Valerian

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Valeriana officinalis L. (syn. V. exaltata J.C. Mikan)

[Fam. Valerianaceae]

Overview

Valerian has a long history of use in Western Europe as a sedative and sleep aid, with medicinal use dating to Hippocrates (ca. 460–377 B.C.E.) (Blumenthal et al., 2000). Valerian is used in countless preparations worldwide. In the U.S., for example, valerian root is known extensively as a dietary supplement in the form of alcoholic tinctures, aqueous infusions (teas), and as a crude-root, powdered and dried extract in capsules and tablets. Often, valerian is combined with other herbs traditionally known to promote sedation or sleep, e.g., hops (Humulus lupulus), passion flower (Passiflora incarnata), and lemon balm (Melissa officinalis) (Blumenthal et al., 1998). Three such combination products have been clinically studied and are described in the section of this book dealing with proprietary products. Valerian ranked eighth in total sales in mainstream retail outlets in the U.S. in 2000, with sales totaling approximately $17 million (Blumenthal, 2001).

Valerian root and two of its preparations, valerian root powder and valerian extract, are official in the United States Pharmacopeia (USP) 25th edition, and National Formulary (NF) 20th edition. Crude valerian root, fluid extract, alcoholic tincture, and ammoniated tincture were formerly official in the USP from 1820 through 1930 (Boyle, 1991; Lloyd, 1929) and the NF (Grieve, 1979; Leung and Foster, 1996). Valerian root is official in the national pharmacopeias of Austria, France, Great Britain, Hungary, Russia, and Switzerland, among others (Blumenthal et al., 2000). In Germany, valerian is official in the German Pharmacopoeia, and approved in the Commission E monographs for its sedative and sleep-promoting activity (Blumenthal, et al., 1998).

Description

Valerian root extract consists of the fresh or carefully dried (below 40°C) subterranean parts of Valeriana officinalis L. (syn. V. exaltata J.C. Mikan) [Fam. Valerianaceae] (Blumenthal et al., 1998), including the rhizome, roots, and stolons. The whole dried root contains no less than 0.5% (v/m) volatile oil, and the cut dried root contains no less than 0.3% (v/m) volatile oil. The dried root contains no less than 0.17% of sesquiterpenic acids expressed as valerenic acid, calculated with reference to the dried drug (Ph. Eur. 2001). The NF requires dried valerian root to contain no less than 0.5% volatile oil, and not less than 0.05% valerenic acid (USP-NF, 1999). Valerian root dry extract consists of the native extractive yielded from comminuted valerian root, extracted in 70% alcohol, manufactured according to the German Pharamacopoeia monograph. The drug-to-extract ratio ranges from 3:1 to 6:1 (w/v) (DAB, 1999). The NF requires that the dry extract contain no less than 0.3% of valerenic acid, with a drug-to-extract ratio between 4:1 and 7:1 (USP, 2002).

Primary Uses

Neurology

Anxiety: The World Health Organization (WHO) lists uses supported by clinical data, including as a mild sedative and sleep-promoting agent; a milder alternative or possible substitute for stronger synthetic sedatives (e.g., benzodiazepines); and for treatment of nervous excitation and sleep disturbances induced by anxiety (WHO, 1999). This indication is supported by numerous clinical trials (Bourin et al., 1997; Sousa et al., 1992; Kohnen and Oswald, 1988; Panijel, 1985; Boeters, 1969).

Insomnia: The German Commission E approved the use of valerian for sleep disorders, insomnia, and restlessness based on nervous disorders (Blumenthal et al., 1998). The European Scientific Cooperative on Phytotherapy (ESCOP) notes that valerian is used for “tenseness, restlessness, and irritability, with difficulty in falling asleep” (ESCOP, 1997). These approved indications are supported by numerous clinical trials of varying size, design, and duration for various types of valerian preparations (i.e., valerian only, valerian with other sedative herbs, and valepotriate-only preparations) (Dominguez et al., 2000; Dorn, 2000; Donath et al., 2000; Cerny and Schmid, 1999; Rodenbeck et al., 1998; Schmitz and Jackel, 1998; Dressing et al., 1996; Orth-Wagner, 1995; Schultz et al., 1994; Dressing and Reimann, 1992; Lindahl and Lindwall, 1989; Balderer and Borberly, 1985; Leatherwood and Chauffard, 1985; Gessner and Klasser, 1984; Leatherwood et al., 1982).

Other Potential Uses

Increased mood related to enhanced sleep (Vorbach et al., 1996; Kamm-Kohl et al., 1984)

Fibromyalgia (as bath) (Ammer and Melnizky, 1999)

Dosage

Internal

Infusions: 2–3 g of fresh or dried root per cup, one to several times daily (Blumenthal et al., 1998).

Tincture: 1/2–1 teaspoon (1–3 ml), one to several times daily (Blumenthal et al., 1998).

Extracts: Amount equivalent to 2–3 g of crude herb, one to several times daily (Blumenthal, et al., 1998).

Tea or dry extract (sleep aid): Single dose 1/2 to 1 hour before bedtime, with an earlier dose in the evening, if necessary (ESCOP, 1997). For adults, the dose should be in proportion to body weight; use as a tea infusion or dry extract. Children from 3–12 years old should use valerian only under medical
supervision (ESCOP, 1997).

External

Bath: 100 g for one full bath; equivalent preparations (Blumenthal et al., 1998).

Infusion: 2–3 g, in 150 ml water (Blumenthal, et al., 1998).

Duration of Administration

Many authoritative sources have set no time limit for the use of valerian (Blumenthal et al., 1998; ESCOP, 1997; WHO, 1999; Upton, 1999). Although long-term valerian use in European clinical practice indicates relative safety, clinical trials of longer than 30 days have not been conducted.

Chemistry

Valerian contains over 150 chemical constituents, many of which are physiologically active. The primary active constituents can be divided into four categories: the essential oils and their sesquiterpenes (e.g., valerenic acid), the iridoids (iridoid esters: valepotriates, valtrate, isovaltrate, acevaltrate, dihydrovaltrate, and isovaleroxyhydroxydihydrovaltrate [IVHD] and their degradation products [baldrinal and derivatives]), amino acids (arginine, GABA, glutamine, tyrosine), and alkaloids (Upton, 1999; Bruneton, 1999; Leung and Foster, 1996). The iridoids are chemically unstable and degrade in moisture, heat (above 40°C), or acidity (pH<3) to baldrinal and isopropylbaldrinal (Bruneton, 1999) and, therefore, are not found in most commercial preparations (Blumenthal et al., 1998). Other constituents include caffeic acid, chlorogenic acid, b-sitosterol, methyl 2-pyrrolketone, choline, tannins, gum, alkaloids, and resin (Bradley, 1992; ESCOP, 1997; Newall et al., 1996).

