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Valeriana officinalis.

Botanic name: Valeriana officinalis

Common name: Valerian

Botanical description

Reaching a height of 1.5 metres, valerian is a perennial herb with creeping, aromatically pungent rhizomes, and hollow stems (Weiss 1988, Heinrich 2004). Oblong and ovate shaped, the fruits have 4 ridges and are single seeded. Its leaves are compounded and its flowers are white/pinkish and arranged in flat topped terminal clusters (Wyk 2009, WHO 1999). Due to the isovaleric acid released on the decomposition of the valepotriates, a distinctive pungent odor is produced (Mills 2000, Culpeper 1826).

Part/s used

The plant materials of interest are the dried roots, rhizomes and stolons (British Herbal Pharmacopeia 1976).

Relevant constituents

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(Barnes 2007, Hechtman 2012)

Preparation method/s

Valerian is native to Europe and Asia and was naturalised in North America but has been observed as being a difficult herb to cultivate in Australia (Wyk 2009, Hall 1988). Preferring a moist lime rich soil with roots in the shade, its flowering parts favour gentle morning sun. In cultivation, the flowers are removed to encourage rhizome growth; the rhizomes and roots are then harvested in the second year once the leaves have died off (Bown 2008, Hall 1988, American Herbal Pharmacopoeia (AHP) 1999). The essential oil content can vary with harvest times and older literature reports the ideal time is the autumn. Other factors influencing plant chemistry are growing conditions, age of root, drying techniques and method of analysis (AHP 1999). The roots and rhizomes must be dried carefully at a temperature not above 40[degrees]C according to ESCOP (1996). Interestingly, depending on this development it has been observed that valerian may show individually different results, even though commercially it is more cost effective to harvest the roots the same year the plants are sown rather than in the second year (AHP 1999, Hall 1988). According to Adams (2006), the liquid extract is made at a ratio of alcohol to water of 45:55.

Historical information

Valerian is considered one of the most important herbal sedatives and is also considered the most widely recognised herbal tranquilliser in Australia (Wyk 2009, Hechtman 2012). Valerian has a history that is over 2000 years old with Dioscorides (AD 40-80) writing on several species of it, with others also reporting on its sedative effects, including Galen (ca AD 131-208) (AHP 1999). Valerian has a rich folklore tradition of use in many countries, although its origin is considered to be placed in Europe, Asia and then naturalised in North America. It is rumoured to have been used by the Pied Piper of Hamelin in his quest to remove vermin as well as being associated with strange behaviour in felines (Hall 1988, Sarris 2010, Weiss 1988). The name itself, valerian, was first used in domestic books of home remedies around the 11th century. It was described for use to treat epilepsy in the late 16th century by Fabius Columba (AHP 1999, Griggs 1997). According to its energetics, valerian was considered by Disocorides to possess 'warming properties' and it was widely used by Eclectic physicians who commented that valerian was 'one of the best calmatives for the collective condition termed nervousness' (Sarris 2010, Hechtman 2012). It was included in King's American Dispensatory and quoted as an aromatic stimulant as well as having some other unique indications. One of them includes having 'bitter' properties (Bown 2008, Culpeper 1826, AHP 1999). Finally it was listed in both the United States Pharmacopoeia (USP) from 1820-1936 and the British Herbal Pharmacopeia (BHP) in 1867 and then in the European Scientific Cooperative of Phytotherapy in 1996. Additionally it is now included in Commission E (Thomsen 2009, ESCOP 1996). Valerian has been used as a flavouring agent in some foods and liqueurs as well as being used as bait to trap wild cats and rodents (Bown 2008). Valerian now continues to be both a safe and effective herbal remedy for many uses which will be discussed in the next section.

Medicinal actions (contemporary usage)

Medicinal actions include sedative (AHP 1999), hypnotic (BHP 1976), anxiolytic (Mills 2000), spasmolytic (Bone 2003), hypotensive (Barnes 2007, AHP 1999), carminative (BHP 1976), mild anodyne (Barnes 2007), nervine tonic (Thomsen 2009), cerebral stimulant (Felter 1922). Other uses include antiarrhythmic (the valepotriates thought to be responsible are unlikely to be present in commercial products).

