Phytotherapy Review & Commentary: Valerian; Clinical Overview

A major challenge facing healthcare practitioners today is safe and non-addictive medications for anxiety and insomnia. This category has largely been dominated in the last two decades by benzodiazepines like diazepam and alprazolam. While these drugs have been very useful in the management of more severe cases of anxiety, potential addiction and serious side effects secondary to withdrawal have cast a shadow over their long-term efficacy. Clearly, there is a need for gentler, non-addictive substances for the long-term management of insomnia and anxiety - particularly for initial intervention in milder forms of these conditions.

Extracts of valerian root, usually in combination with other plant medicines, are often prescribed in Europe as a substitute for benzodiazepines in the management of insomnia and anxiety. Valerian root extracts are derived from the plant Valeriana officinalis, an upright perennial that grows wild in woodlands, along river banks and in damp meadows all over Europe. Most of the plants used for medicinal preparations are cultivated.

The root of the plant is used medicinally. The root contains 0.4 -1.4% volatile oils where the primary active constituents are found.( 1) These constituents include monoterpenes and sequiterpenes with the primary focus on valerenic acid and valeranone. Current monographs on valerian require a minimum of 0.5% volatile oil content for medicinally used valerian root?

Historical Use

Valerian species were widely recommended by Greek physicians. Dioscorides recommends valerian for digestive problems, nausea, liver problems, and even urinary tract disorders. Galen (131-201A.D.) prescribed valerian as a treatment for insomnia.

The modern application of valerian for the treatment of insomnia and nervous conditions did not really pick up steam until the late 16th century. By the 18th century, it was firmly established as a medicinal treatment for nervous disorders associated with digestive problems and as a general sedative. Among its more infamous applications in the 19th century was the nervous condition in women referred to as "vapors." This rather sexist label apparently referred to a hysterical condition manifested by noises in the head, chills, impatience, and involuntary movements.

Mechanism of Action

While valerian root has been used for centuries in traditional herbal medicine preparations (and more recently in modern European extracts) for sleep disorders, nervousness, and even gastrointestinal pains of nervous origin, the mechanism of action for the active constituents has only recently been elucidated.

The breakthrough report on valerian's mechanism of action was published in 1989. Drs. J. Holzl and P. Godau of the Institute for Pharmaceutical Biology in Marburg, Germany, discovered that valerian binds benzodiazepine receptors in vitro.( 3) Valerian and its active constituents was shown to actually displace flurodiazepam off isolated benzodiazepine receptors from guinea pig brains.

Another in vitro study, completed in Milan, Italy, demonstrates the ability of valerian to bind GABA-A receptors.( 4) This deepens our understanding about the activity of valerian in the central nervous system. Sedation in the CNS is primarily mediated through GABA-A receptors. Important modulatory sites have been shown for the GABA-A chloride channel receptor complex, like central benzodiazepine receptors and barbiturate receptors.

Emphasis should be placed on the fact that the active constituents of valerian root appear to weakly bind benzodiazepine receptors when compared to drugs like diazepam or alprazolam. While exerting an effect on these receptors, valerian root is not associated with dependence and potential addiction.

Clinical Applications

Insomnia

Sleep disorders are rampant in our society. Various epidemiological reports have shown that approximately one-third of the adult population suffers from initial and/or continued sleep disorders.( 5) Treatment is indicated in about 15% of these cases.

Clinical research has indicated the ability of valerian root to reduce sleep latency. Two placebo-controlled clinical studies examined the ability of an aqueous extract of valerian to both reduce sleep latency and improve sleep quality in humans suffering from insomnia. Using dosages of 400 to 900 rag. of valerian root at bedtime, researchers found that valerian not only shortened sleep latency but also resulted in a reduction in night awakenings as well as an increase in dream recall. Perhaps most important was the observation that the morning "hangover" commonly associated with benzodiazepines was absent with use of valerian root.( 6, 7) The lower dosage range of 400 to 450 mg. was shown to be as effective as the higher dosages recommended.

A more recent study in Germany compared a standardized valerian product, containing a concentrated extract of valerian root and an extract of lemon balm (Melissa officinalis), with triazolam on sleep in twenty healthy volunteers ages 30 to 50 years.( 8) The median values of sleep efficiency of the volunteers established the criteria for the formation of two groups of "good" or "bad" sleepers. The valerian/lemon balm combination contains 160 mg. of valerian root extract and 80 mg. of lemon balm extract per tablet. Subjects were randomized to receive either one tablet of this combination or 0.125 mg. of triazolam at h.s. Sleep was monitored over nine nights.

