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PLANTS-CIMICIFUGA

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Cimicifuga species are used in herbal preparations for a wide variety of ailments. Cimicifuga racemosa is used specifically for gynecological disorders.

Specific Substances

    A) CONSTITUENTS OF THE GROUP
    1) Actaeae racemosae (L.)
    2) Black Cohosh
    3) Black Snakeroot
    4) Black Root
    5) Bugbane
    6) Bugwort
    7) Herbe Aux Punaises
    8) Macrotys actaeoides (Raf.)
    9) Rattleweed
    10) Rattleroot
    11) Rattlesnake Root
    12) Richweed
    13) Squaw Root
    14) Tall Bugbane

Available Forms Sources

    A) FORMS
    1) The seeds are thought to contain several triterpene alkaloids, including actein, cimicifugoside, deoxyacetylacteol, and 27-deoxyactein (Pepping, 1999). Also contains methylcytosine, 16.2% protein and 32.6% fat (Duke, 1985).
    2) There is an amorphorous resin-like compound called cimicifugin (macrotin) (5% to 20%) and a bitter substance named racemosin. Two glycosides, actein and cimigoside, have been isolated (Tyler, 1982) Windholz et al, 1983).
    3) A bitter saponin and a glycoside-tannin containing philogaphene have also been discovered (Mercier & Balansand, 1935).
    4) REMIFEMIN(R) is an ethanol extract made from the rhizome of Cimicifuga racemosa. It is recommended for hot flushes in women (Duker et al, 1991). This product is standardized for 1 mg of 27-deoxyactein per 20 mg tablet (Pepping, 1999).
    B) USES
    1) Black cohosh has been used as an herbal for the treatment of primarily gynecological conditions, especially menopause. It has also been used for symptoms of malaria, kidney problems, malaise, rheumatism, and sore throat. Other species of Cimicifuga have been used for their anti-inflammatory, analgesic, and antipyretic actions. The German Commission E (which approves herbal agents in Germany) has approved Cimicifuga racemosa for premenstrual discomfort, dysmenorrhea, or menopausal vegetative ailments (Pepping, 1999; Duke, 1985; Tyler, 1982).
    2) Black cohosh was one of the primary components of Lydia Pinkham's Vegetable Compound which was used for menstrual abnormalities (Duke, 1985). Other ingredients included unicorn root (Aletris farinosa), life root (Senecio aureus), pleurisy root (Asclepias tuberosa), and fenugreek seed (Trigonella foenumgraecum) (Netland & Martinez, 2000).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) There has been little study done on the toxic effects of Cimicifuga racemosa and there have been few overdoses reported. Most of the symptoms listed come from texts that do not cite specific case histories.
    0.2.5) CARDIOVASCULAR
    A) Actein, a triterpene found in Cimicifuga, has been shown to lower blood pressure in animals. No hypotensive effects have been noted in humans. Bradycardia has followed ingestions of preparations of this plant.
    0.2.7) NEUROLOGIC
    A) Dizziness, tremors, headache, and relaxation have been reported after excessive therapeutic doses.
    0.2.8) GASTROINTESTINAL
    A) Nausea and vomiting have been reported after excessive doses. This may have been due to the tannin content.
    0.2.9) HEPATIC
    A) WITH THERAPEUTIC USE
    1) Acute hepatitis is a rare event following therapeutic use.
    0.2.10) GENITOURINARY
    A) Although recommended by herbalists as an aid to stimulate menstruation or ease postmenopausal symptoms, the estrogenic effects of this plant could not be verified. The herb's effects may not involve estrogen effects.
    0.2.20) REPRODUCTIVE
    A) The exact effect in pregnancy is unknown, but an overdose may cause premature birth. Herbal preparations containing Cimicifuga racemosa have been used as abortifacients.