Homeopathic uses include neuralgic pains, rapid pulse and blood congestion in the head (Lockie 2000).

Medicinal indications (contemporary usage)

Medicinal indications for the use of valerian include insomnia (Bent 2006), restlessness and anxiety (Thomsen 2009), dysmenorrhea (Mirabi 2011), nervous headache (Sarris 2010), nervous tension (Mills 2000), hypochondriasis (BHP 1976), symptoms of menopause (Wyk 2009), nervous palpitations (Weiss 1988), nervous asthma (AHP 1999), benzodiazepine withdrawal (Head 2009b), restless leg syndrome (Cuellar 2009), rheumatic pains (BHP 1976), ADHD (AHP 1999), migraine (Thomsen 2009), chorea (Bone 2003), intestinal colic (BHP 1976), cholecystitis (Hechtman 2012), epilepsy (Griggs 1997), obsessive compulsive disorder (Pakseresht 2011), anxiety and alterations in hyperthyroidism (Hechtman 2012).

Externally it is indicated for treatment of eczema (Bown 2008), ulcers (Bown 2008), minor injuries (Bown 2008) and may be used as a bath additive for its sedative properties and effects on fibromyalgia (Mills 2000, Braun 2010). The specific indication for valerian is conditions presenting with nervous excitability (BHP 1976).

Pharmacokinetics

Authors Barnes et al (2007) state that there is limited data on the pharmacokinetics of Valeriana officinalis. Furthermore the AHP (1999) has reported that the only available data is regarding its valepotriates, although they have shown that when administered to rats (in vivo) the valepotriates were absorbed poorly with only 0.19% absorption efficiency. They also observed that the greatest quantity was from the stomach lining and intestines.

According to Barnes et al (2007) the mean elimination half-life for valerenic acid in valerian is 1.1 hours. The pharmacokinetics for valerian were explored with six healthy volunteers in a single dose study receiving a 70% ethanol extract of valerian root (5:1) equating to 600 mg in the morning. Maximum serum concentrations of valerenic acid occurred between one and two hours after administration. For one subject however, maximum blood serum concentration peaked at both one and five hours after administration. It appears that the direct antispasmodic activity of valerian is attributed not to its work on the ganglion receptors but to the smooth muscle receptors. Valerian oil exhibited antispasmodic activity on isolated guinea pig uterine muscle, however it proved inactive when tested in vivo (Anderson 2005). Authors Donovan et al (2004) and Barnes et al (2007) also found that typical doses of valerian in healthy volunteers were unlikely to produce significant effects on CYP3A4 activity (the protein that catalyses many reactions involved in drug metabolism) and no effect on CYP2D6 (liver microsomal enzymes) pathways of metabolism. Although both a small and preliminary investigation, it does indicate that valerian is unlikely to participate in interactions with drugs that are dependent on those pathways of metabolism. Further research is needed however, in regards to the pharmacokinetics of valerian, including those of different constituents and preparations.

Pharmacodynamics

Much of the research into the pharmacological action of Valeriana officinalis has been focused on its sedative and spasmolytic properties (AHP 1999). The essential oils appear to have the sedative effect; while the valepotriates seem to have a regulatory effect on the autonomic nervous system (Head 2009a). This effect appears to be due to the fact that valerian interacts with neurotransmitters such as gamma-aminobutyric-acid (GABA). As well as producing a release of GABA that is dose dependant, it also inhibits the enzyme induced breakdown of GABA in the brain, with an affiliated sedation. Additionally Head and Gregory (2009a) and Heinrich et al (2004) state that it binds to benzodiazepine receptors and this also confirms other research reported by Braun & Cohen (2010) that found it comparable to oxazepam in a double blind trail. There appears to be an interaction between hydroethanolic extracts of valerian root and the GABA benzodiazepine-chloride receptor channel complex in in vitro experiments (ESCOP 1996). There was an affinity for GABA receptors (Wyk 2009) although at this stage the constituents responsible for the activity were not identified. In short the neuropharmacological activity of valerian appears to be complex, and only partially understood.

