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Botanical Name: Valeriana officinalis L.
Pharmacopoeial Name: Valerianae radix.
Common Name: Valerian.

Summary Table
Drug/Class Interaction TypeMechanism and SignificanceManagement
Herb may reduce side effects of benzodiazepine withdrawal acting as partial agonist at GABAA-benzodiazepine receptor complex, as well as antidepressant, muscle relaxant, and other effects.Consider incorporating valerian into nutritional/botanical support protocols for drug tapers.
Central nervous system (CNS) depressants

Herb will combine additively with centrally acting depressants at multiple receptor subtypes (5-HT, GABAA, H1, D2, and adenosine). Effects shown to be additive not supra-additive.Avoid herb-drug coadministration except in short-term/acute circumstances or specialized settings with professional management. (See benzodiazepines.)
GABA , Gamma-aminobutyric acid; 5-HT , hydroxytryptamine (serotonin); H , histamine; D , dopamine.
herb description



Related Species

There are several hundred members of the Valeriana genus, and several species are traded as medicinal valerian root. In North America these include Mexican valerian ( V. edulis Nutt.); Indian valerian ( V. wallichi DC) and Pacific valerian ( V. sitchensis Bong). Ornamental Valerianaceae genera such as Centranthus may sometimes be called “valerians,” but these are nonmedicinal.

Habitat and Cultivation

Valerian is cultivated widely in Europe and North America and Russia, with Europe providing the bulk of the commercial material.

Parts Used

Fresh or dried rhizomes, roots, and stolons.

Common Forms

  • Dried Root:   Cut or powdered.

  • Tincture, Fluid Extract:   70% ethanol.

  • Solid Concentrates:   Between 4:1 and 7:1. Standardization to total valerenic acid (0.8%) has been suggested, but a consistent standard has not been established to date. Manufacturers’ preparations may vary.

herb in clinical practice


Valerian root is widely known as a mild sedative-hypnotic herb with a strong, characteristic odor when dried. It is used medicinally to reduce sleep latency, to treat mild to moderate insomnia, and to relieve spasmodic conditions of the smooth muscle. The herb is chemically and pharmacologically complex, and its sedative mechanisms are not fully understood. Herbalists consider that valerian is capable of producing paradoxical effects, but it is not established whether this is caused by the variability in constituent composition resulting from differences in growing conditions, harvesting times, and preparation methods or by constitutional variability among patients or consumers, or both. There is known chemotypic variation in the quantity and distribution of sesquiterpenes and valepotriates among different species, and polyploidal variants exist within species, including V . officinalis . Chemical differences between fresh and dried root preparations caused by the instability of the monoterpene valepotriates add to the overall variability. In clinical practice, valerian is usually combined with other sedative herbs, such as hops, passionflower, or lemon balm, rather than used alone.

Valerian has therapeutic monographs from the German Commission E, 1 World Health Organization (WHO), 2 European Scientific Cooperative on Phytotherapy (ESCOP), 3 and the American Herbal Pharmacopoeia ( AHP ). 4 Literature reviews are available by Houghton, 5 Morazzoni and Bombardelli, 7 and McKenna et al. 8 The established indications for valerian root are sleep promotion, relief of temporary mild anxiety, and reduction of sleep latency. More than a dozen clinical trials support the use of valerian for insomnia, although a systematic review found the overall evidence for efficacy of the herb was inconclusive based on nine trials included in the metastudy. 9

Historical/Ethnomedicine Precedent

Valerian has been in documented use in Western herbal medicine since Greco-Roman times. It was initially used as an aromatic and digestive remedy and subsequently became known as a treatment for epilepsy and for various nervous disorders. It was listed in the United States Pharmacopeia ( USP ) from 1820 to 1930 and continues to be listed in the British Pharmacopoeia and the major homeopathic materia medicas. 10 The Eclectic physicians used valerian for patients with impaired cerebral circulation associated with depression. 11 It has a traditional history of popular use in the United Kingdom, reputedly for treatment of “shell shock” in both world wars and as a home remedy for promotion of sleep, without addictive effects or cognitive impairment. 12 Valerian root is unusual in that the traditional alcoholic tincture remains a favored preparation, partly because of the complex chemistry of the root, which defies straightforward standardization to a unique “active” ingredient.

