HERBAL
MEDICINAL
PLANT
VALERIAN
VALERIAN
Valeriana officinalis L. (Valerianaceae) + + +
BY
RETTODWIKART THENU
VALERIAN
(vuh-lir’ee-uhn)
Valeriana
officinalis L. (Valerianaceae) + + +
SUMMARY AND PHARMACEUTICAL COMMENT
The traditional use of valerian as a mild sedative and hypnotic is
supported by evidence from preclinical and some clinical studies. Clinical
trials, however, have been heterogeneous in their design, outcomes, and products
assessed, such that the evidence for the hypnotic and sedative effects of
valerian root is inconclusive when considered collectively or for individual preparations.
The chemistry of valerian root is welldocumented.
The sedative activity of valerian has been attributed to both
the volatile oil and iridoid valepotriate fractions, but it is still unclear
whether other constituents in valerian represent the active components. The
valepotriate compounds are highly unstable and, therefore, are unlikely to be
present in significant concentrations in finished products and probably degrade
when taken orally. In view of this, the clinical significance of both the
sedative and cytotoxic/ mutagenic activities of valepotriates documented in vitro is unclear.
There are only limited data on safety aspects of valerian preparations
from clinical trials. Randomised, placebocontrolled trials involving healthy
volunteers or patients with diagnosed insomnia indicate that adverse events
with valerian are mild and transient. Post-marketing surveillance-type studies
are required to establish the safety of valerian preparations, particularly with
long-term use. Some studies suggest that valerian may have a more favourable
tolerability profile than certain benzodiazepines, particularly in view of its apparent
lack of ’hangover’ effects, although this requires further investigation.
Intake of valerian preparations immediately (up to two hours)
before driving or operating machinery is not recommended. Excessive consumption
of alcohol whilst receiving treatment with valerian root preparations should be
avoided. Patients should seek medical advice if symptoms worsen beyond two weeks’
continuous treatment with valerian. Patients with known sensitivity to valerian
should not use valerian root preparations. The potential for preparations of
valerian to interfere with other medicines administered concurrently, particularly
those with similar (such as barbiturates and other sedatives) or opposing
effects, should be considered.
There are isolated reports of adverse effects, mainly hepatotoxic
reactions, associated with the use of singleingredient and combination
valerian-containing products.
However, causal relationships for these reports could not be established
as other factors could have been responsible for the observed effects.
GENERAL COMMENTS
The subterranean root parts of Valeriana
officinalis L.,
dried at temperatures below 40°C, are used in medicine. The drug consists of the
rhizomes, roots, and stolons of the plant and preparations of the same.
TRADE NAMES
Valerian Root
(available from numerous manufacturers,) Herbal Sure Valerian Root, NuVeg
Valerian Root, Valerian Root Alcohol Free, Valerian Power Time Release,
Valerian Root Power, Standardized Valerian, Natural Herbal Valerian Root,
Nature's Root Nighttime, Quanterra Sleep
OTHER COMMON NAMES
All Heal, Amantilla,
Baldrianwurzel, Capon’s Tail, Great Wild Valerian, Herba Benedicta,
Katzenwurzel, Phu Germanicum, Phu Parvum, Setewale, Setwell, Theriacaria,
Valeriana
DESCRIPTION
MEDICINAL PARTS: The medicinal
parts are the carefully dried underground parts and the dried roots.
FLOWER AND FRUIT: The androgynous,
bright, pink-to-white flowers are in panicled cymes. The calyx consists of 10 revolute
tips. The corolla is funnel-shaped with a 5-sectioned margin. The tube has a
bump at the base. There are 3 stamens. The ovary is inferior and has 3
chambers. The fruit is ovate-oblong, yellow, indehiscent and has a 10-rayed
tuft of white hair.
LEAVES, STEM AND ROOT: The plant is 50
to 100 cm high and has a short, cylindrical rhizome with finger-length, bushy round
roots. The stem is erect and unbranched. The leaves are odd-pinnate with 11 to 23
lanceolate, indented-dentate leaflets. The lower ones are petiolate and the
upper ones sessile and clasping with a white sheath.
CHABRACTERISTICS:
The
flowers are fragrant and the rhizome smells strongly when dried. The odor is
not present in the fresh plant. Hydrolysis of componants in the root form isovaleric
acid which is responsible for the offensive smell. HABITAT: The plant is found in Europe and in the
temperate regions of Asia. It is cultivated mainly in central Europe, England,
France, eastern Europe, Japan and the U.S.
PRODUCTION: Valerian root, consisting
of fresh underground plant parts, or parts carefully dried below 40° C of the species
Valeriana officinalis. Cultivation is possible in lowlying, sandy, humus soil
that is well supplied with lime and situated in a damp area. The root is
harvested in September. The fresh roots are washed, chopped, and carefully
dried in circulating air under 403 C.
NOT TO BE CONFUSED WITH: Confusion with
other species seldom occurs since the plant is primarily supplied via cultivation.
The most dangerous adulteration of the plant occurs by the addition of the
roots of Veratrum album.
SPECIES (FAMILY)
Valeriana officinalis
L. (Valerianaceae).
SYNONYM(S)
All-Heal,
Belgian Valerian, Common Valerian, Fragrant Valerian, Garden Valerian Garden
heliotrope; Baldrian (Ger.)
ORIGIN
Valerian is a perennial that is
now cultivated throughout the world.
PHARMACOPODIAL AND OTHER MONOGRAPHS
American Herbal Pharmacopoeia(1, G1)
BHC 1992(G6)
BHP 1996(G9)
BHMA 2003(G66)
BP 2007(G84)
Complete German Commission E(G3)
EMEA HMPC Community Herbal Monograph(G80)
ESCOP 2003(G76)
Martindale 35th edition(G85)
Ph Eur 2007(G81)
USP29/NF24(G86)
WHO volume 1 1999(G63)
LEGAL CATEGORY (LICENSED PRODUCTS)
GSL(G37)
CONSTITUENTS
See
also References 1–5.
Alkaloids
Pyridine type. Actinidine, chatinine, skyanthine, valerianine and valerine.
Iridoids
(valepotriates) Valtrates (e.g. valtrate, valtrate isovaleroxyhydrin, acevaltrate,
valechlorine), didrovaltrates (e.g. didrovaltrate, homodidrovaltrate,
deoxydidrovaltrate, homodeoxydidrovaltrate, isovaleroxyhydroxydidrovaltrate)
and isovaltrates (e.g. isovaltrate, 7-epideacetylisovaltrate). Valtrate and didrovaltrate
are documented as the major components. Valerosidate (iridoid glucoside).(6)
The valepotriates are unstable and decompose on storage or processing; the main
degradation products are baldrinal and homobaldrinal. The baldrinals may react
further and are unlikely to be present in finished products.
Steroids
b-sitosterol, clionasterol 3-b-O-glucoside and a mixture of
60-O-acyl-b-D-glucosyl clionasterols where the acyl moieties are hexadecanoyl
(major), 8E,11E-octadecadienoyl and 14-methylpentadecanoyl.(7)
Volatile Oils 0.5–2%. Numerous identified
components include monoterpenes (e.g. a- and b-pinene, camphene, borneol,
eugenol, isoeugenol) present mainly as esters, sesquiterpenes (e.g. bbisabolene,
caryophyllene, valeranone, ledol, pacifigorgiol, patchouli alcohol, valerianol,
valerenol and a series of valerenyl esters, valerenal, valerenic acid with
acetoxy and hydroxy derivatives).(8–11)
Other Constituents Amino acids (e.g.
arginine, g-aminobutyric acid (GABA), glutamine, tyrosine),(1, 12) caffeic and
chlorogenic acids (polyphenolic), methyl 2-pyrrolketone, choline, tannins (type
unspecified), gum and resin.
Quality Of Plant Material And
Commercial Products
According
to the British and European Pharmacopoeias, valerian consists of the dried
underground parts of V. Officinalis L., including the rhizome surrounded by the
roots and stolons.(G81, G84) It contains not less than 5 mL/kg of essential oil
for the whole drug and not less than 3 mL/kg for the cut drug, both calculated with
reference to the dried drug, and not less than 0.17% of sesquiterpenic acids
expressed as valerenic acid, calculated with reference to the dried drug.(G81)
As with other plants, there can be variation in the content of active compounds
(e.g. valerenic acid derivatives and valepotriates) found in valerian rhizomes
and roots.(13) Detailed descriptions of V. officinalis root for use in botanical,
microscopic and macroscopic identification have been published, along with
qualitative and quantitative methods for the assessment of V.
officinalis root raw material.(1, G1)
CHEMICAL COMPONENTS
COMPOUNDS
Iridoids: valepotriates
(valeriana-epoxy-triacylates, iridoide monoterpenes, 0.5-2.0%) chief components
(50-80%). Isovaltrate (up to 46%), isovaleroxyhydroxy didrovaltrate (IVDH-valtrate,
10-20%), including among others, didrovaltrate, acevaltrate
Volatile Oil (0.2-1.0%): chief components
(-)-bornyl isovalerenate and isovalerenic acid (both aroma-carriers), including
among others, (-)-bomyl acetate, isoeugenyl valerenate, isoeugenyl
isovalerenate, also with some strains valerenal,
valeranone,
cryptofaurinol
Sesquiterpenes: valerenic acid
(0.1-0.9%), 2-hydroxyvalerenic acid, 2-acetoxy-valerenic acid
Pyridine Alkaloids (traces, cat pheromone): actinidine, valerianine,
alpha-methylpyrrylketone
Caffeic Acid Derivatives: chlorogenic acid. The subspecies within the collective
species differ in their constituent substances spectra.
USES
USES
Valerian is used to treat nervous disorders such as
anxiety, restlessness, and insomnia.
