AmericanHerbal Pharmacopoeia

and !herapeutic "ompendium

™

Black Cohosh Rhizome

Actaea racemosa L.
syn. Cimicifuga racemosa (L.) Nutt.
Standards of Analysis, Quality Control,
and Therapeutics

2002
Editor: Roy Upton Herbalist
Associate Editor and Monograph
Development Coordinator
Alison Graff PhD
Research Associate
Diana Swisher BA

Board of Directors
Roy Upton Executive Director
American Herbal Pharmacopoeia™
Santa Cruz, CA

Michael McGuffin President

American Herbal Products Association
Silver Spring, MD

Joseph Pizzorno ND President Emeritus

Bastyr University
Kenmore, WA
 Authors Quantitative Standards and Daniel Fabricant BS
Norman Farnsworth PhD
Aviva Romm CPM Herbalist (AHG)
President
International Status
Department of Medicinal Chemistry American Herbalists Guild
History Josef Brinckmann and Pharmacognosy Canton, GA
Research and Development Manager University of Illinois
Michael A Flannery MA MLS Clarissa Smith Herbalist LAc
Traditional Medicinals Inc Chicago, IL
Assistant Professor Seattle, WA
Sebastopol, CA
Associate Director for Historical Dr Christoph Gorkow
Collections Robin Suggs Executive Director
Therapeutics Department of Medical Sciences Yellow Creek Botanical Institute
Lister Hill Library of the Health Bionorica Arzneimittel
Sciences Pharmacokinetics, Pharmacodynamics, Robbinsville, NC
and Clinical Efficacy Neumarkt, Germany
University of Alabama Andrew Weil MD
Birmingham, AL Leonard Wisneski MD FACP Dr Hansjörg Hagels Program in Integrative Medicine
Clinical Professor of Medicine Analytical Development Division School of Medicine
Botanical Identification George Washington University Medical Schaper-Brümmer GmbH & Co KG University of Arizona
Center Salzgitter, Germany Tucson, AZ
Robin Bencie
Washington, DC Tori Hudson ND
Alison Graff PhD Eric Yarnell ND RH (AHG) President
American Herbal Pharmacopoeia™ Medical Indications Supported by Portland Naturopathic Clinic Botanical Medicine Academy
Santa Cruz, CA Traditional and Modern Experience Portland, OR Sisters, OR
Jill Stansbury ND Chair Frank Jaksch PhD President
Macroscopic Identification and Department of Botanical Medicine Chromadex Inc
Commercial Sources and Handling National College of Naturopathic Laguna Hills, CA Final Reviewers
Medicine
Tammi Hartung Herbalist Jim Kroll MS Adriane Fugh-Berman MD
Portland, OR
Desert Canyon Farm and Learning Senior Chemist Assistant Clinical Professor
Center Safety Profile Waters Corporation Department of Medicine
Canyon City, CO Milford, MA Department of Health Care Sciences
James Reinhart RPh George Washington University School of
Microscopic Identification Director of Pharmacy Prof Dr Eckehard Liske
Medicine
Selma Community Hospital International Medical Support Division
Prof Dr Reinhard Länger Washington, DC
Selma, CA Schaper-Brümmer GmbH & Co KG
Institute for Pharmacognosy Salzgitter, Germany Prof Dr Hubertus Jarry
Center of Pharmacy Department of Clinical and
Dr Reinhard März
University of Vienna
Vienna, Austria
Review Committee Department of Medical Sciences
Experimental Endocrinology
University of Göttingen
Erdal Bedir PhD Bionorica Arzneimittel
Göttingen, Germany
Constituents National Center for Natural Products Neumarkt, Germany
Research Fredi Kronenberg PhD
Mythili Nagarajan MS Joe-Ann McCoy MS
School of Pharmacy Richard and Hinda Rosenthal Center for
Research and Development Chemist Research Associate
University of Mississippi Complementary and Alternative
Enzymatic Therapy Clemson University
University, MS Medicine
Green Bay, WI Clemson, SC
Columbia University
Kerry Bone MCPP FNHAA FNIMH Amanda McQuade Crawford Herbalist College of Physicians and Surgeons
Analytical Herbalist MNIMH (AHG) Director New York, NY
MediHerb PTY Ltd Ojai Center of Phytotherapy
Substantiating Laboratories Helene Leonetti MD
Warwick, Queensland Ojai, CA
High Performance Thin Layer Associate Professor
Australia
Chromatography (TLC/HPTLC) Beat Meier PhD Department of Obstetrics and
Kathrin Thiekoetter Mary Bove Herbalist ND Zeller AG, Herbal Medicinal Products Gynecology
Eike Reich PhD Brattleboro Naturopathic Clinic Romanshorn, Switzerland Temple University
CAMAG Brattleboro, VT Philadelphia, PA
Muttenz, Switzerland William Mitchell ND
Francis Brinker ND Seattle, WA
High Performance Liquid Eclectic Institute and
Chromatography (HPLC) Program in Integrative Medicine Prof Dr Adolf Nahrstedt
Paula Brown MS School of Medicine Editor Planta Medica
Ryan Takahashi University of Arizona Pharmaceutical Biology and
Herbal Evaluation and Analysis Tucson, AZ Phytochemistry
Laboratory University of Münster
Chanchal Cabrera Herbalist MNIMH Münster, Germany
Forensics Department (AHG)
British Columbia Institute of Gaia Garden Herbals Gwynn Ramsey PhD
Technology Vancouver, BC Professor of Biology Emeritus
Burnaby, British Columbia Curator, Ramsey-Freer Herbarium
Canada Dr Volker Christoffel Lynchburg College
Department of Medical Sciences Lynchburg, VA
Institute for Nutraceutical Advancement Bionorica Arzneimittel
(INA) Neumarkt, Germany Joseph Romano MA
Methods Validation Program (MVP) Marketing Manager
Apex, NC Steven Dentali PhD Waters Corporation
Dentali Associates Milford, MA
Boca Raton, FL

ISBN: 1-929425-14-7 ISSN: 1538-0297

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Medical Disclaimer Design & Composition
The information contained in this monograph represents a syn- Beau Barnett
thesis of the authoritative scientific and traditional data. All Felton, CA
efforts have been made to ensure the accuracy of the informa- Cover Photograph
tion and findings presented. Those seeking to utilize botanicals Black cohosh (Actaea racemosa) © 2002
as part of a health care program should do so under the guid- courtesy of Martin Wall Photography,
ance of a qualified health care professional. Pleasant Garden, NC
Statement of Nonendorsement
The reporting on the use of proprietary products reflects studies
conducted with these and is not meant to be a product endorse-
ment.
N O M E N C L AT U R E and botrus (a bunch), referring to the large raceme of fruits
(follicles). Later another botanist, De Candolle, mistakenly
Botanical Nomenclature referred to it as Macrotys, a name that stuck and was pre-
Actaea racemosa L. ferred by the Eclectics (Lloyd and Lloyd 1931b).
syn. Cimicifuga racemosa (L.) Nutt. According to Native American ethnobotanical litera-
ture, black cohosh was used for a wide range of conditions
Botanical Family by eastern tribes including the Cherokee, Delaware,
Iroquois, Mikmaq (Micmac), and Penobscot. Medicinal
Ranunculaceae
uses among these tribes included its application as a seda-
Definition tive, anodyne, gynecological remedy, treatment for
rheumatic conditions, and treatment for hives (Moerman
Black cohosh consists of the fresh or dried rhizome and 1986). The first reference to black cohosh in published lit-
roots of Actaea racemosa L. conforming to the methods of erature is unclear. Some attribute the initial citation to
identification provided. Leonard Plunkenet as early as the 1680s, but this is not
definitive. A more conclusive listing of black cohosh (as
Common Names Actaea racemosa) occurs in a translation of Carl von Linne’s
United States: Black cohosh (standardized common botanical work of 1749 in which it was classified as a repel-
name), black bugbane, black snakeroot, lant (reducing swelling), diaphoretic, and anodyne, and as
rheumatism weed (McGuffin and others useful for “female debility” (Whitlaw 1829).
2000). The American medical botanist Benjamin Smith
Germany: Traubensilberkerze, Wanzenkraut. Barton gave more extensive treatment to the plant in his
Collections for an Essay Towards a Materia Medica of the
History United States (1810). He acknowledged its medicinal use by
Black cohosh is an indigenous North American medicinal
plant that was widely used by Native Americans and
Eclectic physicians and continues to be utilized by modern
midwives and practitioners of herbal medicine. Botanically,
black cohosh is best known by its former scientific name
Cimicifuga racemosa (L.) Nutt. It has recently been reclassi-
fied into the genus Actaea, where it was originally placed by
Linnaeus (1753) (Compton and others 1998). Actaea comes
from the word aktea, which is Greek for the elder tree
(Sambucus spp.). Presumably it was called such due to the
similarity in leaf morphology found between the two genera
(Ford 1997). Texts from the early 1800s to the present place
black cohosh in the genus Cimicifuga, a name derived from
the Latin cimex (bedbug) and fugare (to drive away) in ref-
erence to a European species in this genus commonly
known as bugbane and used as an insect repellant. This
common name was later misapplied to our domestic
Cimicifuga (Felter and Lloyd 1909; Lloyd 1921). The
species name racemosa is derived from the Latin racemosus,
meaning “full of clusters”, in reference to the large inflores-
cence of many small white flowers.
Throughout American history black cohosh has been
known by several other common names including baneber-
ry, black snakeroot, and rheumatism weed, although the
most widely applied has been black cohosh. According to
Lloyd and Lloyd (1931a), “cohosh” is an Algonquin word
meaning “it is rough” (with hairs) and was originally applied
to the bristly fruit of Ribes lacustre. Its application by whites
to blue cohosh (Caulophyllum thalictroides), species of
Actaea such as red and white baneberry (A. rubra and A.
pachypoda, respectively), as well as black cohosh, none of
which have hairs, has not been explained (Erichsen-Brown
1979; Lloyd and Lloyd 1931b). The noted medical botanist
and naturalist Constantine Rafinesque in 1808 gave black Figure 1 Black cohosh (Actaea racemosa)
cohosh the name Macrotrys from the Greek makros (large) Source: Good, The Family Flora and Materia Medica (1845).

American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002 1

 Table 1 Historical timeline of the medical use of black cohosh (Actaea racemosa)
Native American use Black cohosh was widely used by many tribes including the Cherokee, Delaware, Iroquois, Mikmaq, and Penobscot
as a sedative, anodyne, antirheumatic, and general gynecological remedy.
1808 The noted medical botanist Constantine Rafinesque gives black cohosh the name Macrotrys, which is subsequently
changed to Macrotys by the botanist De Candolle.
1810-1830 The medical use of black cohosh by Native Americans is reported in the works of such early American medical
botanists as Benjamin Smith Barton, Jacob Bigelow, Constantine Rafinesque, and Elisha Smith.
1830-1920 Black cohosh is official in the primary list of the United States Pharmacopoeia.
1831 Young publishes a paper on the medical use of black cohosh in the American Journal of Medical Science .
1832 The Thomsonian practitioner Howard reports on the use of black cohosh for the treatment of small pox.
1832-1955 Black cohosh is listed in the United States Dispensatory.
1835 John King introduces the resin preparation of black cohosh, sold as cimicifugin, macrotyn, and macrotin, into
Eclectic medical practice. In addition to its use as a parturient, black cohosh subsequently becomes a popular
Eclectic remedy for use in the treatment of nervous conditions, myalgia, neuralgia, infections, false and true labor
pains, dysmenorrhea, and ammenorrhea.
1980-present The pharmacology and therapeutic efficacy of black cohosh are intensively studied in Germany. Black cohosh is
reclassified from Cimicifuga racemosa (L.) Nutt. back to the original Linnean designation Actaea racemosa L.
2001 Black cohosh is proposed for re-inclusion in the United States Pharmacopeia – National Formulary.

Native Americans and observed that as a sore throat remedy
“a strong decoction of the root was used, with great benefit,
as a gargle”. Other prominent medical writers of the time
such as Elisha Smith and Jacob Bigelow also wrote about
black cohosh but they simply reported on the Native uses of
the plant, adding no new information regarding its medical
application (Lloyd 1921). It was not until 1831 that black
cohosh was definitively introduced into medical practice in
the United States by Young, who published a paper in the
American Journal of Medical Science. In 1889, Sir Lauder
Brunton recommended black cohosh as a stomachic, car-
diac tonic, and expectorant (Macht and Cook 1932).
In 1832, the Thomsonian practitioner Howard enthusi-
astically supported the use of black cohosh (Macrotys) for
the treatment of small pox. This use was supported by a Dr
GH Norris 40 years later (1872) in a paper read before the
Alabama State Medical Association in which it was reported
that families consuming Macrotys prophylactically as a tea
during a smallpox epidemic remained “absolutely free” of
the disease. Howard noted significant differences between
the use of the tea and alcohol extracts. Of particular histori-
cal interest, in 1848, the Committee of the American
Medical Association “uniformly found Macrotys to lessen
the frequency and force of the pulse, to soothe pain and
allay irritability” and held it to be “the most purely sedative
agent we possess” (Lloyd 1921).
Black cohosh was a popular Eclectic remedy used in
“muscular pains; uterine pains, with tenderness; false pains;
irregular pains; rheumatism of the uterus; dysmenorrhea”
(Felter and Lloyd 1909). Its reputation as a virtual cure-all
made black cohosh one of the most popularly prescribed
drugs according to one 1912 survey (Crellin and Philpott
1990; Lloyd 1912). According to Felter and Lloyd (1898),
the rise in popularity of the use of black cohosh among the
Eclectics was due to the medical experience of John King
who began using it in 1832 when few other Eclectics were
doing so. Consequent to King introducing a resin prepara-
tion (sold as cimicifugin, macrotyn, and macrotin) in 1835,
black cohosh was found in general practice by around 1850
(Felter and Lloyd 1898). King reported that the effects of
black cohosh on the heart and circulatory system were sim-
ilar, though less pronounced, to those of Digitalis, stating it
slowed the heart and increased the heart’s contractile force
and arterial tension. For use in obstetrical practice, King
considered black cohosh to be a superior and safer oxytocic
agent than ergot.
Based on its widespread use, black cohosh was also
prominent in the 19th century armamentarium of conven-
tional medical practitioners. It appeared on the secondary
list of substances in the first United States Pharmacopeia
(USP) of 1820, where it was listed as an anti-inflammatory
and antispasmodic. It soon rose to the primary list in 1830,
a position it held until the 10th decennial revision of 1920
(Boyle 1991). Black cohosh appeared in the first edition of
the United States Dispensatory (USD) in 1833 and
remained through 1955 for a total of 122 years. The first
USD stated that “Cimicifuga unites, with a tonic power, the
property of stimulating the secretions, particularly those of
the skin, kidneys, and pulmonary mucous membrane. It is
thought by some to have a particular affinity for the uterus.
Its common name black snakeroot was probably derived
from its supposed power of curing the disease arising from
the bite of the rattlesnake” (Wood and Bache 1833).
Carrying forward the traditional Native American use of

2 American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002

black cohosh for women’s ailments and Barton’s use for throat
complaints, current therapeutics finds the plant used “in a
number of preparations for coughs and for gynecological dis-
orders” (Reynolds 1996). In 2001, both the rhizome and the
dry extract of black cohosh were proposed once again for
inclusion in the United States Pharmacopeia – National
Formulary (USPF 27[4] 2001).
Asian species of Actaea (cited as Cimicifuga) are official
in the pharmacopoeias of China and Japan. Actaea racemosa,
however, is not included in modern official Western pharma-
copoeias, although it is listed in the British Herbal
Pharmacopoeia (1996) and a monograph by the World Health
Organization is currently in preparation. Black cohosh is
approved by the German Health Authority (Commission E)
for “premenstrual discomfort, dysmenorrhea, or climacteric
(menopausal) neurovegetative ailments” (Blumenthal and Figure 2a Black cohosh (Actaea racemosa) in flower in its natural
others 1998). habitat
Photograph © 2002 courtesy of Martin Wall Photography, Pleasant Garden, NC

I D E N T I F I C AT I O N
Botanical Identification
Actaea racemosa L. Herbaceous perennial from rhizome.
Stem: Erect, solitary, to 2.5 m tall, glabrous. Leaves: Basal
and cauline, alternate, 2-4-ternately compound, petioles 15-
60 cm long, bases clasping stem; leaflets 20-70; terminal
leaflet of central division 3-lobed, 6-15 cm long, 6-16.5 cm
wide, with 3 prominent veins arising from base; sub-terminal
leaflets with blades ovate-lanceolate to obovate, 4-12 cm long
and 3-8 cm wide; margins toothed to deeply incised; green
above, paler below; glabrous or rarely pubescent along veins
of undersurface. Inflorescence: Terminal panicle of 4-9 slen-
der branches, each 7-60 cm long, pubescent; 1 bract sub-
tending each pedicel. Flowers: Perfect, radially symmetric;
sepals 4, greenish-white, caducous; petals 0; staminodes (1-) 4
(-8), petaloid, cream-colored, 2-3 mm long, clawed, apex
Figure 2b Black cohosh (Actaea racemosa) leaves
bifid; stamens 55-110; pistils 1 (-3), glabrous to pubescent,
Photograph © 2002 courtesy of Martin Wall Photography, Pleasant Garden, NC
ovary superior, style short, stigma 0.5 mm wide. Fruit: Many-
seeded follicle, 5-10 mm long, ovoid, laterally compressed with
curved, stout beak (peristent style), pubescent; seeds hemi-
spheric, brown, scales lacking. Chromosome number: n = 8.
Distribution: Moist deciduous forests, ravines, moist mead-
ows, creek margins, mountainous terrain. Flowers June to
September. Native to eastern North America from Ontario
south to Georgia and west to Missouri (Compton and others
1998; Linnaeus 1753 [original citation]; Ramsey 1965, 1987,
1997).
There are currently two varieties of A. racemosa recog-
nized based on differences in leaf morphology: var. racemosa
and var. dissecta. The former variety has triternate-pinnate
leaves with serrate margins, while the latter has quadriternate-
pinnate leaves that are deeply incised with serrate lobes
(Compton and others 1998). Variety dissecta is only known
from very few herbarium specimens, all of which were col-
lected well over 100 years ago, making this taxon of uncertain
Figure 2c Black cohosh (Actaea racemosa) in flower
taxonomic significance (Ramsey 1997). Photograph © 2002 courtesy of Martin Wall Photography, Pleasant Garden, NC

American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002 3

Table 2 Botanical characteristics distinguishing black cohosh
(Actaea racemosa) from yellow cohosh (Actaea podocarpa syn. Aroma: Slightly sweet and musty in both the fresh and dried
Cimicifuga americana) rhizome and root, pungent and somewhat unpleasant. Taste:
Slightly bitter, acrid, slightly mucilaginous.
Character Black cohosh Yellow cohosh
Powder: Light to dark brown in color with a heavy and dis-
agreeable aroma that fades with age (BHP 1996; Kraemer
1920; Lloyd and Lloyd 1931b; Mansfield 1937; Osol and
Farrar 1947; Sayre 1917; Steinegger and Hänsel 1992;
Fruit Youngken 1930).