Known or Potential Therapeutic Uses

Anxiety; epileptic seizure; fibromyalgia; gastric spasm and colic hyperactivity; infantile convulsions; insomnia; menstrual cramps; mild tremor; nervous asthma; nervous tension; posttraumatic stress disorder (PTSD), including “combat fatigue;” sleep disturbances; spasmodic conditions of the gastrointestinal and urogenital tracts.

Key Constituents

Essential oil (0.1%-2.0%), containing three classes of sesquiterpenes (kessane, valerenic aid, valeronone skeletons) and monoterpenes, principally bornyl acetate.

Valepotriates (0.5%-14.5%): epoxy iridoid esters and their degradation products (baldrinals).

Amino acids, including arginine, γ-aminobutyric acid (GABA), glutamine.

Alkaloids (0.01% to 0.05%), lignans, and flavonoids.

Therapeutic Dosing Range

  • Dried Root:   3 to 9 g daily

  • Tincture:   Based on 1:1 equivalent, 1 to 3 mL three times daily

  • External (Bath):   100 g per bath

interactions review

Strategic Considerations

The majority of authoritative monographs on valerian maintain that the herb does not exhibit any notable interactions with pharmaceutical drugs. This is corroborated by an absence of any clear-cut case reports in the literature. However, the central nervous system (CNS) depressant properties of the herb have been substantiated, and as a result, several secondary sources including the USP , suggest that the herb may potentiate the effects of a variety of CNS depressant drugs. 12,13Also, valerian may interfere with antiepileptic medications 14 ; this speculation has been eloquently refuted by Eadie 15 in a historical review that concluded valerian is in fact antiepileptic. Although inconclusive, experimental data from the 1980s and 1990s tended to favor a GABAergic mechanism of the sedative effects of the herb. 16 Reverse extrapolations from this putative pharmacological mechanism have also been used to support suggestions of interactions with CNS depressants that act at the GABA-benzodiazepine-chloride channel complex. 13 This includes speculations that the herb will interact with anesthetics. 17 Such reverse extrapolations are better described as “potential contraindications” rather than interactions. Although the possibility of additive effects with CNS depressant drugs is examined as a potential interaction here, the available evidence suggests that synergistic interactions (vs. simple additive effects) between valerian and pharmaceutical sedatives do not exist.

The more recent ligand-binding studies suggest multiple possible actions at different neural receptors, including melatonin and serotonin subtypes, as well as partial GABAAreceptor agonism and H1histamine and D2dopamine receptor binding. 18-24In clinical practice, valerian has been used, as with kava, to facilitate withdrawal from benzodiazepenes. 25 In this context the clinical coadministration of herb and drug is a valid exception to the general rule of avoiding concomitant use of herbs and drugs that have similar neurotransmitter effects. (See also benzodiazepines section of the Kava monograph.)

The “psychiatric” indications for valerian are anecdotally well known by the herb-consuming public. Populations who have previously used psychiatric drugs such as sedatives and anxiolytics are arguably more likely to self-prescribe valerian. This may lead to inadvertent additive effects from what would be regarded as contraindicated herb-drug combinations in a professional setting. Unfortunately, literature reviews such as the recent survey by Ernst 26 suggest valerian is ineffective as an anxiolytic, confusing the issue, even if strictly correct in terms of meta-analysis methodology. The poor quality of trials on valerian as a single agent is likely to produce such a conclusion; in practice, valerian is used in combination with other sedative or anxiolytic herbs. Generally, combinations of “nervine herbs,” such as hops, lemon balm, and passionflower, with valerian demonstrate greater efficacy than single agents. 27-29

