Valeriana – Valerian Root (Valerianae radix)
|Latin name of the genus:||Valeriana|
|Latin name of herbal substance:||Valerianae radix|
|Botanical name of plant:||Valeriana officinalis l.|
|English common name of herbal substance:||Valerian root|
Latin name of the genus: Valeriana
Latin name of herbal substance: Valerianae radix
Botanical name of plant: Valeriana officinalis L.
English common name of herbal substance: Valerian Root
- I INTRODUCTION
- II NON-CLINICAL STUDIES
- II.1 Pharmacodynamics
- II.1.1 Isolated substances
- II.1.2 Aqueous and aqueous-ethanolic valerian root extracts
- II.1.3 Conclusion
- II.2 Toxicology
- II.2.1 Acute Toxicity
- II.2.2 Sub-acute/Chronic Toxicity
- II.2.3 Reproductive Toxicity
- II.2.4 Mutagenicity/Carcinogenicity
- II.2.5 Conclusion
- III CLINICAL PHARMACOLOGY
- III.1 Pharmacodynamics
- III.1.1 EEG trials
- III.1.2 Volunteer trials in stress situations
- III.2 Safety Studies
- III.3 Pharmacokinetics & bioavailability
- III.3.1 Pharmacokinetics
- III.3.2 Bioavailability
- III.4 Interactions
- III.4.1 Pharmacodynamic interactions
- III.4.2 Pharmacokinetic interactions
- IV.1 Efficacy
- IV.1.1 Dose-Finding Trials
- IV.1 2 Controlled Clinical Trials
- IV.1.3 Clinical Experience in Children
- IV.2 T
- IV.3.1 Europe
- IV.3.2 Asia
- IV.3.3 USA
This assessment report reviews scientific data available on Valerianae radix (Valeriana officinalis L.). This report takes into account the ‘Core Data for Valerianae radix’ prepared by the EMEA ad hoc Working Group on Herbal Medicinal Products in 1998. Since, several clinical and preclinical trials have been published that supplement valuable information on clinical efficacy and possible modes of action of the herbal substance. This information is reflected in the Community herbal monograph.
This report focusses on findings with aqueous and
Use of extraction solvents such as dichloromethane and other highly lipophilic solvents may result in substantial differences in the extract composition. No information on comparability of highly lipophilic extracts to conventional valerian roots extracts with respect to constituents and/or biological response and clinical effects is available. For this reason, there is no rational basis for discussion of these kinds of extracts in this report.
The extracts used in the trials are specified in the comments as far as possible. Unfortunately, in many publications correct specifications of solvent and
Dependent on the extraction technique, valerian root extracts contain differing amounts of monoterpenes (such as bornyl esters, camphene and pinenes), sesquiterpenes (including valerenal and valeranone), and less volatile sesquiterpene carboxylic acids (valerenic acid and derivatives), aminoacids like
Among the components listed above, no single or main active ingredient has been identified for valerian root. Various trials with isolated constituents could not fully explain the observed pharmacological activities of valerian root in total. A possible synergistic action of several components is assumed. The whole extract of valerian root must therefore be considered as the active ingredient.
II.1.1 Isolated substances
Hydroxyvalerenic acid and acetoxyvalerenic acid weakly inhibited the catabolism of GABA at synaptic junctions of the CNS in vitro (Riedel et al., 1982). Due to the high concentrations of both compounds needed to achieve this effect, the data probably have no clinical relevance.
The intraperitoneal application of sesquiterpenoid compounds like valerenic acid, valerenal and valeranone isolated from the essential oil of valerian root revealed a sedative and muscle relaxant acitivity. In addition, valerenic acid and valeranone were found to prolong the barbiturate induced sleeping time (Hendriks et al., 1981, 1985, Rücker et al., 1978, Torrent et al., 1972, Haensel et al.,
1 The herbal substance shall comply with the European Pharmacopoeia monograph: Valerianae radix (ref. 01/2005:0453).
1994). Valerenic acid caused an inhibitory effect on
The lignan hydroxypinoresinol, recently found in valerian root, showed a high affinity with IC50 of 2.5 µmol/L for the
An olivil derivate was found to be a potent partial agonist at A1 adenosine receptors in vitro (Schumacher et al., 2002). Agonistic activity was also shown for valerian root extract (methanol 45 %, Mueller et al., 2002). Activation of this receptor type has a sedative effect while antagonists like caffeine have a stimulant effect.