Seeds

Pistils, pedicels, and bracts

Figure 3 Freshly harvested rhizome and roots of black cohosh
(Actaea racemosa)
Source: Lloyd and Lloyd (1931a).

Staminodia

Source: Ramsey (1987).

Macroscopic Identification
Black cohosh may be traded as a mixture of whole, broken,
or cut pieces of the rhizome and roots, usually dried but
sometimes fresh. In the retail market it is sold dried, cut and
sifted. The whole rhizome is 2-15.2 cm long and 0.5-3 cm
in diameter, with many tightly clustered upright or upward-
ly curving branches. Externally it is brownish-black, some- Figure 4a Freshly harvested black cohosh rhizome and roots
times drying to a grayish-brown. The entire surface is slight- (Actaea racemosa)
ly annulate due to the many leaf scales. The upper surface Photograph © 2002 courtesy of Martin Wall Photography, Pleasant Garden, NC
has many stem buds and deep, cup-shaped scars from past
stems. The lower surface has many root scars and few to
many wiry roots. The dry rhizome is resinous with a fibrous
texture and horny fracture (hard and uneven), and the fresh
rhizome is brittle and breaks with a nearly clean fracture. In
cross section the rhizome is almost round and has dark
green or brown bark approximately 1 mm thick, dark brown
wood 4-5 mm thick, and a whitish or dark brown and waxy
pith 3-5 mm in diameter. The xylem is visible as wedges
alternating with medullary rays.
The roots are 3-16 cm long and 1-5 mm in diameter,
dark brown externally, and longitudinally wrinkled. When
dry they are brittle with a short fracture. In cross section they
are round or broadly angled with a dark brown to black bark
and light to dark brown or yellowish wood. The wood is
Figure 4b Freshly harvested black cohosh rhizome and roots
arranged in a characteristic cross-like pattern with 4, some-
(Actaea racemosa)
times 2-6, radiating, widely separated strands.
Photograph © 2002 courtesy of Roy Upton, Soquel, CA

4 American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002

Figure 4c Freshly harvested black cohosh rhizome and roots Figure 5a Cut dried black cohosh (Actaea racemosa)
(Actaea racemosa) Photograph © 2002 courtesy of Roy Upton, Soquel, CA
Photograph © 2002 courtesy of Roy Upton, Soquel, CA

Figure 4d Dried black cohosh rhizome and roots (Actaea racemosa) Figure 5b Dried slices of black cohosh (Actaea racemosa)
Photograph © 2002 courtesy of Roy Upton, Soquel, CA Photograph © 2002 courtesy of Roy Upton, Soquel, CA

Figure 4e Freshly harvested yellow cohosh (Actaea podocarpa) Figure 5c Dried slices of sheng ma (Actaea sp.; left) and an adul-
rhizome and roots terant (Serratula sp.; right) of sheng ma
Photograph © 2002 courtesy of Thomas Dadant, Santa Cruz, CA Photograph © 2002 courtesy of David Eagle, Santa Cruz, CA

American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002 5

Microscopic Identification
Rhizome: Beneath a dark brown exodermis is the colorless
parenchyma of the cortex. The walls of the cortical cells are
thickened, particularly at the cell corners, and between
most cells is a small triangular intercellular space. The vas-
cular bundles are arranged radially around the central pith
and are separated by broad medullary rays. The vessels of
the secondary xylem are grouped with fibers. The vessels are
up to 60 µm in diameter, with bordered pits or reticulate
secondary wall thickenings. In the outermost region of the
stele, a few fibers and sclereids are embedded in each
phloem bundle. The phloem regions are elongated with the
tissue directly outside of the bundles appearing compressed
and different from the surrounding cortical parenchyma.
Root: The root is covered by an exodermis of dark brown
papillous cells with a considerably thickened and striated
outer wall. The cell walls of the cortical parenchyma are
thickened and the innermost layer of the cortex is a well-
defined endodermis. Large areas of secondary xylem alter-
nate with small areas of the primary xylem; the parenchyma
is completely replaced by xylary fibers.
Starch granules are abundant in the water preparation; they
are mostly solitary, rarely in aggregates of 2 or 3. Solitary
granules are roundish and up to 10 µm in diameter.
Powder: Preparation in water: starch. Preparation in chloral
hydrate: xylary fibers and vessels in longitudinal view;
phloem fibers and sclereids; parenchyma cells.

Exodermis
Fibers
Secondary phloem

Secondary xylem

Pith
5.

1.
6.
Cortex

Endodermis

Xylem
2.

7.

8.

3. Figure 6a Microscopic characteristics of black cohosh rhi-

zome and root (Actaea racemosa)
1. Rhizome (cross section).
2. Root (cross section).
3. Cortical parenchyma of the rhizome (cross section).
4. Phloem fibers in the rhizome (cross section).
5. Phloem tissue with sclereid in the rhizome (longitudinal
view).
6. Vessels with bordered pits and a xylary fiber in the rhizome
(longitudinal view).
7. Root exodermis (cross section).
8. Starch granules.
4. Microscopic drawings courtesy of Reinhard Länger, University of Vienna.

6 American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002

1. 6.

2. 7.

Figure 6b Microscopic characteristics of black cohosh rhizome

and root (Actaea racemosa)
1. Rhizome (cross section). Note small strands of vessels and
fibers and broad medullary rays; in the secondary phloem,
parenchyma predominates with small bundles of fibers exte-
rior to the sieve cells.
2. Rhizome with vessels and fibers on the right and part of a
medullary ray on the left (cross section).
3. Secondary phloem parenchyma of the rhizome (cross sec-
tion).
4. Vessels with bordered pits in the rhizome (longitudinal view).
3. 5. Root (cross section).
6. Root with detail of the endodermis (cross section).
7. Starch granules in the powder.
Microscopic images courtesy of Reinhard Länger, University of Vienna.

4.

5.

American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002 7

COMMERCIAL SOURCES AND
HANDLING
The entire supply of black cohosh comes from the United
States. The major producers of black cohosh are Kentucky
and Tennessee, with additional supplies coming from
Georgia, Ohio, North Carolina, Michigan, South Carolina,
Virginia, West Virginia, and Wisconsin. Although there are
reports of black cohosh being grown in China and India for
export, the true identity of the cultivated material has not
been verified and may well be an Asian species of Actaea
such as A. cimicifuga (syn. Cimicifuga foetida) (HRF and
YCBI 2001).
In 1998, 600,000-700,000 pounds (272-318 metric tons
[mt]) of black cohosh were harvested in North America.
Approximately 95% or more of this was wild harvested. As
much as 60% (320,000 pounds [145 mt]) of total produc-
tion in 1998 was exported, and more than 75% of total
exports went to Germany. Exports reportedly increased to
over 400,000 pounds (181 mt) in 1999, and then declined
sharply to 22,046-33,069 pounds (10-15 mt) in 2001. Some
of this decline was due to over-stocking of raw material from
the 1998 and 1999 harvests, the remainder of which was
used to fill current demand (HRF and YCBI 2001).
Concern over the conservation of black cohosh due to
increasing demand makes this species a good candidate for
cultivation.
Collection
Traditionally, black cohosh has been harvested after plants
become reproductive, which occurs anywhere from two to
eight years of age in cultivated plants depending on growing
techniques (see Cultivation). Rhizomes and roots should be
harvested in autumn when the plant is dormant. At that
time the underground portions of the plant have lower
moisture content than in other seasons. Fall harvesting also
allows plants to produce mature seeds before being uproot-
ed. A portion of the rhizome with a visible bud on it should
be left in the ground to re-sprout the following year. There
is no published information on the relationship between
the constituent profile of the rhizome and its age, growing
conditions, or place of origin, although such studies are
underway (Fabricant and others 2001).
The impact of harvest on wild populations of black
cohosh is currently unknown and sources differ in their
opinion about it. While some maintain that current levels
of harvest threaten the viability of wild populations, others
feel that sustainable harvesting is possible at current levels
of demand. A study of sustainable harvest limits is currently
underway (McCoy, personal communication to AHP;
unreferenced). The regulatory status regarding the trade of
black cohosh is under review by the Convention on
International Trade of Endangered Species (CITES).
Refraining from harvesting plants until after they have set
seed and leaving a portion of the rhizome in the ground to
resprout are key components to sustainable harvesting.
8 American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002
Cultivation
Black cohosh is grown from rhizome cuttings or seeds and
requires some shading depending on altitude and other
environmental conditions. If grown from rhizome cuttings,
a plant takes two to three years to become reproductive;
grown from seed sown in the greenhouse and then planted
out, it takes four to six years; direct-seeded it may take from
six to eight years. For more complete information regarding
cultivation, see Franke and others (2000). Preliminary work
indicates that black cohosh can be propagated successfully
using in vitro techniques (Lata and others 2001).
Handling and Processing
Rhizomes with roots may be processed fresh or dried. They
should be thoroughly washed directly after harvest and then
laid out to dry. Freshly harvested roots should be solid but
not woody.
Drying
Rhizomes with roots are cut and air-dried at 35-45 °C. They
are fully dried when they are brittle and snap easily and
when no moisture is evident in cross section, either visibly
or to the touch.
Storage
Follow general guidelines for storage by packing in airtight
containers protected from light, heat, moisture, and insect
infestation.
Adulterants
Other species of Actaea, especially yellow cohosh (A.
podocarpa syn. Cimicifuga americana), have commonly but
unintentionally been mixed with A. racemosa due to the sim-
ilarity in above-ground appearance between species. The two
species can be distinguished by differences in their freshly
harvested underground parts: the fresh rhizome of A.
podocarpa has a distinct yellowish hue, whereas that of A.
racemosa is black (Figures 4a-e). The rhizomes of both
species are far more difficult to tell apart when dry because
A. podocarpa darkens upon drying. A. podocarpa has the fol-
lowing other characteristics that distinguish it from A. race-
mosa (Table 2): where the base of the stem emerges from the
ground, it is slightly grooved to flat on one side rather than
completely round (Fletcher, personal communication to
AHP; unreferenced); the adaxial side of the petiole is slight-
ly grooved rather than angled or terete; the pistils and fruits
are short stipitate rather than sessile; the fruit beak is slender
and elongated with a minute tip rather than short and stout
with a broad tip; the seeds are scaly; and it blooms approxi-
mately three weeks later than A. racemosa (Ramsey 1997).
The underground portions of baneberry (Actaea pachy-
poda and A. rubra) occur as occasional adulterants of black
cohosh supplies. Fruiting plants of baneberry may be distin-
guished from black cohosh by their fleshy white or red poi-
sonous berries which contrast with the dry follicles of black
cohosh (Compton and others 1998; Ford 1997; Ramsey
1997). No information was available on how to distinguish
the underground portions of black cohosh and baneberry
from each other. According to one herb dealer, the roots of
baneberry are smaller than those of black cohosh and there-
fore are not often harvested by wildcrafters (Fletcher, per-
sonal communication to AHP; unreferenced). In the Pacific
Northwest, Actaea elata (syn. Cimicifuga elata) is collected
for medicinal use (Moore 1993). There is no published
information on chemical means of distinguishing the rhi-
zomes of any of the above species. However, work using
random amplified polymorphic DNA (RAPDs) to identify
plant taxa both at (Xu and others 2001) and below (Novy
and others 1994) the species level make it likely that such
DNA testing would be useful in the identification of Actaea
species. The work by Xu and others (2001) was able to dis-
tinguish black cohosh from other medicinal plant species
using RAPDs.
Various Asian species of Actaea are sold as Chinese
Cimicifuga, including sheng ma (A. cimicifuga syn.
Cimicifuga foetida), xing an sheng ma (A. dahurica syn. C.
dahurica), and da san ye sheng ma (A. heracleifolia syn. C.
heracleifolia; also known as guan sheng ma) (McGuffin and
others 2000). Guang dong sheng ma, a member of the
Serratula genus, is a common substitute for sheng ma in the
Asian market. While these species are generally not found as
adulterants of black cohosh, they are mentioned here due to
similarities in medicinal use and the increasing overlap of
the Asian and American herb markets.
Preparations
Whole and powdered dried herb, as well as hydroalcoholic
and dry extracts, are commercially available as singles and in
combination products. A number of black cohosh extracts are
marketed as yielding 2.5% triterpene glycosides calculated as
27-deoxyactein (correctly named 23-epi-26-deoxyactein, see
Constituents). Different manufacturers include varying num-
bers of compounds in this calculation. Therefore, this decla-
ration of contents is not sufficient for ensuring that all prod-
ucts are similarly characterized (see Analytical).
Fluid Extract (1:1):
1:1 g/mL prepared in 60% (V/V) ethanol*.
1:1 g/mL prepared in 71%-78% (V/V) alcohol (NF 1936).
Dry Extract (1:1):
1:1 g/mL prepared in 40% (V/V) isopropanol*.
Tincture (1:5):
1:5 g/mL prepared in 79%-85% (V/V) alcohol (NF 1936).
* Formulation based on the commercial product Remifemin® (Schaper
and Brümmer), delivering 20 mg of black cohosh per tablet or per 20
drops.
CONSTITUENTS
Triterpene Glycosides
Black cohosh contains at least 20 known cycloartane-type
triterpene glycosides. The major constituents are actein
(Corsano and others 1969; Linde 1964, 1967a, 1967b, 1968;
Radics and others 1975), 23-epi-26-deoxyactein* (Chen and
others 2002; Linde 1968) and cimiracemoside A** (Bedir
and Khan 2000; Shao and others 2000). Actein is a xyloside
of acetylacteol that has a 16,23:23,26:24,25-triepoxy side
chain. Xylosides and arabinosides of cimigenol, which is
16,23:16,24-diepoxy-9,19-cyclo-9β-lanostane-3,15,25-triol,
are also present (Bedir and Khan 2000; Corsano 1965;
Corsano and others 1965; Corsano and Piancatelli 1967;
Shao and others 2000). Cimicifugoside is a xyloside of
cimigenol and possesses a 7,8-didehydro-acetylacteol as its
aglycone (Corsano and Piancatelli 1967; Kusano and others
1977). Other cycloartane-type triterpene glycosides,
cimiracemosides E, G, and H, cimiaceroside A, and acetyl
shengmanol xyloside, have also been identified (Bedir and
Khan 2000; Shao and others 2000).
*This compound is incorrectly cited in the literature and on commercial
products as 27-deoxyactein. When the carbons in this compound are count-
ed according to the guidelines set by the International Union of Pure and
Applied Chemistry (IUPAC), its correct name is 23-epi-26-deoxyactein
(Chen and others 2002).
** Cimiracemoside A was originally identified by Bedir and Khan (2000).
This compound appears to be the same as the cimiracemoside F and dif-
ferent from the cimiracemoside A described in the work by Shao and oth-
ers (2000). Publication priority dictates that the version of cimiracemoside
A in Bedir and Khan (2000) be accepted.
Aromatic Acids
Ferulic acid, isoferulic acid, and acyl caffeic acid. The fol-
lowing five hydroxy cinnamic acid esters of fukiic acid and
piscidic acid were isolated from the aqueous ethanolic extract
of black cohosh: 2-E-caffeoylfukiic acid (fukinolic acid), 2-E-
feruloylfukiic acid (cimicifugic acid A), 2-E-isoferuloylfukiic
acid (cimicifugic acid B), 2-E-feruloylpiscidic acid (cimi-
cifugic acid E), and 2-E-isoferuloylpiscidic acid (cimicifugic
acid F) (Hagels and others 2000; Kruse and others 1999).
Flavonoids
Three flavonoids, biochanin A, formononetin, and
kaempferol, have been reported to occur in black cohosh
rhizome but have subsequently not been detected. The pres-
ence of biochanin A was reported by McCoy and Kelly
(1996) but was not found by Hagels and others (2000).
Kaempferol was isolated by Schmitz (1993, cited in Hagels
and others 2000) but was later found only in the aerial por-
tions of the plant, not in the rhizome and roots (Hagels and
others 2000). Formononetin was reported to be present by
Jarry and others (1985) and Wagner and Bladt (1996).
However, five recent studies have failed to detect it in crude
material or preparations (Fabricant and others 2001; Hagels
and others 2000; Kennelly and others 2001; McCoy and
Kelly 1996; Struck and others 1997). The presence of these
three compounds has been considered to be clinically rele-
vant due to their potential phytoestrogen activity. It appears
clear that formononetin is not present in black cohosh. The
absence or presence of biochanin A and kaempferol require
further confirmation.
Other Constituents
Tannins, resins, fatty acids (oleic, linoleic, linolenic,
palmitic), starch, and sugars (Beuscher 1996; Harnischfeger
and Stolze 1980; List and Hörhammer 1973).
American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002 9

