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VALERIAN

*Common Name:*	Valerian
*Botanical Name:*	Valeriana officinalis
*Family:*	Valerianaceae
*Plant Part Used:*	Root and rhizome
*Common Name:*	Mexican valerian
*Botanical Name:*	Valeriana edulis
*Family:*	Valerianaceae
*Plant Part Used:*	Root and rhizome

PRESCRIBING INFORMATION

Actions	Valerian and Mexican valerian:anxiolytic, mild sedative, hypnotic, spasmolytic
Potential Indications	Based on appropriate evaluation of the patient, practitioners should consider prescribing valerian in formulations in the context of: • Insomnia (2,4,5) • Insomnia, in combination with lemon balm or hops (2) • Depression, in combination with St. John’s wort (2) • Stress (3) • Anxiety, in combination with St. John’s wort (3) • Restlessness, nervous tension (4,5) • Depression, anxiety, migraine, nervous headache, cramps, intestinal colic, dysmenorrhea, rheumatic pains, chorea, mild spasmodic movements, epilepsy (5)

Based on appropriate evaluation of the patient, practitioners should consider prescribing Mexican valerian in formulations in the context of:

• Anxiety (4a,6)

• Insomnia (2,6)

Contraindications None known. Warnings and Precautions None required. Interactions

Although no reports to date have been presented, valerian may increase the effects of central nervous system depressants or alcohol when taken together, according to the U. S. Pharmacopeia. Despite this warning, early animal studies indicated that valepotriates do not add to the depressant effect of alcohol. A human study confirmed that simultaneous intake of alcohol with a valerian and St. John’s wort combination did not increase the effects of the herbal product, and a mixture of valepotriates (valtrate, acevaltrate, and didrovaltrate [200 to 400 mg]) combined with ethanol did not cause a reduction of efficiency.

Valerian root extract may attenuate some symptoms of benzodiazepine withdrawal, based on animal models.¹

Use in Pregnancy and Lactation No adverse effects expected. Side Effects In some individuals, valerian can aggravate a sensation of tiredness or drowsiness, particularly in higher doses, but this is usually more a case of an increased awareness of the body’s needs rather than a negative depressant effect. A few individuals find valerian stimulating and should avoid its use. Headaches have been reported after overdose with valerian. A male patient taking multiple medications experienced serious cardiac complications and delirium following a surgical procedure.² The man had self-medicated for “many years” with valerian root extract (530 mg to 2 g/dose, five times daily). However, given the person’s multiple medications, valerian cannot be causally linked to his symptoms. These other factors may have increased the risk of a withdrawal reaction. Dosage Valerian: Dose per day^* Dose per week^* 2-6 ml of 1:2 liquid extract 15-40 ml of 1:2 liquid extract Mexican valerian: Dose per day^** Dose per week^** 1.5-4.5 ml of 1:2 liquid extract 10-30 ml of 1:2 liquid extract

* This dosage is extrapolated from the British Pharmaceutical Codex 1949, the British Herbal Pharmacopoeia 1983, the British Herbal Compendium 1992, and the author’s education and experience.