Marder et al. (2002) isolated
The same authors discovered
The valepotriates, mainly occurring in freshly harvested roots, are very unstable compounds due to their unstable epoxide structure and decompose under different conditions (alkali, acids, storage) into baldrinal and its derivatives, valerianic and isovalerianic acid, and undefined polymers. Dried valerian root has therefore a characteristic malodorous aroma, partly due to the content of isovalerianic acid (Hänsel et al., 1999). Since valepotriates are rapidly degraded during storage and their oral bioavailability seems to be very low (Wagner et al., 1980), in vitro and in vivo effects observed with isolated valepotriates, their degradation products or with valerian root extracts containing valepotriates in vitro or in vivo, must be disregarded in the assessment of valerian root extracts (they are mentioned for the purpose of completeness). Similarly the baldrinals, the decomposition products of valepotriates, are either not detected or detected only in small quantities.
II.1.2 Aqueous and
aqueous-ethanolic valerian root extracts
•Interaction with neurotransmitter receptors in vitro
Due to the essential inhibitory functions of GABA, the interest has focused on possible interactions of valerian root with the
lower than IC of GABA) affinity for the GABAA receptor in vitro. The chemical nature of the compounds responsible for this activity could not be correlated with sesquiterpenes or valepotriates (Mennini et al., 1993).
–Aqueous and ethanolic (extraction with absolute ethanol, dry extract diluted with water) extracts
of valerian root showed in vitro an interaction with the
acid no effect was shown. The authors, as well as Yuan et al., concluded that this interaction could be caused by the content of GABA in the extracts.
Further evidence for this conclusion comes from other investigations:
–An aqueous extract inhibited the uptake and induced the
The high content of GABA in certain valerian root extracts cannot explain pharmacodynamic effects in vivo since it does not readily cross the
Still, there are data pointing to interaction with the
–In other experiments by the group of Santos (Santos 1994 c, Ferreira et al., 1996), the effect of different valerian root extracts on the uptake and release of GABA in synaptosomes isolated
from rat brain cortex was investigated. While an aqueous and an
–These results were confirmed by Ortiz et al. (1999). They showed that, besides influence on
inhibited at higher extract concentrations. These results may point to at least two different biological activities interacting with
–Another in vitro experiment demonstrated the interaction of a hydroalcoholic extract of valerian root with adenosine receptors, but not with benzodiazepine receptors. However, this extract contained 1.38 % of valtrate whereas an aqueous extract devoid of valepotriates produced only a weak effect under similar conditions (Balduini 1989).
–Valerian tincture reduced spontaneous motility after intraperitoneal administration of the valerian tincture in mice (Torrent et al., 1972).
–Effects on spontaneous motility, thiopental
modifications of spontaneous motility, nociception or body temperature and no palpebral ptosis were observed, whereas diazepam at doses of up to 2 mg/kg clearly reduced spontaneous motility, lowered body temperature and produced a weak ptosis. However, the extract showed a significant prolongation of
–Cats with implanted electrodes showed no changes in their EEGs following oral administration of 100 or 250 mg of valerian root extract per kg body weight. The muscle tonus was reduced in 30 – 40 % of the animals (Holm et al., 1980).
administration in the magnitude of ipsapirone, a
As a whole, the results point to both a sedative and an anxiolytic effect, possibly mediated by different constituents, which both might contribute to sleep promotion and improvement in nervous state. These data are consistent with clinical observations. With respect to safety concerns, the prolongation of thiopental sleeping time by an aqueous extract in a dose dependent manner in mice must be highlighted. The deduction of a relevant drug interaction of valerian root and barbiturates under clinical conditions from the cited study is of course questionable. In view of the fact that there is no information available on experiences with the combination of valerian root and barbiturates in humans, a
Experimental data on the toxicological properties of Valerian root extract and its single compounds are limited.
For whole extracts or isolated compounds with the exception of valepotriates and their degradation products in various experiments a low order of toxicity was found as shown below.
II.2.1 Acute Toxicity
–In acute oral toxicity tests the LD50 of the sesquiterpene valeranone was greater than 3 g/kg in both rats and mice which corresponds to low toxicity (Rücker et al., 1978).
–The LD50 of essential oil of valerian root, 1,500 mg in rats weighing 100 g, was found to be the highest of 27 essential oils tested, including for example, peppermint and anise oils (von Skremlik, 1959).
–The LD50 of an ethanolic valerian root extract made from the defatted herbal substance administered intraperitoneally to mice amounted to 3.3 g/kg, a value, which corresponds to a low toxicity (Rosecrans et al., 1961).
