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PHARMACOLOGICAL ACTIVITIES - TOXICOLOGY - DRUG INTERACTIONS

Valeriana officinalis (Garden Valerian)

Clinical data indicates that Radix Valerianae is a mild sedative and sleep promoting agent. It is
often used as a milder alternative or a possible substitute for stronger synthetic sedatives, such
as benzodiazepines, in the treatment of states of nervous excitation and anxiety-induced sleep
disturbances (WHO, 1999). The mechanism of action of Radix Valerianae in general and as a
mild sedative in particular, remains unknown. Radix Valerianae extracts appear to have some
affinity for the GABA (A) receptor, a class of receptors on which benzodiazepines are known
to act (Holzl & Godau, 1989; Mennini, et al., 1993). Aqueous extracts of the roots contain
appreciable amounts of GABA that could directly cause sedation (Houghton, 1999). Valerenic
acid in animals appears to inhibit the enzyme system responsible for the central catabolism of
GABA, increasing GABA concentration and decreasing CNS activity, and direct binding of
valerenic acid to GABA-receptors has been demonstrated (Benke et al., 2009). Cats given 10 mg/
kg of a Radix Valerianae extract by gastric lavage had a significant decrease in restless, fearful and
aggressive behaviors (Von Eickstedt, 1969).

Toxicity for Radix Valerianae has not been documented in dogs and cats when administered orally in therapeutic
doses. An unusual feature of Valeriana officinalis is that the essential oil of Radix Valerianae is a cat attractant
similar to catnip. Radix Valerianae contains the cat attractant actinidine. Cats with implanted electrodes showed
no changes in their EEGs following oral administration of 100 or 250 mg/kg of body weight of Radix Valerianae
extract (EMEA, 2007).

In acute oral toxicity tests the LD of the sesquiterpene valeranone was greater than 3 g/kg of body weight in
TOXICOLOGY both rats and mice which corresponds to low toxicity. The LD of essential oil of Radix Valerianae is 1,500 mg
50
50
in rats weighing 100 g. The LD of an ethanol Radix Valerianae extract made from the defatted herbal substance
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administered intraperitoneally to mice amounted to 3.3 g/kg of body weight, a value, which corresponds to a low
toxicity. Valerenic acid caused inhibition of spontaneous motility after intraperitoneal administration to mice at
a dose of 50 mg/kg of body weight; ataxia and temporary immobility at a dose of 100 mg/kg of body weight,
muscle spasms at doses of 150-200 mg/kg of body weight; and severe convulsions and mortality at a dose of 400
mg/kg [6 of 7 animals ad exitum 24 hours after administration] (EMEA, 2007).

Equivalent toxic dose in 20 kg dog: 66 g IP of ethanol Radix Valerianae extract.
Equivalent toxic dose in 5 kg cat: 16.5 g IP of ethanol Radix Valerianae extract.

DRUG Radix Valerianae lengthens the sedation time induced by barbiturates and may have synergistic
INTERACTIONS effects with benzodiazepines (Carrasco et al., 2009). Radix Valerianae may have an additive
effect with haloperidol, causing hepatic damage (Dalla et al., 2008). Radix Valerianae may
interact with anaesthetics (Ang-Lee et al., 2001).

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