Laboratory Monitoring

    A) There are no specific laboratory measures indicated for overdose by Cimicifuga racemosa.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) This agent does not appear to be highly toxic. If large amounts have been ingested, activated charcoal may be of some use.
    B) ACTIVATED CHARCOAL: Administer charcoal as a slurry (240 mL water/30 g charcoal). Usual dose: 25 to 100 g in adults/adolescents, 25 to 50 g in children (1 to 12 years), and 1 g/kg in infants less than 1 year old.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

    A) Minimum lethal and maximum tolerated human exposures have not be delineated. Rats have tolerated 90 times the human dose without complications.

Clinical Effects

Summary Of Exposure

    A) There has been little study done on the toxic effects of Cimicifuga racemosa and there have been few overdoses reported. Most of the symptoms listed come from texts that do not cite specific case histories.

Cardiovascular

    3.5.1) SUMMARY
    A) Actein, a triterpene found in Cimicifuga, has been shown to lower blood pressure in animals. No hypotensive effects have been noted in humans. Bradycardia has followed ingestions of preparations of this plant.
    3.5.2) CLINICAL EFFECTS
    A) HYPOTENSIVE EPISODE
    1) Actein (steroidal triterpene in Cimicifuga) has been shown to lower blood pressure in cats and rabbits, but not in dogs. No hypotensive effects were seen in either normal or hypertensive humans, but some peripheral vasodilation was seen in dogs (Corsano et al, 1969; Genazzani & Sorrentino, 1962).
    B) BRADYCARDIA
    1) Bradycardia was reported after ingestions of preparations of this plant (Tyler et al, 1988).
    C) TACHYARRHYTHMIA
    1) Tachycardia occurred in 2 patients after ingesting herbal preparations containing black cohosh (Netland & Martinez, 2000).

Neurologic

    3.7.1) SUMMARY
    A) Dizziness, tremors, headache, and relaxation have been reported after excessive therapeutic doses.
    3.7.2) CLINICAL EFFECTS
    A) DIZZINESS
    1) Dizziness may be seen in overdose (Tyler et al, 1988; Duke, 1985).
    2) A general relaxation or giddiness may be seen in overdose (Osol & Farrar, 1955).
    B) TREMOR
    1) Tremors may be seen following ingestion of large amounts of preparations of this plant (Netland & Martinez, 2000; Tyler et al, 1988).
    C) HEADACHE
    1) Overdose is said to produce intense headache (Netland & Martinez, 2000; Osol & Farrar, 1955).
    D) SEIZURE
    1) CASE REPORT - A 45-year-old female presented to the ED following her third nocturnal tonic-clonic seizure in a 3-month period. The patient had been taking Cimicifuga racemosa, vitex agnus-castus, and evening primrose oil for 4 months for regulation of menstrual cycle (Shuster, 1997; Shuster, 1996). An association between the development of seizures and the ingestion of the Cimicifuga racemosa was not clearly established.

Gastrointestinal

    3.8.1) SUMMARY
    A) Nausea and vomiting have been reported after excessive doses. This may have been due to the tannin content.
    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) Nausea and vomiting have been reported in overdose. This may be due to the tannin content (Anon, 1986). About 7% of patients taking black cohosh during a retrospective open-label study experienced gastrointestinal problems (Pepping, 1999).
    2) Nausea and vomiting was reported in 2 patients following ingestion of an herbal preparation containing black cohosh as an abortifacient (Netland & Martinez, 2000).