FOOD USE
Valerian
is not generally used as a food. Valerian is listed by the Council of Europe as
a natural source of food flavouring (root: category 5) (see Appendix 3, Table
1).(G17) Previously, valerian has been listed as GRAS (Generally Recognised As
Safe).
HERBAL USE
Valerian
is stated to possess sedative, mild anodyne, hypnotic, antispasmodic,
carminative and hypotensive properties. Traditionally, it has been used for
hysterical states, excitability, insomnia, hypochondriasis, migraine, cramp,
intestinal colic, rheumatic pains, dysmenorrhoea, and specifically for
conditions presenting nervous excitability.(G2,G6, G7, G8, G32,G64) Modern
interest in valerian is focused on its use as a sedative and hypnotic.
A
Community Herbal Monograph adopted by the European Medicines Agency's Committee
on Herbal Medicinal Products states the following therapeutic indications for
valerian root: traditional use, for support of mental relaxation and to aid natural
sleep; well-established use, for the relief of mild nervous tension and
difficulty in falling asleep.(G80)
Figure 1. Valerian (Valeriana officinalis).
Figure 2. Valerian – dried drug substance (rhizome).
ACTIONS
Antianxiety
Action
Valerian has been studied almost as extensively as St.
John’s wort. Its effects are primarily neurochemical, acting on gamma-aminobutyric
acid A (GABA) receptors and possibly also with other presynaptic components
(Ortiz et al, 1999). Other studies support this action (Cavadas et al, 1995;
Sakamoto et al, 1992; Simmen et al, 1999).
Antiinsomnia
Action
The largest study included 121 patients with severe insomnia
(Vorbach et al, 1996). They saw signifi cant improvement within 28 days. This
may indicate valerian is most effective in long-term treatment.
Other
Actions
Valerian has shown positive results in the treatment of
angina, decreasing the frequency and shortening the duration of anginal attacks
(Yang et al, 1994).
PHARMACOLOGICAL ACTIONS
·
Drug: Valerian root
(Valerianae radix).
·
Important Constituents: Iridoids
(valepotriate, 0.5–2.0 %); essential oil, 0.2– 1.0 % (bornyl-isovalerianate, isovalerianic
acid; sometimes also valerenal and valeranone), and sesquiterpenes (valerenic
acid, 0.1–0.9 %).
·
Pharmacological Properties: Valerian has
central depressant, sedative, anxiolytic, spasmolytic, and muscle relaxant
effects in animals and has a benzodiazepine- like effect on the GABA system.
Valepotriates have a sedative effect on the autonomic nervous system. The
essential oil has sedative and spasmolytic effects on the central nervous
system. The efficacy of valerian preparations depends largely on the quality
and freshness of the starting material, the extraction process, and the
freshness of the extract. In humans it reduces the sleep induction time and has
sedative action during the daytime.
Warning: Although Valerian tea and tincture do not
contain any valepotriates (because they are unstable), they do contain
degradation products with similar action. The long-term safety of these
products has not been determined.
Sedative
and hypnotic properties have been described for certain valerian rhizome/root
preparations following preclinical and clinical studies. However, the available
scientific evidence is strong; also it remains unclear precisely which of the
constituents of valerian are responsible for the observed sedative and hypnotic
properties.(5) Attention had focused on the volatile oil, and then the
valepotriates and their degradation products, as the constituents responsible.
However, it appeared that the effects of the volatile oil could not account for
the whole action of the drug, and the valepotriates, which degrade rapidly, are
unlikely to be present in finished products in significant concentrations.
Current thinking is that the overall effect of valerian is due to several different
groups of constituents and their varying mechanisms of action. Therefore, the
activity of different valerian preparations will depend on their content and
concentrations of several types of constituent.(4) One mechanism of action is
likely to involve increased concentrations of the inhibitory transmitter GABA
in the brain. Increased concentrations of GABA are associated with a decrease
in CNS activity and this action may, therefore, be involved in the reported
sedative activity.
IN VITRO AND ANIMAL STUDIES
Sedative properties have been documented for valerian and have been
attributed to both the volatile oil and valepotriate fractions.(16, 17)
Screening of the volatile oil components for sedative activity concluded
valerenal and valerenic acid to be the most active compounds, causing ataxia in
mice at a dose of 50 mg/ kg by intraperitoneal injection.(16) Further studies
in mice described valerenic acid as a general CNS depressant similar to pentobarbitone,
requiring high doses (100 mg/kg by intraperitoneal injection) for activity.(18)
A dose of 400 mg/kg resulted in muscle spasms, convulsions and death.(18) Valerenic
acid was also reported to prolong pentobarbitone-induced sleep in mice, resulting
in a hangover effect. Biochemical studies have documented that valerenic acid
inhibits the enzyme system responsible for the central catabolism of GABA.(19) An
aqueous extract of roots and rhizomes of V. officinalis (standardised to 55 mg valerenic
acids per 100 g extract) inhibited the uptake and stimulated the release of
radiolabelled GABA in isolated synaptosomes from rat brain cortex.(20, 21) Further
work suggested that this aqueous extract of valerian induces the release of
GABA by reversal of the GABA carrier, and that the mechanism is Naþ dependent
and Ca2þ independent.(21) The extract contained a high concentration of GABA
(about 5 mmol/L) which was shown to be sufficient to induce the release of radiolabelled
GABA by this type of mechanism.(22) Aqueous and hydroalcoholic (ethanol)
extracts of valerian root displaced radiolabelled muscimol binding to synaptic
membranes (a measure of the influence of drugs on GABAA receptors). However,
valerenic acid (0.1 mmol/L) did not displace radiolabelled muscimol in this
model.(23) Other in vitro studies using rat brain tissue have shown that
hydroalcoholic and aqueous total extracts of V. officinalis root, and an
aqueous fraction derived from the hydroalcoholic extract, show affinity for GABAA
receptors, although far lower than that of the neurotransmitter itself.(24)
However, a lipophilic fraction of the hydroalcoholic extract, hydroxyvalerenic
acid and dihydrovaltrate did not show any affinity for the GABAA receptor in
this model.
The effects of valerian extracts on benzodiazepine binding to rat
cortical membranes have also been explored. Very low concentrations of
ethanolic extract of V. officinalis had no effect on radiolabelled
flunitrazepam binding in this model, although concentrations of 10_10 to 10_8 mg/mL
increased radiolabelled flunitrazepam binding with an EC50 of 4.13 _ 10_10
mg/mL.(25) However, flunitrazepam binding was inhibited at higher
concentrations (0.5–7.0 mg/mL) of valerian extract (IC50 4.82 _ 10_1 mg/ mL).
In other investigations, valerian extract potentiated radiolabelled GABA
release from rat hippocampal slices, and inhibited synaptosomal GABA uptake,
confirming the effects of valerian extract on GABAA receptors.(25)
Radiolabelled ligand binding studies have also shown that constituents
of dichloromethane and petroleum ether extracts of valerian have strong binding
affinities for 5-HT5a receptors but only weak binding affinities for 5-HT5b
receptors.(26) At concentrations of 50 mg/mL, the petroleum ether and
dichloromethane extracts inhibited binding of radiolabelled lysergic acid diethylamide
to 5-HT5a receptors by 86% and 51%, respectively. Generation of an IC50 curve for
the petroleum ether extract produced a biphasic curve. Valerenic acid, a
constituent of both extracts, had an IC50 of 17.2 mmol/L. In other
radiolabelled ligand binding experiments, a 45% methanol extract of valerian
root (drug to extract ratio 4–6 : 1; containing
valerenic acids 0.388%, and no valepotriates) had an IC50 value of 450 mg/mL at
melatonin-1 (ML) receptors obtained from chicken brain, whereas a 45% methanol extract
of hops' cones (containing flavonoids 0.479%, calculated as rutin) had an IC50
value of 71 mg/mL at these receptors. A preparation (ZE-91019) containing both extracts
had an IC50 value of 97 mg/mL, suggesting a synergistic action between the two
extracts at ML1 receptors.(27) CNS-depressant activities in mice following
intraperitoneal injection have been documented for the valepotriates and for
their degradation products, although activity was found to be greatly reduced
following oral administration.(28) A study explored the effects of a mixture of
valepotriates on the behaviour of diazepamwithdrawn male Wistar rats in the
elevated plus-maze test (a measure of the anxiolytic or anxiogenic properties
of drugs).(29) Rats were given diazepam (up to 5 mg/kg for 28 days) then
vehicle only for three days to induce a withdrawal syndrome. Rats given diazepam
or a mixture of valepotriates (stated to contain dihydrovaltrate 80%, valtrate
15% and acevaltrate 5%) administered intraperitoneally (12 mg/kg) spent a
significantly greater proportion of time in the 'open' arms of the maze than
did those in the control group.
Another specific valepotriate fraction, Vpt2, has been
documented to exhibit tranquillising, central myorelaxant, anticonvulsant, coronary-artery
dilating and anti-arrhythmic actions in mice, rabbits, and cats.(30, 31) The
fraction was reported to prevent arrhythmias induced by Pituitrin vasopressin
and barium chloride, and to exhibit moderate positive inotropic and negative chronotropic
effects.
Antispasmodic activity on intact and isolated guinea-pig ileum has
been documented for isovaltrate, valtrate and valeranone.(32) This activity was
attributed to a direct action on the smooth muscle receptors rather than
ganglion receptors. Valerian oil has been reported to exhibit antispasmodic
activity on isolated guinea-pig uterine muscle,(33) but proved inactive when
tested in vivo.(34)
In-vitro inactivation of complement activation has been reported
for the valepotriates.(35) In-vitro cytotoxicity (inhibition of DNA and protein
synthesis, and potent alkylating activity) has been documented for the valepotriates,
with valtrate stated to be the most toxic compound.(36) Valepotriates (valtrate
and didrovaltrate) isolated from the related species Valeriana wallichii, and
baldrinal (a degradation product of valtrate) have been tested for their cytotoxic
activity in vitro using cultured rat hepatoma cells.