Figure 7 Primary constituents of black cohosh
A N A LYT I C A L
The thin layer chromatography (TLC/HPTLC) method
presented provides a triterpene glycoside and organic acid
fingerprint of black cohosh developed by CAMAG
(Muttenz, Switzerland). The high performance liquid chro-
matography (HPLC) method presented utilizes an evapora-
tive light scattering detector (ELSD) and was initially vali-
dated by the Methods Validation Program (MVP) of the
Institute for Nutraceutical Advancement (INA). Its primary
purpose is for the quantitation of triterpene glycosides in
black cohosh root raw material and extract. The method was
subjected to further validation by one American Herbal
Pharmacopoeia™ collaborating laboratory. This validation
work has provided additional information that must be con-
sidered by individual laboratories and product marketers
when analyzing black cohosh or evaluating products.
10 American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002
Discussions of these issues are included below.
As noted in the Constituents section above, the nomen-
clature of a number of compounds in black cohosh have
been cited in the literature inconsistently. Some of these
inconsistencies were reflected in the original INA method
and are pointed out below. More importantly, in the original
method total triterpene glycoside content was calculated
based on response factors that were relative to 23-epi-26-
deoxyactein (27-deoxyactein). This was done due to the gen-
eral lack of availability of the reference standards and for
ease of calculation. More reference standards were included
in the additional validation work and it was determined that
the response factors are specific to each compound and need
to be quantified individually. Additionally, retention times
are not reliable for determining peak identity because they
may vary due to the complexity of the matrix and the nature
of chromatography. The use of known reference standards
or alternative methods of chemical identification, such as
mass spectroscopy, should be employed for peak identifica-
tion. As presented herein, the method is applicable for
ensuring batch-to-batch consistency of a product. It should
only be used to quantify triterpene glycosides in sample
matrices against known reference standards and individually
calculated response factors analyzed under the same chro-
matographic conditions. The INA has revised their method
according to this new information.
High Performance Thin Layer
Chromatography (HPTLC) for the
Identification of Black Cohosh
1) Analysis of Triterpene Glycosides
Sample Preparation
Place 0.5 g of powdered black cohosh rhizome in a round-
bottom flask, add 5 mL methanol, sonicate for 10 minutes,
then filter through filter paper. Wash the filter 4 times with
1 mL methanol. Place the combined filtrates into a 10-mL
volumetric flask and adjust to volume with methanol.
Transfer 1 mL of the solution into a small sample vial. This
is the test solution.
Standard Preparation
Dissolve 2.5 mg of actein in 10 mL of ethanol and water
(6:4). Dissolve 1 mg of 23-epi-26-deoxyactein in 10 mL of
methanol. These are the standard solutions.
Reagent Preparation
Anisaldehyde-sulfuric acid reagent: 5 mL of 98% H2SO4 are
carefully added to 95 mL of an ice-cooled mixture of 340 mL
methanol, 40 mL acetic acid, and 2 mL anisaldehyde.
Note: This reagent is colorless and should be stored in the refrigerator. If a
color develops the reagent must be discarded.
Chromatographic Conditions
Stationary Phase:
HPTLC plates 10 x 10 or 20 x 10 cm silica gel 60 F254
(Merck or equivalent).
Mobile Phase:
Ethyl formate:toluene:formic acid (30:50:20).
Sample Application: Results:
2 µL of the test and standard solutions are applied each Compare to the chromatograms provided.
as an 8-mm band with 4 mm distance between bands. Note: The chromatograms were developed on HPTLC plates which allow
Application position should be 8 mm from the lower for better separation, sharper zones, reduced development times, and
require less solvent consumption than standard TLC plates. The method
edge of the plate. can also be run with standard TLC plates adjusting the sample volume as
Development: needed.
10 x 10 or 20 x 10 Twin Trough chamber (CAMAG or
equivalent), pre-saturation for 10 minutes (with filter
paper), 5 or 10 mL, respectively, developing solvent per
trough. Developing distance 70 mm from the lower
edge of the plate. Dry plate in a stream of warm air.
Detection:
Immerse plate in the reagent for one second, dry in a
stream of cold air. Heat plate at 105 ˚C for one minute.
Examine plate under white light.
Results:
Compare to the chromatograms provided.
2) Analysis of Organic Acids
Sample Preparation
Place 0.5 g of powdered black cohosh rhizome in a round-
bottom flask, add 5 mL of ethanol and water (1:1), sonicate
for 10 minutes, then filter through filter paper. Wash the fil-
ter 4 times with 1 mL ethanol (95%) and water (1:1). Place
the combined filtrates into a 10-mL volumetric flask and
adjust to volume with ethanol and water (1:1) and mix well.
Transfer 1 mL of the solution into a small sample vial. This
Figure 8 Anisaldehyde-sulfuric acid reagent, white light
is the test solution.
Standard Preparation Figure 8 HPTLC chromatogram of triterpene glycosides in black
Dissolve 0.5 mg of caffeic acid in 10 mL of methanol. This cohosh (Actaea racemosa)
is the standard solution. Lane 1: Wildcrafted black cohosh rhizome.
Reagent Preparation Lane 2: Actein.
Natural Products Reagent (NP Reagent): Dissolve 0.5 g Lane 3: 23-epi-26-deoxyactein.
diphenylboric acid aminoethylester in 100 mL methanol.
Discussion of Chromatogram:
Chromatographic Conditions 8) Anisaldehyde-sulfuric acid reagent, white light: The standards
Stationary Phase: actein (Lane 2) and 23-epi-26-deoxyactein (Lane 3) show violet
HPTLC plates 10 x 10 or 20 x 10 cm silica gel 60 F254 bands at Rf = 0.41 and 0.38, respectively. Black cohosh rhizome
(Merck or equivalent). (Lane 1) shows several violet bands in the middle of the chro-
Mobile Phase: matogram and some yellow-brown bands near the start line. There
Ethyl formate:toluene:formic acid (30:50:20). are two bands corresponding in color and Rf to actein and 23-epi-
Sample Application: 26-deoxyactein.
2 µL of the test and standard solutions are applied each
as an 8-mm band with 4 mm distance between bands.
Application position should be 8 mm from the lower
edge of the plate.
Development:
10 x 10 or 20 x 10 Twin Trough chamber (CAMAG or
equivalent), pre-saturation for 10 minutes (with filter
paper), 5 or 10 mL, respectively, developing solvent per
trough. Developing distance 70 mm from the lower
edge of the plate. Dry plate in a stream of warm air.
Detection:
a) UV 254 nm.
b) NP reagent: The dried plate is sprayed with NP
reagent and examined under UV 366 nm.

American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002 11

Figure 9 Anisaldehyde-sulfuric acid reagent, white light
Figure 9 HPTLC chromatogram of triterpene glycosides in various
samples of black cohosh (Actaea racemosa), yellow cohosh
(Actaea podocarpa syn. Cimicifuga americana), and Chinese
species of Actaea and Serratula
Lane 1: Chinese Guang Dong sheng ma rhizome
(Serratula sp.).
Lane 2: Wildcrafted black cohosh rhizome, sample A.
Lane 3: Chinese sheng ma rhizome (Actaea sp.).
Lane 4: Wildcrafted yellow cohosh rhizome.
Lane 5: Wildcrafted black cohosh rhizome, sample B.
Lane 6: Actein.
Lane 7: 23-epi-26-deoxyactein.
Discussion of Chromatogram:
9) Anisaldehyde-sulfuric acid reagent, white light: The standards
actein (Lane 6) and 23-epi-26-deoxyactein (Lane 7) show violet
bands at Rf = 0.41 and 0.38, respectively. These appear in the black
cohosh samples in Lanes 2 and 5, with an additional violet band
directly above the Rf of actein. Chinese sheng ma (Lane 3) shows a
weak band at the Rf of actein and an additional violet band directly
above it with no band at the position of 23-epi-26-deoxyactein.
Yellow cohosh (Lane 4) shows a violet band at the Rf of 23-epi-26-
deoxyactein and three additional violet bands below it, with no band
at the position of actein. Chinese Guang Dong sheng ma (Lane 1)
shows neither standard. Samples in Lanes 1, 2, 4, and 5 all have two
to three yellow-green bands at and just above the start line.
12 American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002
Figure 10 Anisaldehyde-sulfuric acid reagent, white light
Figure 10 HPTLC chromatogram of triterpene glycosides in black
cohosh (Actaea racemosa) raw material and commercial products
Lane 1: Wildcrafted black cohosh rhizome.
Lane 2: Actein.
Lane 3: 23-epi-26-deoxyactein.
Lane 4: Combination black cohosh rhizome dry extract and pow-
dered rhizome product.
Lane 5: Black cohosh rhizome dry extract.
Discussion of Chromatogram:
10) Anisaldehyde-sulfuric acid reagent, white light: The standards
actein (Lane 2) and 23-epi-26-deoxyactein (Lane 3) show violet
bands at Rf = 0.41 and 0.38, respectively. These appear in the black
cohosh sample in Lane 1 and in the two commercial preparations in
Lanes 4 and 5. In all samples, two green bands can be observed in
the lower Rf region above the start line and one or two violet bands
above the bands of the reference standards. The chromatogram
demonstrates that the two preparations (Lanes 4 and 5) contain the
same compounds as the raw material (Lane 1), but in differing con-
centrations.
 Figure 12b NP reagent, UV 366 nm

Figures 12a-b HPTLC chromatograms of plant acids in various

Figure 11a UV 254 nm Figure 11b NP reagent, UV 366 nm
Figures 11a-b HPTLC chromatograms of plant acids in black
cohosh (Actaea racemosa)
Lane 1: Wildcrafted black cohosh rhizome.
Lane 2: Caffeic acid.
Discussion of Chromatograms:
11a) UV 254 nm: The standard caffeic acid (Lane 2) gives a weak
dark band at Rf = 0.41. Black cohosh rhizome (Lane 1) shows a weak
band corresponding in color and Rf to caffeic acid, as well as a
weak band at Rf = 0.47 and two other bands near the start line at Rf
= 0.21 and 0.09.
11b) NP reagent, UV 366 nm: The standard caffeic acid (Lane 2)
shows a sharp fluorescent blue band at Rf = 0.41. Black cohosh rhi-
zome (Lane 1) shows several bands, most of them with blue fluo-
rescence. One of the bands corresponds in color and Rf to caffeic
acid. It also shows a green band at Rf = 0.26 and blue bands at Rf =
0.22, 0.12, and 0.09.
samples of black cohosh (Actaea racemosa), yellow cohosh
(Actaea podocarpa syn. Cimicifuga americana), and Chinese
species of Actaea and Serratula
Lane 1: Chinese Guang Dong sheng ma rhizome (Serratula sp.).
Lane 2: Wildcrafted black cohosh rhizome, sample A.
Lane 3: Chinese sheng ma rhizome (Actaea sp.).
Lane 4: Wildcrafted yellow cohosh rhizome.
Lane 5: Wildcrafted black cohosh rhizome, sample B.
Lane 6: Caffeic acid.
Discussion of Chromatograms:
12a) UV 254 nm: The standard caffeic acid (Lane 6) is barely visible
in this chromatogram at Rf = 0.41. A band at the same Rf as caffeic
acid is in both black cohosh samples (Lanes 2 and 5). The other
species show either no band (Lane 1) or only very weak bands
(Lanes 3 and 4). In the Chinese Guang Dong sheng ma (Lane 1), only
a single band is visible in the lower Rf region. Characteristic bands
are seen in the black cohosh samples (Lane 5 and weaker on Lane
2). At least six bands are visible in the black cohosh sample on Lane
5. Additional bands are seen in the middle Rf region of the yellow
cohosh sample (Lane 4).

12b) NP reagent, UV 366 nm: The standard caffeic acid (Lane 6)

shows a sharp fluorescent blue band at Rf = 0.41 which appears in
the black cohosh samples (Lanes 2 and 5) but not in any of the other
species (Lanes 1, 3, 4). Chinese Guang Dong sheng ma (Lane 1),
Chinese sheng ma (Lane 3), and both black cohosh samples (Lanes 2
and 5) have a fluorescent blue band at the start position. Chinese
sheng ma and yellow cohosh (Lanes 3 and 4) have characteristic flu-
orescent blue bands near Rf = 0.2, with weaker blue bands below
these. Both black cohosh samples (Lanes 2 and 5) have a character-
istic fluorescent blue band above the start position, with several
weaker bands above these.

Figure 12a UV 254 nm

American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002 13

 Discussion of Chromatograms:
13a) UV 254 nm: The standard caffeic acid (Lane 2) shows a weak
dark band at Rf = 0.41. At least six bands, one corresponding to caf-
feic acid and one above it, are visible in the black cohosh rhizome
sample (Lane 1). The two black cohosh preparations (Lanes 3 and 4)
display a similar profile including the presence of caffeic acid and
several bands with poor separation in the lower Rf region. Two of
the bands in the lower Rf region are sharper in the raw material
(Lane 1) compared to the preparations (Lanes 3 and 4), indicating a
higher concentration of compounds in the raw material.

13b) NP reagent, UV 366 nm: The standard caffeic acid (Lane 2)

shows a sharp fluorescent blue band at Rf = 0.41, which also
appears in all of the samples (Lanes 1 and 3-4) along with an addi-
tional weak blue band above it. Two of the bands in the lower Rf
region are sharper in the raw material (Lane 1) compared to the
preparations (Lanes 3 and 4), indicating a higher concentration of
compounds in the raw material.

High Performance Liquid Chromatography

(HPLC) for the Determination of Triterpene
Figure 13a UV 254 nm Glycosides
Reagents
Water, acetonitrile, methanol: HPLC grade
Formic acid: 98%
Ethanol: denatured HPLC grade
Sample Preparation
a) Raw material (rhizome and roots): Accurately weigh 1.0
g (± 0.01 g) of ground plant material and place into a 50-mL
centrifuge tube. Add exactly 40 mL of 50:50 (V/V)
ethanol:water to the tube and shake on an orbital or wrist
action shaker (or equivalent) for 24 hours at room tempera-
ture. Filter, place into an HPLC vial, and cap.
b) Extract: Accurately weigh 300 mg (± 0.01 mg) of pow-
dered extract and place into a 10-mL volumetric flask. Add
approximately 7 mL of methanol and sonicate for 30 min-
utes with frequent shaking. Cool to room temperature,
dilute to volume with methanol, and mix well. Filter, place
into an HPLC vial, and cap.
Standard Preparation
Accurately weigh 5 mg (± 0.01 mg) of 23-epi-26-deoxyactein
(“27 deoxyactein”, available from Addipharma, Hamburg,
Germany and Chromadex Inc, Laguna Hills, CA) and place
into a 10-mL volumetric flask. Add approximately 7 mL of
Figure 13b NP reagent, UV 366 nm methanol and sonicate until completely dissolved. Cool to
room temperature, dilute to volume with methanol, and mix
Figures 13a-b HPTLC chromatograms of plant acids in black well. This is the 500 µg/mL stock standard. Dilute the stock
cohosh (Actaea racemosa) raw material and commercial products standard with methanol to create a minimum of a 4-point
standard calibration curve that includes the stock standard.
Lane 1: Wildcrafted black cohosh rhizome.
Suggested standard dilutions include 1:25, 1:10, and 2:10;
Lane 2: Caffeic acid.
further dilutions may be made for additional data points.
Lane 3: Combination black cohosh rhizome dry extract and pow-
The AOAC International recommends a minimum of six
dered rhizome product.
data points for accurately determining the linear response of
Lane 4: Black cohosh rhizome dry extract.
a single analyte (Weirmont 1985).
Note: Refrigerate all reference standards.

14 American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002

Linearity Range: Detection:**
Prepare a calibration curve with the origin ignored using Richard Scientific/Seder Sedex-75 ELSD
the natural log of peak area versus the natural log of con- (or equivalent)
centration (µg/mL). Perform linear regression analysis on Gas pressure: 2.3 bar
the data. The correlation coefficient must be ≥ 0.995. Temperature: 50 ˚C
Note: Because ELSDs are inherently non-linear, correlation coefficients Gain: 7
may be achieved by plotting peak area versus concentration (µg/mL) and Alltech 5000 ELSD:
fitting to a quadratic equation.
Gas Flow: 1.78 standard liters per minute
Chromatographic Conditions Gas Pressure: 48 psi
Column: Drift Tube Temperature: 40 ˚C
Phenomenex Prodigy ODS (3), 5 µm, 4.6 x 250 mm Low Temperature Adapter: 40 ˚C
or equivalent*. Analog Output: No attenuation
Column Temperature: Injection Volume:
Ambient (27 ± 2 ˚ C). 20 µL.
Mobile Phase: * Also validated using YMC J’ sphere ODS-M80, 4 µm, 4.6 x 250 mm.
Gradient: acetonitrile: 0.1% formic acid. ** Both detectors were used in the validation process.
Minutes % Acetonitrile % Formic Acid Peak Identification:
0 30 70 Peak Triterpene Relative
30 40 60 Number Glycoside Retention Time
60 60 40
1. Cimiracemoside F* 0.551-0.596
70 30 70
2. Epi-actein 0.770-0.820
Flow Rate:
3. Unknown 0.807-0.878
1.0 mL/minute.
4. Unknown 0.861-0.954
5. 26-deoxycimifigoside and

Figure 14 HPLC chromatogram of the triterpene glycosides in black cohosh (Actaea racemosa)*
* The names of the peaks follow the nomenclature provided by the original INA method and some are now out-dated. For correct nomenclature, see Analytical, Peak Identification.