Pharmacological Actions

Human

Coronary artery dilating and anti-arrhythmic effects. Valerian is included in a German heart tonic to maintain neuro-cardiac stability (Mowrey, 1986). In an open, multi-center trial of 2,243 patients with a variety of functional cardiac disorders, an herbal combination (valerian, hawthorn [Crataegus spp.], night-blooming cereus [Selenicereus grandiflorus], and camphor [Cinnamomum camphora]) was associated with improvement (Bussany-Caspari, 1986). No controlled trials have evaluated valerian’s effects in patients with specific cardiovascular disorders.

Sedative-hypnotic. Case series and randomized controlled trials have demonstrated valerian extract is effective in treating mild-to-moderate sleeping disorders without adverse effects on REM sleep, and without significant hangover effects (See the table, “Clinical Studies on Valerian,” at the end of this monograph).

Animal

Coronary artery dilating and anti-arrhythmic effects. Valepotriates prevented the appearance of acute coronary insufficiency, abolished vasopressin-induced arrhythmia, provoked a short-lived increase in coronary blood flow, and had moderate positive inotropic and negative chronotropic effects (Petkov, 1979). In mice, valeranone, found in small quantities in valerian and in larger amounts in its relative, Nardostachys jatamansii, exerted weak hypotensive effects (Morazzoni and Bombardelli, 1995). In cats, intravenous injection of valerian extracts produced a significant increase in coronary blood flow, a transient fall in blood pressure, and a decrease in heart rate (Zhang et al., 1982).

Spasmolytic. In guinea pig ileum, valerenic acid, valtrate, and valeranone exert a spasmolytic action through direct effects on smooth muscle (Hazelhoff et al., 1982; Wagner and Jurcic, 1979).

Sedative-hypnotic. In mice, intraperitoneal injections of valerenic acid, valerenal, and whole herb extracts produced significant sedation, ataxia, and anti-convulsant effects (Hendriks et al., 1981; Veith et al., 1986). Intraperitoneal injections of 100 mg/kg had sedative effects as strong as barbiturates, doses of 400 mg/kg led to death (Hendriks et al., 1985). In comparison with diazepam and chlorpromazine, valerian extract had weak anti-convulsive properties (Leuschner et al., 1993). Valerian root extract (Valdispert^®) reduced motility and increased thiopental-induced and pentobarbital-induced sleeping time (Capasso et al., 1996; Hiller, 1996; Leuschner et al., 1993). The aroma of valerian root exerted sedative effects in mice (Buchbauer et al., 1992). In rats, valerian had sedative effects on electroencephalogram (EEG) activity (Fink and Hoelzl, 1984). Valerian extract, but not its individual chemical constituents, significantly decreased glucose metabolism in the brain (Grusla et al., 1986). Valepotriates suppressed symptoms associated with diazepam withdrawal in rats (Andreatini and Leite, 1994). This has led some authors and clinicians to propose that valerian may be useful in treating benzodiazepine withdrawal syndrome in humans (Brinker, 2001; Rasmussen, 1997). Cats given 10 mg/kg of a valerian extract by gastric lavage had a significant decrease in restless, fearful, and aggressive behaviors (vonEickstedt, 1969). Unlike diazepam, valerian did not affect spontaneous ambulation, rearing, or approach-avoidance conflict in mice in a water-lick conflict test. However, valerian and imipramine significantly inhibited immobility induced by a forced swimming test in rats, and significantly reversed reserpine-induced hypothermia in mice, leading researchers to conclude that valerian may be a useful antidepressant (Sakamoto et al., 1992).

In vitro

Valerian extracts containing amino acids and valerenic acid bind weakly with the GABA (A) receptor in rat brain assays (Ferreira et al., 1996; Holzl and Godau, 1989; Mennini et al., 1993). In rat brain cortex, aqueous extract of valerian inhibited the uptake and stimulated the release of GABA, leading to increased concentrations of GABA in synaptic clefts (Santos et al., 1994a; 1994b; 1994c); these effects may be due in part to the presence of GABA in valerian root extracts (Cavadas et al., 1995), or may be due to valerenic acid’s ability to inhibit GABA breakdown (Riedel et al., 1982; Wichtl and Bisset, 1994; Hendriks et al., 1981).

Mechanism of Action

Although the sedative effects of valerian have been demonstrated in human clinical studies, scientists have struggled to agree upon the single chemical compound responsible for valerian’s activity. Valerian’s effects on the central nervous system (CNS) have been attributed variously to valepotriates, their breakdown products (baldrinals), valerenic acid, valerenal, and valeranone, and other constituents in the essential oil (Wichtl and Bisset, 1994; Bradley, 1992; Houghton, 1988; Hendriks, et al., 1981, 1985; Hendriks, 1977; Holzl, 1998; Wagner, 1980). Multiple compounds may work together synergistically to produce a sedative effect (Upton et al., 1999; Houghton 1999; Weiss and Fintelmann, 2000). Animal studies show that valerenic acid may inhibit enzymes that break down GABA, thus increasing GABA levels and producing a CNS-depressing effect (Newall et al., 1996). An in vitro study to elucidate the sedative activity of valerian demonstrated that valerian extract LI 156 acted upon the melatonin receptor in a dose-dependent manner. This effect was not associated with valerenic acid (Fauteck et al., 1996).

Contraindications

As a general precaution, the WHO contraindicates the use of valerian during pregnancy and lactation, and for children younger than 12 years without medical supervision (WHO, 1999). ESCOP also mentions these same precautions, but contraindicates valerian in children less than three years old. However, German authorities note that the clinical use of valerian in pediatrics is permissible beginning at age three, as long as valepotriate- and baldrinal-free preparations are used (Schilcher, 1997).

Pregnancy and Lactation: ESCOP and the WHO contraindicate valerian during pregnancy due to fact that its safety during pregnancy has not been established clinically (ESCOP, 1997; WHO, 1999). However, in pregnant rats given valepotriates for 30 days, there was no impact on fertility, no fetotoxicity, and no other adverse effect on mother or offspring (Tufik et al., 1994). Research on potential mutagenicity and carcinogenicity of valerian preparations has shown that official valerian preparations are extremely low in valepotriates and that these compounds are mostly destroyed in the extraction process (Bos et al., 1998; WHO, 1999).