–Valerenic acid caused inhibition of spontaneous motility after intraperitoneal administration to mice at a dose of 50 mg/kg, ataxia and temporary immobility at a dose of 100 mg/kg, muscle spasms at doses of 150 – 200 mg/kg, and severe convulsions and mortality at a dose of 400 mg/kg (6 of 7 animals ad exitum 24 hours after administration) (Hendriks et al., 1985).
–An ethanolic valerian root extract given to rats at a daily dose of 300 mg/kg and 600 mg/kg p.o. for a period of 30 days did not influence blood pressure, weight of the heart, lungs, liver, spleen, kidneys, bladder, stomach, intestines or testes, haematological parameters (erythrocytes, leukocytes including differential blood count, haematocrit, haemoglobin) or biochemical parameters (blood sugar, urea, SGOT, SGPT and alkaline phosphates). The animals receiving the higher dose had a slightly higher body weight compared to controls (Fehri et al., 1991).
–An ethanolic valerian root extract given to rats intraperitoneally at doses of 400 – 600 mg/kg over a period of 45 days did not result in any significant changes in body weight, blood count or urine status (Rosecrans et al., 1961).
–In the rat, a dose of 200 – 225 mg valerian root oil per 100 g body weight was found to be a tolerable daily dose p.o. over an experimental period of 8 weeks. With higher doses, loss in body weight, rough and ungroomed coat, apathy and, in some cases, mortality were recorded. At 250 mg daily, 2/5 of the animals died within 3 weeks (von Skramlik, 1959).
–The test of a dietary product with undefined quality in mice showed clear effects on nucleic acid, malondialdehyde and glutathione concentrations in testicular cells and malondialdehyde and glutathione concentrations in hepatic cells. The concentration used was with ~ 4 g/kg much higher than the recommended dosage in humans
II.2.3 Reproductive Toxicity
There are no published studies on reproductive toxicity of preparations from valerian root. A test of a dietary supplement in mice revealed the appearance of sperm head morphology abnormalities (amorphous and triangular head abnormalities). The concentration used was with ~ 4 g/kg much higher than the recommended dosage in humans. A negative influence on male fertility could not be proven due to the unclear quality and dosage of the tested product
There is no published evidence for fertility impairment due to valerian root preparations or isolated components. In Australia, valerian root products are classified in category A; this category is applicable for pharmaceuticals, which have been taken by large numbers of pregnant women and women of
Since there are no experimental investigations to date, as stated in the ESCOP- and the WHO- monograph as well as the
A Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster showed no genotoxic effects for an infusion of valerian root purchased from a local health food store, raising questions concerning the quality of the herbal substance in relation to pharmaceutical properties. The used dose is not specified, the test procedure is not accepted as a standard method for the investigation of genotoxicity. The data cannot therefore be accepted to show the absence of genotoxic effects of valerian root
Alkylating, cytotoxic and mutagenic effects have been described for the valepotriates and their degradation products (Bos et al., 1998, von der Hude, 1986) which are not detectable in valerian root extracts or are found only in very low amounts.
The test of a dietary product with undefined quality in mice showed weak effects on bone marrow micronucleus in high doses. The concentration used was with ~ 4 g/kg much higher than the recommended dosage in humans
Only incomplete experimental data pointing altogether to a low toxicity are available on the toxicology of valerian root preparations. Safety assessment is thus mainly based on many years of experience acquired through extensive therapeutic use in man, which indicate valerian root preparations to be safe. Data on genotoxicity are lacking.
III CLINICAL PHARMACOLOGY
The treatment of
III.1.1 EEG trials
Objective evidence of a mild to moderate sedative or tranquilizing effect of valerian root extract in man is provided by EEG studies in healthy volunteers and in female subjects with sleep disorders, although not all results are consistent and they must not be overemphasized for this reason.
–Further sleep EEG investigations were performed with the same aqueous extract. Eight subjects without major sleep disorders (4 female, 4 male, average age 22.6 years) spent 5 nights in a sleep laboratory. The first night was without medication, on nights 2 and 3 placebo was
administered, on night 4 900 mg of valerian root extract was administered, and on night 5 placebo was administered again. There was no difference between placebo and valerian root extract in the sleep EEG. However, in the subjective assessment of quality of sleep, which was determined by means of a visual analogue scale, the time taken to fall asleep and the time spent awake during the night were reduced under treatment with the valerian root preparation (Balderer and Borbely, 1985).