American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002 15

 cimiracemoside A* 0.901-0.966 THERAPEUTICS
6. Actein 0.938-0.982
7. 27-deoxyactein* 1.000 Pharmacokinetics
8. Acetyl shengmanol xyloside 1.01-1.04 Pharmacokinetic data on black cohosh are not available.
9. Cimiracemoside C and E 1.06-1.17 Work is underway, however, to quantify the in vitro move-
10. Cimicifugoside 1.15-1.24 ment of isolated actein, deoxyactein, and cimiracemoside
Note: These were the retention times determined in the original INA valida- across caco-2 cell monolayers, a model of the human intesti-
tion. Differences in chromatography and detector parameters, such as a vari- nal mucosa. Preliminary results indicate that the com-
ance in ELSD gas pressure and temperature, will affect retention times.
pounds show a linear transport across the monolayer (Khan
* The original nomenclature used by INA was maintained.
Cimiracemoside F is actually cimiracemoside A as determined by Bedir and and others 2001).
Khan (2001). The identity of the cimiracemoside A listed at peak 5 has not
been definitively determined. The 27-deoxyactein cited is more accurately Pharmacodynamics and Clinical Efficacy
known as 23-epi-26-deoxyactein (Chen and others 2001). Care must be
taken in ascertaining the accurate identity of reference standards purchased. Traditionally, black cohosh has been used for aching mus-
cles and joints, neuralgias, rheumatoid arthritis, dysmenor-
Calculation: rhea, amenorrhea, to prepare for labor (partus preparator),
Measuring the areas under the identified triterpene glyco- and as an aid in relieving pain after birth (Felter 1922; Felter
side peaks, calculate the concentration of the triterpene gly- and Lloyd 1898; King 1855; Scudder 1903). In recent years,
cosides using the following equation: black cohosh has increasingly been recommended for use
in the treatment of the physical and psychological symptoms
of menopause (climacteric complaints) and dysmenorrhea.
Concentration (µg/mL) = exp ln (peak area) – intercept
slope The European literature divides physical menopausal com-
plaints into “neurovegetative” symptoms, including hot
ln peak area = the natural log of the area under the peak flashes, cardiac complaints, fatigue, vertigo, and outbreaks
of interest of sweating, and “somatic” symptoms, including muscle
intercept = the intercept from the linear fit of the cal- pain and spasm, joint pain, urinary incontinence, vaginal
ibration curve dryness, and atrophy of the vaginal epithelium. However,
slope = slope from the linear fit of the calibration various authors group symptoms differently, even when
curve referring to the same assessment scales (eg Kupperman
Note: While this calculation uses the natural log (ln), HPLC chromatog- Menopause Index). The terms used in the individual stud-
raphy software uses the base 10 log. Since the natural log is related to the ies have been retained. Psychological symptoms of
base 10 log by the equation ln / base 10 log = 2.303, the common factor menopause include depression, anxiety, nervousness, irri-
2.303 cancels out and the two expressions are equivalent. This can be used
for automated calibration. tability, forgetfulness, sleep disturbances, and depressed
libido.
Quantitative Standards The decline of estrogen and progesterone levels that
Foreign Organic Matter: accompanies menopause is responsible for many climac-
Not to exceed 2% m/m, determined on 100-500 g dried teric symptoms. During the normal reproductive cycle the
root spread out in a thin layer (BHP 1996). relatively high amounts of estrogen that are present result in
Stem Bases: a relatively low level of luteinizing hormone (LH) and folli-
Not to exceed 5% (BHP 1996). cle-stimulating hormone (FSH). A result of this is a prolifer-
Total Ash: ation of the vaginal and uterine epithelium and mainte-
Not to exceed 10%, determined on 1 g of powdered nance of bone density. Problems that may accompany
dried root evenly distributed in a crucible (BHP 1996). decreased levels of estrogen during and after menopause
Acid-insoluble Ash: include hot flashes, mood swings, sleep disturbances, bone
Not to exceed 4%, calculated with reference to 100 g of loss, vaginal atrophy, and a decline in libido.
dried root (BHP 1996). The exact mechanism by which black cohosh elicits its
Water-soluble Extractive: effects on menopausal symptoms has not been elucidated.
Not less than 10% (BHP 1996)*. While some have proposed that its effectiveness is mediated
* Determined on 5 g of powdered dried root macerated with 100 mL chlo-
by an inhibitory effect on the hypothalamus (Einer-Jensen
roform water (2.5 mL chloroform mixed with 900 mL water and diluted with and others 1996) or an effect on neurotransmitters (Löhning
water to 1000 mL) for 24 hours shaking frequently the first 6 hours. Let stand and others 1999; Löhning and Winterhoff 2000; Seidlová-
18 hours. Filter rapidly, evaporate 20 mL of filtrate to dryness in a tared, flat-
bottom, shallow dish at 105 ˚C to constant weight. Calculate the percentage
Wuttke and Wuttke 2000), others have suggested that it has
of water-soluble extractive with reference to the dry herb (BP 1993). a direct estrogenic effect. These latter researchers suggest
that black cohosh contains phytoestrogens, estrogen-like
compounds found in plants (Jarry and others 1999; Kruse
and others 1999; Seidlová-Wuttke and Wuttke 2000; Wuttke
and others 2000). To date, no known phytoestrogens have
been unequivocally identified in black cohosh (see
Constituents). Kruse and others (1999), however, reported

16 American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002

an estrogenic effect of the caffeic acid derivative fukinolic
acid isolated from black cohosh (see Hormonal and Central
Nervous System Effects). An estrogenic activity of black
cohosh is supported by some preclinical and clinical trials
and not by others. Some of the variation in preclinical
results may be attributable to differences in the black
cohosh product used, though this is untested. In the clinical
trials, almost all of which used the same product, it appears
that the variation in results may have begun to be resolved
based upon a broader understanding of the diversity of estro-
gen receptors (see Barnes 1998) and the hypothetical selec-
tive binding of compounds in black cohosh to some of these
receptors and not to others.
There are at least two classes of estrogen receptors:
alpha receptors (ERα) and beta receptors (ERβ). The ERα
are concentrated in the reproductive organs, the pituitary,
and the kidneys, while the ERβ are found mainly in the
brain, bone, vasculature, and prostate. Estrogenic effects
mediated by the ERα receptors include the suppression of
LH and FSH, as well as the proliferation of the vaginal and
uterine epithelium. Estrogenic effects mediated by the ERβ
receptors include the prevention of bone loss. Some
researchers have suggested that black cohosh may primarily
affect the ERβ found in the bone and vasculature, rather
than the ERα found in the pituitary and reproductive
organs (Jarry and others 1999; Seidlová-Wuttke and others
2000; Wuttke and others 2000). Such selectivity in phytoe-
strogens has been documented before (Kuiper and others
1998) and has caused some researchers to refer to phytoe-
strogens as selective estrogen receptor modulators
(phytoSERMs) (Jarry and others 1999). In addition, phytoe-
strogens may act variously as estrogen agonists or antago-
nists, depending upon dose and to which receptor type they
bind. The results of preclinical research addressing these
hypotheses, however, are mixed.
Of theoretical importance in this controversy is the
safety of black cohosh in women with estrogen-sensitive
conditions, such as breast cancer. As the medical use of hor-
mone therapies has increased over the years, the dangers of
long-term treatment with estrogen have become more obvi-
ous. In the 1950s and 1960s, estrogen replacement became
the main treatment for menopause. Not until many years
later were the rising rates of endometrial cancer tied direct-
ly to estrogen replacement therapy. Hormone replacement
therapy (HRT), a combination of estrogen and progestin,
was developed to counteract the dangerous effect of treat-
ment by estrogens alone. There is evidence, however, that
HRT, particularly at high doses and in long-term treatment,
may be linked to higher rates of cancer as well, particularly
breast cancer (Beral and others 1997; Dupont and Page
1991; Henrich 1992; Schairer and others 2000; Steinberg
and others 1991). Along with the possible dangers for a
healthy woman, HRT is also contraindicated for many
women with specific health conditions. These include
breast cancer, endometrial cancer, malignant melanoma,
unexplained bleeding, liver disease, gallbladder disease,
edema, severe diabetes mellitus, endometriosis, venous
thrombosis, thrombophlebitis, pancreatitis, and uterine
fibroids (Grady and others 1995). The association of such
risks with HRT underscores the value of identifying alterna-
tive, non-hormonal therapies. More work needs to be done to
determine whether black cohosh has estrogenic effects, and if
so, on which tissues. Long-term studies are lacking. If black
cohosh extract is estrogenic and competes with estradiol more
strongly at ERβ than ERα receptors, it may elicit many of the
beneficial effects of estrogen without the accompanying risks
and hence be of great benefit as a substitute for HRT.
However, in pharmaceutical research, no risk-free SERM has
yet been identified.
Most pharmacological research has focused on the use of
black cohosh for menopausal symptoms. When evaluating
the data from the studies presented, it should be noted that a
placebo effect is common in studies of menopausal symp-
toms. To date, two placebo-controlled studies investigating
the use of black cohosh extract in menopausal women have
found a large placebo effect (Jacobson and others 2001; Stoll
1987). It is therefore extremely important that clinical studies
are double-blind and placebo-controlled, especially when
they involve self-reported symptom endpoints. Most of the
studies conducted to date do not meet these criteria, creating
the possibility of misleading positive effects following treat-
ment with black cohosh extract.
Effects on Menopausal and Premenstrual
Symptoms
Human Clinical Studies
Of the studies available on menopausal symptoms, two have
been randomized, double-blind, and placebo-controlled
(Jacobson and others 2001; Stoll 1987). One of these
addressed treatment-induced menopausal symptoms in breast
cancer survivors (Jacobson and others 2001). An additional
study was open-label and placebo-controlled (Földes 1959),
while another was double-blind, randomized, and Good
Clinical Practice (GCP)-compliant (Liske and others 2000).
One older case series investigated the effect of black cohosh
on premenstrual symptoms (Görlich 1962), while two looked
at effects on dysmenorrhea and menstrual irregularity
(Görlich 1962; Heizer 1960).
Most clinical research on black cohosh has been done
using the commercial preparation Remifemin® (Schaper and
Brümmer, Germany). Remifemin® comes in liquid (ethanol
extract, 60% by volume) and tablet form (isopropanol extract,
40% by volume). Earlier studies employed a previous formu-
lation of Remifemin® at dosages reported to be equivalent to
48-140 mg of dried herb daily (Boblitz and others 2000),
though the individual studies do not provide full characteri-
zation of the product used. The current recommended ther-
apeutic dosage of the liquid is 20 drops twice daily and that of
the tablet is one tablet twice daily. Both dosages of the current
preparation correspond to 40 mg of dried herb daily. A recent
study reported that both the previous and current formula-
tions have equivalent clinical efficacy at their respective
dosages, supporting the lower dosage recommended for the
current formulation (Liske and others 2000). One of the
recent clinical studies uses the black cohosh extract
Klimadynon®/Menofem® (58% by volume, Bionorica AG
American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002 17
Germany), administered at two capsules daily, a dosage
equivalent to 40 mg dried herb daily. This product contains
the black cohosh extract BNO 1055 (Bionorica AG) which
is used in several of the preclinical studies. Many of the clin-
ical studies compare the effects of black cohosh extract with
standard therapeutic dosages of estrogen.
There have been many standard scales used by black
cohosh researchers to assess the severity of menopausal dis-
orders. These include the Kupperman Menopause (KM)
Index (outdated, although still occasionally used), the
Clinician’s Global Impression scale (CGI), the Profile of
Mood States scale (POMS), the Hamilton Anxiety scale
(HAM-A), and the Self-assessment Depression scale (SDS).
The KM Index lists both psychological and neurovegetative
symptoms of menopause which patients are asked to self-
assess. A score lower than 15 indicates that treatment was
successful. The CGI scale, filled out by the physician, assess-
es the degree of severity of a disease before, during, and after
treatment. The POMS scale is a self-evaluation scale that
gives a quantitative measure to the influence of therapy on
mood state. The HAM-A scale, filled out by the physician,
measures both psychological and somatic anxiety, producing
a total score reflecting a patient’s degree of anxiety. The SDS
scale is sometimes used in conjunction with the HAM-A and
is filled out by the patient. It includes 20 depression criteria
measured by frequency and is useful in quantifying depres-
sive states.
In order to test possible alternatives to long-term estro-
gen therapy, Stoll (1987) performed a randomized, double-
blind, placebo-controlled study investigating the effects of
conjugated estrogens and black cohosh extract on
menopausal symptoms in 80 women (ages 46-58 years).
Twenty-nine patients received 0.625 mg of conjugated estro-
gen, 26 received black cohosh extract (Remifemin®, 4
tablets, each containing 2 mg of extract), and 20 were given
a placebo, each daily for 12 weeks. Outcome measures were
the KM Index, the HAM-A scale, and the vaginal maturity
index (VMI, a measure of estrogenic effects on the vaginal
epithelium). Physical and psychological symptoms were test-
ed every four weeks and the VMI was measured before and
after treatment. The conjugated estrogens showed no differ-
ence compared to placebo although they were administered
at a standard dose used in estrogen supplementation thera-
py. After 12 weeks, the KM Index among patients treated
with Remifemin® had dropped below 15 (P < 0.001, com-
pared to placebo). On the HAM-A scale, scores in the
Remifemin® group also dropped dramatically compared to
those in the other groups (P < 0.001). At the end of treat-
ment, only patients in the Remifemin® group showed a sig-
nificant increase in the number of estrogenized cells of the
vaginal epithelium (P < 0.01). Minor adverse events were
reported by 12 (46%) patients in the Remifemin® group,
including headache, weight problems, mastalgia, a stimulant
effect, heaviness of the legs, and an increase in symptoms
existing prior to treatment. In those receiving conjugated
estrogens, one patient reported weight problems and anoth-
er tachycardia. In the placebo group, two women had strong
adverse events, including headache and weight problems,
18 American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002
resulting in withdrawal from treatment; another woman
complained of headaches but continued treatment.
The effectiveness of black cohosh in treating hot flashes
in breast cancer survivors has recently been studied in a ran-
domized, double-blind, placebo-controlled trial (Jacobson
and others 2001). Black cohosh extract (Remifemin®, 1
tablet twice daily for 60 days, equivalent to 40 mg daily of
dried herb; n = 42) or placebo (n = 43) was administered to
85 women. Fifty-nine of the women were concurrently using
the estrogen antagonist tamoxifen (n = 29 in the black
cohosh group; n = 30 in the placebo group). Patients
assessed the intensity of their hot flashes (mild, moderate, or
severe) for the three days prior to treatment, on days 27-30,
and again on days 57-60. Additional outcome measures used
to assess overall health and well-being included a Visual
Analogue scale (VAS) and an unspecified menopausal symp-
tom index using a Likert scale, both of which were scored by
patients before and after treatment. Serum levels of FSH and
LH were also monitored in selected patients (FSH: n = 16 in
black cohosh group, n = 17 in placebo group; LH: n = 9 in
both groups). Over the study period, the median number
and intensity of hot flashes decreased by approximately 27%
in both the black cohosh and placebo groups. No significant
difference between groups was observed even after adjusting
for differences in tamoxifen usage, indicating that black
cohosh was no more effective than placebo in the treatment
of hot flashes in this study. Neither the VAS nor the
menopausal symptom index found a significant effect of
black cohosh compared to placebo, except with respect to
the symptom of sweating, which showed a significantly
greater improvement in the black cohosh group (P = 0.04).
No significant changes in serum FSH and LH levels were
recorded. Small sample sizes and the confounding effect of
tamoxifen, known to cause hot flashes, may have influenced
these results. The authors stated that the short duration of
their study might have limited its findings (Jacobson and oth-
ers 2001).
In this study, adverse events occurred in a total of 13
patients. Ten “minor” events included constipation, weight
gain, endometrial hyperplasia, another unspecified endome-
trial condition necessitating dilatation and curettage, indi-
gestion, and vaginal bleeding in the black cohosh-tamoxifen
group; arrhythmia and cramping in the black cohosh-no
tamoxifen group; and swollen finger and abdominal rash in
the placebo-tamoxifen group. Endometrial hyperplasia is a
risk factor for endometrial cancer. Two serious adverse
events, an endometrial condition necessitating a hysterecto-
my and breast cancer recurrence, were reported in the black
cohosh-tamoxifen treatment group. Tamoxifen is known to
cause endometrial abnormalities. The patient with recurrent
breast cancer had an unreported increase in carcinoembry-
onic antigen before entering the study. An appendectomy
was reported in the placebo-tamoxifen group. According to
the researchers, none of the adverse events appeared to be
related to treatment.
Wuttke and others recently performed a randomised,
double-blind, placebo-controlled, GCP-compliant study to
investigate the clinical effects of black cohosh extract
(Klimadynon®/Menofem®, equivalent to 40 mg dried herb
daily for 12 weeks) on menopausal complaints, hormone
levels (estradiol, LH, FSH), and bone metabolism in 80
postmenopausal women (Gorkow, Marz, and Christoffel,
personal communication to AHP; unreferenced).
Preliminary unpublished findings indicate that there was a
significant reduction in the frequency of waking during
night in the black cohosh group compared to placebo (P =
0.04). The placebo response rate exceeded 50% in some cli-
macteric complaints. No change in estradiol levels and a
decrease in FSH levels were observed in the black cohosh
group. In addition, there was a significant increase in a
marker for osteoblast activity (P = 0.01) and a significant
increase in two bone turnover indices in the black cohosh
group (P ≤ 0.007), indicating a protective effect of black
cohosh on bone tissue. Further evaluation of these data is
needed following their publication.
Földes (1959) conducted a placebo-controlled, open-
label, crossover study on 41 women complaining of
menopausal symptoms. The women were first given an
unidentified placebo for an unspecified period of time.
Black cohosh extract was then administered at one tablet tid
(Remifemin® , equivalency unknown) until it became effec-
tive (at approximately one week), at which point the dosage
was reduced by an unspecified amount. Symptoms were
alleviated more frequently during the treatment phase
(improvement, 31 patients; no improvement, 10) compared
to the placebo phase (improvement, 4 patients; no improve-
ment, 37). Three patients complained of stomach pains
while taking the extract.
In a recent randomized, double-blind, GCP-compliant
study, 152 women (ages 42-60 years) with menopausal
symptoms were treated for three or six months with two dif-
ferent doses of black cohosh extract (Remifemin®) equiva-
lent to either 39 mg (n = 74, three months; n = 57, six
months) or 127 mg (n = 75, three months; n = 59, six
months) dried herb daily (Liske and others 2000).
Treatment effect was assessed using the KM Index, SDS,
CGI, and by measuring serum levels of LH, FSH, sex hor-
mone-binding globulin (SHBG), prolactin, and 17-β-estra-
diol, as well as changes in vaginal cytological parameters
(degree of proliferation of the vaginal epithelium [Schmitt]
and karyopyknotic and eosinophil indices). Differences
between dosage groups at various time points were analyzed
statistically, but statistical analyses of changes in outcome
measures over the treatment period were not presented.
Both doses showed similar effects in all outcome measures.
A reduction in the KM Index was apparent after two weeks,
three months, and six months; 70%-72% and 90% of the
patients were considered to be “responders” at three and six
months, respectively (KM Index < 15). Results for the SDS
were similar, with a reduction from scores indicative of mild
depression to normal scores (median 36-37). After three and
six months of treatment, global efficacy (CGI = 3.1) was
good to very good in 80% and 90%, respectively, of the
patients in each group. After six months of treatment, glob-
al tolerability (CGI = 3.2) was good to very good in 100% of
the patients. No changes in serum hormone levels or vagi-
nal cytology were reported. The authors interpreted these
results as confirming the clinical equivalency of the two
dosage forms for relieving menopausal symptoms and as evi-
dence that the black cohosh product used does not have an
estrogenic effect on hormone levels and vaginal tissue.
When the subgroup of premenopausal women was ana-
lyzed, the higher dose was correlated with a significantly
greater reduction in the KM Index compared to the low
dose (P < 0.032). During the first three months, 19 unspec-
ified mild to moderate adverse events were reported, 12 at
the higher dose and 7 at the lower dose. These affected the
gastrointestinal tract (5), the central nervous system (5), the
breasts or female genitals (5), or remained unclassified (4).
One patient experienced metrorrhagia, though a biopsy
showed an inactive endometrium.
In 1988, Lehmann-Willenbrock and Riedel conducted
an open, randomized, comparative study of 60 women
under the age of 40 who had undergone hysterectomies, had
at least one ovary intact, and complained of menopausal
symptoms. The patients were randomly divided into four
groups (n = 15) and treated daily over six months with either
estriol (Ovestin®, 1 mg), conjugated estrogens (Presomen®,
1.25 mg), estrogen-gestagen sequential therapy
(Trisequens®, one tablet containing 2 mg estradiol and 1 mg
norethindrone acetate), or black cohosh extract
(Remifemin® four tablets daily, each containing 2 mg of
extract). Efficacy was measured by a modified KM Index
that included trophic disorders of the genitals. In addition,
LH and FSH levels were monitored. Patients were tested at
baseline and after 4, 8, 12, and 24 weeks of therapy. The
modified KM Index decreased significantly (P < 0.01) in all
four groups with no significant differences between groups.
Hormonal levels were not significantly affected in any of the
treatment groups. After six months of therapy, most patients
were symptom-free. Adverse events were not discussed.
In an uncontrolled, open, prospective study by Pethö
(1987), 50 women who had previously received at least 1-2
Gynodian® Depot injections (a combination of estradiol
and prasteron, an androgen) for menopausal symptoms were
tested to see if black cohosh extract (Remifemin®, two
tablets twice daily for six months, equivalency unknown)
could adequately replace hormone therapy. Hormone injec-
tions were to be given only if the black cohosh preparation
alone was not satisfactory at controlling the symptoms.
Patients were checked by a physician after 2, 4, and 6
months of treatment. Outcome measures were the number
of hormone injections needed, the KM Index, and the sub-
jective statements of the patients regarding their physical
and psychological symptoms. Over the six-month testing
period, 28 (56%) of the 50 patients requested no supple-
mental hormones, 21 (42%) requested a single injection,
and 1 (2%) patient requested two injections. The KM Index
decreased significantly from a mean of 17.6 to 9.2 over the
course of the study (P < 0.001). Neurovegetative symptoms
were rated by the patients as “moderately pronounced”
before and “mild” afterwards. Psychological and somatic
symptoms were mild at the beginning and had almost dis-
appeared after treatment. The physician rated the therapeu-
American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002 19
tic success as excellent (all-round improvement) for 21
patients, good (evident change for the better) for 20, and
light (further treatment advised) for 9 patients. No adverse
events occurred during treatment.
In 1985, Warnecke conducted a randomized, open,
comparative study to test the effectiveness of black cohosh
extract on the physical and psychological symptoms associ-
ated with menopause. The effect of black cohosh was com-
pared with hormonal treatment and a psychotropic drug
(diazepam). Sixty patients (ages 45-60) with menopausal
symptoms were allocated to three (n = 20) treatment groups.
One group received 40 drops of black cohosh extract twice
daily (Remifemin®, equivalency unknown), another
received 0.625 mg daily of conjugated estrogens, and the
third received 2 mg of diazepam daily. These treatments
were administered over 12 weeks, and patients were tested
before start of therapy and after 2, 4, and 12 weeks of treat-
ment. Outcome measures included a modified KM Index,
HAM-A, SDS, and CGI. Estrogenic stimulatory effects on
the vaginal epithelium were measured using the karyopy-
knosis and eosinophil indices. At the end of therapy, using
all four symptom scales, a “highly significant” or “good”
effect of treatment on menopausal symptoms was seen
equally in all three treatment groups (P-values not given,
though statistical tests were performed). After the fourth
week, vaginal cytology indices revealed a “trend” towards
estrogenic stimulation in both the black cohosh extract and
estrogen groups. Adverse events were not discussed.
In the early to mid 1980s, two other uncontrolled open
studies were conducted on patients with menopausal symp-
toms (Daiber 1983, n = 36; Vorberg 1984, n = 50). In both
studies, patients were treated with 40 drops of black cohosh
extract twice daily for 12 weeks (Remifemin® , equivalency
unknown). The results were measured using the KM Index,
the CGI scale, and in the Vorberg study only, the POMS
scale. According to all three scales, all symptoms improved
significantly in the 12 weeks of treatment (P < 0.001). The
Daiber study did not discuss adverse events. In the Vorberg
study, four women reported mild gastrointestinal distur-
bances in the early stages of therapy, although this did not
interfere with treatment.
Stolze (1982) conducted a multicenter, observational,
cohort study on 704 women suffering from climacteric com-
plaints. The study investigated the effectiveness of black
cohosh extract (Remifemin®, 40 drops twice daily for six to
eight weeks, equivalency unknown) on neurovegetative and
psychological menopausal symptoms. Symptoms were eval-
uated after 4, 6, and 8 weeks of treatment, both by the physi-
cian and the patient. Of the 629 evaluable patients, 75%
were symptom-free or showed improvement in symptoms
after 4 weeks, while 80% showed an improvement in symp-
toms after 6 and 8 weeks of treatment. Among the total
patient population, 93% reported no adverse events, while
7% noted short-lived unspecified ones (mostly slight stom-
ach complaints) that did not interfere with treatment.
Three recent observational studies investigated the use
of black cohosh extract for alleviating menopausal symp-
toms. Nesselhut and Liske (1999) found that a high dose of
20 American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002
black cohosh extract (Remifemin® tablets, equivalent to 136
mg dried herb daily) given daily for approximately three
months to 28 postmenopausal women had a good to very
good effect on 10 neurovegetative symptoms in 80% of the
patients and did not alter endometrial thickness, vaginal cell
status, or serum hormone levels (LH, FSH, prolactin, estra-
diol). No adverse events were observed during treatment.
Mielnik (1997) found that significant clinical improvement
(KM Index < 10) occurred after one month in 26 (76%) of
34 menopausal women given an uncharacterized black
cohosh extract (4 mg daily for six months). All 34 women
had a KM Index > 20 at the beginning of treatment. Four of
the women showed no improvement and four dropped out
of the study and began HRT. No adverse events were
observed. In the study of Georgiev and Iordanova (1997),
subjective symptoms evaluated using the KM Index and
HAM-A scale were found to improve in 45 (90%) of 50 post-
menopausal women following administration of black
cohosh extract (characterization and dosage undisclosed) for
three months. The VMI was increased in 40% of the
patients, while endometrial thickness did not change in any
patients. Adverse events were not discussed.
In an older case series, Görlich (1962) reported on the
effects of black cohosh extract (Remifemin®) in 258 women
with various gynecological complaints including primary
and secondary amenorrhea, polymenorrhea, menorrhagia,
metrorrhagia, dysmenorrhea, premenstrual symptoms, ovu-
lation pain, menopausal disorders, and “uterine hypopla-
sia”, as well as pregnancy. Evaluation criteria and dosage
were largely unspecified. Overall, the extract alleviated the
majority of menstrual irregularities unless they were caused
by other primary disorders (eg hypo- and hyperthyroidism,
hypertension). Patients with premenstrual symptoms were
given one tablet or 20 drops of the extract three times daily
(tid) for 12-14 days before menstruation. In 41 of the 49 sub-
jects suffering from premenstrual symptoms, symptoms
including mood swings, impaired performance, circulatory
disorders, and headaches were eliminated. In 24 cases of
dysmenorrhea, 16 patients given 10 drops or 1/2 tablet of
extract tid (between days 10-20 of cycle) were better able to
tolerate cramping. Görlich also noticed a significant
improvement in ovulatory pain following treatment with the
extract. Symptoms disappeared in 35 (85%) of the 41
women treated for menopausal symptoms. In 18 cases of
morning sickness, black cohosh extract controlled vomiting;
antiemetic drugs were used in only two cases. The success-
ful treatment of threatened miscarriage was reported in six
women with a history of miscarriage. They took black
cohosh extract (25 drops hourly until bleeding disappeared
followed by 20 drops four times daily for four to six weeks)
and reported that no miscarriages occurred during treat-
ment. Adverse events were not discussed.
In two additional older case series, black cohosh extract
(Remifemin®) was given to women with natural or surgical-
ly-induced menopausal symptoms. In a study of Heizer
(1960), among 66 menopausal women with intact uteri, 31
(47%) showed a positive response to the extract (30 drops or
1-2 tablets tid for 2-18 months, equivalency unknown),
Table 3 Summary of results from clinical studies on the treatment of menopausal complaints1 with black cohosh extract
Reference Study Product, daily dosage, Outcome Results
design, n2 and treatment duration measure
Stoll 1987 DBRPCT Remifemin®;4 tablets, KMI, HAM-A Alleviation of symptoms (KMI, P < 0.001, com-
n = 26 each containing 2 mg pared to placebo; HAM-A, P < 0.001, compared
extract3; 12 weeks to placebo and estrogen groups).

