer treatment. It has been recommended to treat vasomotor symptoms associated with breast cancer patients in some clinical contexts, but caution is warranted given potential pharmacokinetic interactions with tamoxifen (discussed below). Evidence is uncertain and potentially confounded by drug interaction concerns.
6. Body Systems Associated with Bugbane
- Female Reproductive System: The primary area of use, including menopausal symptoms, dysmenorrhea, amenorrhea, and PMS.
- Central Nervous System: Many menopausal symptoms — hot flashes, mood swings and anxiety, insomnia — are mediated through the central nervous system (CNS) and may be alleviated through a variety of mechanisms.
- Musculoskeletal System: Historically used for rheumatism, and some contemporary research has explored effects on joint pain and osteoporosis.
- Cardiovascular System: Bradycardia has been found in the literature in association with black cohosh use, though this is uncommon.
- Hepatic (Liver) System: Subject to safety signals (see below).
- Skeletal System: Possible effects on bone remodeling biomarkers, as documented in some studies.
7. Dosage Forms and Clinical Dosages
Preparations Studied in Clinical Research
The most commonly studied black cohosh extracts in clinical trials are Remifemin® and Menofem/Klimadynon®. Remifemin® has changed formulation from a 60% ethanol extract to a 40% isopropanol extract, and the extract preparation is not consistently reported in trials.
Products containing black cohosh extract are frequently standardized to provide at least 1 mg triterpene glycosides per daily dose. Remifemin, a commercial product used in several studies included in a 2012 Cochrane Review, is an extract currently standardized to be equivalent to 40 mg black cohosh root/rhizome (extracted with isopropyl alcohol) per daily dose of two tablets, but it is not standardized to triterpene glycoside content.
Dose Ranges Reported in Studies
Black cohosh doses in clinical trials evaluating efficacy have ranged from 6.5 to 160 mg/day for 1 to 12 months. The German Commission E recommends 40 mg/day of alcohol extracts of black cohosh, not to exceed 6 months of use. The manufacturer of Remifemin® recommends a dose equivalent to approximately 5 mg/day, taken as two tablets containing 2.5 mg black cohosh root/rhizome per day.
Clinical studies performed before 1996 used doses of 48–140 mg of black cohosh extract per day. A more recent clinical study compared two different dosages of Remifemin — 40 mg vs. 127 mg daily — for 6 months and found similar safety and efficacy profiles for both dosages. The current recommendation of 40 mg per day was based on the results of this trial. However, the dosage used in most clinical trials to date is 80 mg daily of black cohosh extract.
If using an isopropanolic extract (usually sold under the brand name Remifemin), 20–40 mg daily is used in doses of 20 mg; this dosage confers 1–2 mg of triterpenoid glycosides. If using an aqueous:ethanolic extract of black cohosh root (i.e., not Remifemin), then doses range from 64–128 mg daily, which are usually taken in two divided doses, contributing about the same amount of triterpenoid glycosides.
One study published in 2009 used black cohosh at 128 mg/day orally in an ethanolic extract containing 5.7% triterpene glycosides.
The most commonly used dosage of Remifemin is two 20-mg tablets twice daily. Maximum effect usually occurs in four to eight weeks.
Standardization Considerations
Not all study authors state that they used the rhizome/root for the extract. In many of the studies, extraction of the preparation was not detailed, nor was a standardization of the extract for specific active compounds accomplished. This variability significantly limits the ability to compare results across trials.
The inconsistent reports on the efficacy of black cohosh products may be due to the variability of the test article used, as few include characterization or standardization. Adulteration of black cohosh products with related species of Actaea has also been documented.
8. Safety Considerations and Drug Interactions
General Short-Term Tolerability
In clinical trials, people have taken black cohosh for as long as 12 months with no serious harmful effects. Black cohosh can cause some mild side effects, such as stomach upset, cramping, headache, rash, a feeling of heaviness, vaginal spotting or bleeding, and weight gain.