Valtrate was the most active compound in this system, leading to
a 100% mortality of hepatoma cells after 24 hours' incubation at a concentration
of 33 mg/mL.(37) More detailed studies using the same system showed that
didrovaltrate demonstrated cytotoxic activity when incubated at concentrations
higher than 8 mg/mL of culture (1.5 _ 10_5 mol/L) and led to 100% cellular
mortality with 24 hours of incubation at a concentration of 66 mg/mL. The cytotoxic
effect of didrovaltrate was irreversible within two hours of incubation with
hepatoma cells. In mice, administration of intraperitoneal didrovaltrate led to
a regression of Krebs II ascitic tumours, compared with control.(37) A
subsequent in vivo study, in which valtrate was administered to mice (by
intraperitoneal injection and by mouth), did not report any toxic effects on haematopoietic
precursor cells when compared with control groups.(38) The valepotriates are
known to be unstable compounds in both acidic and alkaline media and it has
been suggested that their in vivo toxicity is limited due to poor absorption
and/or distribution.(2) Baldrinal and homobaldrinal, decomposition products of
valtrate and isovaltrate respectively, have exhibited direct mutagenic activity
against various Salmonella strains in vitro.(39)
CLINICAL STUDIES
Pharmacokinetics
There are only limited data on the pharmacokinetics of valerian preparations
and their constituent compounds. The pharmacokinetics of valerenic acid were explored
in a single-dose study involving six healthy adults who received a 70% ethanol
extract of valerian root (LI-156, Sedonium, Lichtwer Pharma; drug to extract ratio
5 : 1) 600 mg in the morning. For five participants, maximum serum
concentrations of valerenic acid occurred between one and two hours after valerian
administration and ranged from 0.9 to 2.3 ng/mL; valerenic acid concentrations
were measurable for at least five hours after valerian administration.(40) For
one subject, maximum concentrations occurred at both one and five hours after
valerian administration. The mean (standard deviation (SD)) elimination half-life
(t1/2) for valerenic acid was 1.1 (0.6) hours and the mean (SD) area under the
plasma concentration time curve was 4.80 (2.96) mg/mL/hour. Further investigation
of the pharmacokinetics of valerian is required, including those of different
manufacturers' preparations and their constituents.
Sleep
Disorders, Hypnotic Activity Numerous studies have explored
the effects of valerian preparations on subjective (e.g. participants'
self-assessment of sleep quality) and/or objective (e.g. sleep structure, such
as duration of rapid eye movement (REM) sleep or slow-wave sleep) sleep
parameters. Collectively, the findings of these studies are difficult to
interpret, as different studies have assessed different valerian preparations
and different dosages, and some have involved healthy volunteers whereas others
have involved patients with diagnosed sleep disorders. In addition, other
studies have used different subjective and/or objective outcome measures, and
some have been conducted in sleep laboratories, whereas others have assessed
participants receiving valerian whilst sleeping at home. Overall, several, but not
all, studies have documented a hypnotic effect for valerian preparations with
regard to subjective measures of sleep quality, and some have documented
effects on objective measures of sleep structure. There is a view that investigating
subjective measures of sleep quality may be the most appropriate or relevant
form of assessment.(41) Several trials, including the most recent studies, particularly
those involving individuals with sleep disorders rather than healthy
volunteers, are summarised below.
A randomised, double-blind, placebo-controlled, crossover study
involving 16 patients with previously established psychophysiological insomnia
according to International Classification of Sleep Disorders (ICSD) criteria and
confirmed by polysomnography assessed the effects of single-dose and
longer-term administration of valerian root extract on objective parameters of
sleep structure and subjective parameters of sleep quality.(42)
Participants received a 70% ethanol extract of valerian root
(LI- 156; drug to extract ratio 5 : 1) 600 mg, or placebo, one hour before
bedtime for 14 days, followed by a wash-out period of 13 days before crossing
over to the other arm of the study. There were no statistically significant
effects on objective and subjective parameters of sleep following single-dose
valerian administration.
Similarly, after long-term treatment, there were no
statistically significant differences between groups in sleep efficiency (ratio
of time spent asleep to time spent in bed). There was a statistically significant
difference with valerian on parameters of slow-wave sleep, compared with
baseline values, which did not occur with placebo. However, it is not clear if
this difference was significantly different for valerian, compared with
placebo, as no p-value was given.
The effects of repeated doses of the same valerian root extract (LI-156)
were assessed in a randomised, double-blind, placebocontrolled, parallel-group
trial involving 121 patients with insomnia not due to organic causes.(43) Participants
received valerian extract 600 mg, or placebo, one hour before bedtime for 28
days. At the end of the study, clinical global impression scores were
significantly higher for the valerian group than for the placebo group.
A crossover study assessing the same valerian root extract (LI- 156)
involved 16 individuals aged 50 to 64 years with mild sleep complaints (e.g.
difficulty initiating or maintaining sleep, early morning awakenings) who
received a single 300 mg or 600 mg dose of the extract, or placebo, at 10 pm on
one occasion, with a 6-day wash-out period before crossing over to each of the
other arms of the study.(44) Participants underwent a battery of tests designed
to assess objective and subjective measures of sleep at 7.05 am on the morning
after each treatment intervention. There were no statistically significant
differences between the three groups for any of the outcome variables measured
(p > 0.05).
In a randomised, double-blind, pilot study, 14 older womenwho were
poor sleepers received valerian aqueous extract (Valdispert forte; drug to
extract ratio 5–6 : 1), or placebo (n = 6), for eight consecutive days.(15) Valerian
405 mg was administered one hour before sleep for one night in the laboratory,
then taken three times daily for the following seven days. Valerian recipients
showed an increase in slow-wave sleep, compared with baseline values.
However, valerian had no effect on sleep onset time, rapid eye movement
(REM) sleep or on self-rated sleep quality, when compared with placebo. In another
randomised, double-blind, placebo-controlled study involving older
participants, 78 hospitalised patients with various chronic conditions in
addition to difficulty sleeping received an aqueous valerian root extract (Baldrian
Dispert) 270 mg daily, or placebo, for 14 days.(45) At the end of the study,
sleep latency and sleep duration were significantly improved in the valerian
group, compared with the placebo group (p < 0.001 for both).
A randomised, double-blind, placebo-controlled study involving 128
volunteers explored the effects of an aqueous extract of valerian root (400 mg)
and a proprietary preparation of valerian and hops (Hova) on subjective measures
of sleep quality. Each participant took each of the three preparations at night
for three non-consecutive nights.(14) On the basis of participants'
selfassessment, valerian significantly reduced sleep latency (time to onset of
sleep) and improved sleep quality, compared with placebo (p < 0.05). Subgroup
analysis suggested that the effects of valerian were most marked among participants
who described themselves as 'poor' or 'irregular' sleepers.(14) It was reported
that the valerian–hops preparation did not significantly affect sleep latency or
sleep quality, compared with placebo, only that the valerian– hops preparation
administration was associated with an increase in the number of reports of 'feeling
more sleepy than usual the next morning' (i.e. a 'hangover' effect). The
authors were unable to explain this discrepancy in the results for the two
preparations.
In a subsequent study, eight individuals with mild insomnia each
received aqueous valerian root extract 450 mg, 900 mg or placebo, in a
random-order experimental design over almost three weeks.(46) The time to the
first period of five consecutive minutes without movement, measured using
wrist-worn activity meters, was used as an objective measure of sleep latency.
For this parameter, valerian 450 mg significantly reduced the mean sleep latency,
compared with placebo, although there was no further reduction in sleep latency
with valerian 900 mg. Subjective assessments indicated that participants were
more likely to experience a 'hangover' effect with valerian 900 mg.(46)
The effects of a valerian root/rhizome extract (tablets
containing 225 mg extract equivalent to 1000 mg crude drug, standardised for
total valerenic acids 2.94 mg, valerenal 0.46 mg and valtrates 1.23 mg;
Mediherb, Australia) two tablets at night half an hour before going to bed on
self-assessed sleep parameters were assessed in a series of randomised, double-blind,
placebocontrolled, 'n-of-1' crossover trials involving 24 patients with chronic
insomnia diagnosed by a general practitioner. The trials were conducted in a
general practice setting and involved three pairs of one-week treatments with valerian
extract and placebo (i. e. each n-of-1 trial lasted for six weeks).(47) Statistical
analyses found that participants did not show any response to valerian for any
of the outcome measures either individually or when individual results were
pooled. N-of-1 trials have recognised limitations, including some which can
increase the possibility of false negative results, although these were taken
into consideration during the analysis of these data. Investigation of dosage regimens
involving higher doses of this extract administered for longer periods may be
warranted.(47)
In a randomised, double-blind, placebo-controlled trial
conducted entirely over the Internet, 391 adults who scored at least 40 points
on the State-Trait Anxiety Inventory (STAI) scale and who reported having
sleeping problems on at least two occasions received two capsules containing valerian
extract (each containing valerenic acids 3.2 mg; no further details of
preparation provided) one hour before bedtime, capsules containing kava extract
(each containing total kavalactones 100 mg) one three times daily, or placebo,
for 28 days.(48) At the end of the study, there were no statistically
significant differences between valerian and placebo with respect to the primary
outcome measure changes from baseline in Insomnia Severity Index scores. The
study also assessed effects on anxiety (see Anxiety, depression and other
conditions).