Both groups showed a significant increase in sleep efficiency and in sleep stages 3 and 4 -- especially those in the category of "bad" sleepers. There was no rebound phenomena observed in either treatment group. In contrast to the triazolam group, daytime sedation and impairment of concentration or performance capabilities were not observed in the valerian/lemon balm group.

Anxiety / Affective Disorders

Based on the results with insomnia and sleep improvement in comparison with benzodiazepines, use of valerian combination products is growing among healthcare practitioners in the management of mild to moderate anxiety. Valerian, in combination with either lemon balm or passion flower (Passifiora incarnata), appears to offer a safe and efficacious tool in the early treatment of anxiety as well as the long-term management of those unable to use or attempting to withdraw from benzodiazepines.

An intriguing use for future clinical work with valerian combination products is easing the withdrawal symptoms of patients attempting to discontinue the use of benzodiazepines. It has been my clinical observation that the more potent valerian combinations mentioned above are very useful in this process.

Another European study also indicates that valerian may be a useful tool in patients with affective disorders.( 9) The combination of a concentrated valerian and passion flower extract was compared with the neuroleptic drug, Propaphenin, in 20 psychosomatic and affective disorder patients. Each tablet of the valerian/passion flower combination contained 100 mg. of valerian root and 45 mg. of passion flower. The daily dose was two tablets three times daily. All patients were monitored by EEG as well as depression and anxiety clinical monitoring questionnaires.

EEG changes included selective alpha- and theta-wave increases in both groups. However, in the valerian/passion flower group, these were noted after only two weeks of use as compared to 6 weeks for the neuroleptic group. Depression and anxiety measures were decreased in both groups but side effects like reduced vigilance and orthostatic load were noted only in the neuroleptic group.

Safety of Long-Term Valerian Use

For treatment of insomnia, 300 to 400 mg. of a concentrated valerian root extract standardized to contain at least 0.5% essential oil is recommended. This should be taken approximately one hour before bedtime. For management of anxiety, a morning dose of 200 to 300 mg. is recommended in addition to the evening dose listed above.

Clinical monographs on valerian in Europe list no contraindications to its use during pregnancy and lactation. This has been somewhat controversial as valerian root does contain substances known as valepotriates that were previously thought to be potentially teratogenic and carcinogenic. Recent studies with pregnant rats have shown that valepotriates are probably not harmful during pregnancy when consumed orally.( 10) Erring on the side of caution, commonly used valerian root extracts in Europe have removed valepotriates during the extraction process. Persons using valerian should not take it while using alcohol. Caution should also be used when driving or operating machinery after valerian use.
References

(1.) British Herbal Compendium. British Herbal Medicine Association. 1992.

(2.) Valerianae Radix (Valerian Root). European Monograph. European Scientific Cooperative for Phytotherapy, 1992.

(3.) Holzl J & Godau P: Receptor bindings studies with Valeriana officianlis on the benzodiazepine receptor. Planta Medica 55: 642, 1989.

(4.) Mennini T, Bernasconi P, et al: In vitro study on the interaction of extracts and pure compounds from Valeriana officinalis roots with GABA, benzodiazepine and barbiturate receptors. Fitoterapia 64: 291-300, 1993.

(5.) Bixler EO, Kales A, et al: Prevalence of sleep disorders in the Los Angeles metropolitan area. Am J Psychiatr 136: 1257-62, 1979.

(6.) Leathwood PD & Chauffard F: Aqueous extract of valerian reduces latency to fall asleep in man. Planta Medica 51: 144-8, 1985.

(7.) Leathwood PD, Chauffard F, et al: Aqueous extract of valerian root (Valeriana officinalis L.) improves sleep quality in man. Pharmacol Biochem Behav 17: 65-71, 1982.

(8.) Dressing H, Riemann D, et al: Insomnia: Are valerian/balm combination of equal value to benzodiazepine? Therapiewoche 42: 726-36, 1992.

(9.) Schellenberg V, Schellenberg R & Janig L: Quantitative EEG monitoring in phyto- and psycho-pharmacological treatment of psychosomatic and affective disorders. Schizophrenia Res 9 (2,3): Abstract, 1993.

(10.) Tufik S, Fujita K, et al: Effects of prolonged administration of valepotriates in rats on the mothers and their offspring. J Ethnopharmacol 41: 39-44,1994.

Article copyright Townsend Letter for Doctors & Patients.

~~~~~~~~

By Donald J. Brown

Share this with your friends