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Chapter 19

Jennifer Schumacher and Melanie Johns Cupp
Virginian scullcap, mad-dog scullcap, madweed (Scutellaria laterifolia); common scullcap, greater
scullcap, helmet flower, toque, hoodwort (Scutellaria galericulata); lesser scullcap (Scutellaria
minor) (Grieve, 1971), mad-dog weed (Anonymous, 1993), monkey-flower (Crellin and Philpott,
1990), Scutellaria baicalensis Georgi (Tyler, 1993).
History and Traditional Uses
Scullcap is a perennial that grows mainly in temperate regions and tropical mountains near rivers, lakes
(Grieve, 1971), and moist woods (Anonymous, 1993). It is found in the United States (Scutellaria
laterifolia), Mexico (Scutellaria coccinea), Europe (Scutellaria galericulata, Scutellaria minor)
(Grieve, 1971), and Asia (Scutellaria baicalensis) (Tyler, 1993). Reaching about 3 ft in height, the plant
blooms from July to September and has blue, pink, purple or red flowers (Grieve, 1971; Anonymous,
1993). Scullcap was introduced into American medicine in 1773 by Dr. Lawrence Van Derveer who
used it to treat rabies (Tyler, 1993); hence the common name mad-dog weed (Anonymous, 1998b). It
was believed that Scutellaria lateriflora relieved muscle spasm associated with rabies, but was not
found to cure it. Scullcap later came to be recognized as a tonic, tranquilizer, and antispasmodic, and
was therefore used as an ingredient in many ''patent medicines" for "female weakness" (Tyler, 1993).
Scullcap was also combined with other reputedly calming herbs such as hop and valerian and
promoted as a sedative or anxiolytic (Anonymous, 1993, 1998b). Other traditional uses include
epilepsy, headache, insomnia, various other neurologic and psychiatric disorders, hypertension, fever,
rheumatism, and stress (Anonymous, 1998a).
From Forensic Science: Toxicology and Clinical Pharmacology of Herbal Products Edited by: M. J. Cupp
Humana Press Inc., Totowa, New Jersey

Current Promoted Uses

Scullcap is promoted commercially in the United States as a sedative, anxiolytic, and spasmolytic and is
promoted for the treatment of premenstrual syndrome (PMS), menstrual cramps, depression,
exhaustion, and muscle pain caused by stress (Israel and Youngkin, 1997). Other purported uses include
headache (Grieve, 1971) and epilepsy (Anonymous, 1998b).
Products Available
Scullcap is currently commercially available in the United States as capsules, tea, liquid extract,
tincture, and bulk root. Capsules are commonly available in bottles of 100; the strengths sold include
425 mg and 429 mg and the usual instructions are to take one capsule one to three times a day as
needed. The liquid extract is available in a small brown bottle containing either 1 or 2 oz; instructions
are to put 1012 drops in a glass of water per day and drink. If the dried herb is used, 12 teaspoons
of dried leaf are placed in hot water to make a tea. The products are not sold under a specific brand
name and are labeled as "scullcap" or "skullcap." Scullcap can be found either alone or in combination
with other psychoactive herbs such as valerian or St. John's wort.
Pharmacologic/Toxicologic Effects
Antispasmodic Effects
A study by Pitcher in 1916 found scullcap extract to have very weak ability to inhibit the contractility of
excised guinea pig uterus, and no effect on the uterus in living animals that received what was
considered to be a normal dose (Tyler, 1993). Two species of scullcap (S. galericulata and S.
scordiifolia) studied in 1957 by Kurnakov were also found to show no antispasmodic activity in various
small animals (Tyler, 1993).
See Section 19.5.
Cardiovascular Effects
Neither S. galericulata nor S. scordiifolia was found by Kurnakov to affect blood pressure in cats or
rabbits (Tyler, 1993). A tincture of S. baicalensis was reported by Ursow in 1958 to cause a decline in
blood pressure in dogs. However, this report requires verification (Tyler, 1993).