The effects of preparations of valerian root extract have been compared
with those of certain benzodiazepines. In a randomised, double-blind trial, 75
individuals with non-organic and nonpsychiatric insomnia received valerian root
extract (drug to extract ratio 5 : 1) 600 mg or oxazepam 10 mg; both treatments
were taken 30 minutes before going to bed for 28 days.(49) At the end of the treatment
period, sleep quality had improved significantly (p < 0.001) in both groups,
compared with baseline values, and there was no statistically significant
difference between the two groups (p= 0.70). The effects of a combination
valerian preparation were compared with those of bromazepam in a three-week,
randomised, double-blind trial involving patients with 'environmental' sleep
disorders (temporary dyscoimesis and dysphylaxia) according to Diagnostic and
Statistical Manual (DSM)-IV criteria.(50)
The combination preparation, containing valerian 200 mg and hops
extract 45.5 mg, was reported to be equivalent to bromazepam 3mg with regard to
sleep quality. These findings require confirmation in rigorous studies designed
specifically to test for equivalence.
Several of the studies summarised above(14, 15, 43, 45, 46) were
included in a systematic review of nine randomised, double-blind, placebo-controlled
trials of monopreparations of valerian.(51) All trials included in the review
had different designs and assessed the effects of different valerian preparations
administered according to different dosage regimens, so the validity of
considering their results collectively is questionnable. The review concluded
that the evidence for valerian as a treatment for insomnia is inconclusive and
that there is a need for further rigorous trials.
Several other studies have assessed the effects of valerian
extract in combination with other herb extracts, such as hops (Humulus lupulus)
and/or melissa (Melissa officinalis), on measures of sleep.(52–56) In a
randomised, double-blind, placebo-controlled, parallelgroup trial, 184 adults
with mild insomnia received two tablets of a valerian–hops preparation (each
tablet containing 187 mg of a 45% methanol extract of valerian, drug to extract
ratio 5–8 : 1, and 42 mg of a 45% methanol extract of hops, drug to extract ratio
7–10 : 1; n = 59), or placebo (n = 65), each night for 28 days; a third study
arm received diphenhydramine 50 mg each night for 14 days followed by placebo
for 14 days (n = 60).(52) At the end of the study, there was no statistically significant
difference in sleep latency between the valerian–hops group and the placebo
group (p = 0.08). There were no statistically significant differences between groups
with respect to the sleep continuity variables, as measured by polysomnography,
nor in the duration of sleep stages 3 and 4, and REM sleep. The physical
component, but not the mental component, of the quality-of-life measure used
was significantly improved in the valerian–hops group, compared with the
placebo group after 28 days (p = 0.028).
A randomised, double-blind trial involving healthy volunteers who
received Songha Night (V. officinalis
root extract 120 mg and M. officinalis
leaf extract 80 mg) three tablets daily taken as one dose 30 minutes before
bedtime for 30 days (n = 66), or placebo (n = 32), found that the proportion of
participants reporting an improvement in sleep quality was significantly
greater for the treatment group, compared with the placebo group (33.3% versus 9.4%,
respectively; p = 0.04).(54) However, analysis of visual analogue scale scores
revealed only a slight, but statistically nonsignificant, improvement in sleep quality
in both groups over the treatment period. Another double-blind, placebo controlled
trial involving patients with insomnia who received Euvegal forte tablets (containing
valerian extract 160 mg and lemon balm extract 80 mg) two daily for two weeks
reported significant improvements in sleep quality in recipients of the herbal
preparation, compared with placebo recipients.(55) A placebo-controlled study
involving 'poor sleepers' who received Euvegal forte reported significant improvements
in sleep efficiency and in sleep stages 3 and 4 in the treatment group,
compared with placebo recipients.(56)
In a single-blind, placebo-controlled, crossover study involving
12 healthy volunteers, two different single doses of a combination preparation
(ZE-91019) containing extracts of valerian and hops (valerian 500 mg, hops 120
mg; valerian 1500 mg, hops 360 mg) were assessed for their effects on EEG
recordings.(57) Some slight effects on the quantitative EEG were documented
following administration of the higher dose valerian–hops combination, suggesting
effects on the central nervous system. The same preparation (two or six tablets
as a single dose; n = 16), in addition to caffeine 200 mg, was administered to
healthy volunteers in a controlled (caffeine 200 mg plus placebo; n = 16)
studywhich aimed to determine the pharmacodynamics of co-administration of the two
preparations by measuring EEG responses.(58) EEG recordings at one hour after
administration indicated that the lower dose of the valerian–hops preparation
reduced caffeine-induced arousal and the higher dose inhibited the caffeine-induced
arousal. It was stated that this indicates that the valerian–hops combination
preparation acts via a central adenosine mechanism,(58) although which constituents
are responsible for this effect is not known.
The effects of a related species, V. edulis, on sleep parameters
were assessed in a preliminary randomised, double-blind, placebocontrolled, crossover
trial involving five male children (7 to 14 years) with intellectual deficits
(intelligence quotient < 70).(59) Participants received tablets containing V.
edulis dried crushed root 500 mg (containing 5.52 mg valtrate/isovaltrate,
didrovaltrate and acevaltrate were absent; Mediherb, Australia), or placebo (which
contained 25 mg dried V. edulis root to achieve blinding for odour), at a dose
of 20 mg/kg body weight administered each night at least one hour before bedtime
for two weeks following a two-week run-in period. Participants underwent a
one-week wash-out period before crossing over to the other arm of the study.
Time awake, total sleep time and sleep quality all improved in
the valerian group, compared with baseline values (p < 0.05 for each), whereas
only sleep quality improved in the placebo group, compared with baseline values
(p = 0.04).(59) However, as no statistical analyses appear to have been
conducted to examine any differences between the valerian and placebo groups,
these findings raise the hypothesis that dried V. edulis root has effects on
certain sleep parameters and this requires testing in welldesigned clinical
trials involving adequate numbers of participants.
In a randomised, double-blind, placebo-controlled trial, a preparation
of constituents (Valmane, comprising didrovaltrate 80%, valtrate 15% and
acevaltrate 5%; Whitehall Pharmaceuticals) obtained from the root of V.
wallichii, another related species, was assessed for its effects on sleep
parameters in 19 individuals who had undergone withdrawal from benzodiazepines.(60)
Participants received the valerian preparation at a dose of 100 mg, or placebo,
three times daily starting two days after completing benzodiazepine withdrawal
and continuing for 15 days. At the end of the study, wake time after sleep
onset was significantly reduced in the valerian group compared with the placebo
group, whereas sleep latency was significantly improved in the placebo group,
compared with the valerian group (p < 0.05 for both). The study has
methodological limitations, including the small sample size, and these apparently
conflicting findings require further investigation in well-designed clinical
trials involving adequate numbers of participants.
Anxiety,
Depression And Other Conditions The effects of a preparation
containing a mixture of valepotriate compounds (stated to contain
dihydrovaltrate 80%, valtrate 15%, acevaltrate 5%) were assessed in a
randomised, double-blind, placebocontrolled, parallel-group trial involving 36
patients with generalised anxiety disorder diagnosed according to DSM-III-R
(Diagnostic and Statistical Manual of Mental Disorders) criteria.(61) Participants
received capsules containing the valepotriate mixture 50 mg, diazepam 2.5 mg,
or placebo, for four weeks according to a flexible dosing regimen (one to three
capsules of the active treatments) depending on the participants' response. At
the end of the study, there were no statistically significant differences between
the three groups for the primary outcome variable mean total Hamilton Anxiety
scale scores (p > 0.05) and for State-Trait Anxiety Inventory (STAI) scores.
As a sample size calculation was not carried out, and as the study involved
only a small sample, it is possible that the trial did not have sufficient statistical
power to detect differences (if they exist) between the three groups.
In another randomised, double-blind, placebo-controlled trial, conducted
entirely over the Internet, 391 adults who scored at least 40 points on the
STAI scale and who reported having sleeping problems on at least two occasions
received two capsules containing valerian extract (each containing valerenic
acids 3.2 mg; no further details of preparation provided) one hour before
bedtime, capsules containing kava extract (each containing total kavalactones
100 mg) one three times daily, or placebo, for 28 days.(48) At the end of the
study, there were no statistically significant differences between valerian and
placebo with respect to the primary outcome measure changes from baseline in
STAI anxiety scores. The study also assessed effects on insomnia (see Sleep
disorders, hypnotic activity).
The effects of valerian have also been assessed on mental stress
in laboratory-based studies involving healthy volunteers. In a randomised
controlled trial, 36 participants received valerian root extract (LI-156) 1200
mg (n = 18) or kava root extract (LI-150) 120 mg daily for seven days; a third
group of participants acted as a no-treatment control group.(62) Participants'
heart rate and blood pressure measurements were taken before, during and after a
mental stress test at baseline and seven days later following treatment. The
results suggested that increases in systolic blood pressure in response to
mental stress were lower in the valerian group, compared with those in the
control group. These results, however, can only be considered preliminary as
the control group did not receive placebo. Further investigation using a
randomised, double-blind, placebo-controlled trial design is required.(62)
The effects of another valerian extract at a dose of 100 mg (no further
details of preparation given), with or without propranolol 20 mg, on activation
and performance under experimental social stress conditions were assessed in a
randomised, double-blind, placebo-controlled study involving 48 healthy
volunteers.(63) Valerian was reported to have no statistically significant
effect on physiological activation and to lead to less intensive subjective feelings
of somatic arousal, compared with control.
Several studies have assessed the effects of combinations of valerian
and other herbal ingredients in patients with anxiety or depression. In a
randomised, double-blind study involving 100 patients with anxiety, a combination
of valerian and St John's wort was significantly more effective than diazepam
according to a physician's rating scale and a patient's self-rating scale.(64) In
a randomised, double-blind trial involving 162 patients with dysthymic
disorders, the effects of a valerian and St John's wort combination preparation
(Sedariston) were compared with those of amitriptyline 75–150 mg.(65) Another
randomised, double-blind trial, involving 100 patients with mild-to-moderate
depression compared Sedariston with desipramine 100–150 mg.(66) Pooling the
results of these two studies indicated there were 88 (68%) treatment responders
in the Sedariston group and 66 (50%) in the group that received standard
antidepressants.(67) This difference was not statistically significant. As
valerian root is not known for antidepressant effects, it is likely that any
antidepressant activity observed in the studies described above is attributable
to St John's wort.