± 5.6 years) was compared to that of 1 x 10 mg diazepam, 1 x 1,200 mg lavender extract, 1 x 1,200 mg passion flower extract and 1 x 600 mg Kava kava extract. All substances showed individual action profiles. Compared to diazepam, an increase in the relative strength of the theta frequency band was observed for the plant preparations. Under diazepam the power in the theta frequency band decreased while it increased in the beta band. Valerian root extract increased power in the delta and theta bands and decreased power in the beta band (Schulz et al., 1998).
•Patients with sleep disturbancies
improve sleep quality under certain conditions (Schulz et al., 1994).
– Donath et al. (2000) performed a
–Diaper and Hindmarch (2004) performed a
Valerian root seems to improve sleep structure with a gradual onset of efficacy rather than to exert a general sedating effect. After single intake valerian root changed mainly subjective perception of sleep, while sleep EEG changes were more pronounced after several days of intake. These observations are in concordance with clinical experiences showing a gradual improvement of symptoms over 2 – 4 weeks. Valerian root probably exerts its effects in pathological conditions rather than in healthy volunteers.
III.1.2 Volunteer trials in stress situations
–Cropley et al. (2002) performed an open, randomised study comparing the effect of valerian root,
These results lead to the assumption that valerian root as well as
The results of these trials provide supportive information to the indication ‘mild nervous tension´ for which only limited evidence comes from clinical studies in patients.
III.2 Safety Studies
In view of the assumed sedative effects, several trials with valerian root extracts were undertaken to investigate a possible influence of valerian root extract on the vigilance:
effect, was significantly smaller with flunitrazepam than in both other groups. No group differences were observed with regard to attention and
ethanol 70 %) corresponding to 1.6 g or 3.2 g valerian root, 0.25 mg triazolam and placebo (Hallam et al., 2003). Several cognitive and computer based attentional tasks revealed that performance was significantly worse with triazolam than with both valerian root doses and placebo, accompanied by a marked increase in mental sedation. No sedation was observed after intake of valerian root.
–Glass et al. (2003) compared acute effects of placebo, valerian root 400 and 800 mg (probably powdered herbal substance), temazepam 15 and 30 mg, diphenhydramine 50 and 75 mg in 14 elderly volunteers (mean age 71.6 years, range 65 – 89 years). Temazepam and diphenhydramine
–A valerian root extract (no details given) in liquid form was tested with regard to a “hangover” effect (Phase A) as well as with regard to an acute sedative effect (Phase B) in subjects without sleeping disorders. To test the “hangover effect” (Phase A), four groups, each with 20 subjects (age between 20 and 30 years), received 1 x 10 ml = 800 mg of the valerian root preparation (equivalent to 4 g valerian root) or 1 x 1 mg flunitrazepam or 1 x 600 mg of a valerian root- combination preparation (sugar coated tablet) or 1 x placebo at a given time of night. Eight hours after taking the preparation, apparative test diagnostics were performed and subjective feelings were monitored in the laboratory. A mild “hangover” effect on the morning after medication was shown with flunitrazepam for two test parameters. While the usual learning effect occurred under both phytopharmaceuticals and placebo, this effect was not observed under flunitrazepam. With flunitrazepam, the subjects felt tired, unsteady on their legs, unconcentrated, less able to perform, sedated and less well than in the other groups. There was no evidence of a “hangover” effect with the valerian root
According to the results described above, high doses of valerian root extract may cause a slight sedation during the first few hours after ingestion but in contrast to benzodiazepines valerian root does not reduce vigilance on the next morning when taken in the evening. The corresponding warning (see section 4.7 Effects on ability to drive and use machinery) is recommended in the Community herbal monograph as a general precaution for medicinal products negatively influencing vigilance.
Studies on valerian root as single active substance have not addressed synergistic actions with alcohol. However, data collected for several valerian root combinations, i.e. valerian root and balm (Albrecht et al., 1995), valerian root and hops (Herberg, 1994 a, Kammerer et al., 1996) and valerian root and St. John’s wort (Herberg, 1994), allow to conclude that, unlike synthetic benzodiazepine or barbiturate hypnotics, valerian root does not act synergistically with alcohol.
III.3 Pharmacokinetics & bioavailability
Data on the pharmacokinetic properties of extracts of valerian root or isolated constituents in man are not available. Pharmacokinetic data for valepotriates are not relevant for valerian root extracts.
Data on the bioavailability of extracts or isolated constituents of valerian root are not available.