Hepatic

    3.9.1) SUMMARY
    A) WITH THERAPEUTIC USE
    1) Acute hepatitis is a rare event following therapeutic use.
    3.9.2) CLINICAL EFFECTS
    A) ACUTE HEPATITIS
    1) WITH THERAPEUTIC USE
    a) CASE SERIES/LACK OF EFFECT - In a study of 4 females with assumed hepatotoxicity due to the black cohosh root, a diagnostic algorithm was used to determine a possible causality between drugs and dietary supplements and hepatotoxicity. Of the 4 patients, only 3 could be evaluated due to a lack of adequate information. All 3 patients were found to be taking substantial co-medications with up to 7 additional medications which were potentially hepatotoxic. One patient, who had significant comorbidity and was on multiple medications associated with potential hepatotoxicity, developed hepatic symptoms one week after starting black cohosh. She was successfully treated with steroid therapy, however, it could not be determined if the product taken only contained black cohosh and she was ultimately believed to have autoimmune hepatitis. The other 2 patients did not respond to steroids and received liver transplant; they were ultimately believed to have herpetic hepatitis. The authors concluded that none of these cases had liver disease related to black cohosh (Teschke & Schwarzenboeck, 2009).
    b) CASE REPORTS - There have been rare reports of acute hepatitis following black cohosh use. In one case, jaundice developed in a 47-year-old woman one week after starting black cohosh. Liver enzyme values peaked at: bilirubin 335 micromol/L, alkaline phosphatase 158 units/liter, aspartate aminotransferase 3182 units/liter, alanine aminotransferase 2295 units/liter and gamma glutamyltransferase 163 units/liter. Liver biopsy showed severe hepatitis and the patient required a liver transplant. The other patient was a 43-year-old female with ovarian adenocarcinoma with no liver involvement taking a combination of black cohosh, skullcap, valerian, passionflower and several other botanicals who developed jaundice and elevated liver enzymes. Symptoms resolved with the discontinuation of therapy (Whiting et al, 2002).

Genitourinary

    3.10.1) SUMMARY
    A) Although recommended by herbalists as an aid to stimulate menstruation or ease postmenopausal symptoms, the estrogenic effects of this plant could not be verified. The herb's effects may not involve estrogen effects.
    3.10.3) ANIMAL EFFECTS
    A) ANIMAL STUDIES
    1) UTERINE DISORDER
    a) Although recommended by herbalists as an aid to stimulate menstruation, this estrogenic effect could not be verified in studies done on mice (Siess & Seybold, 1960).
    b) One study utilized an alcoholic extract that contained substances that bound to the estrogen receptors of rat uteri (Jarry & Harnischfeger, 1985).
    c) IP injection of this extract in ovariectomized rats caused a selective reduction in luteinizing hormone level, but with little or no effect on prolactin or FSH concentration (Jarry & Harnischfeger, 1985).

Endocrine

    3.16.2) CLINICAL EFFECTS
    A) DECREASED HORMONAL ACTIVITY
    1) An alcoholic rhizome extract of C. racemosa significantly reduces LH but not FSH after 8 weeks of therapy in postmenopausal woman (Duker et al, 1991).

Reproductive

    3.20.1) SUMMARY
    A) The exact effect in pregnancy is unknown, but an overdose may cause premature birth. Herbal preparations containing Cimicifuga racemosa have been used as abortifacients.
    3.20.2) TERATOGENICITY
    A) LACK OF EFFECT
    1) Tests for mutagenicity and teratogenicity have proven negative (Liske, 1998). One case of a teratogenic effect was noted in 3,200 general pregnancies. The incidence of Cimicifuga use, the type of malformation, and the dose or frequency of Cimicifuga were not stated. No direct correlation was made to Cimicifuga racemosa use (Mellin, 1964).
    3.20.3) EFFECTS IN PREGNANCY
    A) BIRTH PREMATURE
    1) The exact effect in pregnancy is unknown, but an overdose may cause premature birth (Dharmananda, 1979).
    B) ABORTION
    1) Herbal preparations containing Cimicifuga racemosa have been used as abortifacients (Netland & Martinez, 2000).

Carcinogenicity

    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the carcinogenic or mutagenic potential of this agent.
    3.21.4) ANIMAL STUDIES
    A) LACK OF EFFECT
    1) In-vitro tests for carcinogenicity have proven negative (Liske, 1998).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) There are no specific laboratory measures indicated for overdose by Cimicifuga racemosa.
    4.1.2) SERUM/BLOOD
    A) OTHER
    1) There are no specific laboratory measures indicated for overdoses by Cimicifuga racemosa.