Adverse Effects

Unlike benzodiazepines, valerian appears to cause no residual morning sleepiness; however, it may slightly impair judgment and driving ability for two to three hours after intake (Gerhard et al., 1996). Chronic use of high doses of valerian (530 mg to 2 gm per dose, five times per day) for many years raised the possibility that withdrawal symptoms may occur if the herb is discontinued abruptly as documented in a case report of a 58 year-old man who had been taking valerian with numerous conventional drugs (Garges et al., 1998). An authoritative German pharmaceutical text (Hobbs, 1979), suggests that continued use may cause minor side effects e.g., headaches, excitability, and insomnia, but subsequent review by the German Commission E did not find sufficient basis to include these side effect in its official monograph on valerian originally published in 1985 and revised in 1990. Cytotoxic effects have been reported in vitro, but the compounds responsible for these effects (valepotriates) decompose rapidly during storage and following oral administration (Bos et al., 1998; Bounthanh et al., 1981). In a study of 23 patients taking a nonprescription valerian extract preparation (doses from 0.5 to 12.0 grams), no acute or subclinical evidence of liver damage was observed (Chan, 1998; Chan et al., 1995). The adverse effects of valerian include rare cases of headache and upset stomach (Leathwood and Chauffard, 1982; Leathwood et al., 1982; Schulz et al., 2001). However, an intentional overdose as high as 20 grams, 20 times the normal daily dose of powdered root in capsules (40–50 capsules at 470 mg per capsule), was not associated with significant morbidity. The patient was released from the hospital within 24 hours of admission (Willey et al., 1995). In one report of intentional abuse, a young adult drug user attempted to induce a psychoactive effect by injecting an alcoholic solution of valerian; he became ill, but recovered over the next three days (Mullins and Horowitz, 1998).

Drug Interactions

Animal studies suggest that valerian may potentiate the sedative effects of barbiturates (Brinker, 2001; Hendriks et al., 1981; Hiller, 1996; Leuschner et al., 1993; Sakamoto et al., 1992). Although some authors have speculated on potential interactions between valerian, alcohol, barbiturates, and benzodiazepines in humans, no such interactions have been documented (Braeckow et al., 1972; Brinker, 2001; Miller, 1998). One study found no potentiating effects of valerian on alcohol’s impact on concentration, attentiveness, reaction time, or driving performance (Albrecht, 1995).

American Herbal Products Association (AHPA) Safety Rating

Class 1: Herbs that can be safely consumed when used appropriately (McGuffin et al., 1997).

Regulatory Status

Austria: Official in Austrian Pharmacopoeia (Meyer-Buchtela, 1999; Upton, 1999).

Belgium: Oral use as Traditional Herbal Medicine (THM), accepted for specific indications (Bradley, 1992).

Canada: Dried root in tablet, capsule, powder, extract, tincture, or tea bags labeled as THM indicated as sleep aid or sedative; requires premarket authorization and assignment of a Drug Identification Number (DIN) and conformance with the Valerian Labeling Standard (Health Canada, 1996).

European Union: “Whole,” dried, underground parts containing no less than (NLT) 0.5% volatile oil, and “cut,” dried, underground parts (NLT 0.3% volatile oil; NLT 0.17% sesquiterpenic acids), official in European Pharmacopoeia (Ph. Eur., 2001).

France: Oral use as THM accepted for specified indications (Bradley, 1992). Dried root (NLT 0.5% volatile oil), official in French Pharmacopoeia (Upton, 1999).

Germany: Dried root, for preparation of tea infusion, tincture, or extract is an approved nonprescription drug of the German Commission E Monographs (Blumenthal et al., 1998). Tea infusion and hydro-alcoholic tincture forms are approved nonprescription drugs of the German Standard License monographs (Braun et al., 1986 and 1996). Extract or volatile oil for balneotherapy (bath therapy) is approved in the German Commission B8 Monographs (Wichtl and Bisset, 1994). Dry native extract, 3~6:1 (w/w), is official in German Pharmacopoeia (DAB, 1999). The mother tincture (and liquid dilutions) of dried root are official preparations of the German Homeopathic Pharmacopoeia (GHP, 1993)

Italy: Dried root (NLT 0.5% volatile oil) official in Italian Pharmacopoeia (Ph. Ital. 1991).

Russian Federation: Official in State Pharmacopoeia of the Union of Soviet Socialist Republics (Bradley, 1992; Newall et al., 1996).

Sweden: Classified as Natural Remedy for self-medication requiring advance application for marketing authorization. A valerian monograph is published in the Medical Products Agency (MPA) “Authorised Natural Remedies,” which lists four registered monopreparations, and 10 multiple-herb (with passionflower, lemon balm, or hops) preparations (MPA, 1997 and 2001; Tunón, 1999). Two valerian products (Baldrian-Dispert and Neurol) are regulated as Pharmaceutical Specialties, or conventional over-the-counter (OTC) drugs (Tunón, 1999).

Switzerland: Herbal medicine with positive classification (List D) by the Interkantonale Konstrollstelle für Heilmittel (IKS) and corresponding sales category D with sale limited to pharmacies and drugstores, without prescription (Morant and Ruppanner, 2001; Ruppanner and Schaefer, 2000). There are 62 valerian phytomedicines and 11 homeopathic preparations listed in the Swiss Codex 2000/01 (Ruppanner and Schaefer, 2000). Dried root official in Swiss Pharmacopoeia 1997 (Meyer-Buchtela, 1999; Upton, 1999).

U.K.: General Sale List (GSL), Schedule 1, Table A (Bradley, 1992). Dried root (NLT 0.5% volatile oil) and powdered dried root (NLT 0.3% volatile oil) official in British Pharmacopoeia (Health Canada, 1996; Upton, 1999).

U.S.: Generally Recognized as Safe (GRAS) (US FDA, 1998). Dietary supplement (USC, 1994). Application for OTC approval for use as a nighttime sleep aid is pending (Pinco and Israelsen, 1994). Valerian root (NLT 0.5% volatile oil; NLT 0.05% valerenic acid) and powdered valerian (NLT 0.3% volatile oil; NLT 0.04% valerenic acid) are official in U.S. National Formulary (USP, 2002). Powdered valerian extract, 4~7:1 (w/w) (NLT 0.3% valerenic acid) added to NF 19 1st Supplement (USP, 2000). The mother tincture 1:10 (w/v), 55% alcohol (v/v), of fresh or dried root, is an OTC Class C drug official in Homeopathic Pharmacopoeia of the United States (HPUS, 1993).