Several studies have assessed the effects of valerian, or herbal
combination products containing valerian, on performance the morning after
treatment (see Side-effects, Toxicity).
ACTIVITIES
Analgesic
(f; CAN; CRC; MAD; PED; WHO); Antibacterial (1; APA; FAD; PED; WOI);
Anticomplementary (1; CAN); Anticonvulsant (1; APA; BGB; MAB); Antidandruff (f;
CRC); Antidiuretic (1; CRC; FAD; PED); Antiperspirant (f; WHO); Antiseptic (1;
WOI); Antispasmodic (2; PH2; WAM; WHO); Antitumor (1; PNC); Antiulcer (1; PH2);
Anxiolytic (1; MAB; PH2); Aperitif (1; BGB; CAN); Calmative (f; HAD); Carminative
(f; CRC; MAB; PED); Cerebrostimulant (f; MAB); CNS Depressant (1; FAD; PED;
PH2; WHO); CNS Stimulant (1; FAD); Cytotoxic (1; CAN); Digestive (f; WHO);
Diuretic (f; MAD; WHO); Emmenagogue (f; MAD; WHO); Digestive (f; WHO);
GABA-Genic (1; PH2; WHO); GABA-Sparing (1; PH2; PNC); Hepatoprotective (1; APA;
CRC; FAD); Hypnotic (3; BGB; CAN; MAB); Hypotensive (1; APA; CAN; CRC);
Mutagenic (1; CAN; MAB); Myorelaxant (2; MAB; PHR; PH2; WHO); Narcotic (f; CRC;
WOI); Nervine (1; FAD; MAD; PNC); Peristaltic (f; PED); Sedative (3; KOM; PH2;
WAM; WHO); Stimulant (f; CRC); Thymoleptic (1; MAB); Tranquilizer (2; APA; BRU;
FAD); Vermifuge (f; MAD); Vulnerary (f; MAD).
INDICATIONS
Abscess
(f; JLH); Acne (1; APA); Anorexia (1; BGB; CAN); Anthrax (f; MAD); Anxiety (2;
KOM; MAB; PH2; WAM; WHO); Aposteme (f; JLH); Ascarides (f; MAD); Asthma (f;
MAD); Atherosclerosis (f; MAD); Bacteria (1; APA; FAD; PED; WOI); Cancer (1;
JLH; PNC); Candida (f; WHO); Cardiopathy (f; PH2); Catarrh (f; CRC); Cerebrosis
(f; FEL); Cholera (f; CRC; MAB); Chorea (f; FEL; MAB; MAD); Cold (f; CRC);
Colic (f; CAN; MAD; PH2); Colitis (f; WHO); Condyloma (f; JLH); Conjunctivosis
(f; MAD); Convulsion (1; APA; BGB; CRC; MAB; WOI); Cough (f; MAD); Cramp (2;
APA; CAN; FAD; MAD; PH2; WAM; WHO); Dandruff (f; CRC); Depression (1; FAD; FEL;
MAB; PED); Dermatosis (f; APA); Despondency (f; FAD; FEL); Diphtheria (f; MAD);
Dysmenorrhea (f; APA; CAN; CRC; PH2); Dyspepsia (f; CRC; MAB); Eczema (f; PNC);
Enterosis (f; APA; CAN; MAD); Enuresis (f; MAD); Epilepsy (1; APA; FEL; PED;
PH2; WHO); Fatigue (1; CRC; FAD; PNC); Fever (f; FEL; MAB); Flu (f; CRC); Gas
(f; CRC; MAB; PED); Gastrosis (f; MAD); Gingivosis (f; WHO); Headache (f; FAD;
PED; PH2; WHO); Hemicrania (f; FEL); Hepatosis (1; APA; CRC; FAD); High Blood
Pressure (1; APA; CAN; CRC); Hyperactivity (1; WAM); Hypochondria (f; CAN; CRC;
FEL; FAD); Hysteria (f; CAN; CRC; FEL; MAB; MAD; PH2); Infection (1; WOI); Inflammation
(f; CRC; WHO); Insomnia (3; CAN; KOM; PH2; WAM; WHO); Lumbago (f; MAD);
Menopause (f; MAD; PH2); Menstrual Cramp (f; APA; CAN); Migraine (f; CAN); Myalgia
(f; MAD); Nausea (f; WHO); Nervousness (3; APA; BRU; FAD; KOM; PH2; WAM; WHO);
Nervous Tension (3; APA; BRU; FAD; KOM; PH2; WAM; WHO); Neurasthenia (f; CRC;
PH2); Neuropathy (f; CRC; MAB; PH2); Neurosis (f; MAB); Numbness (f; CRC); OCD (1;
WAF); Ophthalmia (f; CRC); Pain (f; CAN; CRC; MAB; MAD; PED; WHO); Palpitation (f;
CRC); Panic (f; APA); Plague (f; APA); Polyp (f; CRC; JLH); Restlessness (2;
APA; KOM); Rheumatism (f; CAN; CRC; MAD); Rhinosis (f; JLH); Shell Shock (f;
MAB); Sore (f; APA; CRC); Sore Throat (f; WHO); Spasm (f; CRC); Stress (2; MAB;
PED); Syncope (f; MAD; PH2); Toothache (f; CRC); Trauma (f; CRC); Tumor (1;
JLH; PNC); Typhus (f; MAD); Ulcer (1; PH2); Uterosis (f; PH2); Vaginosis (f;
WHO); Vertigo (f; MAD); Water Retention (f; MAD; WHO); Worm (f; CRC; MAD);
Wound (f; CRC).
INDICATIONS AND USAGE
Approved by
Commission E:
• Nervousness and Insomnia
Unproven
Uses:
Valerian
is used for restlessness, sleeping disorders based on nervous conditions,
mental strain, lack of concentration, excitability, stress, headache,
neurasthenia, epilepsy, hysteria, nervous cardiopathy, menstrual states of agitation,
pregnancy, menopause, neuralgia, fainting, nervous stomach cramps, colic, uterine
spasticity and states of anxiety.
PRODUCT AVAILABILITY
Capsules, crude herb, extract,
tablets, tea, tincture; combination products containing other herbs
PLANT PARTS USED: Rhizomes, roots
DOSAGES
DOSAGES
Insomnia
·
Adult PO extract: 400-900 mg
1⁄2-1 hr before bedtime (standardized)
·
Adult PO tea (crude herb): 1
tsp crude herb qid
·
Adult PO tincture: 3-5 ml qid
(standardized)
DOSAGE AND
DURATION OF USE
Used internally and externally (hydrotherapy).
·
Tea: Steep 1 teaspoonful (3–5 g) of the chopped roots and
rhizomes in 150 mL of hot water for 10 to 15 minutes.
• Dosage:
2 to 3 cups a day, plus 1 cup
before retiring.
• Daily
Dose: 15 g herb.
·
1 : 5 Tincture: 15–20 drops several times a day.
·
Extract: 2–3 g herb, one to several times a day.
DOSAGES
Dosages
for oral administration (adults) for traditional uses recommended in standard
herbal reference texts are given below.
·
Dried rhizome/root 1–3 g as an infusion or decoction up to three
times daily.(G6)
·
Tincture 3–5mL (1 : 5; 70% ethanol) up to three times daily;(G6,
G50) 1–3 mL, once to several times daily.(G3)
·
Extracts Amount equivalent to 2–3 g drug, once to several times daily;(G3)
2–6mL of 1 : 2 liquid extract daily.(G50)
·
Doses given in older texts vary. For example: Valerian Liquid
·
Extract (BPC 1963) 0.3–1.0 mL; Simple Tincture of Valerian (BPC 1949)
4–8 mL; Concentrated Valerian Infusion (BPC 1963) 2– 4 mL.
Clinical
trials investigating the effects of valerian root extracts on sleep parameters have used varying dosages,
for example, valerian extract 400 mg/day (drug to extract ratio of 3 : 1)(14) and
1215 mg/day (drug to extract ratio of 5 to 6 : 1).(15)
DOSAGES
·
1 tsp (2–3 g) root/cup water
(APA); 2–3 g root 1–3 x /day (APA); 2–3 g root/cup
tea, 1 to several x /day (KOM);
·
2–3 g root/150 ml water 1 x /day (PIP); 0.3–1 g dry root, or in tea, 3 x /day (CAN); 3–9 g dried root/day (MAB);
·
0.5–4 g powdered root (MAD);
2–4 ml concentrated root infusion (PNC); 0.3–1 ml liquid root extract (CAN;
PNC);
·
3–5 ml (0.5–1 tsp) root extract
or tincture (APA); 2–6 ml fluid root extract (1:2)/day (MAB); 5–15 ml root
tincture (1:5)/day (MAB); 4–8 ml root tincture (PNC; SKY); 4–8 ml simple
valerian root tincture, or 2–4 ml concentrated valerian root infusion (CAN);
·
0.5–1 tsp (1–3 ml) root
tincture, 1 to several x/day (KOM); 100 g for one full
bath (KOM); 300–500 mg StX at bedtime (SKY); 300–400 mg StX (0.5% EO) day; 3
(475 mg) root capsules 3 x /day or before bed (APA); 3–6
(475 mg) capsules one-half hour before bed (JAD).
DOSAGES
Mode
of Administration: Valerian is used internally as expressed
juice from fresh plants, tincture, extracts, and other galenic preparations. Externally,
it is used as a bath additive, though efficacy is Unproven for this indication.