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) There are no specific laboratory measures indicated for overdose by Cimicifuga racemosa.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) This agent does not appear to be highly toxic. If large amounts have been ingested, activated charcoal may be of some benefit.
    B) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) ACTIVATED CHARCOAL
    1) This agent does not appear to be highly toxic. If a large amount has been ingested, activated charcoal may be of some use.
    2) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    3) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) SUPPORT
    1) There is no specific antidote or treatment. Care is symptomatic and supportive.
    2) Although not reported in humans, monitor for hypotension.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Enhanced Elimination

    A) LACK OF INFORMATION
    1) No studies have addressed the utilization of extracorporeal elimination techniques in poisoning with this agent.

Range Of Toxicity

Summary

    A) Minimum lethal and maximum tolerated human exposures have not be delineated. Rats have tolerated 90 times the human dose without complications.

Therapeutic Dose

    7.2.1) ADULT
    A) GENERAL
    1) Used as a bitter and expectorant in the form of a liquid extract of the dried roots and rhizomes. Dose (of the 1:1 preparation) is 0.3 to 2 milliliters and 2 to 4 milliliters of a 1 to 10 tincture (Reynolds, 1982). Many studies have used a dose of 40 to 80 milligrams of Remifemin(R) which contains roughly 4 to 8 milligrams of 27-deoxyactein per day (Pepping, 1999).

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) Minimum lethal human exposure is unknown.

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Studies on the effectiveness of Cimicifuga racemosa have been conflicting. Most studies have focused on estrogenic effects (Jarry & Harnischfeger, 1985). It is not known whether or not this plant has cardioprotective or osteoprotective effects such as those of estrogens (Pepping, 1999).
    B) The biological effects of Cimicifuga racemosa are attributed to various triterpene glycosides, including actein, cimicifugoside, deoxyacetylacteol, and 27-deoxyactein (Pepping, 1999).

Physicochemical

Physical Characteristics

    A) This compound has a characteristic, disagreeable odor that is lost with age (Osol & Farrar, 1955).

Molecular Weight

    A) Not available

References

General Bibliography

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    2) Anon: Black Cohosh. The Lawrence Review of Natural Products (April), 1986.
    3) Burgess JL, Kirk M, Borron SW, et al: Emergency department hazardous materials protocol for contaminated patients. Ann Emerg Med 1999; 34(2):205-212.
    4) Chyka PA, Seger D, Krenzelok EP, et al: Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005; 43(2):61-87.
    5) Corsano S, Piacatelli G, & Panizzi L: Gazzetta Chimica Italiana 1969; 99:915-932.
    6) Dagnone D, Matsui D, & Rieder MJ: Assessment of the palatability of vehicles for activated charcoal in pediatric volunteers. Pediatr Emerg Care 2002; 18:19-21.
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    8) Duke JA: Handbook of Medicinal Herbs, CRC Press, Inc, Boca Raton, FL, 1985.
    9) Duker EM, Kopanski L, & Jarry H: Effects of extracts from Cimicifuga racemosa on gonadotropin release in menopausal women and ovariectomized rats. Planta Medica 1991; 57:420-424.
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    14) Graff GR, Stark J, & Berkenbosch JW: Chronic lung disease after activated charcoal aspiration. Pediatrics 2002; 109:959-961.
    15) Guenther Skokan E, Junkins EP, & Corneli HM: Taste test: children rate flavoring agents used with activated charcoal. Arch Pediatr Adolesc Med 2001; 155:683-686.
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    17) Jarry H & Harnischfeger C: Studies on the endocrine effects of the contents of Cimicifuga racemosa: 1. Influence on the serum concentration of pituitary hormones in ovariectomized rats. Planta Medica 1985; 46.
    18) Liske E: Therapeutic efficacy and safety of Cimicifuga racemosa for gynecologic disorders. Adv Natural Ther 1998; 15:45-53.
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