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Antimicrobial Activity
Scullcap has in vitro antimicrobial activity. Scutellaria baicalensis root was boiled, filtered,
lyophylized, and diluted with sterile water to a concentration of 16 mg/mL. Sufficient quantities of this
solution were added to Mueller Hinton Medium to yield final concentrations of 100 g/mL, 200 g/
mL, 400 g/mL, 800 g/mL, and 1600 g/mL. Activity against Klebsiella pneumoniae, Proteus
vulgaris, Alcaligenes calcoaceticus, Staphylococcus aureus, and Mycobacterium smegmatis was noted.
The minimum inhibitory concentration (MIC), defined as the lowest concentration resulting in complete
absence of growth at 36 h post-incubation, was 200 g/mL, 200 g/mL, 800 g/mL, 400 g/mL, and
1600 g/mL for each organism, respectively (Franzblau and Cross, 1986). Whether the antimicrobial
principles of scullcap prepared as a tea, tincture, or dried herb could achieve concentrations necessary
for antimicrobial activity in vivo is unknown.
Anti-Inflammatory Activity
Sialic acids, which are present in cell membranes and mucous secretions, are thought to allow viruses
and other substances to enter cells. Serum sialic acid levels have been shown to increase in certain
disease states such as cancers, rheumatic diseases, other inflammatory diseases, and infections
(Anonymous, 1993). Elevated serum sialic acid levels have also been found in men with coronary
artery disease and type II diabetes mellitus (Pickup et al., 1995). It has been hypothesized that inhibition
of the enzyme sialidase, which is involved in the formation of sialic acid, could be of therapeutic
importance (Anonymous, 1993).
The anti-inflammatory activity of the Asian species S. baicalensis has been studied by Japanese
researchers (Anonymous, 1993). An in vitro study with the Scutellaria components wogonin and
isoscutellarein glucuronide demonstrated significant inhibition of the enzyme sialidase whereas
baicalein, baicalin, and wogonin glucuronide showed no inhibition (Nagai et al., 1989a). Another study
(Nagai et al., 1989b) demonstrated that a hot water extract of the root of Scutellaria baicalensis had
potent mouse liver sialidase inhibition. Flavonoid content for the study was measured by highperformance liquid chromatography (HPLC). The flavonoids wogonin, wogonin glucuronide,
baicalein, and baicalin all demonstrated similar inhibition at higher concentrations (50125 g/mL);
inhibitory activity of wogonin and baicalein was more potent than that of wogonin glucuronide or
baicalin at lower concentrations (10 g/mL). The differences between the two studies may be explained
by differences in the sialidase substrates used (Nagai et al., 1989a). However, baicalin and wogonin

glucuronide are metabolized to baicalein and wogonin in mammals, so in vivo the differences in
activity among these compounds may be insignificant (Nagai et al., 1989a).
Chemotherapeutic Activity
Preliminary animal studies have demonstrated the possibility that scullcap may improve the
tolerability and efficacy of some chemotherapeutic agents. Scutellaria baicalensis Georgi was found to
decrease tumor cell viability and ameliorate myelosuppression when used with cyclophosphamide and
5- fluorouracil in both mice and rats (Razina et al., 1987).
Case Reports of Toxicity Due to Commercially Available Products
Although an herbal reference (Grieve, 1971) states that high doses of scullcap tincture have been
reported to cause giddiness, stupor, confusion, twitching, arrhythmias, and epilepsy, case reports in the
medical literature involve only hepatotoxicity.
One report from Scotland (MacGregor et al., 1989) documents hepatotoxic effects in four women
ranging in age from 41 to 57 who had been taking herbal remedies containing scullcap to relieve stress.
Three were taking Kalms tablets and one woman took Neurelax tablets. Each woman presented with
jaundice, and three with dark urine and pale stools. None of the women had a history of drug or alcohol
abuse, but one woman drank approximately the equivalent of 120 g of alcohol per week. One patient
had taken one tablet of indapamide daily for many years, and another had taken a low-dose oral
contraceptive for the previous 5 yr. All had been in good health previously, and none had traveled
abroad, received blood or blood products, or been in contact with persons with jaundice or hepatitis.
None of the women presented with fever or abdominal pain. Save for one woman who had mild
hepatomegaly on exam, none had signs of chronic liver disease on physical exam. In one case a liver
scan was performed with normal results, and in three women ultrasonography was performed with
normal results. Liver biopsy revealed severe acute hepatitis with centrilobar and bridging necrosis in
one case, moderately active acute hepatitis in another, and chronic aggressive hepatitis with advanced
fibrosis in a third case (this biopsy was performed 3 mo after presentation); biopsy was unsuccessful in
the fourth case. Plasma bilirubin ranged from 232 mmol/L to 484 mmol/L (normal is 217 mmol/L),
alanine aminotransferase (ALT) from 293 IU/L to 1165 IU/L (normal is 1040 IU/L), aspartate
aminotransferase (AST) from 581617 mg/L (normal is 1035 IU/L), alkaline phosphatase from