Jacobson and DBRPCT Remifemin®; 2 tablets, Patient self- No change in median number and intensity of hot
others 2001 n = 42 equivalent to 40 mg assessment; flashes; no change compared to placebo except
dried herb4; 60 days VAS, MSS for symptom of sweating (VAS, MSS, P = 0.04).

Földes 1959 Open, PCTX, Remifemin®, 3 tablets3; Patient self- Greater alleviation of symptoms in black cohosh
n = 41 unspecified assessment group compared to placebo.

Liske and others DBR, GCP Remifemin®, equivalent KMI, SDS, Alleviation of symptoms in both groups (KMI <
2000 n = 57-59 to 39 and 127 mg dried CGI 15 in 90% women; SDS reduced to median of
herb; 6 months 36-37; global efficacy good to very good in 90%
patients). Results similar after 3 months.

Lehman- R, Open Remifemin®, 4 tablets, KMI Alleviation of symptoms in the black cohosh,
Willenbrock and n = 15 each containing 2 mg ovestin, presomen, and trisequens groups (P < 0.01).
Riedel 1988 extract3; 6 months

Pethö 1987 Open Remifemin®, 4 tablets3; 6 KMI, patient Alleviation of symptoms (P < 0.001). Self-
n = 50 months self- assessment indicated that symptoms decreased
assessment from moderate or mild to mild or almost gone.

Warnecke 1985 R, Open Remifemin®, 80 drops3; KMI, HAM-A, Alleviation of symptoms in the black cohosh,
n = 20 12 weeks SDS, CGI conjugated estrogen, and diazepam groups.

Daiber 1983 Open Remifemin®, 80 drops3; KMI, CGI Alleviation of symptoms (P < 0.001).
n = 36 12 weeks

Vorberg 1984 Open Remifemin®, 80 drops3; KMI, CGI, Alleviation of symptoms (P < 0.001).
n = 50 12 weeks POMS

Stolze 1982 Open Remifemin®, 80 drops3; Physician and Alleviation of symptoms in 80% of patients after
n = 629 6-8 weeks patient self- 6 and 8 weeks.
assessment

Nesselhut and Open Remifemin® tablets, unspecified Good to very good alleviation of 10 menopausal
Liske 1999 n = 28 equivalent to 136 mg symptoms in 80% of patients.
dried herb; 3 months

Mielnik 1997 Open Uncharacterized black KMI Alleviation of symptoms in 76% of patients
n = 34 cohosh extract, 4 mg after 1 month (KMI < 10).
daily; 6 months

Georgiev and Open Uncharacterized black KMI, HAM-A Alleviation of symptoms in 90% of patients.
Iordanova 1997 n = 50 cohosh extract, dose
unspecified; 3 months

Görlich 1962 Case series Remifemin® tablets, unspecified Alleviation of symptoms in 85% of patients.
n = 41 dose/duration unspecified

Heizer 1960 Case series Remifemin®, 90 drops unspecified Alleviation of symptoms in 47% of patients with
n = 66 or 3-6 tablets3; 2-18 months intact uteri and in 35% with hysterectomies.

Kesselkaul 1957 Case series Remifemin®, 60 drops3; unspecified Alleviation of symptoms in 95% of patients.
n = 63 2 weeks

Key: DBRPCT = double-blind, randomized, placebo-controlled trial; DBR = double-blind, randomized; R = randomized; PCT = placebo-controlled; X = cross over;
GCP = Good Clinical Practice compliant; CGI = Clinician’s Global Impression scale; HAM-A = Hamilton Anxiety scale; KMI = Kupperman Menopause Index;
MSS = unspecified menopausal index using the Likert scale; POMS = Profile of Mood States scale; SDS = Self-Assessment Depression scale; VAS = Visual Analogue scale.
1 Menopausal symptoms were natural, surgically induced by hysterectomy (Lehman-Willenbrock and Reidel 1988; Heizer 1960), or induced by breast cancer treatment

(Jacobson and others 2001).