How Supplied:
Capsules — 100 mg. 250
mg, 380 mg, 400 mg, 445 mg, 450 g, 475 mg, 493 mg. 495 mg, 500 mg, 530 mg, 550
mg, 1000 mg.
Liquid — 1:1
Tablets — 160 mg. 550
mg
Tea Bags
Preparation: To prepare an
infusion, use 2 to 3 g of drug per cup. A tea is prepared by adding 1
teaspoonful (3 to 5 g) of drug to 150 ml of hot water and strain after 10 to 15
minutes. An extract is prepared by mixing 2 parts root powder to 6 parts spirit
of wine and 9 parts water. For external use, 100 g of comminuted drug is mixed
with 2 liters hot water; this is then added to the bath.
Daily Dosage: The daily dose
of Valerian extract is 100 mg to 3800 mg. Total internal daily dose is 15 g of
root powder.
Infusion — One cup one
to several times per day
Tea — One cup (150
ml) 2 to 3 times daily and before bedtime.
Tincture — 1/2 to 1
teaspoonful (1 to 3 ml) one to several times per day.
Tincture (1:5) — several
times daily 15 to 20 drops in water.
Extract — equivalent 2 to
3 g drug, one to several times per day.
Plant Juice — Adults take 1 tablespoonful 3
times daily. Children take 1 teaspoonful 3 times daily.
External Use — As a bath according to
preparation instructions above.
Sleep Aid — 400 mg to 900 mg of the extract
30 minutes before bedtime
Restlessness — 220 mg
extract three times daily
Storage: Must
be kept from sources of light; tinctures and extracts should be stored at room
temperature in tightly closed, non-plastic containers.
PRECAUTIONS AND ADVERSE REACTIONS
GENERAL: No health
hazards are known in conjunction with the proper administration of designated
therapeutic dosages. Gastrointestinal complaints can occur in rare cases,
contact allergies in very rare ones. With long-term administration, the
following can occasionally appear: headache, restless states, sleeplessness,
mydriasis, disorders of cardiac function. When large skin injuries or acute
skin illnesses, severe feverish or infectious diseases, cardiac insufficiency
or hypertonia are present, entire-body baths with the addition of the volatile
oil or of extracts from the drug should be avoided.
DRUG INTERACTIONS: Valerian may
potentiate the effect of other CNS depressants. Animal studies have shown that Valerian
has an additive effect when used in combination with barbiturates and benzodiazepines
(Leuschner, 1993; Hiller, 1996.) Though there has been no evidence of
potentiation of the CNS depressive effect when combined with alcohol, it is not
recommended that Valerian be used in conjunction with alcohol. Because of the
sedative effect of Valerian, operation of machinery or motor vehicles should be
avoided for several hours after injesting Valerian products.
PREGNANCY: Use of Valerian
during pregnancy or in nursing mothers is not recommended.
CONTRAINDICATIONS, INTERACTIONS, AND SIDE EFFECTS
CLASS 1
(AHP). None reported (PIP). None known (KOM). But Gruenwald (PHR) mentions rare
GI complaints, and even rarer contact allergies. He adds that long-term
administration may occasionally cause cardiac disorders, headache, mydriasis,
restless states, and sleeplessness, the latter two the main indications, now
side effects of prolonged use. Full-body valerian baths should be monitored in
cases of dermatosis, major skin injuries, cardiac insufficiency, or hypertonia
(PHR). No contraindications, adverse effects, or interactions except for the
effect of the tincture on driving ability (AEH). Ironically, “There is some
concern about continual use, which may cause minor side effects, including
headaches, excitability, and insomnia” (Morazzoni & Bombardelli, 1995). AHP
minimizes published concern about toxicity of valepotriates, due to poor
absorption and quick degradation into less toxic metabolites. If we accept this,
we have to minimize medicinal potential of the valepotriates as well. CAN says,
“There have been no reported side effects to valerian. The oil is unlikely to
present any hazard in aromatherapy” (CAN). After all those kind words CAN says,
“The safety of valerian during pregnancy and lactation has not been established
and should, therefore, be avoided.” CNS depressant activity may potentiate
pharmaceutical sedatives (CAN). For some 5% of people (maybe even hyperactives?
JAD), valerian may be slightly stimulating (WAM).
CONTRA-INDICATIONS, WARNINGS
Intake
of valerian preparations immediately (up to two hours) before driving or
operating machinery is not recommended.(G80) The effect of valerian preparations
may be enhanced by consumption of alcohol, so excessive consumption of alcohol whilst
receiving treatment with valerian root preparations should be avoided.(G80)
Patients should seek medical advice if symptoms worsen beyond two weeks'
continuous treatment with valerian.( G80) Patients with known sensitivity to
valerian should not use valerian root preparations.(G80)
Drug Interactions Only
limited data on the potential for pharmacodynamic and pharmacokinetic
interactions with other medicines administered concurrently are available for
valerian root preparations. In view of the documented pharmacological actions of
valerian the potential for preparations of valerian to interfere with other
medicines administered concurrently, particularly those with similar or
opposing effects, should be considered. In particular, co-medication with barbiturates
and other sedatives is not recommended because of the potential for excessive sedation.(G80)
In an open-label, fixed-treatment, crossover study, 12 healthy volunteers
received two tablets containing 500 mg of a 70% ethanol extract of valerian
root (containing total valerenic acids 5.51 mg per tablet) each night for two
weeks.(81) The probe drugs dextromethorphan 30 mg and alprazolam 2mg were
administered before and after valerian exposure to assess the effects of
valerian on CYP2D6 and CYP3A4 activity, respectively. There were no statistically
significant differences in dextromethorphan pharmacokinetics after valerian
exposure, compared with baseline values. The maximum plasma concentration of
alprazolam was significantly increased following valerian exposure, compared
with baseline values (p < 0.05) although there were no statistically significant
differences in other pharmacokinetic parameters measured. Another study
involved healthy volunteers who received valerian root extract (subsequently
found to contain quantities of valerenic acid only at the limits of detection
(10 ng/mL)) 125 mg three times daily for 28 days.(82) No statistically significant
changes in phenotypic ratios for CYP1A2, CYP2D6, CYP2E1 and CYP3A4/5 were
observed for valerian, although the valerian product tested may not be representative
of other valerian preparations and their effects on CYP enzymes.(82) In
in-vitro experiments, aqueous, ethanol and acetonitrile extracts of commercial
monopreparations and combination preparations of valerian root inhibited
cytochrome P450 3A4 activity and Pglycoprotein transport, as determined by an
ATPase assay.(83)
Pregnancy And Lactation
The safety of valerian during pregnancy and lactation has not been established
and, therefore, its use should be avoided.(G80)
CONTRAINDICATIONS
Pregnancy category is 2;
Breastfeeding category is 3A. Caution should be used when giving
valerian to children. Persons with hepatic disease and those with
hypersensitivity to valerian should not use it.
SIDE
EFFECTS/ADVERSE REACTIONS
CNS: Insomnia, headache, restlessness
GI: Nausea, vomiting, anorexia, hepatotoxicity
(overdose)
INTEG: Hypersensitivity reactions
MISC: Vision changes, palpitations
INTERACTIONS
Drug
CNS depressants (alcohol,
barbiturates, benzodiazepines, opiates, sedatives/hypnotics): Valerian may increase the effects of central nervous system depressants; avoid concurrent use.
Cytochrome
P4503A4 substrates: Valerian
may inhibit these enzyme systems.
Iron salts: Valerian may interfere with the absorption of iron
salts; separate by 2 hours.
MAOIs,
phenytoin, warfarin: Valerian
may negate the therapeutic effects of MAOIs, warfarin, and products containing phenytoin;
do not use concurrently.
Lab Test
ALT, AST, total
bilirubin, urine bilirubin: Valerian
may cause increased ALT, AST, total bilirubin, and urine bilirubin.
HERB–DRUG INTERACTIONS: None known
Warning: Valepotriate-free preparations are
currently recommended for pediatric use since the potential risk of mutagenic
and/or genotoxic effects has not yet been satisfactorily defined.
➤ Summary Assessment: Valerian tea,
tincture, and other valepotriate-free preparations promote the induction of
sleep. Preparations containing valepotriates are effective in the treatment of
daytime mental and motor agitation and lack of concentration; they have a
calming effect when taken prior to stress situations. The ability to drive a
motor vehicle or operate machinery is not impaired.
EFFECTS
In
animal experiments, the interaction of the various constituents are centrally
depressive, sedative, anxiolytic, spasmolytic, muscle relaxing and
anti-ulcerogenic. The pharmacological efficacy is heavily dependent on the
quality of the extract used.The main effect in humans is to reduce sleep
induction time. In vitro the valerenic acid componants have been shown to decrease
the degradation of gamma— aminobutyric acid (GABA.) Animal experiments have
demonstrated an increase of GABA at the synaptic cleft via inhibition of
re-uptake and an increase in secretion of the neurotransmitter. The increase of
available GABA is one factor that may be responsible for the sedative
properties of Valerian root (Houghton, 1998; Santos et al, 1994.) One other
mechanism that may contribute to the sedative properties of Valerian could be
the high levels of glutamine present in the extract Unlike GABA, glutamine more
effectively crosses the blood-brain barrier where it can be taken up by the
nerve terminals and converted to GABA (Santos. Fero, 1994.)
CLINICAL TRIALS
Improvements
in sleep quality ratings were demonstrated in a well constructed, randomized, placebo-controlled,
multicenter study involving 121 patients. Subjects were given either 600 mg of
a 70% ethanol extract (5:1, n = 61) of
Valerian
root that was standardized to 0.4 - 0.6% valerenic acid or placebo (n = 60) one
hour before bedtime for 28 consecutive nights. Patients were given two
standardized sleep questionaires; one that measured the depression/mood scale
and another global clinical impression scale. Sixty-six percent of the Valerian
treatment arm rated the therapeutic effect as either good or very good at the
end of the 28 day trial. This compared to only a 29% equally positive rating by
the placebo participants. (Vorbach, 1996).