97 to 730 IU/L (normal is 40100 IU/L), and prothrombin ratio from 1.3 to 1.9. In one patient,
antinuclear antibody and rheumatoid factor were tested and found to be positive. Upon discontinuation
of the herbal medication, liver function tests (LFTs) returned to normal values within 219 mo. The
rapid onset of liver damage after beginning the herbal therapy in three of the women (ranging from 3 d
in one case to 3 wk in two cases) may suggest a hypersensitivity type reaction. The herbal remedies
these women took contained the common ingredients of valerian and scullcap prior to October, 1984;
after this time, Kalms was reformulated to contain valerian, asafetida, hops, and gentian. The authors
of this case study were uncertain if the Kalms tablets taken by their patients were the reformulated
products or the older scullcap-containing formulation. Personnel from the Welsh Drug Information
Center communicated that they had received several reports of jaundice associated with ingestion of
Kalms , Neurolax , Box's Nerve Tablets (which also contained scullcap), scullcap tablets, scullcap in
combination with valerian, and scullcap in combination with mistletoe. Because of the presence of
coingestants and questions about the ingredients in the Kalms tablets ingested, it is not possible to
definitively implicate scullcap as the cause of hepatotoxicity in these four cases.
Another report (Harvey and Colin-Jones, 1981) describes a case of acute hepatitis associated with use
of a preparation containing both mistletoe and scullcap. A 49-yr-old woman presented with nausea,
malaise, and a dull ache in the lower right quadrant. Liver function tests revealed serum albumin levels
of 34 g/L, bilirubin of 42 mmol/L, alkaline phosphatase of 123 U/L, lactate dehydrogenase (LDH) of
395 U/L, and AST of>250 U/L. Liver biopsy revealed light inflammatory infiltration of the portal tracts
with preservation of liver architecture. Hepatitis B and cholelithiasis were ruled out. Liver function tests
returned to normal over 6 mo. Twenty-eight months later she again presented with the same symptoms.
It was then that it was discovered that she had been taking tablets containing motherwort, kelp, wild
lettuce, scullcap, and mistletoe for several weeks before this presentation as well as prior to the
previous admission. LFTs on this admission included an albumin level of 37 g/L, bilirubin of 14
mmol/L, alkaline phosphatase of 55 U/L, LDH of 235 U/L, and AST of 23 U/L. Liver biopsy revealed
light inflammatory infiltrate with occasional focal necrosis, but with preservation of architecture. LFTs
returned to normal over 6 wk. Upon rechallenge with the same herbal medicine, nausea and malaise
appeared after 10 d, and after 14 d liver biopsy showed heavy infiltration of lymphocytes and plasma
cells, considerable focal necrosis, and distortion of liver architecture. LFTs were albumin 41 g/L,
bilirubin 38 mmol/L, alkaline phosphatase 144 U/L, LDH 381 U/L, and AST > 250 U/L. An increase in
serum IgG with no increase in complement concentrations was also noted. With dis-

continuation of the product, the patient's LFTs and liver histology normalized over the next 9
mo. The hepatotoxicity experienced by this woman was attributed to the mistletoe component
of the product because no record of toxic reactions to kelp, motherwort, or scullcap were
found. Although the same was true of mistletoe, the authors believed mistletoe to contain
several potential hepatotoxins.
There is currently no experimental data that document liver toxicity of scullcap (Larrey,
1997). Studies of scullcap products available in the United Kingdom in the early 1980s
revealed that some products contained a species of Teucrium in place of scullcap (Phillipson
and Anderson 1984, Anonymous, 1985). The genus Teucrium is of the same family
(Lamiaceae) as scullcap but is associated with hepatotoxicity. Several cases of liver toxicity
and injury have been associated with Teucrium chamaedrys (Germander) in France, where it
has been used as an herbal weight loss product (Larrey et al., 1992).
In light of these facts, it is important be aware of the toxicities of other herbs that may be
included in scullcap products. It is difficult to attribute hepatotoxicity to scullcap because it
has not been reported with products containing only scullcap. Be aware that many herbal
products contain multiple ingredients, and some ingredients may not even be listed on the
label. For example, scullcap is often formulated with valerian (Foster, 1998). Perhaps an
interaction between scullcap and other herbs is responsible for some of the cases of