** This dose range is extrapolated from the pharmacologic and clinical information available on valepotriates.

SUPPORTING INFORMATION

Traditional Prescribing	Traditional Western herbal medicine uses of valerian include: • Insomnia, hysterical states, excitability, hypochondria, nervousness; migraine, nervous headache, depressive states, reduced cerebral circulation ^3,⁴ • Cramps, intestinal colic, dysmenorrhea, rheumatic pains, chorea, mild spasmodic movements, epilepsy ^3,⁴ Mexican valerian is used traditionally in Mexico for its tranquilizing and sedative effects.⁵ Native Americans used Mexican valerian internally for hemorrhages and tapeworm infestation and topically for rheumatism, swollen and bruised parts, wounds, and to draw out boils.⁶^–⁸
Pharmacologic Research	Valerian root contains iridoids (known as valepotriates), essential oil, and cyclopentane sesquiterpenes (e. g., valerenic acid). Mexican valerian root has a higher percentage of valepotriates (and a larger valtrate-isovaltrate content) than valerian; it does not contain valerenic acid. Valepotriates are unstable compounds; they decompose under acid or alkaline conditions or in alcoholic solutions (such as liquid extracts). However, the initial decomposition products of valepotriates are active as sedatives and are probably among the active products in the human system after ingestion of valerian. • Aqueous extract of valerian induced the release of GABA from brain tissue. Many in vitro studies have investigated the interaction of valerian or its components with receptors mediating sedation, such as GABA, adenosine, and 5-hydroxytryptamine (5-HT_1A, serotonin) receptors. • The sedative effect of the valepotriates has been demonstrated in several experimental models. Oral valepotriates improved coordination, and (by unknown dose route) valepotriates decreased anxiety and aggression. In an experimental model, intraperitoneal administration of valerenic acid demonstrated sedative activity resembling central nervous system depression, rather than muscle relaxation or a neuroleptic effect. • Antispasmodic effects on smooth muscle tissue (ileum) were observed for valepotriates and an essential oil component of valerian in vitro and in vivo (by injection).⁹
Clinical Studies	• The sedative effects of valepotriates on humans was confirmed a number of times in German research conducted in the late 1960s. • A randomized, placebo-controlled, double-blind trial demonstrated single or repeated administrations of valerian did not have a negative impact on reaction time, alertness, and concentration the morning after intake. The dose used was equivalent to 3 g per day of root and was prescribed for 2 weeks.¹⁰ • In a randomized, double-blind trial, valerian tablets demonstrated similar efficacy to oxazepam (10 mg/day) for treating insomnia. The daily dose of valerian corresponded to approximately 3 g of original root.¹¹ • A randomized, double-blind, placebo-controlled, crossover study using valerian extract (equivalent to 3 g/day of root for 14 days) confirmed positive effects on sleep structure and sleep perception in patients with mild psychophysiologic insomnia.¹² The effect of Mexican valerian (MV) and valerian (V) extracts were investigated using polysomnographic recordings in a double-blind, crossover trial involving 20 patients with insomnia. Patients received a single dose of extract in tablet form:the MV extract dose contained 2.4 mg valepotriates; the V extract dose contained 0.3 mg valerenic acid. The following results were obtained:¹³ • Decrease in waking episodes (MV only) • Increase in REM sleep (both extracts, but V better) • Increase in sleep efficiency index (compared with baseline; V better) • Decreased time for stages 1 and 2 in non-REM sleep and an increase in delta sleep (MV better) • Decrease in morning sleepiness (V better) • No residual hypnotic effect (MV better) • In a large, uncontrolled, multicenter trial involving over 11,000 patients, treatment with aqueous valerian extract (equivalent to 0.25 g/day dried root) was rated as successful in treating difficulty in falling asleep (72%), discontinuous sleep (76%), and restlessness and tension (72%). • In a double-blind, placebo-controlled, crossover trial, a combination of valerian (equivalent to 400 mg of root) with hops and lemon balm demonstrated a significant subjective effect on poor sleep compared with placebo (which also contained hops and lemon balm) over 2 consecutive nights. Good sleep was reported in 44% and 89% of patients reported improved sleep. • A Swiss study found that a freeze-dried aqueous valerian extract improved sleep latency and sleep quality without increasing sleepiness the next morning, compared with placebo. The group of participants who rated themselves as good sleepers were largely unaffected by valerian, but the poor or irregular sleepers reported a significant improvement. Valerian did not increase the frequency of “more sleepy than usual (the next morning)” responses. A dosage of approximately 1.2 g of valerian root per day was given over 3 nonconsecutive nights. • A randomized, double-blind study was conducted on patients with diagnosed insomnia. Practitioners rated sleep improvement higher following valerian therapy than they did after placebo. Patients preferred valerian, with significant improvements being noted in sleep quality and the feeling of being rested after sleep. The dose was equivalent to approximately 2.4 g of dried root per day and administered for 4 weeks. • Two randomized, double-blind, placebo-controlled trials compared a number of herbal extracts, including dried ethanolic extract of valerian (equivalent to 6 g of root), in sleep-disturbed volunteers. In contrast to diazepam (10 mg), valerian displayed an increase in delta and theta frequencies and a decrease in beta frequency on electro-encephalographic recordings. In contrast to placebo, most of the herbal extracts (as with diazepam) induced an increase in subjectively evaluated sleepiness. • A double-blind, placebo-controlled crossover trial on healthy volunteers showed valerian tended to normalize the sleep profile, lower periods of wakefulness, and increase the efficiency of the sleep period. Valerian was administered as a single dose (equivalent to 6 g) and as a repeated dose (equivalent to 3 g/day for 14 days). • A combination of valerian and hops extracts reduced the noiseinduced disturbance of sleep stage patterns (slow-wave sleep and REM) in sleep-disturbed volunteers. The combination (equivalent to 1 g/day of valerian root and 2 g/day of hops) was given to volunteers during the second or third of 3 consecutive nights disturbed by heavy traffic noise. A randomized, double-blind, controlled trial demonstrated equivalent efficacy and tolerability for a hops-valerian preparation when compared against a benzodiazepine drug in patients with temporary sleep-onset and sleep-interruption disorders.¹⁴ • A randomized, double-blind, placebo-controlled, multicenter trial investigated the use of a combination of dried aqueous ethanol extracts of valerian and lemon balm in ambulatory patients with light insomnia. Improvements in sleep quality, daily condition, time to fall asleep, total duration of sleep, concentration, and ability to perform occurred with no hangover, withdrawal, or rebound phenomena in the treated group. Doses equivalent to 2.9 g per day of valerian root and 1.7 g per day of lemon balm herb were given for 3 weeks. • In a randomized, controlled, double-blind study, a combination of valerian and St. John’s wort extracts (containing 0.45 to 0.9 mg/day of TH) was shown to have comparable benefits to the antidepressant amitriptyline (75 to 150 mg/day) in treating depression over 6 weeks. Compared with an improvement rate of 77% in the amitriptyline group, benefit was observed for 82% of patients in the herbal group, without the high frequency of side effects of amitriptyline such as dry mouth and lethargy. • In a pilot study, patients with stress-induced insomnia were treated with kava, then valerian, then a combination of kava and valerian, with washout periods in between each treatment. Total stress severity was significantly relieved by kava and valerian single treatments. Stress was measured in the areas of social, personal, and life events. The combination of kava and valerian significantly relieved insomnia.¹⁵ • In a double-blind, multicenter trial, a valerian-St. John’s wort combination demonstrated a comparable reduction in symptoms of fear and depressive mood compared with amitriptyline (75 to 125 mg). The daily dose was 3 to 6 capsules. Each capsule contained valerian extract corresponding to approximately 0.3 g of dried root and St. John’s wort extract containing 0.15 mg of TH. In another doubleblind trial, the same combination demonstrated significant improvement compared with the antidepressant desipramine. • A double-blind study found that 2 weeks of daily treatment with a valerian-St. John’s wort combination (containing approximately 0.2 g of valerian root and 0.3 to 0.6 mg/day of TH) was more effective than diazepam (2 mg) in patients with moderate anxiety. Fewer side effects were observed in the herbal treatment group (4%) compared with diazepam treatment (14%). • A double-blind, placebo-controlled technique examining activation, performance, and mood in healthy volunteers showed that valerian extract influenced subjective feelings of somatic arousal, despite high physiologic activation. No sedative effects were demonstrated, and suggestions were that valerian has thymoleptic activity. • A double-blind, placebo-controlled, three-way crossover trial investigated the effect of a valerian and St. John’s wort extract combination on safety-related performance in 12 volunteers. The herbal product was shown to be comparable to placebo with respect to safety in terms of performance and well being. The effects when taken with alcohol were not greater than those of alcohol alone. • In Germany, the Commission E supports using valerian to treat restlessness and sleeping disorders based on nervous conditions.¹⁶ • ESCOP recommends valerian root for treating tenseness, restlessness, and irritability with difficulty in falling asleep.¹⁷ • Valerian has been reinstated to the USP and is official in the USP24-NF19.