Clinical Review

Twenty-nine studies are outlined in the following table, “Clinical Studies on Valerian,” including more than 5,200 participants. All studies found positive effects for indications including anxiety, sleep disorders, and mood. Five studies (480 participants) report on the effectiveness of valerian for anxiety (Bourin et al., 1997; Sousa et al., 1992; Kohnen and Oswald, 1988; Panijel, 1985; Boeters, 1969). The majority of clinical trials have consistently demonstrated that valerian is significantly more effective than a placebo in improving sleep in persons with sleep disturbances (Balderer and Borbely, 1985; Chauffard et al., 1982; Dressing et al., 1996; Donath et al., 2000; Dorn, 2000; Dressing and Riemann, 1992; Gessner and Klasser, 1984; Jansen, 1977; Kamm-Kohl et al., 1984; Leathwood and Chauffard, 1982, 1985; Leathwood et al., 1982; Lindahl and Lindwall, 1989; Orth-Wagner et al., 1995; Rodenbeck et al., 1998; Schellenberg et al., 1994; Schmidt-Voigt, 1986; Schmitz and Jackel, 1998; Schulz et al., 1994; Vorbach et al., 1996). Modern human studies have investigated the use of valerian in combination with hops, as an alternative to benzodiazepine to treat nonchronic and nonpsychiatric sleep disorders (Schmitz and Jackel, 1998); its use in combination with hops as a sedative to treat disturbed sleep (Fussel et al., 2000; Vonderheid-Guth et al., 2000; Lataster et al., 1996; Vorbach et al., 1996; Kammerer, 1993); its effects in combination with hops on driving safety (Gerhard et al., 1996; Kammerer et al., 1996); its use in combination with St. John’s wort (Hypericum perforatum) as an alternative to diazepam to treat symptoms of anxiety (Panijel, 1985); and its use in combination with camphor, night-blooming cereus (Selenicereus grandiflorus), and hawthorn (Crataegus spp.) to treat functional cardiovascular disorders, hypotension, or meteorosensitivity (Busanny-Caspari, 1986). Three double-blind, placebo-controlled (DB, PC) studies concluded that valerian in combination with lemon balm (Melissa officinalis) improved sleep quality for insomniacs (Dressing et al., 1996; Dressing and Reimann, 1992), and did not impair driving or operating heavy machinery (Albrecht et al., 1995). A randomized (R), DB, PC, crossover study found a combination of valerian, hops, and lemon balm helpful for individuals experiencing sleep difficulties (Lindahl and Lindwall, 1989). A recent R, DB, controlled study concluded that valerian did not adversely influence alertness, reaction time, or concentration (Kuhlmann et al., 1999).

The approved modern therapeutic applications for valerian appear to be supported by its history of use in well-established systems of traditional and conventional medicine, in vitro and in vivo pharmacological experiments on animals, extensive phytochemical investigations, and human clinical studies, all of which tend to show valerian’s central nervous system-depressant
activities (Blumenthal et al., 2000).

Branded Products*

Alluna™: GlaxoSmithKline / One Franklin Plaza / Philadelphia, PA 19102 / U.S.A. / Tel: 888-825-5249 / www.gsk.com. Each tablet contains 500 mg valerian extract (4-6:1) with 120 mg hops extract (5-7:1).

Euphytose^®: Roche Nicholas SA / 33 rue de l’Industrie / 74240 Gaillard / France / Tel: +33-04-50-87-7070. Six herbs, including Crataegus, Ballota, Passiflora, Valeriana, Cola, and Paullinia.

Euvegal^® forte: Dr. Willmar Schwabe Pharmaceuticals / International Division / Willmar Schwabe Str. 4, D-76227 / Karlsruhe / Germany / Tel: +49-721-4005 ext. 294 / www.schwabepharma.com / Email: melville-eaves@schwabe.de. Each tablet contains 160 mg valerian root extract 4.5:1 and 80 mg lemon balm leaf extract 5.5:1.

Harmonicum Much^®: Prof. Dr. Much AG. Information on manufacturer and current product status unavailable.

Hova^®: Gebro Pharma GmbH / A-6391 Fieberbrunn / Austria / Tel: +43-53-54-5300-0 / Fax: +43-53-54-5300-0 / www.gebro.com / E-mail: pharma@gebro.com. Each tablet contains 60 mg valerian and 30 mg hop flower extract.

Ivel^®: Kanoldt Arzneimittel GmbH / c/o Knoll AG / Knollstrasse 50 / 67008 Ludwigshafen / Germany / Tel: +49-06-21-5890 / Fax: +49-06-21-5892-896 / www.knoll.de / Email: info@knoll.de. Each tablet contains 500 mg valerian extract (4-6:1) with 120 mg hops extract (5-7:1).

LI 156: Lichtwer Pharma AG / Wallenroder Strasse 8-14 / 13435 / Berlin / Germany / Tel: +49-30-40-3700 / Fax: +49-30-40-3704-49 / www.lichtwer.de. Each tablet contains 300 mg dry extract of valerian with a drug/extract ratio of 5:1.

Nature’s Way^® Valerian Root capsules: Nature’s Way Products, Inc. / 10 Mountain Spring Parkway / Springville, UT 84663 / U.S.A. / Tel: (801) 489-1500 / www.naturesway.com. Each capsule contains 530 mg valerian root with a guaranteed natural potency of 0.1% valerenic acids.

Novo-Baldriparan^®: Novo-Nordisk A/S / Novo Allé / 2880 Bagsværd / Denmark / Tel: +45-4444-8888 / Fax: +45-4449-0555 / E-mail: webmaster@novonordisk.com. This product is no longer available.

ReDormin^®: Zeller AG / Seeblickstrasse 4 / CH-8590 Romanshorn 1 / Switzerland /  www.zellerag.ch. Contains valerian extract ZE91019.

Sedariston^® Konzentrat: Steiner Arzneimittel / Postfach 450520 / 12175 Berlin / Germany / Tel: +49-03-07-1094-0 / Fax: +49-03-07-1250-12 / www.steinerarznei-berlin.de. Tablets each contain 50 mg of valerian and 100 mg of St. John’s wort.

Sedonium^®: Lichtwer Pharma AG. Contains valerian extract LI 156.

Songha Night^®: Pharmaton Natural Health Products / P.O. Box 368 / Ridgefield, CT 06877 / U.S.A. / Tel: 800-451-6688 / Fax: 203-798-5771 / www.pharmaton.com / Email: askpharmaton@rdg.boehringer-ingelheim.com. Each coated tablet contains 120 mg valerian extract and 80 mg lemon balm extract.