Hepatotoxicity — The Key Safety Signal
Across the world, reports have described at least 83 cases of liver damage — including hepatitis, liver failure, elevated liver enzymes, and assorted other liver injuries — associated with black cohosh use. However, there is no evidence of a causal relationship.
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.
A clear causal relationship between black cohosh and hepatotoxicity is controversial. The reason is multifactorial but is largely due to the fact that products labeled as black cohosh usually contain other compounds and multiple ingredients. Additionally, many reported cases often lack details in regard to temporal relation, co-medications, dosing, source, and preparation of product.
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.
Determining the risk of black cohosh hepatotoxicity is further complicated by variability in both dosage and number of other botanical herbal supplements contained in some preparations. In one documented case, the preparation of black cohosh included 4 other botanicals, one of which — ground ivy — contains a known hepatotoxin, pulegone. This case culminated in liver failure despite discontinuation of the herbal supplement.
Evidence from both in vivo models and in vitro cell studies suggests that BCE can exhibit toxic and genotoxic effects, with its potential to cause hepatotoxicity in humans ranging from mild reactions to acute liver damage. These concerns raise questions regarding public health safety, especially for vulnerable populations such as patients with autoimmune hepatitis or hormone-sensitive cancers.
Some commercial black cohosh products have been found to contain the wrong herb or to contain mixtures of black cohosh and other herbs not listed on the label.
Interaction with Tamoxifen and CYP Enzymes
Women who experience hot flashes as a side effect of tamoxifen therapy often try botanical remedies such as black cohosh to alleviate these symptoms. Since pharmacological activity of tamoxifen is dependent on the metabolic conversion into active metabolites by the action of cytochromes P450 2D6 and 3A4, a key research question is whether black cohosh extracts can inhibit formation of active tamoxifen metabolites and possibly reduce its clinical efficacy.
At 50 µg/ml, a 75% ethanolic extract of black cohosh inhibited formation of 4-hydroxy-tamoxifen by 66.3%, N-desmethyl tamoxifen by 74.6%, and α-hydroxy tamoxifen by 80.3%. In addition, this extract inhibited CYP3A4 and CYP2D6 with IC50 values of 16.5 and 50.1 µg/ml, respectively.
The results of this study suggest that co-administration of black cohosh with tamoxifen might interfere with the clinical efficacy of this drug. However, additional clinical studies are needed to determine the clinical significance of these in vitro results.
Statin Interaction Signal
Preliminary laboratory research, some of it supported by NCCIH, suggests that black cohosh might affect statin medicines, which are used to reduce blood cholesterol levels.
Other Noted Interactions
Dizziness, headaches, nausea, and vomiting also occur when higher-than-normal amounts are ingested. Hepatotoxicity has been reported with the use of black cohosh, and two cases of liver injury resembling autoimmune hepatitis have been cited. A case of coagulation activation, fluid retention, and transient autoimmune hepatitis, as well as bradycardia, has been found in the literature.
Acute onset mania has been reported as associated with black cohosh, likely due to its psychopharmacological activities on serotonergic and dopaminergic receptors.
Populations of Concern
Concerns about safety are particularly raised for vulnerable populations, such as patients with autoimmune hepatitis or hormone-sensitive cancers. Hormone-sensitive conditions such as breast cancer, endometrial cancer, endometriosis, ovarian cancer, uterine fibroids, pregnancy, and lactation are listed as conditions warranting caution or contraindication.
Product Quality and Adulteration
Some commercial black cohosh products have been found to contain the wrong herb or to contain mixtures of black cohosh and other herbs not listed on the label. Among cases of suspected black cohosh hepatotoxicity reported to Health Canada, analysis of retrieved samples showed that none contained authentic black cohosh, but had phytochemical profiles consistent with the presence of other related herbal species. This underscores the importance of product identity verification in both research and consumer use.
References
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