2 Sample size in the black cohosh treatment group.

3 The dried herb equivalents were in the range of 48-140 mg daily (Boblitz and others 2000).

4 Some patients in each group took tamoxifen concurrently.

American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002 21

while 35 (53%) required hormone therapy in addition to the
extract. Among 23 women who had had hysterectomies, 15
(65%) required hormone therapy. In this same study, black
cohosh extract was not effective in treating menstrual irreg-
ularities (n = 16) or pain (n = 5). Adverse events were not dis-
cussed, though general tolerability was reported to be good.
Kesselkaul (1957) found that black cohosh extract (20 drops
tid, equivalency unknown) alleviated menopausal symptoms
after two weeks of treatment in 60 (95%) patients. Three
patients complained of gastrointestinal complaints during
treatment.
In addition to the clinical studies presented above, two
studies have investigated the effects of a combination prod-
uct containing extracts of black cohosh and St. John’s wort
(Hypericum perforatum) on psychological and neurovegeta-
tive symptoms associated with menopause. The product
used, Remifemin® Plus (Schaper and Brümmer), was stan-
dardized to 1 mg triterpene glycosides calculated as 27-
deoxyactein (correctly named 23-epi-26-deoxyactein) and
0.25 mg total hypericin per coated tablet. One trial used a
randomized, double-blind, placebo-controlled design to
study the efficacy of the preparation in the treatment of pro-
nounced psychological symptoms associated with
menopause such as anxiety, lack of motivation, depressed
mood, nervousness, and irritability (Boblitz and others
1999). For six weeks, 87 women were administered
Remifemin® Plus (1 tablet twice daily) and 92 patients were
given placebo. Treatment efficacy was evaluated using the
KM Index. The decrease in the KM Index following active
treatment was significantly greater than that in the placebo
group (P < 0.001). Six minor adverse events were reported in
five patients in each treatment group without differences in
frequency or severity.
The other trial was an observational cohort study of 911
pre-, peri-, and postmenopausal women (Liske and others
1997). Patients received either two (n = 619, 68%) or four (n
= 292, 32%) tablets daily for 12 weeks. Treatment efficacy
was evaluated using the CGI scale and patient self-assess-
ment of seven psychovegetative symptoms. Patients were
evaluated prior to treatment and at 4 and 12 weeks. Over the
12-week period, significant improvement (P < 0.001) in hot
flashes, depression, and insomnia was experienced by 77%,
75%, and 72%, respectively, in the 811 patients assessed on
all three dates. Change in CGI scale over the treatment peri-
od indicated that drug efficacy was good or very good in 41%
and 40% of the patients, respectively. A stronger effect was
observed at the higher dosage. The medication was tolerated
very well by 99% of the patients. Adverse events that were
likely to be correlated with therapy included mild nausea
and moderate diarrhea; adverse events possibly correlated
with the medication included dry skin, itching skin, and dry
tongue.
Summary
In summary, clinical evidence provides support for the use
of black cohosh extract in the treatment of menopausal
symptoms (Table 3). One double-blind placebo-controlled
study found a significant improvement of menopausal symp-
22 American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002
toms in patients treated with black cohosh extract compared
to placebo (Stoll 1987), as did one open placebo-controlled
study (Földes 1959). However, one other double-blind,
placebo-controlled study found no effect of black cohosh
compared to placebo, except with respect to the symptom of
sweating (Jacobson and others 2001). This study, however,
was on breast cancer survivors and the effects of black cohosh
may have been confounded with those of tamoxifen, an anti-
estrogenic compound. The other studies that were not place-
bo-controlled support the effectiveness of black cohosh in
treating menopausal symptoms, though the possibility of a
placebo effect in these studies cannot be ruled out and the
assessment criteria of the older studies cannot be relied
upon.
Few studies have investigated the efficacy of black
cohosh extract in treating conditions other than menopausal
complaints, and those that exist are uncontrolled case series.
The case series by Görlich (1962) reported efficacy of black
cohosh in treating premenstrual symptoms. Of the two case
series looking at the effect of black cohosh on menstrual
irregularities and dysmenorrhea, one reported positive effects
(Görlich 1962), while the other showed no effect (Heizer
1960). Görlich (1962) reported a beneficial effect of black
cohosh in the treatment of morning sickness and threatened
miscarriage, though data are insufficient to accurately assess
efficacy.
Hormonal and Central Nervous System Effects
Human Clinical Studies
Conflicting evidence exists with regard to the hormonal
effects of black cohosh extract. In a 1991 placebo-controlled
study, Düker and others tested the ability of black cohosh
extracts to reduce gonadotropin secretion in 110 menopausal
women with climacteric symptoms. Half the patients were
treated with black cohosh extract (Remifemin®, two tablets
daily, each containing 2 mg of dried extract, yielding 8 mg of
native extract daily), while the other half received a placebo.
A blood sample was drawn after two months of treatment and
LH and FSH levels were tested with a radioimmunoassay. In
the black cohosh patients, mean LH levels were reported to
be significantly less than in the placebo group (P < 0.05).
Mean FSH levels remained similar in both groups.
According to the researchers, these results indicate that black
cohosh may have an estrogenic effect. Because baseline lev-
els of hormones were not measured, it is not known whether
the groups were comparable at the beginning of the study,
making the value of the results questionable.
Seven of the human clinical studies on the effect of
black cohosh extract on menopausal symptoms (presented in
more detail above) also investigated the extract’s estrogenic
effects (Georgiev and Iordanova 1997; Jacobson and others
2001; Lehmann-Willenbrock and Riedel 1988; Liske and
others 2000; Nesselhut and Liske 1999; Stoll 1987;
Warnecke 1985; see Table 4). The extract had no effect on
hormone levels in the four studies investigating this parame-
ter (Jacobson and others 2001; Lehmann-Willenbrock and
Riedel 1988; Liske and others 2000; Nesselhut and Liske
1999). This is in contrast to the study of Düker and others
(1991) which found a decrease in LH levels. Among the five
studies looking at black cohosh treatment effects on vaginal
and/or uterine tissue, three found positive proliferative
effects on vaginal tissue (Stoll 1987; Georgiev and Iordanova
1997: Warnecke 1985) and two did not (Liske and others
2000; Nesselhut and Liske 1999), while two found no pro-
liferative effects on the endometrium (Georgiev and
Iordanova 1997; Nesselhut and Liske 1999). Unfortunately,
all of the studies to date have been for 6 months or less,
whereas at least 12 months is necessary to reveal an estro-
genic effect on vaginal or uterine tissue.
Animal and In Vitro Studies
Several animal and in vitro studies have investigated the
potential estrogenic activity of black cohosh extract by mea-
suring its effects on serum hormone level, various tissues and
cell lines, receptor binding, and gene regulation. Other stud-
ies have tested black cohosh’s effects on neurotransmitters.
The findings of this research are mixed. A number of the
studies reported reflect preliminary findings from work pub-
lished as abstracts, mostly in conference proceedings.
Because removal of ovaries results in cessation of estro-
gen production, ovariectomized (ovx) rats are used as an ani-
mal model for menopause. As estrogen production ceases in
women, the serum concentration of FSH and LH greatly
increases, while secretion of prolactin by the pituitary
decreases. If estrogen or estrogen-like substances are intro-
duced exogenously, LH and FSH secretion is reduced while
prolactin secretion is stimulated. The administration of
estrogen or estrogen-agonistic substances to ovx rats is
expected to cause similar estrogenic effects. Many of the ani-
mal studies use an increase in uterine weight as an indicator
of an estrogenic effect of black cohosh extract. Other
researchers have pointed out that uterine weight is a poor
indicator of unopposed estrogenic endometrial effects such
as hyperplasia (Johnson and others 2001).
Effects on Hormone Levels
In a vehicle-controlled experiment designed to test for estro-
genic effects of black cohosh extract, Jarry and
Harnischfeger (1985) studied the effect of the extract on LH
secretion in ovx rats. They used black cohosh liquid extract
(Remifemin®) evaporated or lyophilized to dryness and
reconstituted in a solution of water and 1,2 propanediol
(70/30 V/V) to a concentration of 40 mg dried extract per
mL injection vehicle. The extract or the vehicle alone was
administered twice daily at 0.3 mL/animal ip for 1, 3, or 14
days. Each treatment group consisted of eight rats. After
treatment, the rats were sacrificed and serum levels of the
pituitary hormones LH, FSH, and prolactin were measured
in trunk blood using radioimmunoassay. Only under the
three-day treatment period did rats treated with the extract
have significantly lower LH levels than vehicle-treated rats
(P < 0.01). Prolactin and FSH levels were not affected under
any treatment regime. The dichloromethane fraction of the
extract (= 27 mg dry residue ip per animal), but not the
ethanol or water fractions, had LH-suppressive effects. The
non-hydrolyzed (glycosilated) dichloromethane fraction was
more effective than the hydrolyzed (aglycone) fraction.
Vaginal cytology did not change following treatment with
the dichloromethane fraction. The black cohosh methano-
lic extract was further fractionated by the same research
group in an effort to identify the active compound(s) (Jarry
and others 1985). The water phase was inactive. Three
active compounds were isolated from the chloroform phase,
including a compound thought to be formononetin, a
known phytoestrogen. The presence of formononetin in
black cohosh has since been disputed. Although this com-
pound did bind to estrogen-receptors, it did not have an LH-
suppressive effect compared to the dichloromethane frac-
tion or vehicle.
Düker and others (1991) tested the ability of a lipophilic
black cohosh extract (8 mg extract daily) and its uncharac-
terized fractions to lower LH levels in ovx rats. All test sub-
stances were dissolved in a vehicle (miglyol). Mature ovx rats
received seven injections of either the extract, one of its eight
fractions, or the vehicle alone at 12-hour intervals over three
and one-half days. Three hours after the seventh injection,
the first of 10 blood samples was drawn, followed by the
other 9 at 20-minute intervals. The lipophilic extract showed
a strong suppressive effect on LH levels in the rats. Four of
the fractions showed significant LH-suppressive effects (P <
0.01, compared to vehicle). The researchers went on to test
the ability of the fractions to compete in vitro with 17-β-
estradiol and vehicle for estrogen receptor binding sites. Of
the four fractions that lowered LH levels in vivo, one showed
no receptor binding activity, while three showed activity
comparable to that of estradiol. Another fraction showed pos-
itive receptor binding but did not lower LH levels in vivo
under the dosage regime administered. Given as a single
injection, however, it did have an LH-lowering effect similar
to that of estradiol in vivo. The researchers suggest that this
fraction contains estrogenic compounds which may be
metabolized so quickly that only a transient LH suppressive
effect is exerted. Thus the endocrine effect could be missed
in the chronic administration of the fraction, but not in the
acute administration.
In a dimethyl-benzanthracene (DMBA) animal model
(see Effects on Estrogen-sensitive Tumors and Cell Lines),
black cohosh extract (Remifemin®) po at 1x, 10x, and 100x
the human therapeutic dose showed no estrogen agonistic
effects on hormone levels (LH, FSH, prolactin)
(Freudenstein and others 2000).
Löhning and others (1999) measured the effect of black
cohosh extract (uncharacterized) on prolactin secretion in
pituitary cell cultures. They found that both basal and thy-
rotropin-releasing hormone (TRH)-stimulated prolactin
secretion was significantly reduced by dosages of 10 and 100
µg/mL. This effect was reversed by the dopamine (D2/D4)-
antagonist haloperidol, suggesting dopaminergic activity of
the extract.
Effects on Uterine, Vaginal, and Bone Tissue
A positive estrogenic effect of black cohosh extract on vagi-
nal or uterine tissue has been reported in four preclinical
studies. Using mice as a model, Liu and others (2001b)
reported an increase in uterine weight with increasing dose
American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002 23
of black cohosh extract (uncharacterized) (75, 150, 300
mg/kg ig for 14 days). Treatment with the extract also signif-
icantly prolonged the number of days of estrus (P < 0.05 at
the 300 mg/kg dose). The authors interpreted this as evi-
dence of an estrogenic effect. It should be noted that other
researchers have pointed out that uterine weight is a poor
indicator of unopposed estrogenic endometrial effects such
as hyperplasia (Johnson and others 2001).
In 1997, Eagon and others tested an extract of black
cohosh root (characterization and dose undisclosed) for
estrogenicity in ovx rats. The extract was added to a standard
liquid rat diet and administered for three weeks. Changes in
uterine tissue growth and uterine c-myc mRNA levels
(increased by estrogens) were tested. Hepatic estrogenic
response was also measured by testing for changes in serum
ceruloplasmin levels and liver ceruloplasmin mRNA. The
extract did have a positive effect on uterine tissue growth,
but did not effect a change in uterine c-myc mRNA levels.
While it did raise the serum ceruloplasmin level, it did not
affect the liver ceruloplasmin mRNA levels. These
researchers concluded that black cohosh root extract did
show signs of measurable estrogenic activity.
In the Allan-Doisy test, doses of 0.3 mL twice daily of
black cohosh extract (Remifemin®) induced estrus in eight
out of nine ovx rats; lower doses did not have this effect
(Földes 1959). This was taken as evidence of an estrogenic
effect. Twelve three-week-old female mice were given 0.2
mL of the extract for four days and were sacrificed on day 6.
Uterine weight was increased in the treatment group com-
pared to the controls. The results from this study were not
evaluated statistically.
Knüvener and others (2000) tested black cohosh
ethanolic extract (50%; 50-600 mg daily po for three days)
for estrogenic activity in ovx mice. Placebo controls received
water and positive controls received mestranol or 17-β-estra-
diol. Both positive controls induced estrus in the mice,
while black cohosh extract was ineffective. An estrogenic
effect on vaginal cytology was seen in the black cohosh
group. When co-administered, black cohosh extract (250
mg/kg) significantly antagonized the estrogenic effects of
mestranol.
In contrast to the findings of the above studies, three
other studies found no estrogenic effect of black cohosh
extract on vaginal or uterine tissues. Wuttke and others
(2000) tested the effect of black cohosh extract (BNO 1055)
on uterine tissue, bone loss, and liver and lipid metabolism.
Ovariectomized rats were treated with estradiol or BNO
1055 for six hours, seven days, or three months (dose and
route unspecified). Whereas estradiol caused tissue prolifer-
ation in the uterus, black cohosh extract did not. However,
the extract reportedly mimicked the effects of estradiol in
preventing and opposing the development of osteoporosis. It
also displayed beneficial effects on the liver and lipid metab-
olism. The authors suggested that the results support the
hypothesis that black cohosh acts as a SERM, since the
uterus contains predominantly ERα sites, while bone has a
high concentration of ERβ sites.
In a DMBA animal model (see Effects on Estrogen-sen-
24 American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002
sitive Tumors and Cell Lines), black cohosh extract
(Remifemin®) po at 1x, 10x, and 100x the human therapeu-
tic dose showed no estrogenic influence on histologically
analyzed uterine tissue (Freudenstein and others 2000).
Einer-Jensen and others (1996) similarly found no
estrogenic effect of a black cohosh dry extract (50% ethano-
lic extract) in immature female mice and ovx rats. The mice
(n = 215) were divided into groups of 10 and given 6, 60, or
600 mg/kg daily of the extract orally for 3 days. A placebo
control group received 1 mL/kg of suspension vehicle and a
positive control group received 0.4 mg/kg estradiolbenzoate
sc. Uterine weight was measured after sacrifice on day 4. In
the same study, 47 ovx rats were divided into groups of 12,
each receiving either 6, 60, or 600 mg/kg daily sc of the
extract for three days. Vaginal smears were taken on day 4.
There were no signs of uterotrophic or vaginotrophic effects
in either the mice or the rats.
Receptor Binding Effects
Following their in vivo study demonstrating the LH-sup-
pressive effects in ovx rats of black cohosh extract and its
fractions, Jarry and others (1985) tested the estrogen recep-
tor-binding effects of the various fractions. They found that
the dichloromethane (lipophilic) extract and various frac-
tions of the chloroform phase competed with radio-labelled
estrogen for binding sites on estrogen receptors isolated from
rat uteri. In a follow-up study, the same research group
(1999) found that the lipophilic fraction of black cohosh
extract (BNO 1055) had significant estrogen receptor bind-
ing activity, while the hydrophilic fraction did not. The in
vitro work of Düker and others (1991), presented above,
showed a positive estrogen receptor binding effect of some
of the fractions of the lipophilic extract of black cohosh. In
contrast to the above three studies, Liu and others (2001a)
found no estrogen receptor-binding activity of a black
cohosh extract.
Effects on Estrogen-regulated Genes
Jarry and others (1999) attempted to differentiate between
the potential ERα- and ERβ-binding effects of black cohosh
extract. They investigated the effects of black cohosh extract
(BNO 1055) on the bone, brain (both containing a pre-
dominance of ERβ), and uterine tissue (containing mostly
ERα) from ovx rats. Over a three-week period, the rats were
treated with 60 mg/rat sc or ip of the extract (a
dichloromethanol phase of the dried extract was used to
enrich lipophilic compounds) or 8 µg/rat of 17-β-estradiol;
both preparations were dissolved in 5% cremophor. A con-
trol group received only 5% cremophor. Following sacrifice,
the brains, uteri, and femoral arteries were removed from
the animals and assays investigating ERα- and β-regulated
gene activation were conducted. Both black cohosh extract
and estradiol reduced serum LH levels (P < 0.08 and P <
0.01, respectively, compared to controls) and activated estro-
gen-regulated genes in both brain and bone tissue (P < 0.05,
both treatment groups). However, only estradiol activated
estrogen-regulated genes in the uterus, causing an increase
in uterine weight (P < 0.01). The activity of the extract in
brain and bone tissue and not in uterine tissue suggests that
a compound in the extract, at the doses given, binds prefer-
entially to ERβ.
Seidlová-Wuttke and others (2000) performed another
study designed to differentiate between potential ERα and
ERβ effects of black cohosh extract. After administration of
estradiol (3.5 µg/rat for seven days or three months) or the
black cohosh extract (BNO 1055, 62.5 mg/rat daily for seven
days or three months, route unspecified), gene expression in
the uterus (ERα), bone, liver, and the aorta (ERβ) was
examined. While the black cohosh treatment mimicked the
effects of estradiol in the bone, liver, and aorta, it had no
effect in the uterus. The above results support the possibili-
ty that black cohosh may act as a SERM, selectively target-
ing ERβ.
Oketch-Rabah and others (2002) tested black cohosh
hexane, ethyl acetate, and water extracts (concentrations not
specified) for estrogenicity using several assays. None of the
extracts enhanced estrogen-inducible alkaline phosphatase
enzyme activity in Ishikawa cells. In addition, none of the
extracts modulated estrogen receptor function as evaluated
using the ERE luciferase reporter assay nor did they have a
regulatory effect on genes that are known to be regulated by
estradiol in estrogen receptor positive breast cancer cells
(ERα, PgR, pS2). In a study by Liu and others (2001a), black
cohosh methanolic extract did not stimulate progesterone
receptor mRNA or the estrogen-inducible gene presenelin-2
in S30 breast cancer cells or endometrial (Ishikawa) cells.
Effects on Estrogen-sensitive Tumors and Cell Lines
Freudenstein and others (2000) studied the effect of an iso-
propanolic extract of black cohosh (Remifemin®) on estro-
gen receptor-positive breast tumors in young female rats.
Five to nine weeks after experimental tumor induction with
DMBA, the ovaries of the rats were removed. Beginning at
day 10 after the operation, one group received the synthetic
estrogen mestranol (450 µg/kg daily), three groups received
black cohosh extract po (doses comparable to 1x, 10x, and
100x the human clinical dose), while the control group
received no treatment. After another seven weeks, the ani-
mals were sacrificed and tumor number and size were
recorded, plasma hormone levels were analyzed, and the
uterine tissue was examined. After ovariectomy, the tumors
regressed in all animals, presumably due to the lack of
endogenous estrogen production. Mestranol caused a new
increase in tumor size that was not found in either the black
cohosh or control groups. At death, no difference in tumor
size or number existed between the black cohosh and con-
trol groups.
Nesselhut and others (1993) found no cell-proliferative
effect of black cohosh in the breast cancer cell line MD-435.
The MCF-7 and T-47D human breast cancer cell lines are
characterized by estrogen-dependent cell proliferation.
Using MCF-7 cells and dilutions of black cohosh extract
(Remifemin®), Freudenstein and Bodinet (1999) found that
cell proliferation was “completely” and “significantly” inhib-
ited by dilutions of 10-3 (approximately 100 µg/mL) and 10-
6, respectively (statistical tests not reported). The cell-prolif-
erative effect of estradiol was antagonized by co-incubation
with the extract and the anti-estrogenic tumor-inhibiting
effect of tamoxifen was increased by co-incubation with the
extract. Zava and others (1998) found that incubation of T-
47D breast cancer cells with a 1/500 dilution of black cohosh
ethanolic extract (50%, 2:10 g/mL) had no effect on cell pro-
liferation (statistical tests not reported). Also using the T-47D
cell line and the same black cohosh extract, Dixon-Shanies
and Shaikh (1999) reported a 22% and 71% decrease in cell
growth by the extract at concentrations of 0.1 and 1.0, respec-
tively (P < 0.01). Oketch-Rabah and others (2002) found that
neither the hexane, ethyl acetate, nor water extracts of black
cohosh at concentrations of 0-20 µg/mL had any effect on
the growth of estrogen-sensitive breast cancer cells. As pre-
sented above, they also found that the extracts did not regu-
late estradiol-regulated genes found in ER-expressing breast
cancer tissue. As noted above, another study found that black
cohosh extract did not stimulate progesterone receptor
mRNA or the estrogen-inducible gene presenelin-2 in S30
breast cancer cells (Liu and others 2001a).
In contrast to such reports suggesting that black cohosh
extract does not have a cell proliferative effect on estrogen-
receptor-positive breast cancer cells, two other studies (Liu
and others 2001b; Löhning and others 1998) found a cell-
proliferative effect of the extract in MCF-7 cell lines. Liu
and others (2001b) found that, compared to a blank control,
both black cohosh extract and estradiol shortened the dou-
bling time of MCF-7 breast cancer cell growth. They also
noted a significant increase in estrogen receptors in the
MCF-7 cells compared to the control (P < 0.01). Löhning
and others (1998) found that the 50% or 96% ethanolic
extract of black cohosh at dosages of 0.1-10 µg/mL and
0.001-1 µg/mL, respectively, stimulated MCF-7 cell growth,
while a high dose (100 µg/mL) of the 50% extract did not.
The cell-proliferative effect of the extract was abolished in
the presence of the estrogen receptor antagonist IC 182,780.
Kruse and others (1999) isolated fukinolic acid, a caffe-
ic acid ester, from black cohosh rhizome and tested its estro-
genicity on MCF-7 cell proliferation. At doses of 5 x 10-7 and
5 x 10-8 M, fukinolic acid increased cell proliferation up to
119.7% ± 5.8 (P < 0.05) and 126.3% ± 5.1 (P < 0.001),
respectively; the effect at these doses was equivalent to that of
estradiol at 10-10 M. Higher doses (5 x 10-9 M) of fukinolic
acid were ineffective.
Central Nervous System Effects
In vivo and in vitro studies suggest that black cohosh extract
may have a dopaminergic effect. An acute dose (25-100
mg/kg po) given to mice was found to decrease body tem-
perature in a dose-dependent manner and prolonged keta-
mine-induced sleeping time (Löhning and others 1999).
The highest dose had an effect comparable to that of the D2-
agonist bromocriptine (5 mg/kg ip). These effects were like-
ly mediated by dopamine D2 receptors, since they were
blocked by pretreatment with sulpiride. Löhning and
Winterhoff (2000) went on, in a controlled study, to measure
neurotransmitter levels in the striatum, hippocampus, and
hypothalamus of mice after they were pretreated with black
cohosh extract for 21 days. In the striatum, both serotonin
American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002 25
Table 4 Summary of results from clinical studies on the effect of black cohosh extract on hormone levels and vaginal and endometrial cell
status in menopausal1 women
Reference Study Product and daily Treatment Estradiol3 FSH3 LH3 Vaginal cell Endometrial
design, n2 dosage duration proliferation3 thickness3
Stoll 1987 DBRPCT Remifemin®, 4 tablets 12 weeks _ _ _ !* _
n = 26 each containing 2 mg
extract4