Valdispert^®: Solvay Arzneimittel GmbH / Hans-Bockler-Allee 20 / Hannover 30173 / Germany / Tel: +49-511-8-5724e +006 / Fax: +49-511-8-57312e +006 / www.solvay.com. Unable to verify dosage or manufacturing status.

Valdispert^® forte: Solvay Arzneimittel GmbH. Each tablet contains 45 mg Valeriana officinalis radix dry aqueous alkaline extract (5–6:1), corresponding to 225–270 mg of dried root, standardized to contain 0.05 mg valerenic acid and acetoxyvalerenic acid.

Valerina Natt^®: Pharbio Medical International AB / c/o Cederroth International AB / Box 715 / S-19427 Upplands Väsby / Sweden / Tel: +46-85-90-9630-0 / Fax: +46-85-90-9647-1 / Email: info@cederroth.com / www.pharbio.cederroth.com. Contains 100 mg valerian extract (4:1), corresponding to 400 mg dried root; 45 mg hops (Humulus lupulus) extract (8.5:1), corresponding to 382 mg dried strobile; 25 mg lemon balm (Melissa officinalis) leaf extract (6.5:1), corresponding to 162 mg dried leaf; and 275 mg of excipient materials.

Valmane^®: Lyssia GmbH / c/o Solvay Arzneimittel GmbH. Each tablet contains 50 mg of a valepotriate mixture. Unable to verify current availability of product.

Valverde^®: Ciba-Geigy AG / Novartis Consumer Health AG / Route de l’Etraz / CH 1260 Nyon 1 / Switzerland / www.consumer-health.novartis.com. This product is no longer available.

Ze91019: Zeller AG / Seeblickstrasse 4 / CH-8590 Romanshorn 1 / Switzerland / www.zellerag.ch.  Extract used in Alluna™ Sleep, Ivel^®, and ReDormin^®.

* American equivalents, if any, are found in the Product Table beginning on page 398.

References

Albrecht M. Psychopharmaceuticals and safety in traffic. Z Allg Med 1995;71:1215–21.

Albrecht M, Bergner W, Laux P, Martin C. Psychopharmaceuticals and traffic safety: The influence of Euvegal® forte sugar-coated tablets on driving ability and combination effects with alcohol. Zeitschrift fur Allgemein Medizin 1995;71:1215–1225.

Ammer K, Melnizky P. Medicinal baths for treatment of generalized fibromyalgia. [in German]. Forsch Komplementarmed 1999;6:80–5.

Andreatini R, Leite J. Effect of valepotriates on the behavior of rats in the elevated plus-maze during diazepam withdrawal. Eur J Pharmacol 1994;260:233–5.

Anon. Herb sales in the mainstream market –1998 vs. 1997. Information Resources Inc.; 1999.

Balderer G, Borbely A. Effect of valerian on human sleep. Psychopharmacology 1985;87:406–9.

BHP. British Herbal Pharmacopoeia (BHP). Exeter: British Herbal Medicine Association; 1996.

Blumenthal M. Herb sales down 15% in mainstream market. HerbalGram 2001;51:69.

Blumenthal M, Busse WR, Goldberg A, Gruenwald J, Hall T, Riggins CW, Rister RS (eds.). Klein S, Rister RS (trans.). The Complete German Commission E Monographs—Therapeutic Guide to Herbal Medicines. Austin, TX: American  Botanical Council; Boston: Integrative Medicine Communication; 1998; 226–7.

Blumenthal M, Goldberg A, Brinckmann J. Herbal Medicine: Expanded Commission E Monographs. Newton, MA: Integrative Medicine Communications; 2000;394–7.

Boeters U. Treatment of control disorders of the autonomic nervous system with valepotriate (Valmane®). Munch Med Wochenschr 1969;111:1873–6.

Bos R, Hendriks H, Scheffer J, Woerdenbag H. Cytotoxic potential of valerian constituents and valerian tinctures. Phytomedicine 1998;5:219–25.

Bos R, Woerdenbag HJ, DeSmet PAGM, Scheffer JJC. Valeriana species. In: Adverse Effects of Herbal Drugs Vol. 3. DeSmet PAGM, Keller K, Hänsel R, Chandler RF. New York: Springer-Verlag, 1997;165–80.

Bounthanh C, Bergmann C, Beck J, Haag-Berrurier M, Anton R. Valepotriates, a new class of cytotoxic and antitumor agents. Planta Med 1981;41:21–8.

Bourin M, Bougerol T, Guitton B, Broutin E. A combination of plant extracts in the treatment of outpatients with adjustment disorder with anxious mood: controlled study versus placebo. Fundamental & Clin Pharmacol 1997;11:127–32.

Boyle W. Official Herbs: Botanical Substances in the United States Pharmacopeia–1820–1990. East Palestine, OH: Buckeye Naturopathic Press, 1991.

BP. British Pharmacopoeia (BP). London: Her Majesty’s Stationery Office; 1988.

Bradley P (ed.). British Herbal Compendium — A Handbook of Scientific Information on Widely Used Plant Drugs, Volume I. Exeter, U.K.: British Herbal Medicine Association (BHMA); 1992;214–8.

Braeckow R, Eickstedt K, Kuhne U. Effects of chlorpromazine and valtratum on ethanol anesthesia and ethanol blood level. Arzneimittelforschung 1972;22:1977–80.

Braun R, Surmann P, Wendt R, Wichtl M, Ziegenmeyer J (eds.). Baldrianwurzerl. In: Standardzulassungen für Fertigarzneimittel–Text und Kommentar, 11. Ergänzungslieferung. Stuttgart, Germany: Deutscher Apotheker Verlag; Zulassungsnummer; 1996 Feb;6199.99.99.

Braun R, et al. (eds.). Baldriantinktur. In: Standardzulassungen für Fertigarzneimittel–Text und Kommentar. Stuttgart, Germany: Deutscher Apotheker Verlag; Zulassungsnummer; 1986;6099.99.99.

Braeckow R, Eickstedt K, Kuhne U. Effects of chlorpromazine and valtratum on ethanol anesthesia and ethanol blood level. [in German]. Arzneimittelforschung 1972;22:1977–80.

Brinker F. Herb Contraindications and Drug Interactions, 3d ed. Sandy, OR: Eclectic Institute; 2001:196–7.

Brown D. Herbal Prescriptions for Better Health, 2nd ed. Rocklin, CA: Prima Publishing; 2000.

Bruneton, J. Pharmacognosy, Phytochemistry, Medicinal Plants. Paris: Lavoisier Publishing; 1999;595–600.