III.4.1 Pharmacodynamic interactions
Pharmacodynamic interactions of whole extracts or isolated constituents of valerian root with other medicinal products, food or alcohol in man have not been observed. For
III.4.2 Pharmacokinetic interactions
While no information on possible interactions of valerian root and its preparations was available up to 2004, results of two trials were published recently:
–Lefèbre et al. (2004) investigated interactions of several valerian root preparations available on the US market with CYP 3A4 in vitro. The data point to a possible inhibition of CYP 3A4- mediated metabolism and
–The influence of an
pathway while for CYP 3A4 a slight inhibition was shown: Cmax of alprazolam increased after valerian root extract intake from 25 +/- 7 ng/ml to 31 +/- 8 vs (p < 0.05), the AUC at baseline was 88.9 % of the AUC after valerian root extract intake (n.s.). The authors rated the magnitude of this moderate increase not as clinically relevant and concluded that valerian root is unlikely to have clinically relevant effects on the disposition of medications primarily dependent on the CYP 2D6 or the CYP 3A4 pathways.
–Gurley et al. (2005) confirmed these results in another open crossover trial in 12 young adults for intake of 375 mg/d valerian root extract (DER 4:1, extraction solvent not specified by manufacturer). They found no relevant interaction for CYP 1A2, CYP 2D6, CAP 2E1 and CYP 3A4/5.
The results of the
The dose recommendations of the ESCOP monograph, the German Commission E monograph and the WHO monograph on valerian root (single doses of 2 – 3 g crude herbal substance (ESCOP: 1 – 3 g) given once or several times daily according to indication or requirements) are based on broad clinical experience, on
valerian root may achieve clinically relevant results, but most experience confirms the dose regimen mentioned above.
5.8min, 450 mg extract = 9.0 ± 3.9 min, 900 mg extract = 11.4 ± 5.2 min) while total sleep time and total number of movements remained unchanged. With the higher dose patients felt more sleepy the next morning than with placebo.
–These results were confirmed in a trial in 10 healthy volunteers (age between 24 and 44 years), who took placebo, 450 or 900 mg of an aqueous valerian root extract corresponding to 1.2 or
2.4g of the herbal substance in a crossover schedule. Estimated
IV.1 2 Controlled Clinical Trials
Several controlled clinical trials have been performed, mainly in patients with
–Ziegler et al. (2002) demonstrated that the efficacy of valerian root extract in
–The results of Ziegler are confirmed by another randomised,
–A crossover trial comparing an aqueous valerian root extract (400 mg corresponding to 1,200 mg of the herbal substance), placebo and a combination of valerian root dry extract (120 mg) + hop strobile dry extract (60 mg) was performed by Leathwood et al. (1982) in 166 volunteers, who were partly poor sleepers. DER for the latter preparation is not given. The volunteers took one dose of a total of nine doses (three/preparation) on
The interpretation of these data is restricted by the lack of a confirmatory analysis. No detailed demographic data are given, no validated questionnaires were used in this trial. It is not clear from the publication whether the medications were taken in a randomised order. Nevertheless, the results are congruent with those of better designed and reported trials.
–A trial conducted in general practices using a series of randomised
6 outcome variables (latency to sleep, number of night awakenings, total sleep time, quality of sleep, level of perceived refreshment
•Nervous tension + insomnia
–Jacobs et al. (2005) performed a completely
•Review on insomnia
The review of Stevinson and Ernst (2000) gave an overview of nine published randomised, clinical trials summarizing the evidence for valerian as inconclusive and demanding rigorous trials to determine its efficacy. The following studies that were not included in the review are included in this assessment report: Coxeter PD et al. (2003); Cropley M et al. (2002); Diaper A et al.(2004); Donath F et al. (2000); Dorn M (2000) Hallam KT et al. (2003); Ziegler G (2002).
A further problem of the above mentioned review is that the randomised clinical trials (RCTs) were not separately evaluated regarding the different herbal preparations used. Most of the assessed RCTs were performed with aqueous extracts of valerian root with the content mentioned as mg extract without any information on DER, so that the recalculation of the amount of herbal substance used is partly impossible without further information.
Many of the older pharmacodynamic and clinical trials included in the review were done with aqueous extracts of valerian root. Because these data were not convincing to the HMPC, herbal teas were included in the ‘traditional use’ part of the monograph. Regarding these extracts, this assessment is concordant with the review of Stevinson and Ernst, 2000. Some pharmacodynamic trials (i.e. Schulz et al. (1994); Vorbach et al. (1996); Donath et al. (2000); Diaper et al. (2004); Dorn (2000); Ziegler (2002) were also performed using ethanolic extracts of valerian root supporting the inclusion of these herbal preparations in the
use” part of the monograph. Especially the trials published since 2000 are of a better quality, including GCP compliance.