Effects on Drug Metabolism and Bioavailability

Several in vitro studies have examined the effects of valerian extracts on cytochrome P450 (CYP450) enzymes. Strandell et al. 30 used fluorometric screening methodology and found a moderate inhibition of recombinant human microsomal CYP450 3A4 with a dimethyl sulfoxide (DMSO) extract derived from one of two valerian preparations tested, whereas no effect was found on CYP450 2C19 or 2D6. The effect was not observed when an ethanol extract rather than DMSO was used, and the second valerian product exhibited no inhibitory effects on CYPs. Lefebvre et al. 31 also used fluorometric assay methodology to examine the effects of 14 different commercial preparations of valerian on CYP3A4. They noted wide variation in the composition of the valerian products, with valerenic acid content varying from 21 to 2661 ppm. They found an inhibitory effect on CYP3A4 and also on P-glycoprotein (P-gp), using an ATPase-dependent assay system with a verapamil control. The effect varied with solvents used, with water being the least inhibitory and acetonitrile the most inhibitory. By contrast, earlier fluorometric study of 3A4 inhibition by Budzinski et al. 32 found that both valerian extract and pure valerenic acid were unable to inhibit 3A4 at clinically relevant concentrations and were the weakest inhibitors of the various herbs and pure compounds tested.

Gurley et al. 33,34performed a study on valerian (and three other herbs) with 12 healthy volunteers consuming the extract for a month. Preadministration and postadministration data for a variety of probe substrates relating to CYP450 3A4, 1A2, 2E1, and 2D6 were determined. No significant changes were found for valerian (125 mg three times daily for 28 days), and the authors concluded that valerian is unlikely to cause pharmacokinetic interactions mediated by the major CYP450 enzymes. Donovan et al. 35 used higher doses of herb (1000 mg containing 11 mg valerenic acid) taken every night for 14 days by 12 healthy volunteers. They used probe drugs (dextromethorphan and alprazolam) to test for effects on CYP2D6 and CYP3A4. No significant changes in baseline preadministration levels were found.

From the available data, clinically significant pharmacokinetic interactions between valerian and prescription drugs appear to be unlikely despite conflicting results from in vitro studies.