REFERENCES

Except when specifically referenced, the following book was referred to in the compilation of the pharmacologic and clinical informationMills S, Bone K. Principles and Practice of Phytotherapy: Modern Herbal Medicine. Edinburgh: Churchill Livingstone, 2000.

1 Andreatini R, Loire JR. Eur J Pharmacol. 1994;260:233-235.

2 Garges HP, Varia I, Doraiswamy PM. JAMA. 1998;280(18):1566-1567.

3 British Herbal Medicine Association’s Scientific Committee. British herbal pharmacopoeia. Bournemouth: BHMA, 1983.

4 Felter HW, Lloyd JU. King’s American dispensatory, ed 18. Portland: Eclectic Medical Publications, 1905. rev 3, reprinted 1983

5 Valeriana edulis, Secretaria de Medio Ambiente, Recursos Naturales y Pesca (SEMARNAP, a Mexican government environmental department). Information available via URL: http:www.semarnap.gob.mx/.

6 Chamberlin RV. Mem Am Anthropol Assoc. 1911;2(5):331-405.

7 Smith HH. Bull Public Mus City Milw. 1923;4:1-174.

8 Smith HH. Bull Public Mus City Milw. 1928;4:175-326.

9 Hazelhoff B, Malingre TM, Meijer DK. Arch Int Pharmacodyn Ther. 1982;257(2):274-287.

10 Kuhlmann J, et al. Pharmacopsychiatry. 1999;32(6):235-241.

11 Dorn M. Forsch Komplementarmed Klass Naturheilkd. 2000;7(2):79-84.

12 Donath F, et al. Pharmacopsychiatry. 2000;33(2):47-53.

13 Herrera-Arellano A, et al. Planta Med. 2001;67(8):695-699.

14 Schmitz M, Jackel M. Wien Med Wochenschr. 1998;148(13):291-298.

15 Wheatley D. Phytother Res. 2001;15(6):549-551.

16 Blumenthal M, et al, editors. The complete German Commission E monographs: therapeutic guide to herbal medicines. Austin: American Botanical Council, 1998.