Buchbauer G, Jager W, Jirovetz L, Meyer F, Dietrich H. Effects of valerian root oil, borneol, isoborneol, bornyl acetate and isobornyl acetate on the motility of laboratory animals (mice) after inhalation. [in German]. Pharmazie 1992;47:620–2.

Busanny-Caspari Eea. Indications: Functional heart complaints, hypotension and weather sensitivity. [in German]. Therapiewoche 1986;36:2545–50.

Capasso A, DeFeo V, DeSimone F, Sorrentino L. Pharmacological effects of aqueous extract from Valeriana. Phytother Res 1996;10:309–12.

Cavadas C, Araujo I, Cotrim M, et al. In vitro study on the interaction of Valeriana officinalis L. extracts and their amino acids on GABA-A receptor in rat brain. [in German]. Arzneimittelforschung 1995;45:753–5.

Cerny A, Schmid K. Tolerability and efficacy of valerian/lemon balm in healthy volunteers (a double-blind, placebo-controlled, multicentre study). Fitoterapia 1999;70(3):221–8. 

Chan T. An assessment of the delayed effects associated with valerian overdose [letter]. Int J Clin Pharmacol Ther 1998;36:569.

Chan T, Tang C, Critchley J. Poisoning due to an over-the-counter hypnotic sleep-Qik (hyoscine, cyproheptadine, valerian). Postgrad Med J 1995;71:227–8.

Chauffard F, Heck E, Leathwood P. Detection of mild sedative effects: Valerian and sleep in man. Experimentia 1982;37:622.

DAB. See: Deutsches Azneibuch.

Deutsches Arzneibuch (DAB Ergänzungsbuch 1999). Stuttgart, Germany: Deutscher Apotheker Verlag. 1999.

Dominguez R, Bravo-Valverde R, Kaplowitz B, Cott J. Valerian as a hypnotic for Hispanic patients. Cultur Divers Ethni Minor Psychol 2000 Feb;6(1):84–92.

Donath F, Quispes S, Diefenbach K, et al. Critical evaluation of the effect of valerian extract on sleep structure and sleep quality. Pharmacopsychiatry 2000;33:47–53.

Dorn M. Efficacy and tolerability of Baldrian versus oxazepam in non-organic and non-psychiatric insomniacs: a randomized, double-blind, clinical, comparative study. [in German]. Forsch Komplementarmed Klass Naturheilkd 2000, Apr;7(2):79–84.

Dressing H, Kohler S, Muller W. Improvement in sleep quality with a high dose valerian-melissa preparation. Psychopharmacotherapy 1996;3:123–30.

Dressing H, Riemann D. Insomnia: are Valeriana/Melissa combinations of equal value to benzodiazepine? [in German]. Therapiewoche 1992;42:726–36.

Drozdov D. Use of aminazine with valerian in hypertensive disease. Vrach Delo 1975;48–50.

ESCOP. Valeriana radix. Monographs on the medicinal uses of plants. Exeter: European Scientific Cooperative on Phytotherapy; 1997.

Europäisches Arzneibuch, 3rd ed. Stuttgart: Deutscher Apotheker Verlag; 1997.

European Pharmacopoeia (Ph. Eur.) (3rd edition 1997, Supplement 2001). Strasbourg, France: Council of Europe; 2001;1575–7.

Farmacopea Ufficiale della Repubblica Italiana (Ph.Ital. IX 1985 suppl. 1991). Rome, Italy:Ministerio della Sanita; 1991.

Fauteck J–D, Pietz B, Winteroff H, Wittkowski W. Interaction of Valerian officinalis with melatonin receptors: A possible explanation of its biological action. [Abstract]. 2nd International Congress on Phytomedicine. Munich, Germany, September 11–14,1996.

Ferreira F, Santos M, Faro C, et al. Effect of extracts of Valeriana officinalis on [3H] GABA. Revista Portuguesa de Farmacia 1996;46:74–7.

Fink C, Hoelzl J. Wirkungen vonvaltrat auf das EEG des isoliert perfundierten ratenhirns. Arzneimittelforshung 1984;34:170–4.

Flynn R, Roest M. Your guide to standardized herbal products. Prescott, AZ: One World Press; 1995.

Fugh-Berman A, Cott J. Dietary supplements and natural products as psychotherapeutic agents. Psychosom Med 1999;61:712–28.

Fussel A, Wolf A, Brattström A. Effect of a Fixed Valerian-Hop Extract Combination (Ze 9109) on Sleep Polygraphy in Patients with Non-organic Insomnia: A Pilot Study. Eur J Med Res 2000;5:385-390.

Garges H, Varia I, Doraiswamy P. Cardiac complications and delirium associated with valerian root withdrawal [letter]. JAMA 1998;280:1566–7.

Gerhard U, Linnenbrink N, Georghiadou C, Hobi V. Vigilance-decreasing effects of 2 plant-derived sedatives. Schweiz Rundsch Med Prax 1996 April;85(15):473–81.

German Homeopathic Pharmacopoeia (GHP), 1st ed. 1978 with supplements through 1991. Translation of the German “Homöopathisches Arzneibuch (HAB 1), Amtliche Ausgabe.” Stuttgart, Germany: Deutscher Apotheker Verlag; 1993;893–5.

Gessner B, Klasser M. Studies on the effect of Harmonicum Much® on sleep using polygraphic EEG recordings. EEG EMG Z Elektroenzephalogr Verwandte Geb 1984;15:45–51.

GHP. See: German Homeopathic Pharmacopoeia.

Grieve M. A Modern Herbal. New York: Dover Publishers; 1979;824 –8.

Grusla D, Holzl J, Kriegelstein J. Activity of valerian in the rat brain. [in German]. Deutsche Apotheker Zeitung 1986;126:2249–53.

Hazelhoff B, Malingre T, Meijer D. Antispasmodic effects of valeriana compounds: an in-vivo and in-vitro study on the guinea-pig ileum. Archives Internationales de Pharmacodynamie et de Ther 1982;257:274–87.

Health Canada. Valerian Labelling Standard. Ottawa, Ontario: Health Canada Therapeutic Products Programme. 17. May 1996.1-6.

Hendriks H. Eugenyl isovalerate and isoeugenyl isovalerate in the essential oil of valerian root. Phytochemistry 1977;16:1853–4.

Hendriks H, Bos R, Allersma D, Malingre T, Koster A. Pharmacological screening of valerenal and some other components of essential oil of Valeriana officinalis. Planta Med 1981;42:62–8.