For the clinical use of valerian root, a substantial body of general evidence is available from handbooks, expert reports etc. Valerian root has been used for centuries in many countries. Additional evidence results from several randomised, controlled,
All together, the evidence available from literature and from clinical trials with valerian root extracts in adults confirms that
IV.1.3 Clinical Experience in Children
No controlled clinical trials have been performed with valerian root in children, and only limited experience in drug monitoring trials has been published.
The dosage was increased in 8.8 % of all cases and reduced in 6.9 %. Efficacy was rated after 2 and 4 weeks. There was a clear tendency towards better ratings after 4 than after 2 weeks. After 4 weeks, the parents rated efficacy for children with restlessness alone as “good” or “very good” in 89 % of the cases, for children with difficulties in falling asleep alone in 100 % and for children with both symptoms in 87 %.
Although the treatment results may be due to a placebo effect in a substantial proportion of patients, in view of the positive feedback by parents and physicians the treatment can be considered as a useful alternative to chemically defined compounds in both indications ‘relief of sleep disorders’ and ‘relief of mild nervous tension’.
2 As referred to in the HMPC ‘Guideline on the assessment of clinical safety and efficacy in the preparation of Community herbal monographs for
Müller SF et al (2006) Phytomedicine (article in press):
In an open multicenter observational study n = 918 children ≤12 years (n = 719 ≥ 6 years) have been treated with a combination product (coated tablets containing 160 mg valerian root dry extract (DER 4 – 5:1, extraction solvent ethanol 70% (V/V) + 80 mg lemon balm dry extract (DER 4 – 6:1, extraction solvent 30% ethanol (V/V)) for 4 weeks ±1 week. 80% of the children ≥ 6 years received the full adult dose without any tolerability problems. The study can be accepted to support the use of valerian root extract as a single active substance in children ≤ 12 years of age concerning tolerability regarding reduced doses of 2/3 of the adult dose. The indication of restlessness and sleeping problems covers developmental particularities in children, due to which data on efficacy in children of the different age groups ≤ 12 years are necessary.
Although promising results with use of valerian root extracts in children have been published, the data are still too scarce to justify a general recommendation. A recommendation for use of medicinal products containing valerian root in children below the age of 12 years should be substantiated by specific clinical experience. The lack of experience is addressed as a relative contraindication in the Community herbal monograph. Restlessness and sleep disorders in children of the different age groups can be common symptoms of specific age dependent diseases/conditions (i.e. attention- deficit/hyperactivity disorder (ADHD); developing sleep patterns in toddlers, school problems). They must be differentiated and diagnosed. General recommendations cannot therefore be given and a treatment should exclusively follow medical advice.
There is no need for clinical trials or specific warnings for adolescents between 12 to 18 years of age taking into account the excellent tolerability of valerian root and its preparations.
Approximately 620 patients or subjects received a valerian root extract preparation in the controlled clinical trials (including human pharmacological studies) listed above.
Valerian root was generally well tolerated while in the same studies chemical substances like oxazepam, flunitrazepam, temazepam and diphenhydramine showed typical undesirable effects like drowsiness, fatigue and
There is a high exposure to valerian root preparations in the EU Member States: according to data provided by IMS Health, sales in the EU in 2002 exceeded 50 million units. Nearly 50 % were sold in Germany. The following adverse events probably linked to the consumption of valerian root have been reported: gastrointestinal symptoms e.g. nausea, abdominal cramps (unknown frequency).
No unequivocal dependencies have been reported. A case of withdrawal symptoms is reported in a
No organ toxicities have been observed in connection with valerian root intake.
One case of acute overdose has been reported. An
including liver values were normal. Tetrahydrocannabinol (THC) was detected in the urine. The patient was treated with active charcoal; the symptoms had completely disappeared after 24 hours. The authors ascribed the overdose symptoms to taking valerian root, although the positive proof of THC in the urine could indicate that marihuana abuse also made a contribution. However, THC can often be detected in urine several weeks after last consuming cannabis; the patient denied using cannabis in the previous two weeks. The case report shows that valerian root is only slightly toxic and the overdose of approximately 20 g valerian root did not lead to any severe clinical symptoms (Willey et al., 1995).
Therapeutic use of valerian root and its preparations probably goes back to the ancient Greeks and Romans who used a
The following compilation is restricted to the use of Valeriana officinalis L., radix. as monotherapy in the modern phytotherapeutic tradition going back to the year 1800.
–Chamisso (1781 – 1831) describes valerian root as antispasmodic, effective against worm diseases and as strengthening.
Information on preparations and dose recommendations is not available (according to Benedum et al.).