Relevance of pharmacodynamics research to contemporary usage

There is a wide variety of opinions about whether the research information and the contemporary usage of valerian are consistent. For example in 2010 a metaanalysis of eight randomised control trials (RCTs) was selected to investigate the use of valerian in the treatment of insomnia. The authors Fernandez-Sab-Martin et al concluded that although its effectiveness for 'subjective' improvement of insomnia was verified, they recommend that to improve insomnia, future investigations should be oriented towards other 'more promising treatments'. It was also said that valerian has not been demonstrated to be effective through 'quantitative or objective measurements'. Furthermore Anderson et al (2005) stated that 'the evidence for the efficacy of valerian to improve sleep remains weak'. However many authoritative herbal texts, both old and new, affirm its use (AHP 1999, BHP 1976, Felter 1922). In light of this the evidence base on valerian will need to be improved.

A further systematic review and meta-analysis was published in the American Journal of Medicine. Authors Bent et al (2006) stated that after an 'extensive literature search' they found 16 randomised controlled trials. Of these only 6 studies were methodologically robust enough to include. The authors concluded that there were 6 studies with a dichotomous outcome of quality of sleep that showed statistically significant benefit, although there was evidence present of publication bias in this summary measure. It should also be noted that 9 of the studies did not have positive outcomes with regard to sleep quality, but the authors did determine that 'the available evidence suggests that valerian might improve sleep quality without producing side effects.

Future studies should assess a range of doses of standardised preparations of valerian and include standard measures of sleep quality and safety'. There was also agreement with Bent et al (2006) from Fernandez-Sab-Martin et al (2010) that there was a 'statistically significant improvement in the subjective variable of sleep quality'. Bent et al (2006) argues that there was an 80% greater chance of sleep improvement when compared with placebo. Furthermore the AHP (1999) argues that their research suggests the contemporary valerian usage is consistent with the research information. In the cases where the research and valerian usage is not consistent one may hypothesise that there may be bias in the research publication (Bent 2006). Of course this opinion is argued by others, such as Fernandez-Sab-Martin et al (2010) who claim there is no publication bias in the very same research.

As we have seen, valerian has over two centuries of use. The two different epistemological approaches (traditional evidence vs. statistical and scientific evidence) are not likely to always be consistent and sometimes, but not always, yield different results. However it seems that both approaches typically refer to the efficacy of valerian in sleep disturbances.

Cautions

Valerian appears to be quite a safe herb. Authors Fernandez-Sab-Martin et al (2010) stated that 'the safety factor valerian offers makes it highly desirable compared to pharmacological alternatives for insomnia'. While in theory morning somnolence is a possible side effect of therapy as with numerous pharmaceutical sedatives, evidence suggests that this is not associated with valerian (Braun 2010). However for concurrent use of valerian with pharmaceutical drugs, authors Barnes et al (2007) state that there is only limited data available for potential interactions with other medicines. They went on to further say that there may be interactions with barbiturates and that concurrent sedative use is not recommended. According to Braun & Cohen (2010) the use of valerian and alcohol appears to be acceptable. As for the toxicity of valerian, one case study reported a dose taken at 20-fold the recommended therapeutic dose and appeared to not be life threatening. Furthermore physical addiction appears unlikely and illustrates valerian's therapeutic attractiveness when compared with its pharmaceutical counterparts (Braun 2010).

In older literature it was reported that atropine decreases the hypotensive activity of valerian by 50%, although the cause has not been established (AHP 1999). In addition hepatotoxicity has been associated in the past, admittedly isolated (Heinrich 2004). One study did report vivid dreams, headache and gastrointestinal symptoms occurring, although this is considered rare (Braun 2010). Use with pregnancy appears unrestricted although safety in pregnancy has not yet been established (Braun 2010). It should be noted that in some rare cases valerian may cause nervousness and heart palpitations in some sensitive individuals (AHP 1999).