Jacobson and DBRPCT Remifemin®, 2 tablets, 60 days _ " " _ _

others 2001 n = 42 equivalent to 40 mg
dried herb4, 5

Liske and others DBR, Remifemin®, 6 months " " " " _
2000 GCP equivalent to 39 mg
n = 57-59 dried herb

Remifemin®, equivalent " " " " _

to 127 mg dried herb

Lehman- R, Open Remifemin®, 4 tablets, 6 months _ " " _ _

Willenbrock and n = 15 each containing 2 mg
Riedel 1988 extract4

Warnecke 1985 R, Open Remifemin®, 80 drops4 _ _ _ ! _

n = 20

Nesselhut and Open Remifemin® tablets, 3 months " " " " "
Liske 1999 n = 28 equivalent to 136 mg
dried herb

Georgiev and Open Unidentified black 3 months _ _ _ ! (in 40% of "

Iordanova 1997 n = 50 cohosh extract, dose treated
unspecified women)

Düker and others PCT Remifemin®, 2 tablets, 2 months _ "5 #* 5 _ _

1991 n = 55 each containing 2 mg
extract4, 6

Key: DBRPCT = double-blind, randomized, placebo-controlled trial; DBR = double-blind, randomized; R = randomized; PCT = placebo-controlled; GCP = Good Clinical Practice
compliant; - = no data; ‚ #= decrease; ! = increase; " = no change; * = P < 0.05.
1 Menopausal symptoms were natural, surgically induced by hysterectomy (Lehman-Willenbrock and Reidel 1988), or induced by breast cancer treatment (Jacobson and others
2001).
2 Sample size in the black cohosh group.

3 Unless otherwise noted, results in placebo-controlled trials express differences in change over time of the parameter in the treatment group compared to placebo; in uncon-
trolled trials, results express change over time of the parameter between baseline and end of treatment.
4 The dried herb equivalents were in the range of 48-140 mg daily (Boblitz and others 2000).

5 Some patients in each group took tamoxifen concurrently.

6 The change in hormone levels reported in this study was based on a comparison between the black cohosh and placebo groups after two months of treatment; baseline hor-
mone levels were not measured.