Hendriks H, Bos R, Woerdenbag H, Koster A. Central nervous depressant activity of valerenic acid in the mouse. Planta Med 1985;1:28–31.

Hiller K. Neuropharmacological studies on ethanol extracts of Valeriana officinalis L: Behavioral and anticonvulsant properties. Phytother Res 1996;10:145–51.

Hobbs C. Valerian: A literature review. HerbalGram 1989;21:19–34.

Hobbs H. Hagers Handbuk der Pharmazeutischen, Praxis; 1979. p. 25. cited in Morazzoni and Bombardelli, 1995.

Hoffmann D. The Complete Illustrated Holistic Herbal. Rockport, MA: Element Books Inc.; 1996.

Holzl J. Valerian–Valeriana officinalis. [in German]. Z Phytother 1998;19:47–54.

Holzl J, Godau P. Receptor binding studies with Valeriana officinalis on the benzodiazepine receptor. Planta Med 1989;55.

Homeopathic Pharmacopoeia of the United States (HPUS) — Revision Service Official Compendium from July 1, 1992. Falls Church, VA: American Institute of Homeopathy; 1993 Dec;9413:VLRN.

Houghton PJ. The biological activity of valerian and related plants. J Ethnopharmacol 1988;22:121–42.

Houghton PJ. The scientific basis for the reputed activity of valerian. J Pharm Pharmacol 1999;51:505–12.

HPUS. See: Homeopathic Pharmacopoeia of the United States.

Jansen W. Double-blind study with baldrisedon. [in German]. Therapiewoche 1977;27:2779–86.

Kamm-Kohl A, Jansen W, Brockmann P. Moderne baldriantherapie gegen nervose storungen im senium. Med Welt 1984;35:1450–4.

Kammerer E. Phytogenic sedatives-hypnotics—does a combination of valerian and hops have a value in the modern drug repertoire? [in German]. Z Arztl Fortbild (Jena) 1993;87:401–6.

Kammerer E, Brattstöm A, Herberg K-W. Effects of a hop-valerian combination on fitness and driving safety. Der Bay Int 1996;16(3):32-36.

Kohnen R, Oswald W. The effects of valerian, propranolol, and their combination on activation, performance, and mood of healthy volunteers under social stress conditions. Pharmacopsychiatry 1988;21:447–8.

Kuhlmann J, Berger W, Podzuweit H, Schmidt U. The influence of valerian treatment on “reaction time, alertness and concentration” in volunteers. Pharmacopsysciatry 1999;32:235–41.

Lataster MJ, Brattström A. The treatment of patients with sleep disorders: efficacy of tolerance of valerian-hop tablets. Notabene Medici 1996;4:182-185.

Leathwood P, Chauffard F. Aqueous extract of valerian reduces latency to fall asleep in man. Planta Med 1985;144–8.

Leathwood P, Chauffard F. Quantifying the effects of mild sedatives [review]. J Psych Res 1982;17:115–22.

Leathwood P, Chauffard F, Heck E, Munoz-Box R. Aqueous extract of valerian root (Valeriana officinalis L.) improves sleep quality in man. Pharmacol Biochem Behav 1982;17:65–71.

Leung A, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics, 2nd ed. New York: John Wiley & Sons, Inc.; 1996.

Leuschner J, Mueller J, Rudmann M. Characterization of the central nervous depressant activity of a commercially available valerian root extract. [in German]. Arzneimittelfforschung 1993;43:638–41.

Lindahl O, Lindwall L. Double blind study of a valerian preparation. Pharmacol Biochem Behav 1989;32:1065–6.

Lloyd JU. Origin and History of All the Pharmacopoeial Vegetable Drugs. Cincinnati, OH: Caxton Press, 1929.

Mayer B, Springer E. Psychoexperimental studies on the effect of a valepotriate combination as well as the combined effects of valtratum and alcohol. [in German]. Arzneimittelforschung 1974;24:2066–70.

McGuffin M, Hobbs C, Upton R, Goldberg A. American Herbal Products Association’s Botanical Safety Handbook: Guidelines for the Safe Use and Labeling for Herbs of Commerce. Boca Raton: CRC Press; 1997.

Medical Products Agency (MPA). Naturläkemedel: Authorised Natural Remedies (as of January 24, 2001). Uppsala, Sweden: Medical Products Agency. 2001.

Medical Products Agency (MPA). Naturläkemedelsmonografi: Valeriana. Uppsala, Sweden: Medical Products Agency. 1997.

Mennini T, Bernasconi P, Bombardelli E, Morazzoni P. In vitro study on the interaction of extracts and pure compounds from Valeriana officinalis roots with GABA, benzodiazepine and barbiturate receptors in rat brain. Fitoterapia 1993;64:291–300.

Meyer-Buchtela E. Tee-Rezepturen: Ein Handbuch für Apotheker und Ärzte. Stuttgart, Germany: Deutscher Apotheker Verlag. 1999;Baldrianwurzel.

Miller L. Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med 1998;158:2200–11.

Morant J, Ruppanner H (eds.). Arzneimittel-Kompendium der Schweiz® 2001. Basel, Switzerland: Documed AG. 2001.

Morazzoni P, Bombardelli E. Valeriana officinalis: traditional use and recent evaluation of activity. Fitoterapia 1995;66:99–112.

Mowrey D. The Scientific Validation of Herbal Medicine. New Canaan, Conn.: Keats Pub; 1986; 316.

MPA. See: Medical Products Agency.

Mullins M, Horowitz B. The case of the salad shooters: intravenous injection of wild lettuce extract. Vet & Human Toxicol 1998;40:290–1.

Newall C, Anderson L, Phillipson J. Herbal Medicines: A Guide for Health-Care Professionals. London: Pharmaceutical Press; 1996;260–2.

Orth-Wagner S, Ressin W, Friederich I. Phytosedative for sleeping disorders containing extracts from valerian root, hop grains and balm leaves. [in German]. Z Phytother 1995;16:147–52, 155–6.

Panijel M. Treatment of moderately severe anxiety states. [in German]. Therapiewoche 1985;35:4659–68.

Petkov V. Plants and hypotensive, antiatheromatous and coronarodilating action. Amer J Chinese Med 1979;7:197–236.

Ph. Eur. See: European Pharmacopoeia.

Ph. Ital. See: Farmacopea Ufficiale della Repubblica Italiana.

Pinco RG, Israelsen LD. European-American Phytomedicines Coalition Citizen Petition to Amend FDA’s Monograph on Nighttime Sleep-aid Drug Products for Over-the-Counter (“OTC”) Human Use to Include Valerian; 1994.