17 Scientific Committee of the European Scientific Cooperative on Phytotherapy [ESCOP]. ESCOP monographs: Valerianae radix. Argyle House, Gandy Street, Exeter, Devon, EX4 3LS, United Kingdom: European Scientific Cooperative on Phytotherapy, ESCOP Secretariat, July 1997.

VERVAIN

*Botanical Name:*	Verbena officinalis
*Family:*	Verbenaceae
*Plant Part Used:*	Aerial parts

PRESCRIBING INFORMATION

Actions	Nervine tonic, mild antidepressant, mild diaphoretic, astringent
Potential Indications	Based on appropriate evaluation of the patient, practitioners should consider prescribing vervain in formulations in the context of: • Infantile colic, in combination with lemon balm, chamomile, licorice, and fennel (3) • Anorexia, gastrointestinal irritation, jaundice (5) • Depression, nervous breakdown, epilepsy (5) • Feverish conditions including influenza, debility following illnesses or fever (5) • Promotion of lactation (5)

Contraindications Vervain is sometimes recommended as contraindicated during pregnancy, resulting from in vitro Chinese research conducted in 1975 and earlier in vivo studies using one of its constituents (verbenalin). This contraindication is not carried in most traditional Western herbal medicine texts, TCM texts, or the German Commission E monographs. Warnings and Precautions None required. Interactions Vervain tea reduced the absorption of iron by 59% from a bread meal (compared with a water control) in adult volunteers. The inhibition was dose-dependent and related to its polyphenol content (phenolic acids, monomeric flavonoids, polymerized polyphenols). Inhibition by black tea was 79% to 94%.¹ This finding indicates a potential interaction for concomitant administration of vervain during iron intake. In anemia and cases for which iron supplementation is required, vervain should not be taken simultaneously with meals or iron supplements. Use in Pregnancy and Lactation No adverse effects expected. Side Effects None expected if taken within the recommended dose range. Dosage Dose per day^* Dose per week^* 3-6 ml of 1:2 liquid extract 20-40 ml of 1:2 liquid extract

* This dose range is extrapolated from the British Herbal Pharmacopoeia 1983 and the author’s education and experience.

SUPPORTING INFORMATION

Traditional Prescribing	Traditional Western herbal medicine uses include: • Depression, nervous breakdown, epilepsy ² • As a galactagogue,² amenorrhea³ • Feverish conditions, debility following acute conditions, especially influenza ^2,³ • Anorexia, intestinal colic,⁴ gallbladder pain, jaundice² • As a poultice for headache, earache, rheumatism, hemorrhoids ⁴
	Uses from TCM include amenorrhea and dysmenorrhea, as well as malaria, abdominal masses, inflammation of the throat, boils, acute infections of the urinary tract, and edema.⁵
	The Eclectics regarded Verbena hastata, a species of Verbena, as having similar properties to V. officinalis. Verbena hastata was official in the NF from 1916 to 1926 and was used as a diaphoretic and expectorant. Native Americans used Verbena hastata to treat stomachache and as a beverage.⁶
Pharmacologic Research	The aerial parts of vervain contain a number of constituents, including iridoid glycosides (e. g., verbenalin) and caffeic acid derivatives.⁷ • Synergistic effects were observed on contraction of isolated uterus by the combination of vervain with either prostaglandin E₂ or prostaglandin F_2α. The Chinese researchers suggested using vervain preparations with prostaglandin E₂ for inducing abortion.⁸Verbenalin has been reported to exhibit uterine stimulation-contraction in vivo (route unknown).^9,¹⁰ • Vervain extracts were active against the following viruses in vitro: influenza A, parainfluenza type 1, and respiratory syncytial virus. Stimulation of phagocytosis and increased secretion of IL-6 was also observed.¹¹ However, this observed activity might be caused by the polyphenols and may not translate to in vivo activity. • Verbenalin by oral administration demonstrated hepatoprotective activity in acute carbon tetrachloride–induced liver injury.¹² • Antiinflammatory activity was observed for vervain extract in experimental models after topical and oral administration (in high doses).¹³
Clinical Studies	• A double-blind study on babies with colic investigated the effect of an instant herb tea preparation containing vervain, lemon balm, chamomile, licorice, and fennel. After 7 days, the colic improvement scores were significantly better in the herbal tea group, and more babies in the treatment group had their colic eliminated. The tea preparation was offered with every episode of colic, up to 150 ml per dose, but not more than three times per day. The exact composition of the preparation was not defined.¹⁴ • In an uncontrolled trial conducted in China, a high dose of vervain decoction (60 g/day) was successful in treating malaria.¹⁵