26 American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002

and dopamine metabolism were significantly reduced in the
treatment group compared to the control group. The
authors suggest that such a non-estrogenic effect of black
cohosh on neurotransmitters may be responsible for the
botanical’s effectiveness in reducing the incidence of hot
flashes in women, a mechanism also suggested by Seidlová-
Wuttke and Wuttke (2000).
Such effects on dopamine and serotonin suggest a
monoamine oxidase inhibition (MAO) activity. Because
MAO inhibitors are used as antidepressants, Löhning and
Winterhoff (2000) studied black cohosh for an antidepres-
sant effect in female mice using the tail-suspension test. The
extract increased mobility time, suggesting an antidepres-
sant effect that the authors suggest may explain the use of
black cohosh in treating the psychological symptoms of
menopause.
Summary
In summary, more work is needed to clarify the mechanisms
of action of black cohosh. Based on the accumulated data,
it cannot be conclusively determined if black cohosh elicits
estrogenic activity. A number of studies report an estrogenic
effect while an almost equal number do not. Clinical data
regarding the potential estrogenic effects of black cohosh are
inconclusive. One of the five studies that measured the
effect of black cohosh on serum hormone levels found a sig-
nificant LH-suppressive effect (Düker and others 1991;
placebo-controlled) though that study suffered from an
inadequate experimental design. Of the six clinical studies
measuring the effects of black cohosh treatment on vaginal
cell status, only one found a significant increase in cell pro-
liferation (Stoll 1987; placebo-controlled), while two found
increases that were not analyzed statistically (Georgiev and
Iordanova 1997; Warnecke 1985; both open and uncon-
trolled). Two studies followed endometrial thickness as an
outcome measure and both found no effect of black cohosh
on this parameter, although statistical analyses were not pre-
sented (Georgiev and Iordanova 1997; Nesselhut and Liske
1999). Jacobsen and others (2001) reported endometrial
hyperplasia as an adverse event in one patient in the black
cohosh-tamoxifen treatment group and noted other
endometrial abnormalities in two other patients in the same
group (Jacobson, personal communication to AHP; unrefer-
enced). In making an overall evaluation of the clinical data
available on the estrogenic effects of black cohosh, it should
be noted that many of the studies might not have been of
sufficient duration to determine efficacy in some of the para-
meters reported. For example, the two studies reporting no
changes in endometrial thickness were of short duration
(three months) and are of little relevance in evaluating estro-
genic activity in this tissue, as a minimum of 12 months of
therapy is required before any such changes can be expect-
ed. Summarizing the present clinical data, a conclusive
determination regarding an estrogenic effect of black
cohosh cannot be made.
Preclinical studies have given mixed results with respect
to the estrogenic effects of black cohosh extract, perhaps in
part due to differences in the product used in research and
perhaps in part due to the selectivity of the tissues studied.
Such mixed results, combined with the difficulty in extrap-
olating from preclinical data to activity in human tissues,
make the interpretation of these findings problematic.
Three of four studies found an LH- or prolactin-suppressive
effect of black cohosh extract in animals (Düker and others
1991; Jarry and Harnischfeger 1985; Löhning and others
1999). Of the seven preclinical studies looking at the effect
of black cohosh extract on uterine or vaginal tissue, four
found positive estrogenic effects (Eagon and others 1997;
Földes 1959; Knüvener and others 2000; Liu and others
2001b) while three did not (Einer-Jensen and others 1996;
Freundenstein and others 2000; Wuttke and others 2000).
These data are difficult to evaluate given that it has been
pointed out that uterine weight is a poor surrogate for
endometrial effects including hyperplasia (Johnson and oth-
ers 2001).
Three estrogen receptor-binding studies (Düker and
others 1991; Jarry and others 1985, 1999) have shown that
black cohosh extract competes for binding with estradiol,
while one study had negative results (Liu and others 2001a).
Definitive data regarding the effect of black cohosh extract
on estrogen-regulated genes and estrogen-sensitive breast
cancer tumors and cell lines are lacking. While two studies
found that black cohosh did not regulate estrogen-regulated
genes found in breast or endometrial tissues (Liu and others
2001a; Oketch-Rabah and others 2002), two other studies
found that the extract regulated estrogen-sensitive genes in
some tissues but not in others (Jarry and others 1999;
Seidlová-Wuttke and others 2000). These latter studies,
along with a study by Wuttke and others (2000), found that
black cohosh extract may elicit an estrogenic activity with a
stronger affinity to tissues rich in ERβ sites, such as bone,
rather than tissues rich in ERα sites, such as the uterus,
lending support to the SERM hypothesis. Six of the eight
studies on breast cancer found no cell-proliferative effect of
black cohosh (Dixon-Shanies and Shaik 1999; Freudenstein
and Bodinet 1999; Freudenstein and others 2000; Nesselhut
and others 1993; Oketch-Rabah and others 2002; Zava and
others 1998). Another study found a dopaminergic effect of
black cohosh, suggesting that its use against hot flashes and
the psychological symptoms of menopause may be related
to effects on neurotransmitters rather than an estrogenic LH-
suppressive effect (Löhning and Winterhoff 2000).
Other Effects
Cardiovascular Effects
The resinous chloroform fraction of black cohosh extract
(1-10 mg/kg) had a dose-dependent hypotensive effect in
unanesthetized rabbits and urethanized cats. No such effect
was found in dogs or humans. In humans, black cohosh
extract was found to increase peripheral blood flow at doses
of 0.5 mg/kg (Genazzani and Sorrentino 1962). In an ex
vivo study using rat aortic strips, fukinolic acid caused a
vasorelaxant effect in strips experimentally contracted with
norepinephrine, while cimicifugic acids A, B, and E and
fukiic acid did not (Noguchi and others 1998).
American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002 27
Anti-inflammatory Effects
In an in vitro study by Löser and others (2000), fukinolic
acid was shown to be a strong inhibitor of neutrophil elas-
tase which may explain the anti-inflammatory activity his-
torically attributed to various species of Actaea (syn.
Cimicifuga), including black cohosh which was a primary
remedy for rheumatism.
Other Species of Actaea
Asian species of Actaea (A. cimicifuga [syn. A. foetida], A.
dahurica, and A. heracleifolia) have been used as analgesics,
anti-inflammatories, antipyretics, and anticonvulsants
(Yamahara and others 1985; Yen 1992), actions that are con-
sistent with the use of A. racemosa among herbalists.
Conclusion
There is evidence from double-blind placebo-controlled
clinical trials for a beneficial effect of black cohosh in the
treatment of menopausal complaints. Less well-designed tri-
als offer additional positive evidence; however, the possibil-
ity of a placebo effect occurring in the black cohosh treat-
ment groups in these studies cannot be ruled out. Evidence
in support of the use of black cohosh for premenstrual symp-
toms and dysmenorrhea is lacking from the scientific litera-
ture. Human, animal, and in vitro studies give mixed results
regarding the estrogenic effects of black cohosh extract.
Studies on the effects of black cohosh extract on vaginal or
endometrial tissue have been of too short a duration to rule
out the possibility of estrogenic stimulation of these tissues.
Therefore, long-term, double-blind, placebo-controlled
studies need to be conducted in order to determine whether
black cohosh possesses any of the same risks as pharmaceu-
tical HRT. Clinical data regarding other medicinal uses of
black cohosh are lacking.
Medical Indications Supported by Clinical
Trials
Black cohosh extract, equivalent in dosage and characteri-
zation to that shown to be effective in clinical trials, is indi-
cated for use in the treatment of menopausal complaints
including hot flashes, outbreaks of sweating, and anxiety.
Medical Indications Supported by Traditional
and Modern Experience
The traditional Eclectic literature reports on the use of black
cohosh as a mild stomach tonic, gastric bitter, and alterative
(White 1903) with a reported affinity for the nervous, mus-
culoskeletal, and especially female reproductive systems. A
summary of traditional indications includes: nervous disor-
ders such as chorea, epilepsy, myalgia, neuralgia, hysteria,
depression, nervousness and anxiety, and sciatica; cardiovas-
cular disorders such as arrhythmia and hypertension due to
vascular or nervous tension; various infectious diseases; and
gynecological disorders such as amenorrhea, dysmenorrhea,
leukorrhea, atony of the uterus, cramps during pregnancy,
premature labor, postpartum hemorrhage or pains, and
pelvic pain. Black cohosh was also used traditionally as a par-
tus preparator and for pain of the prostate and testes.
28 American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002
Nervous System and Musculoskeletal Indications
Some of the earliest recorded indications of black cohosh
among the Eclectics included rheumatic pain, nervous ten-
sion, and muscular tightness (Scudder 1903). It was consid-
ered particularly effective for nervous people with heavy-
feeling limbs and uterine cramps that radiated across the
pelvis and down the thighs (Harper-Shove 1952), syndromes
which the Eclectics referred to as “rheumatic neuralgia”.
Hysterical convulsions, chorea, epilepsy, and particularly
postpartum seizure were among the traditional indications
for black cohosh. The Physiomedicalist William Cook
(1869) recommended black cohosh for nervous excitation
and agitation suggesting that it be combined with lady’s slip-
per (Cypripedium spp.) and skullcap (Scutellaria lateriflora)
for neuralgic pain; with prickly ash bark (Xanthoxyllum sp.)
and poke berry (Phytolacca sp.) for rheumatism; and with
blue cohosh (Caulophyllum thalictroides) for hysteria and
general spasms. Finley Ellingwood (1919) reported black
cohosh to be specific for muscle aches and pains and for hys-
teria presenting a flushed face, restlessness, and excitement.
King recommended minute doses (1/4-1/2 drop) of the satu-
rated tincture in the ear or eye every two hours for pains of
neuralgic origin (Felter and Lloyd 1898). Modern practi-
tioners continue to use black cohosh for nervous conditions
associated with muscular pain, including fibromyalgia, and
for seizures and allaying spasmodic, irritable coughs.
However, its most widespread use as a nervine among
herbalists and naturopathic physicians has been for pre-
menstrual anxiety with muscle tension and headache and
hormone-related anxiety and depression, as may occur pre-
menstrually and perimenopausally.
Cardiovascular Indications
Black cohosh was used as a cardiotonic by Eclectic physi-
cians, specifically for cases of fatty degeneration of the heart,
rheumatic carditis, and pericarditis and was also used for
angina and cardiac arrhythmia due to excessive nervous
stimulation of the heart. William Cook (1869) recommend-
ed the rhizome for relaxing nervous stimulation of the heart
and lungs in cases of hypertension, asthma, and pertussis
and reported that black cohosh can be used to slow the pulse
and improve capillary circulation. Black cohosh is less com-
monly used in these ways at the present time and substanti-
ation for these indications are lacking.
Use in Infections
The Eclectics used black cohosh for serious infectious dis-
eases including pertussis, scarlet fever, smallpox, lung infec-
tions, and especially postpartum infections. It was indicated
for the acute onset of febrile illnesses, especially when asso-
ciated with chills and muscle aching (Ellingwood 1919).
Tincture of black cohosh, often combined with cramp bark
(Viburnum opulus), has also been employed for flu and per-
tussis in children by modern practitioners (Romm, personal
communication to AHP; unreferenced). In his Medical
Botany, Griffith (1847) reported black cohosh to promote
secretions of skin, kidney, and lungs.
Gynecological Indications
Uterine Indications
The Eclectics used black cohosh extensively for gynecolog-
ical problems including amenorrhea, dysmenorrhea, leuko-
rrhea, uterine cramps, prolapse of the uterus, and cervical
excoriation (Ellingwood 1919; Felter and Lloyd 1898; Jones
and Scudder 1858). King recommended a vaginal douche
of black cohosh and Geranium spp. infusion for cases of
leukorrhea, uterine prolapse, and vaginal laxity (King 1855).
He recommended a typical dose of black cohosh to be 1 tsp
of a mixture of 10 drops to 3.5 mL of “specific macrotys” (a
black cohosh product developed by Lloyd and of undis-
closed characterization) per 4 oz of water or 1.5-7.5 mL of
the fluid extract (1:1)*. To induce labor, King recommend-
ed dosing with 1/16 oz of the powdered rhizome in water or
1.5 mL of the tincture every 15-20 minutes until labor
begins (Felter and Lloyd 1898).
* It should be noted that 7.5 mL of a 1:1 fluid extract is equivalent to 7500
mg of black cohosh dried herb, a dose substantially higher than the 40-80
mg typically used in clinical trials. In general, the dosages of black cohosh
cited in the Eclectic medical literature and those used by modern herbal
practitioners are substantially higher than dosages used in clinical trials.
Black cohosh is thought to be a true amphoteric uterine
tonic, relaxing uterine tone when excessive and spastic, yet
increasing tone when lax and atonic. As such, black cohosh
has been used both to relax the uterus in order to halt pre-
mature labor or prevent miscarriage (Felter 1922) and to
promote the menses (emmenagogue) and facilitate labor
(partus preparator) (Culbreth 1917; Ellingwood 1919; Jones
and Scudder 1858). Black cohosh is said to be a “sedative
emmenagogue” that promotes blood flow when uterine ten-
sion, cramps and congestion are hindering flow, but will not
induce excessive flow when used to improve uterine tone.
Black cohosh was also considered specific for ovarian pain
(Felter 1891).
Indications in Pregnancy
The Eclectics recommended the use of black cohosh in late
pregnancy as a uterine tonic and partus preparator
(Ellingwood 1919; Felter 1891; Felter and Lloyd 1898;
Scudder 1903). King (1855) reported black cohosh to be a
partus accelerator in cases of stalled labor due to uterine
atony. Black cohosh is believed to act on the uterus increas-
ing muscle tone, but decreasing the pain of labor by pro-
moting more efficient, well-orchestrated contractions
(Ellingwood 1919). King (1855) considered black cohosh to
be of value in differentiating between false and true labor
pains with false labor pains dissipating and true labor pains
increasing upon its use. He also considered it the best and
safest agent for relieving after-pains, as did other Eclectics
(Bartholow 1882; Felter 1891). Cook (1869) reports black
cohosh to be indicated for rigidity of the cervical os during
labor. He also recommended black cohosh combined with
wake robin (Trillium sp.) and lady’s slipper for after-pains.
There was one report among the Eclectics of the “free
use” of black cohosh during pregnancy being correlated
with “premonitions of abortion”; the author considered
such cases “exceptions” (Cook 1869). Ellingwood (1919)
noted six cases in which the use of black cohosh during
labor was followed by severe uterine hemorrhage during
birth.
Today, black cohosh is used by midwives for leg cramps,
hypertension, and spasmodic cough during pregnancy, as a
partus preparator for women who have previously had diffi-
cult labors, and in cases of prolonged or delayed labor. In
these latter cases its relaxing effect on the uterus is thought
to allow for proper, coordinated uterine contractions. For
these purposes, black cohosh is often used in combination
with other herbs. Some midwives also use black cohosh in
threatened miscarriage with premature labor contractions
with or without bleeding and consider it a safer agent than
terbutaline (breathine). For this indication, it is often used
in combination with cramp bark (Viburnum opulus) and
wild yam (Dioscorea spp.) (2.5-5 mL up to three times daily
or 2.5 mL every 30 minutes with active presenting symp-
toms). This is continued for up to three days after symptoms
have subsided (Romm 2001).
Menopausal Indications
Based primarily on modern German research (see
Pharmacodynamics and Clinical Efficacy), many naturo-
pathic physicians and herbalists are now using black cohosh
to allay hot flashes, correct menopausal bleeding irregulari-
ties, sleep disturbances, and nervous complaints such as anx-
iety and depression (Hobbs 1998). It should be noted that
long-term use for the treatment of menopausal symptoms is
a new indication compared to the short-term use of black
cohosh employed traditionally by herbal practitioners.
Actions
Pharmacological: Mechanisms of action have not been
determined. Estrogenic agonism, antagonism, and no estro-
genic effects have been reported in clinical and preclinical
studies.
Traditional: antispasmodic, anxiolytic, emmenagogue
(when menstruation is inhibited due to uterine tension),
nervine, partus preparator, uterine relaxant, uterine tonic.
Substantiation for Structure and Function
Claims
Based on a review of the currently available data, substanti-
ation for the development of a structure and function claim
is lacking.
Dosages
Dried rhizome and root:
1 g up to three times daily (Osol and Farrar 1947).
Tincture (1:10):
0.4 mL daily (40%-60% alcohol V/V) (Blumenthal and
others 2000).
Fluid Extract (1:1):
20 drops twice daily (60% ethanol V/V; equivalent to 40
mg dried herb daily).*
* Dosage based on research using the commercial product Remifemin®
(Schaper and Brümmer) or Klimadynon® (Bionorica AG, contains the
extract BNO 1055).
American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002 29
S A F E TY P R O F I L E
Side Effects
Taken in doses equivalent to those used in clinical trials,
black cohosh appears to be very well tolerated. A detailed
reporting of side effects, when available, accompanies each
study presented under Therapeutics. Among the minor
adverse events reported, the most frequent was mild gas-
trointestinal upset (average of 5.6% of subjects across five
studies) (Földes 1959; Jacobson and others 2001; Kesselkaul
1957; Liske and others 2000; Vorberg 1984). Among the
other minor adverse events reported were headache, vertigo,
weight gain, mastalgia, heavy feeling in the legs, and a stim-
ulant effect (Jacobson and others 2001; Stoll 1987). In the
study by Jacobson and others (2001), minor adverse events
occurred in 8 of 42 subjects in the black cohosh treatment
group (n = 6 with, and n = 2 without tamoxifen) and in 2 of
43 subjects in the placebo-tamoxifen group. In the Stoll
(1987) study, minor adverse events occurred in 12 subjects
in the black cohosh treatment group and 2 each in the
placebo and conjugated estrogen groups. In the unpub-
lished study by Wuttke and others, the incidence of non-seri-
ous adverse events was similar between the black cohosh,
estrogen, and placebo groups (Gorkow, Marz, and
Christoffel, personal communication to AHP; unrefer-
enced). Three studies reported no adverse events in the
black cohosh treatment groups (Mielnik 1997; Nesselhut
and Liske 1999; Pethö 1987) and six made no mention of
adverse events (Daiber 1983; Georgiev and Iordanova 1997;
Görlich 1962; Heizer 1960; Lehmann-Willenbrock and
Reidel 1988; Warnecke 1985).
Other reported side effects that were variously classified
as adverse events or outcome measures and which may have
been due to an estrogen stimulatory effect include vaginal
bleeding and endometrial hyperplasia (Jacobson and others
2001; Liske and others 2000). Endometrial hyperplasia is a
risk factor for endometrial cancer. In the Jacobson and oth-
ers (2001) study, vaginal bleeding and endometrial hyper-
plasia occurred once each in the black cohosh-tamoxifen
group. In this same study, two unspecified endometrial con-
ditions in the black cohosh-tamoxifen group resulted in a
dilatation and curettage and a hysterectomy (Jacobson, per-
sonal communication to AHP; unreferenced). As stated pre-
viously, the effects of black cohosh are confounded with
those of tamoxifen in this study, making the findings unreli-
able; tamoxifen is known to cause endometrial abnormali-
ties. The authors concluded that it was not likely that any of
the adverse events found in the study were related to treat-
ment. In the study by Liske and others (2000), a biopsy
showed an inactive endometrium in a patient presenting
metrorrhagia. In the unpublished study of Wuttke and oth-
ers, vaginal bleeding occurred at least twice as frequently in
the black cohosh treatment group compared to the placebo.
The authors noted that the more frequent occurrence of
vaginal bleeding and the non-significant increase in vaginal
cell proliferation and endometrial thickness may be inter-
preted as a moderate estrogenic effect of black cohosh
extract (Gorkow, Marz, and Christoffel, personal communi-
30 American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002
cation to AHP; unreferenced).
In the study of Jacobson and others (2001), breast can-
cer recurrence was reported in one woman taking black
cohosh with tamoxifen. The patient had an unreported
increase in carcinoembryonic antigen before entering the
study.
Modern herbalists have observed that some clients get
severe frontal headaches taking black cohosh preparations
at various dosages (Anderson-Geller and Winston, personal
communications to AHP; unreferenced), some occasionally
at tincture doses greater than 20 mL in a 24-hour period or
even a single dose greater than 3-5 mL (McQuade
Crawford, personal communication to AHP; unreferenced).
The dosages used by modern herbalists tend to be much
higher than those used in clinical trials. A single anecdotal
report was received from a woman who in one day con-
sumed 400 mg of a black cohosh extract characterized to
2.5% 27-deoxyactein. She experienced a sense of well being
and broke out in a rash (Upton, personal communication to
AHP; unreferenced).
Contraindications
Based on the available data, no conclusive determination
can be made at this time (see Precautions).
Precautions
Both estrogenic and anti-estrogenic activities have been
reported for black cohosh and no long-term clinical studies
exist. Historically, black cohosh was used for relatively short
periods of time. The long-term use of it for the management
of menopausal symptoms is a new indication. Therefore,
women using black cohosh for long-term management of
menopausal symptoms or those with a history of breast can-
cer (see Carcinogenicity) should do so only under the super-
vision of a qualified health care professional. Black cohosh
should not be used during pregnancy except under the
supervision of a qualified health care professional (see
Pregnancy, Mutagenicity, and Reproductive Toxicity).
There appears to be no indication for long-term use of black
cohosh in children. According to the forthcoming World
Health Organization (WHO) monograph on black cohosh,
there is no therapeutic rationale for the use of black cohosh
in children. According to traditional and contemporary
herbalists, however, black cohosh may be safely used for the
short-term treatment of acute respiratory infections in chil-
dren (see Medical Indications Supported by Traditional and
Modern Experience). The German Commission E
(Blumenthal and others 1998) recommends that treatment
with black cohosh not exceed six months. This is based on
the current standard of practice in Germany that recom-
mends the reassessment every six months of the need for
pharmacological treatment of menopausal symptoms.
Interactions
No clinical interactions have been reported. In one in vitro
study, black cohosh extract potentiated the anti-estrogenic
effect of tamoxifen in breast cancer cell lines and antago-
nized the cell-proliferative effects of estradiol (Freudenstein
and Bodinet 1999). However, a clinical trial investigating
the effect of black cohosh in breast cancer survivors found
no apparent interaction between tamoxifen and black
cohosh as indicated by similar serum hormone levels in
tamoxifen users taking black cohosh and those not taking
black cohosh (Jacobson and others 2001). In rats, black
cohosh extract enhanced the effects of mestranol on induc-
tion of ovulation (Löhning and others 2000). The relevance
of such in vitro data to humans is not known.
Pregnancy, Mutagenicity, and Reproductive
Toxicity
Black cohosh should not be used during pregnancy except
under the supervision of a qualified health care profession-
al. Black cohosh was traditionally used by the Eclectics as a
partus preparator and for uterine cramping and is still used
in this way by midwives today. One early case series
(Görlich 1962) and contemporary use by midwives indicate
that black cohosh may be used early in pregnancy as an anti-
abortifacient (Romm, personal communication to AHP;
unreferenced). In contrast to such uses, two anecdotal
reports among the Eclectics cited the rare occurrence of
threatened abortion or hemorrhage following the use of
black cohosh in pregnancy or labor, respectively (Cook
1869; Ellingwood 1919; see Medical Indications Supported
by Traditional and Modern Experience). According to the
forthcoming WHO monograph on black cohosh, the use of
black cohosh during pregnancy or lactation is contraindi-
cated. This is a general policy of WHO when safety data are
lacking regarding herb use during pregnancy and lactation
(Mahady and others 2001).
There have been two reports of birth defects or injury
associated with maternal use of black cohosh. It is not possi-
ble to identify black cohosh as the causative agent in either
case. In the first case, according to a letter to the New
Zealand Medical Journal, a pregnant woman gave birth to a
baby with basal ganglia and parasagittal hypoxic injury after
using a combination of black and blue cohosh
(Caulophyllum thalictroides) to induce labor (there may
have been other botanicals in the combination) (Gunn and
Wright 1996). The woman reportedly had a normal preg-
nancy and birth. According to the primary reporters, a con-
stituent of blue cohosh, caulosaponin, was likely to have
been responsible for this effect due to its reported ability to
cause coronary blood vessel constriction and direct myocar-
dial toxicity. In a study of prenatal influences on fetal devel-
opment and survival, researchers followed 3200 pregnan-
cies; three of the mothers used black cohosh (dose and dura-
tion unspecified). In one of these cases, the child was born
with an unspecified malformation (Mellin 1964).
The Ames test showed no evidence of a mutagenic
potential of an isopropanolic extract of black cohosh equiv-
alent to 30.3 mg. In comparison to the negative control
used, the extract showed no genotoxic effects (Beuscher
1996; Boblitz and others 2000).
Lactation
Data regarding the effects of black cohosh use during lacta-
tion on infants or milk supply are lacking. Based on a review
of the available literature and the experience of modern
practitioners, no adverse effects are to be expected. There
appears to be no indication for long-term use of black
cohosh in lactating mothers.
Carcinogenicity
Endometrial hyperplasia, a precancerous condition, was
reported in one out of 29 subjects taking black cohosh and
tamoxifen concurrently (Jacobson and others 2001). This
condition is a known side effect of tamoxifen, so its occur-
rence cannot necessarily be attributed to black cohosh. One
animal study found no effect of black cohosh on estrogen-
receptor-positive tumors in rats (Freudenstein and others
2000). Seven studies investigated the effect of black cohosh
on breast cancer cell lines. Six of these found no cell-prolif-
erative effect (Dixon-Shanies and Shaik 1999; Freudenstein
and Bodinet 1999; Liu and others 2001a; Nesselhut and oth-
ers 1993; Oketch-Rabah and others 2002; Zava and others
1998), whereas two did (Liu and others 2001b; Löhning and
others 1998). The relevance of such in vitro data to effects
in human tissues is unknown and requires further testing.
Influence on Driving
Based on current knowledge, no negative effects are to be
expected when black cohosh is taken at the suggested
dosages.
Overdose
King’s American Dispensatory notes that impaired vision and
dilation of the pupil have been known to occur with large
doses (undefined) of black cohosh (Felter and Lloyd 1898).
The 22nd edition of The Dispensatory of the United States of
America states that “In overdoses it [black cohosh] is said to
cause general relaxation, vertigo, tremors, decided reduc-
tion of the pulse; occasionally it causes vomiting, but its
emetic action is never violent…In large doses it produces
giddiness, with intense headache and prostration” (Wood
and others 1937). The German reference Hager’s
Handbuch reports large doses of black cohosh to be 5 g of
the dried drug or 12 g of the fluid extract (List and
Hörhammer 1973).
Treatment of Overdose
No data available.
Toxicology
Female Wistar rats received 250, 1800, and 5000 mg/kg
Remifemin® granulate daily by oral gavage over a 26-week
period. The highest dose corresponds to 500 times the
human therapeutic dose. After an eight-week post-treatment
observational phase, no toxic effects were observed in the
treatment group compared to control (Korn 1991). In the
study by Schindler (1992), the minimum lethal dose of
black cohosh (preparation unknown) following single doses
American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002 31
was reported to be > 500 mg/kg ip in mice, > 1000 mg/kg po ments. Action: Estrogen-like action; luteinizing hormone
in rats, and > 70 mg/kg in guinea pigs. Following subchron- suppression; binding to estrogen receptors (Blumenthal and
ic administration (30 days) of the preparation, the minimum others 1998).
lethal dose was > 6 mg/kg po in guinea pigs and > 10 mg/kg
Sweden
ip in mice.
Classified as a natural remedy intended for self-medication,
Genazzani and Sorrentino (1962) reported on the min-
requiring advanced application for marketing authorization
imum lethal dose of actein as follows: > 70 mg/kg iv single
(DeSmet and others 1993; Zhang 1998).
dose in rabbits; > 500 mg/kg ip for 10 days in mice; > 1000
mg/kg gastric single dose in rats. The conclusion of these Switzerland
researchers was that actein was not acutely toxic and that no Black cohosh single-ingredient medicines are classified by
effects on heart or spontaneous movement in animals was the Interkantonale Kontrollstelle für Heilmittel (IKS-List D)
observed. as non-prescription drugs with sale limited to pharmacies
and drugstores (Morant and Ruppanner 2001-2).
Classification of the American Herbal Products Indications: Menopausal complaints, hot flashes, sweating,
Association sleep disorders, nervousness, and mood disorders (climac-
The Botanical Safety Handbook of the American Herbal teric complaints).
Products Association (AHPA) assigns black cohosh the fol- United Kingdom
lowing classifications (McGuffin and others 1997): Occurs in the British Herbal Pharmacopoeia (BHP 1996).
Class 2b: Herbs not to be used during pregnancy unless oth- Black cohosh dried rhizome and root is an herbal medicine
erwise directed by an expert qualified in the use of the indicated for conditions capable of self diagnosis as specified
described substance.* in the General Sale List, Schedule 1 (medicinal products
Class 2c: Herbs not to be used while nursing unless other- requiring a full product license), Table A (for internal or
wise directed by an expert qualified in the use of the external use); 200 mg maximum single dose (Bradley 1992;
described substance.** GSL 1984-94). Exemptions from licensing are contained in
section 12 of the 1968 Medicines Act (Zhang 1998).
Notice: Emmenagogue, uterine stimulant. Indications: Menopausal disorders, premenstrual com-
Editor’s note: Occasional gastrointestinal discomfort may plaints, dysmenorrhea, uterine spasm (Bradley 1992).
occur. Large doses may cause vertigo, headache, nausea, Actions: Anti-inflammatory (BHP 1996), antirheumatic,
impaired vision, vomiting, and impaired circulation. An endocrine (pituitary, estrogen-mimetic) activity, emmena-
estrogenic effect and lowering of blood pressure have been gogue (Bradley 1992).
recorded (McGuffin and others 1997).
* See Pregnancy, Mutagenicity, and Reproductive Toxicity. WHO
** See Lactation. Black cohosh rhizome is the subject of a forthcoming mono-
graph by the World Health Organization (Mahady and oth-
ers 2001).
I N T E R N AT I O N A L S TAT U S
United States
Regulated as a dietary supplement. Black cohosh dried rhi-
zome and root, both whole and powdered, and black cohosh
dry extract have been proposed for inclusion in the United
States Pharmacopeia – National Formulary (USPF 27 [4]
2001).
Canada
Black cohosh will be listed as a Natural Health Product
under new regulations if a health claim is made or if it is
provided in specific dosage forms. Crude herbs in bulk form
will remain regulated as “foods”. When identified as a
Traditional Herbal Medicine, black cohosh preparations are
regulated as non-prescription over-the-counter drugs requir-
ing pre-market registration and assignment of a drug identi-
fication number (HC 1995, 2001; Zhang 1998).
Germany
The fresh or dried rhizome with attached roots is an
approved non-prescription drug for oral use according to the
German Commission E Monographs (Blumenthal and oth-
ers 1998). Indications: Premenstrual disorders, dysmenor-
rhea, or climacteric [menopausal] neurovegetative ail-

32 American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002

American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002 33
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American Herbal Pharmacopoeia™ • Black Cohosh Rhizome • 2002

TABLE OF CONTENTS
Nomenclature 1
Botanical Nomenclature
Botanical Family
Definition
Common Names

History 1
Identification 3
Botanical Identification
Macroscopic Identification
Microscopic Identification

Commercial Sources and Handling 8

Collection
Cultivation
Handling and Processing
Drying
Storage
Adulterants
Preparations

Constituents 9
Analytical 10
High Performance Thin Layer Chromatography (TLC/HPTLC)
High Performance Liquid Chromatography (HPLC)
Quantitative Standards

Therapeutics 16
Pharmacokinetics
Pharmacodynamics and Clinical Efficacy
Effects on Menopausal and Premenstrual Symptoms
Hormonal and Central Nervous System Effects
Other Effects
Conclusion
Medical Indications Supported by Clinical Trials
Medical Indications Supported by Traditional or Modern Experience
Actions
Substantiation for Structure and Function Claims
Dosages

Safety Profile 30
Side Effects
Contraindications
Precautions
Interactions
Pregnancy, Mutagenicity, and Reproductive Toxicity
Lactation
Carcinogenicity
Influence on Driving
Precautions
Overdose
Treatment of Overdose
Toxicology
Classification of the American Herbal Products Association

International Status 32
References 34

American Herbal Pharmacopoeia™

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