Rasmussen P. A role for phytotherapy in the treatment of benzodiazepine and opiate drug withdrawal. Eur J Herb Med 1997;3:11–21.

Riedel E, Hansel R, Ehrke G. Inhibition of gamma-aminobutyric acid catabolism by valerenic acid derivatives. Planta Med 1982;48:219–20.

Rodenbeck A, Simen S, Cohrs S, et al. Alterations of the sleep stage structure as a feature of GABAergic effects of a valerian-hop preparation in patients with psychophysiological insomnia. Somnologie 1998;2:26–31.

Ruppanner H, Schaefer U (eds.). Codex 2000/01 — Die Schweizer Arzneimittel in einem Griff. Basel, Switzerland: Documed AG. 2000.

Sakamoto T, Mitani Y, Nakajima K. Psychotropic effects of Japanese valerian root extract. Chem & Pharm Bull 1992;40:758–61.

Santos M, Ferreira F, Cunha A, et al. An aqueous extract of valerian influences the transport of GABA in synaptosomes. Planta Med 1994a;60:278–279.

Santos M, Ferreira F, Cunha A, et al. Synaptosomal GABA release as influenced by valerian root extract: Involvement of the GABA carrier. Archives Internationales de Pharmacodynamie et de Therapie. 1994b;327:220–31.

Santos M, Ferreira F, Faro C, et al. The amount of GABA present in aqueous extracts of valerian is sufficient to account for [3H]GABA release in synaptosomes [letter]. Planta Med 1994c;60:475–6.

Schellenberg R, Schwartz A, Schellenberg V, Jahing L. Quantitative EEG-monitoring and psychometric evaluation of the therapeutic efficacy of Biral N in psychosomatic diseases. Naturamed 1994;4:9.

Schilcher H. Phytotherapy in Pediatrics: Handbook for Physicians and Pharmacists, 2nd ed. Stuttgart: Medpharm Scientific Publishers; 1997;58–61,181.

Schmidt-Voigt J. Treatment of nervous sleep disorders and unrest with a sedative of purely vegetable origin. [in German]. Therapiewoche 1986;36:663–7.

Schmitz M, Jackel M. Comparative study for assessing quality of life of patients with exogenous sleep disorders (temporary sleep onset and sleep interruption disorders) treated with a hops-valerian preparation and a benzodiazepine drug. [in German]. Wien Med Wochenschr 1998;148:291–8.

Schulz H, Stolz C, Mueller J. The effect of valerian extract on sleep polygraphy in poor sleepers: A pilot study. Pharmacopsychiatry 1994;27:147–51.

Schulz V, Hänsel R, Tyler VE. Rational Phytotherapy: A Physicians’ Guide to Herbal Medicine, 4th ed. Berlin: Springer; 2001:87–97.

Sousa M, Pacheco P, Roldao V. Double-blind comparative study of the efficacy and safety of Valdispert® vs. clobazapam. KaliChemie Medical Research and Information. 1992.

Straube G. The importance of valerian roots in therapy. Ther Ggw 1968;107:555–62.

Tufik S, Fujita K, Seabra M, Lobo L. Effects of a prolonged administration of valepotriates in rats on the mothers and their offspring. J Ethnopharmacol 1994;41:39–44.

Tunón H. Phtyotherapie in Schweden. [in German]. Z Phytother 1999;20:268–77.

United States Congress (USC). Public Law 103–417: Dietary Supplement Health and Education Act of 1994. Washington, DC: 103rd Congress of the United States. 1994.

United States Food and Drug Administration (U.S. FDA). Code of Federal Regulations, Title 21, Part 182 – Substances Generally Recognized as Safe. Washington, DC: Office of the Federal Register National Archives and Records Administration; 1998;427–433.

United States Pharmacopeia (USP 24th Revision) The National Formulary (NF 19th Edition). Rockville, MD: United States Pharmacopeial Convention, Inc.; 1999;2533–2534.

United States Pharmacopeia (USP 25th Revision) The National Formulary (NF 20th Edition) Rockville, MD: United States Pharmacopeial Convention, Inc.; 2002.

Upton R (ed.). Valerian Root: Valeriana officinalis. Analytical, Quality Control, and Therapeutic Monograph. American Herbal Pharmacopoeia and Therapeutic Compendium. Santa Cruz, CA, USA: American Herbal Pharmacopoeia; 1999.

US FDA. See: United States Food and Drug Administration.

USC. See: United States Congress.

USP. See: United States Pharmacopeia.

Veith J, Schneider G, Lemmer B, Willems M. The effect of degradation products of valepotriates on the motor activity of light-dark synchronized mice. Planta Med 1986;179–83.

Vonderheid-Guth B, Todorova A, Brattstöm A, Dimpfel W. Pharmacodynamic effects of valerian and hops extract combination (Ze 9109) on the quantitative-topographical EEG in healthy volunteers. Eur J Med Res 2000;5:139-144.

vonEickstedt K. Modification of the alcohol effect by valepotriate. [in German]. Arzneimittelforschung 1969;19:995–7.

Vorbach E, Gortelmayer R, Bruning J. Treatment of insomnia: efficacy and tolerance of a valerian extract. [in German]. Psychopharmakother 1996;3:109–15.

Wagner H. Comparative studies on the sedative action of Valeriana extracts, valepotriates and their degradation products. Planta Med 1980;39:358–65.

Wagner H, Jurcic K. On the spasmolytic activity of Valeriana extracts. Planta Med 1979;37:84–6.

Weiss RF, Fintelmann V. Herbal Medicine, 2d ed. New York:Thieme. 2000;261–4.

WHO. WHO Monographs on Selected Medicinal Plants Vol. I. Geneva: World Health Organization. 1999.

Wichtl M (ed.). Teedrogen und Phytopharmaka, 3. Auflage: Ein Handbuch für die Praxis auf wissenschaftlicher Grundlage. Stuttgart, Germany: Wissenschaftliche Verlagsgesellschaft mbH. 1997;603–7.

Wichtl M, Bissett N. Herbal Drugs and Phytopharmaceuticals, 2nd ed. Stuttgart: MedPharm CRC Press; 1994;566.

Willey L, Mady S, Cobaugh D, Wax P. Valerian overdose: A case report. Vet Human Toxicol 1995;37:364–5.

Zhang B, Meng H, Wang T, et al. Effects of Valeriana officinalis L extract on cardiovascular system. [in Chinese]. Yao Hsueh Hsueh Pao - Acta Pharmaceutica Sinica 1982;17:382–4.