–Vietz (1800) recommends valerian root for all spasmodic and convulsive diseases, for epilepsy, hysteric attacks, worm diseases and against nervous fever.
Information on preparations and dose recommendations is not available (according to Benedum et al.).
–Hager (1873/74) refers to the use of valerian root for cramps, epilepsy, worm diseases and hysterical ailments.
Information on preparations and dose recommendations is not available (according to Benedum et al.).
–Dragendorff (1898) describes the use of the root as antispasmodic, as remedium nervinum and antihysteric. No details on preparations and dosages are given.
–Madaus (1938) recommends the use of the dried root, the powdered herbal substance, tincture or fresh root: trituration
Dosages according to different therapists cited by the author:
•powdered herbal substance: 0.5 – 4 g several times/day
•powdered herbal substance 0.5 – 5 g
•4.8 g of the herbal substance for cold extract
•1 – 3 tbl. (each corresponding to 0.125 g fresh valerian root) of trituration ‚Teep‘, for sleeplessness 2 tbl. in the evening
Recommendations for valerian root as single therapy:
•For sleeplessness and neurasthenia:
cold extract (1 teaspoon, corresponding to approximately 5 g of the herbal substance, for 24 hours in 1 glass of water, intake in sips over the day, for sleeplessness consumption of the whole extract in the evening)
•as enema against worms and cramps in the lower abdomen: 10 – 12 g of the herbal substance as decoct in 250 ml water
Traditional indications according to several authors cited by Madaus:
aphrodisiac, diuretic, analgesic, emmenagogue, analeptic, stomachic, carminative. Against cough, asthma, flatulence, chronic diarrhoea, obstipation, worm infections, anthrax, hysteria, cramps of the neck muscles and paresis due to acute infectious diseases. For internal injuries. After severe typhoid or diphteria. Before salvarsan injection as prophylaxis of a salvarsan- induced shock.
headache, reddened and painful eye, wound healing. Bath against acute rheumatism.
For these indications the root was used in most cases, only exceptionally the leaves. Details on herbal preparations and dosages are not given.
–Ward (1936) recommends valerian root for use in hysteria, neuralgia and nervous debility. Preparation/Dosage: an infusion of 1 ounce to 1 pint of boiling water in wineglass doses three or four times daily.
–Weiss (1944) emphasizes the following established indications for valerian root: Nervous agitation, nervous sleeplessness, nervous palpitations.
Preparations and dose recommendations:
• dried root: tea infusion with two teaspoons / cup infusion 10.0/15.0, to take in sips
cold maceration with two teaspoons/glass of cold water
•tinctura valerianae, single dose ½ – 2 teaspoons
•tinctura valeriana aetherea: to be dosed drop by drop
•extractum valerianae fluidum (no dose recommendation for single use given)
–The Hungarian Pharmacopoeia (Edition VI. Volume III. 1967) lists the following valerian root preparations:
• tinctura valerianae aethera (1:5, ethanol 70 % and aether 7.5:2.5 m/m), single dose 200 – 500 mg
•tinctura valerianae spirituosa (1:5, ethanol 70 % V/V), single dose 200 – 500 mg
•valerianae rhizoma et radix, single dose 0,5 – 1 g
•valerian extract (B.P.C. 1954). Single dose 60 – 300 mg
• valerian liquid extract (B.P.C.), DER 1:1, extraction solvent ethanol 60 %. Single dose 0.3 – 1 ml.
•concentrated valerian infusion (B.P.C.), DER 1:5, prepared by percolation with ethanol (25 %). Single dose 15 – 30 ml.
•valerian infusion: Dilution of 1 vol. of the concentrated infusion to 8 vol. with water.
•tinct. valerian. simp. (B.P.C. 1949), DER, prepared by maceration with ethanol (60 %). Single dose: 4 – 8 ml.
Indications: hysteria and other nervous condition, carminative.
–The British Herbal Pharmacopoeia (1976) gives the following recommendations:
Indications: Hysterical states, excitability, insomnia, hypochondriasis, migraine, cramp, intestinal colic, rheumatic pains, dysmenorrhoea
Preparations/Dose recommendations (three time daily)
•dried rhizome and root: 0.3 – 1 g by infusion or decoction
•liquid extract 1:1 (60 % ethanol): 0.3 – 1 ml
•tincture simple 1:8 (60 % ethanol): 4 – 8 ml
•concentrated infusion 1:5 (25 % ethanol): 2 – 4 ml
–Hager’s Handbuch (1979) lists the following indications for valerian root:
Mild sedative in nervous exhaustion, sleeplessness, mental overwork, nervous heart ailments, headache, neurasthenia, hysteria. As antispasmodic for stomach cramps, colics etc.