ADVERSE EFFECTS: No known health hazards.
Gastrointestinal symptoms are rare side effects and contact allergies are very
rare. Headaches, anxiety, insomnia, mydriasis and disturbance of heart action
occasionally occur during prolonged use of high doses.
SIDE-EFFECTS, TOXICITY
CLINICAL DATA
There are only limited clinical data on safety aspects of
valerian preparations from clinical trials. Clinical trials have the
statistical power to detect only common, acute adverse effects and
postmarketing surveillance-type studies are required to establish the safety of
valerian preparations, particularly with long-term use.
Few controlled clinical trials of valerian preparations have provided
detailed information on safety. Where adverse event data were provided,
randomised, placebo-controlled trials involving healthy volunteers or patients
with diagnosed insomnia reported that adverse events with valerian were mild
and transient, and that the types and frequency of adverse events reported for
valerian were similar to those for placebo.(44, 47, 51, 68) One study involving
small numbers of patients reported a lower frequency of adverse events with
valerian than with placebo; the authors did not suggest an explanation for
this.(42) Studies comparing valerian preparations with benzodiazepines have
reported that valerian root extract (LI-156) 600 mg daily for 14 days(68) or 28
days(49) had a more favourable adverse effect profile than flunitrazepam 1mg daily
for 14 days(68) and oxazepam 10 mg daily for 28 days,(49) respectively.
There is an isolated report of cardiac complications and delirium
associated with valerian root extract withdrawal in a 58- year-old man with a
history of coronary artery disease, hypertension and congestive heart
failure.(69) The man had been taking valerian root extract (530 mg to 2 g, five
times daily), multiple other medications and had undergone surgery, therefore a
causal link with valerian could not be made. There have been isolated reports
of hepatotoxic reactions following the use of combination products containing
valerian, although these products contained other herbal ingredients which
could also be implicated.(70, G18, G21) Several other reports document
hepatotoxic reactions with single-ingredient valerian products, although it is possible
that these were idiosyncratic reactions.(71) There is a lack of data on the safety
of the long-term use of valerian.
Cases of individuals who had taken overdoses of valerian or valerian-containing
products have been documented. One case involved an 18-year-old female who
ingested 40–50 capsules of powdered valerian root 470 mg, approximately 20
times therapeutic doses.(72) The patient presented three hours after ingestion with
fatigue, crampy abdominal pain, chest tightness, tremor and lightheadedness.
Liver function test values were normal; a urine screen tested positive for
tetrahydrocannabinol. The patient was treated with activated charcoal, and
symptoms resolved within 24 hours. Several cases (n = 47) have been documented
of overdose with a combination valerian-containing product ('Sleep-Qik'; valerian
dry extract 75 mg, hyoscine hydrobromide 0.25 mg, cyproheptadine hydrochloride
2 mg).(73, 74) Individuals had ingested tablets equivalent to 0.5–12 g valerian
extract. Liver function tests were carried out for most patients and yielded results
within normal ranges.
Effects On Cognitive And Psychomotor
Performance
Studies assessing the effects of valerian preparations on
measures of performance report conflicting results: some suggest that there is
slight impairment for a few hours following ingestion of single doses of
valerian, whereas other studies report no effects on performance following
administration. As these studies have assessed the effects of different
preparations of valerian, the conflicting results may simply relate to
differences in the chemical composition of the products tested. Further
research is needed to establish whether or not specific valerian preparations
impair performance following ingestion. In contrast, the few studies investigating
the potential for impaired performance the morning following treatment (i.e.
'hangover' effects) with valerian preparations have found that such impairment
does not occur, at least with the preparations and dosages tested. Several of
the studies examining these aspects are summarised below.
In a randomised, double-blind, placebo-controlled, crossover study,
nine healthy participants each received a 70% ethanol extract of valerian root
(containing valerenic acid 0.25%; drug to extract ratio 4 : 1) 500 mg, 1000 mg,
and triazolam 0.25 mg, as a single dose with a one-week wash-out period between
treatments.
There were no statistically significant differences in the
outcomes of cognitive and psychomotor tests performed before and two, four and
eight hours after each treatment dose between the valerian and placebo
groups.(75) A similar finding was obtained in a randomised, double-blind, placebo-controlled,
crossover study involving ten healthy participants who underwent assessments of
mood and psychomotor performance before and after receiving a valerian root
extract (LI-156) at doses of 600, 1200 and 1800 mg, and diazepam 10 mg, with a
one-week wash-out period between treatments. Compared with placebo, valerian
had no statistically significant effects on mood or on cognitive and
psychomotor performance.(76)
The two studies described above involved younger (aged less than
30 years) participants. Another randomised, double-blind, placebo-controlled,
crossover study involved 14 healthy older participants (mean age 71.6 years,
range 65–89 years) who received valerian 400 mg and 800 mg (Jamieson, Canada;
subsequently reported to contain valerenic acid, 1-acetoxyvalerenic acid and 1-hydroxyvalerenic
acid 0.63%), temazepam 15 mg and 30 mg, and diphenhydramine 50 mg and 75 mg,
with a three-day wash-out period between treatments. No statistically significant
differences on measures of psychomotor performance or sedation were found for
valerian, compared with placebo.(77)
In a randomised, double-blind trial involving 102 healthy volunteers,
the effects of single-dose valerian extract (LI-156) 600 mg on reaction time, alertness
and concentration were compared with those of flunitrazepam 1mg and
placebo.(68) The treatment was administered in the evening and psychometric
tests were carried out the next morning. After a one-week wash-out period, 91
volunteers continued with the second phase of the study, which comprised 14
days' administration of valerian extract 600 mg or placebo. Single-dose valerian
extract administration did not impair reaction time, concentration or
coordination. A 'hangover' effect was reported by 59% of flunitrazepam
recipients, compared with 32% and 30% of placebo and valerian recipients, respectively
(p < 0.05 for flunitrazepam versus valerian). At the end of the 14-day
study, there was no statistically significant difference (p = 0.45) between valerian
extract and placebo on mean reaction time (a measure of performance).
A randomised, double-blind, placebo-controlled study involving 80
volunteers compared the 'hangover' effects of tablets containing valerian and
hops, a syrup containing valerian only, and flunitrazepam 1 mg, all given as a
single dose.(78) Performance the morning after treatment, measured both
objectively and subjectively, was impaired only in the flunitrazepam group.(78)
Side effects occurred more frequently in the flunitrazepam group (50%),
compared with the valerian and placebo groups (10%). In a further
placebo-controlled study involving 36 volunteers who received valerian–hops
tablets, valerian syrup, or placebo, and who underwent a battery of cognitive
psychomotor tests 1–2 hours after drug administration, there was a slight, but
statistically significant, impairment in vigilance with valerian syrup and impairment
in the processing of complex information with valerian–hops tablets, compared
with placebo.(78)
PRECLINICAL DATA
Toxicological studies documented in the older literature have reported
an LD50 of 3.3 mg/kg for an ethanolic extract of valerian administered
intraperitoneally in rats, and that daily doses of 400–600 mg/kg, administered
intraperitoneally for 45 days, did not lead to any changes in weight, blood or
urine measurements, compared with controls.(1) Literature cited in a review of
the safety of valerian describes LD50 values of 64 mg/kg for valtrate, 125
mg/kg for didrovaltrate and 150 mg/kg for acevaltrate in mice after intraperitoneal
injection.(G21) Another study in mice reported that valerenic acid 150 mg/kg,
given by intraperitoneal injection, caused muscle spasms and that 400 mg/kg
caused heavy convulsions.(18) The latter dose was lethal to six of seven mice.
In vitro cytotoxicity and mutagenicity have been documented for
the valepotriates. The clinical significance of this is unclear, since the
valepotriates are known to be highly unstable and, therefore, probably degrade
when taken orally. Only traces of valepotriates or their degradation products
(in part, baldrinals) are likely to be found in finished products.(G80)
In toxicological studies in rats, there were no changes in bile value
and liver enzyme activity in animals treated with a valerian preparation
(Indena, Italy; no further details provided) as a single dose (0.31 to 18.6
g/kg) or 3.1 g/kg for 28 days. In vitro, incubation of human hepatoma cells
with the same valerian preparation at a concentration of 20 mg/mL led to
increased cell death, compared with values for control.(79) No such effect was
seen for the valerian preparation at a concentration of 2 mg/mL, when compared
with control.
A study in rats involved the administration of valepotriates (6,
12 and 24 mg/kg administered orally) during pregnancy up to the 19th day when
animals were sacrificed.(80) There were no differences between valepotriate-treated
rats and control rats as determined by fetotoxicity and external examination
studies, although the two highest doses of valepotriates were associated with
an increase in retarded ossification evident on internal examination.
CLIENT CONSIDERATIONS
ASSESS
·
Assess for hypersensitivity
reactions. If present, discontinue the use of valerian and administer an
antihistamine or other appropriate therapy.
·
Assess liver function studies
(AST, ALT, bilirubin) if the client is using valerian for long-term treatment.
If results are elevated, discontinue use of the herb.
·
Assess medications used (see
Interactions).
ADMINISTER
·
Instruct the client that
valerian products should be kept away from heat and moisture.
TEACH CLIENT/FAMILY
·
Inform the client that
pregnancy category is 2 and breastfeeding category is 3A.
·
Advise the client to use
caution when giving valerian to children.
·
Advise the client not to
perform hazardous activities such as driving or operating heavy machinery until
physical response to the herb can be evaluated. Valerian causes sedation and
dizziness.