Contraindications

It is not recommended to administer valerian to children under 3 years of age (Thomsen 2009).

Dosage

The dosage range for valerian varies considerably in the literature, particularly in older texts (Barnes 2007).

* 3-9 g dried root/rhizome per day (Bone 2003)

* 2-6 mL 1:2 liquid extract per day or 5-15 mL 1:5 tincture per day (Mills 2000)

* 1-3 g as an infusion or decoction up to three times a day (Barnes 2007)

* Essential oil 0.05-0.25 mL (2-6 drops) up to two times daily (AHP 1999)

* As a bath additive 100 mg (AHP 1999) Clinical trials provide the following recommendations:

* Insomnia: doses vary from 400 mg per day (3:1) to 1215 mg per day (5 to 6:1) (Barnes 2007)

* Restless leg syndrome: 800 mg dried root/rhizome per day (Cuellar 2009)

* Dysmenorrhea: 255 mg (Mirabi 2011)

* Nervous tension (anxiety): 600 mg per day (Braun 2010)

* Fibromyalgia: 100 mg as a bath additive (AHP 1999, Braun 2010)

* Obsessive compulsive disorder: 765 mg (Pakseresht 2011)

* Anticonvulsant for epilepsy: an upper limit of 10 g per day (Eadie 2004)

* Benzodiazepine withdrawal with sleep disturbance: 100 mg three times daily (Head 2009a, Braun 2010).

References

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American Herbal Pharmacopeia. 1999. American Herbal Phamacopeia. R. Upton Ed. Santa Cruz: AHP.

Anderson GD, Elmer GW, Kantor ED, Templeton IE, Vitello MV. 2005. Pharmacokinetics of valerenic acid after adminstration of valerian in healthy subjects. Phytother Res 19:9;801-3.

Barnes J, Anderson L, Phillipson J. 2007. Herbal Medicines 3rd edn. London: Pharmaceutical Press.

Bent SP, Moore D, Patterson M, Wehling W. 2006. Valerian for sleep: a systematic review and meta-analysis. Am J Med 119:12;1005-12.

Bone K. 2003. A Clinical Guide to Blending Liquid Herbs. Sydney: Churchill Livingstone.

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British Herbal Pharmacopoeia. 1976. British Herbal Pharmacopoeia - Part One. West Yorks: British Herbal Medicine Association.

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Donovan JL, Donovan CD, Chavin KD, Wang J, Gibson B, Gefroth HA et al. 2004. Multiple night-time doses of valerian (Valeriana officinalis) had minimal effects on CYP3A4 activity and no effect on CYP2D6 activity in healthy volunteers. Drug Metab Dispos 32:12;1333-6.

Eadie MJ. 2004. Could valerian have been the first anticonvulsant? Epilepsia 11:45;1338-43.

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Head KA, Kelly GS. 2009b. Nutrients and botanicals for treatment of stress: adrenal fatigue, neurotransmitter imbalance, anxiety and restless sleep. Alt Med Rev 14:2;122.

Hechtman L. 2012. Clinical Naturopathic Medicine Revised edn Chatswood NSW Australia: Elsevier.

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Mirabi P, Dolatian M, Mojab F, Majd HA. 2011. Effects of valerian on severity and systemic manifestations of dysmenorrhea. Int J Gynecol Obstet 115:3;285-8.

Pakseresht S, Boostani H, Sayyah M. 2011. Extract of valerian root (Valeriana Officinalis L.) vs. placebo in treatment of obsessive-compulsive disorder: a randomized double-blind study. J Comp Integ Med 8:1;201-12.

Sarris J, Wardle J. 2010. Clinical Naturopathy. Sydney: Churchill Livingstone.

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Jeremy Brown, Australasian College of Natural Therapies, Sydney
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Title Annotation:Undergrad copy
Author:Brown, Jeremy
Publication:Australian Journal of Herbal Medicine
Geographic Code:8AUST
Date:Dec 1, 2012
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