Recommended preparations: dried powdered herbal substance, tincture (extraction solvent ethanol 60 %), fresh dried herbal substance.
The dose range for the single dose, taken from several pharmacopoeias, is 0.3 – 1 g, for the total daily dose 2 – 15 g.
–Haffner et al. (1991) recommend the following single doses for the use of valerian root preparations:
• Traditional use in EU countries
Medicinal products containing aqueous and
–Several preparations containing pressed juice of the fresh valerian root were traded in the year 1975 and have been fully registered.
Indications: for nerve calming and sleep disturbances, spasmolytic in general spasmophily, nervous gastrointestinal disorders, nervous cardiac disorders.
Dose recommendation: 3 x 1 table spoon/day
–A preparation with valerian root oil for oral use with registration as “traditional remedy” has been notified in the year 1978.
Indication: Traditionally used for improvement of
–Powdered herbal substance for preparation of a tea (tradition proven in cited literature) is registered for the indications “restlessness” and
Dose recommendation: single dose 2.5 g, once or several times daily.
–Several products containing dry extract with methanol/water (methanol 45 % V/V) have been registered during the last year. Traditional use for at least 30 years is not proven.
The French Competent Authority recommends the following traditional use of valerian root preparations:
“Traditionally used in symptomatic treatment of neurotonic conditions of adults and children, particularly in cases of minor sleep disturbances.”
According to Usmanghani (1997, Pakistan), valerian root and rhizomes are used in traditional formulations to relieve disorders of the spinal cord, ‘nervous debility’, failing reflexes, as hypnotic, for nervous disorders during menopause, for insomnia due to nervous exhaustion and mental overwork, against neurosis, hysteria and epilepsy.
Herbal preparations: Only the names of traditional preparations are given.
Dosage: approximately 3 – 5 g (it is not specified whether this is a single or a daily dose)
The authors remark that valerian root is described as harmful for kidney function if taken in large doses or for long period.
Due to the lack of information, the plausibility of the Pakistanian tradition cannot be rated. Since the herbal preparations are not common in Europe, no traditional use can be supported in this report
–Sayre’s Materia Medica (1917) lists valerian root as a ‘gentle nerve stimulant and antispasmodic’, employed in hysterical disorders.
•Herbal substance (single dose: 1 – 4 g)
•Tincturae Valerianae (20 %), single dose 4 – 8 ml
•Tinctura Valerianae Ammoniata (20 %), single dose 2 – 4 ml
–Culbreth (1927) recommends the use of valerian root in the following indications:
Hysteria, hypochondria, hemicrania, nervous coughs,
•Tinctura Valerianae, single dose: 2 – 8 ml.
•Fluidextractum Valerianae (80 % ethanol), single dose: 1 – 4 ml.
Culbreth also mentions unofficial preparations (abstract, extract, infusion, syrup and aqueous extracts).
For valerian root and some of its preparations, a tradition can be claimed within the EU:
–dried valerian root
–dry extracts prepared with water
–expressed juice from fresh root
–valerian root oil
Traditional indications comprise a multitude of conditions, which are only in part comprehensible from a contemporary point of view. Sedative and anxiolytic effects, which have been discussed in detail above, are well reflected in the common indications for valerian root preparations. Besides that, spasmolytic and anticonvulsive properties have been demonstrated in several nonclinical investigations (Ruecker et al., 1978, Hazelhoff et al., 1982, Leuschner et al., 1993, Hiller et al., 1996). These effects are in congruence with the clinical use for dysmenorrhea and gastrointestinal cramps due to nervous conditions which has been outlined in most of the references cited above.
For all other indications, a rational basis is lacking; they are not acceptable in view also of the facts that effective alternatives are available nowadays and that sufficient information on the herbal preparations and dose recommendations are missing.
Recommended dose range for traditional valerian root and its traditional preparations (single dose): Adolescents over 12 years of age, adults, elderly
–0.3 to 1 g dried valerian root (e.g. as powdered herbal substance)
–1 to 3 g dried valerian root for preparation of a tea
–dry extracts prepared with water corresponding to 1 to 3 g of the herbal substance
–valerian tincture corresponding to 0.3 to 1 g of the herbal substance
–15 ml of expressed juice
–15 mg of valerian root oil
For relief of mild symptoms of mental stress up to 3 times daily.
To aid sleep, a single dose half to one hour before bedtime with an earlier dose during the evening if necessary.
Maximum daily dose: 4 single doses