·
Advise the client to
discontinue the use of valerian if symptoms worsen.
PREPARATIONS
PROPRIETARY SINGLE-INGREDIENT
PREPARATIONS
Argentina:
Nervisatis. Australia: Herbal Sleep Formula. Belgium: Dormiplant; Relaxine;
Valerial. Brazil: Noctaval; Recalm; Sonoripan; Valeriane; Valerimed; Valerin;
Valerix; Valezen; Valmane. Canada: Nytol Natural Source; Sleep-Eze V Natural;
Unisom Natural Source. Chile: Sominex. Czech Republic: Koren Kozliku
Lekarskeho; Valdispert. Finland: Valrian. Germany: Baldorm; Baldriparan Stark;
Baldrivit; Baldurat; Cefaluna; Dolestan; Euvegal Balance; Luvased mono;
Recvalysat; Sedonium; Sporal mono; Valdispert. Israel: Relaxine; Valeton. Italy:
Ticalma. Mexico: Neolaikan. Netherlands: Dormiplant; Valdispert. Portugal: Valdispert.
Russia: Novo-Passit (Ново-Пассит). South Africa: Calmettes. Spain: Ansiokey;
Coenrelax; Valdispert; Valeriana Orto; Valsedan. Sweden: Baldrian-Dispert; Neurol;
Valerecen. Switzerland: Baldriparan pour la nuit; Natu-Seda; ReDormin; Sedasol
eco natura; Sedonium; Valdispert. UK: Phytorelax; Sedonium. Venezuela: Floral
Pas.
PROPRIETARY MULTI-INGREDIENT
PREPARATIONS
Argentina:
Armonil; Dioxicolagol; Nervocalm; SDN 200; Sedante Dia; Serenil; Sigmasedan;
Valeriana Oligoplex. Australia: Calmo; Coleus Complex; Dan Shen Compound; Executive
B; Extralife Sleep-Care; Goodnight Formula; Humulus Compound; Lifesystem Herbal
Plus Formula 2 Valerian; Macro Anti-Stress; Multi-Vitamin Day & Night;
Natural Deep Sleep; Pacifenity; Passiflora Complex; Passionflower Plus; Prosed-X;
Relaxaplex; Valerian Plus Herbal Plus Formula 12; Valerian. Austria: Baldracin;
Baldrian AMA; Eryval; Euvekan; Hova; Nervenruh; Nerventee St Severin; Sedadom;
Sedogelat; Songha; Species nervinae; Thymoval; Valin Baldrian; Wechseltee St
Severin. Belgium: Natudor; Seneuval; Songha. Brazil: Passicalm; Sominex;
Sonhare. Canada: Herbal Nerve; Herbal Relax; Herbal Sleep Aid; Herbal Sleep
Well. Chile: Armonyl; Recalm; Valupass. Czech Republic: Baldracin; Bio-Strath; Contraspan;
Dr Theiss Rheuma Creme; Dr Theiss Schwedenbitter; Euvekan; Hertz- und
Kreislauftee; Nervova Cajova Smes; Novo-Passit; Persen; Sanason;
Schlaf-Nerventee N; Songha Night; Species Nervinae Planta; Valofyt Neo;
Visinal. France: Biocarde; Euphytose; Mediflor Tisane Calmante Troubles du
Sommeil No 14; Mediflor Tisane Circulation du Sang No 12; Neuroflorine; Passinevryl;
Spasmine; Sympaneurol; Tranquital. Germany: Ardeysedon; Avedorm duo; Baldrian-Dispert
Nacht; Baldriparan N Stark; Biosedon; Boxocalm; Cefasedativ; Dormarist;
Dormeasan; Dormo-Sern; Dormoverlan; Dr. Scheffler Bergischer Krautertee Nerven-
und Beruhigungstee; Dreierlei; Euvegal Entspannungs- und Einschlaftropfen; Gutnacht;
Gutnacht; Heumann Beruhigungstee Tenerval; Hingfong-Essenz Hofmanns; Hyperesa;
Klosterfrau Beruhigungs Forte; Kytta-Sedativum; Leukona-Beruhigungsbad; Luvased;
Moradorm S; Mutellon; Nervendragees; Nervenkapseln; Nervoregin forte; Neurapas;
Nitrangin compositum; Oxacant-sedativ; Pascosedon; Phytonoctu; Plantival novo;
Pronervon Phyto; Schlaf- und Nerventee; Schwedentrunk Elixier; Sedacur; Sedariston
Konzentrat; Sedariston plus; Sedaselect D; Selon; Sensinerv forte; Tornix;
Valdispert comp; Valeriana comp novum; Valeriana mild; Valverde Baldrian Hopfen
bei Einschlafstorungen und zur Beruhigung; Vivinox Day. Hungary: Euvekan; Hova.
India: Well-Beeing. Israel: Calmanervin; Calmanervin; Nerven-Dragees;
Passiflora Compound; Passiflora; Songha Night. Italy: Anevrasi; Biocalm; Dormiplant;
Fitosonno; Florelax; Glicero-Valerovit; Noctis; Parvisedil; Reve; Sedatol;
Sedopuer F. Mexico: Nervinetas; Plantival. Portugal: Neurocardol; Songha;
Valesono. Russia: Doppelherz Vitalotonik (Доппельгерц Витало- тоник); Herbion
Drops for the Heart (Гербион Сердечные Капли); Persen (Персен); Sanason (Санасон).
South Africa: Avena Sativa Comp; Biral; Entressdruppels HM; Helmontskruie; Krampdruppels;
Restin; Stuidruppels; Wonderkroonessens. Spain: Natusor Somnisedan; Nervikan;
Relana; Sedasor; Sedonat; Valdispert Complex. Switzerland: Baldriparan;
Dormeasan; Dormiplant; Dragees pour la detente nerveuse; Dragees pour le coeur
et les nerfs; Dragees pour le sommeil; Dragees sedatives Dr Welti; Hova;
Nervinetten; ReDormin; Relaxane; Relaxo; Songha Night; Soporin; Strath Gouttes
pour le nerfs et contre l'insomnie; Tisane calmante pour les enfants; Tisane
pour le sommeil et les nerfs; Valverde Coeur; Valverde Detente dragees;
Valverde Sommeil; Valviska; Zeller Sommeil. UK: Avena Sativa Comp; Bio-Strath
Valerian Formula; Boots Alternatives Sleep Well; Boots Sleepeaze Herbal
Tablets; Calmanite Tablets; Constipation
Tablets; Daily Tension & Strain Relief; Digestive; Fenneherb Newrelax;
Fenneherb Prementaid; Gerard House Serenity; Gerard House Somnus; Golden Seal
Indigestion Tablets; Herbal Indigestion Naturtabs; Herbal Pain Relief; HRI Calm
Life; HRI Golden Seal Digestive; HRI Night; Indigestion and Flatulence; Kalms
Sleep; Kalms; Laxative Tablets; Menopause Relief; Modern Herbals Stress;
Napiers Digestion Tablets; Napiers Sleep Tablets; Napiers Tension Tablets; Natrasleep;
Natural Herb Tablets; Nerfood Tablets; Nervous Dyspepsia Tablets; Newrelax; Nighttime
Herb; Nodoff; Period Pain Relief; PMT Formula; Prementaid; Quiet Days; Quiet
Life; Quiet Nite; Quiet Tyme; Relax Bþ; Roberts Alchemilla Compound Tablets;
Scullcap & Gentian Tablets; Sominex Herbal; Stressless; SuNerven; Sure- Lax
(Herbal); Unwind Herbal Nytol; Valerina Day Time; Valerina Day-Time; Valerina
Night-Time; Valerina Night- Time; Vegetable Cough Remover; Wellwoman; Wind
& Dyspepsia Relief. USA: Calming Aid; Stress Complex; StressEez. Venezuela:
Cratex; Equaliv; Eufytose; Lupassin; Nervinetas; Pasidor; Pasifluidina;
Rendetil.
EXTRACTS
Valerenic
acid causes ataxia at 50 mg/kg ipr mus, CNS depressant 100 mg/kg ipr mus, but
400 mg kg was antispasmodic, convulsant, and fatal (CAN). Valepotriate fractions
exhibit antiarrhythymic, anticomplement, anticonvulsant, coronadilating,
cytotoxic, mutagenic, myorelaxant, and vasodilating activities. Valerian, in
combo with Hypericum, in a double blind 2-week trial of 100 patients,
was more effective than diazepam in treating symptoms of anxiety (CAN).
Baldrinal is mutagenic to Salmonella (CAN). Alkaloids are antibacterial,
antidiuretic, and may help prevent liver necrosis (PED). Valerian, valerenic
acid, and the eugenyl and isoeugenyl esters are antispasmodic. Valerenic acid
and derivatives inhibit GABA. (PNC). Ldlo for acevaltrate, didrovaltrate, and
valtrate = >4600 mg/kg orl mus (MAB)
REFERENCE
Barnes, J., Anderson, L. A., and Phillipson, J. D. 2007. Herbal
Medicines Third Edition. Pharmaceutical Press. Auckland and
London.
Duke, J. A. with Mary Jo Bogenschutz-Godwin, Judi duCellier, Peggy-Ann K.
Duke. 2002. Handbook of Medicinal Herbs 2nd Ed. CRC Press
LLC. USA.
Gruenwald, J., Brendler,
T., Jaenicke, Ch. 2000. PDR for Herbal
Medicines. Medical Economics Company, Inc. at Montvale, NJ
07645-1742. USA
Kraft
Linda S-Roth. 2010. Mosby’s Handbook Of Herbs & Natural
Supplements, Fourth Edition. Mosby Elsevier. USA
Figure 3. Primary Chemical Components and Possible Actions
(Linda, S-R. 2010)
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