herb-drug interactions
Barbiturates and Other Central Nervous System Depressants
theoretical, speculative, and preliminary interactions research, including overstated interactions claims
  • 1.Blumenthal M, Busse W, Goldberg A et al. The Complete German Commission E Monographs. Austin, Texas: American Botanical Council: Integrative Medicine Communications; 1998.
  • 2.WHO. Radix valerianiae. WHO Monographs on Selected Medicinal Plants. 1 vol. Geneva: World Health Organization; 1999:267-276.
  • 3.ESCOP. Valerianae radix. ESCOP Monographs: the Scientific Foundation for Herbal Medicinal Products. 2nd ed. Exeter, UK: European Scientific Cooperative on Phytotherapy and Thieme; 2003:539-546.
  • 4.AHP. Valerian root. In: Upton R, ed. American Herbal Pharmacopoeia. Scotts Valley, Calif; 1999.
  • 5.Houghton PJ. Valerian: The genus Valeriana. Medicinal and Aromatic Plants: Industrial Profiles. 51 vol. Amsterdam: Harwood Academic; 1997:505-512.
  • 6.Houghton PJ. The scientific basis for the reputed activity of valerian. J Pharm Pharmacol 1999;51:505-512.View Abstract
  • 7.Morazzoni P, Bombardelli E. Valeriana officinalis: traditional use and recent evaluation of activity. Fitoterapia 1995;66:99-112.
  • 8.McKenna D, Jones K, Hughes K, Humphrey S. Valerian. Botanical Medicines. 2nd ed. Binghamton, NY: Haworth Press; 2002:1007-1037.
  • 9.Stevinson C, Ernst E. Valerian for insomnia: a systematic review of randomized clinical trials. Sleep Med 2000;1:91-99.View Abstract
  • 10.Boyle W. Official Herbs: Botanical Substances in the United States Pharmacpoeias 1820-1990. East Palestine, Ohio: Buckeye Naturopathic Press; 1991.
  • 11.Felter H, Lloyd J. Valeriana. King’s American Dispensatory. 2 vol. 1898 Reprint ed. Sandy, Ore: Eclectic Medical Publications, Reprint 1983; 1898:2041-2043.
  • 12.Mills S, Bone K. Principles and Practice of Phytotherapy. Edinburgh: Churchill Livingstone; 2000.
  • 13.Brinker F. Herb Contraindications and Drug Interactions. 3rd ed. Sandy, Ore: Eclectic Medical Publications; 2001.
  • 14.Spinella M. Herbal medicines and epilepsy: the potential for benefit and adverse effects. Epilepsy Behav 2001;2:524-532.View Abstract
  • 15.Eadie MJ. Could valerian have been the first anticonvulsant? Epilepsia 2004;45:1338-1343.
  • 16.Spinella M. The Psychopharmacology of Herbal Medicine. Cambridge, Mass: MIT Press; 2001.
  • 17.Ang-Lee MK, Moss J, Yuan CS. Herbal medicines and perioperative care. JAMA 2001;286:208-216.View Abstract
  • 18.Abourashed EA, Koetter U, Brattstrom A. In vitro binding experiments with a valerian, hops and their fixed combination extract (Ze91019) to selected central nervous system receptors. Phytomedicine 2004;11:633-638.
  • 19.Muller CE, Schumacher B, Brattstrom A et al. Interactions of valerian extracts and a fixed valerian-hop extract combination with adenosine receptors. Life Sci 2002;71:1939-1949.View Abstract
  • 20.Schellenberg R, Sauer S, Abourashed EA et al. The fixed combination of valerian and hops (Ze91019) acts via a central adenosine mechanism. Planta Med 2004;70:594-597.
  • 21.Granger RE, Campbell EL, Johnston GAR. (+)- And (−)-borneol: efficacious positive modulators of GABA action at human recombinant [alpha]1[beta]2[gamma]2L GABAA receptors. Biochem Pharmacol 2005;69:1101-1111.
  • 22.Dietz BM, Mahady GB, Pauli GF, Farnsworth NR. Valerian extract and valerenic acid are partial agonists of the 5-HT5a receptor in vitro. Brain Res Mol Brain Res 2005;138:191-197.View Abstract
  • 23.Yuan CS, Mehendale S, Xiao Y et al. The gamma-aminobutyric acidergic effects of valerian and valerenic acid on rat brainstem neuronal activity. Anesth Analg 2004;98:353-358, table of contents.View Abstract
  • 24.Oliva I, Gonzalez-Trujano ME, Arrieta J et al. Neuropharmacological profile of hydroalcohol extract of Valeriana edulis ssp. procera roots in mice. Phytother Res 2004;18:290-296.View Abstract
  • 25.Rasmussen P. Phytotherapy for the treatment of drug withdrawal. Eur J Herbal Med 1997;3:11-22.
  • 26.Ernst E. Herbal remedies for anxiety: a systematic review of controlled clinical trials. Phytomedicine 2006;13:205-208.View Abstract
  • 27.Muller SF, Klement S. A combination of valerian and lemon balm is effective in the treatment of restlessness and dyssomnia in children. Phytomedicine 2006;13:383-387.View Abstract
  • 28.Kennedy DO, Little W, Haskell CF, Scholey AB. Anxiolytic effects of a combination of Melissa officinalis and Valeriana officinalis during laboratory-induced stress. Phytother Res 2006;20:96-102.
  • 29.Morin CM, Koetter U, Bastien C et al. Valerian-hops combination and diphenhydramine for treating insomnia: a randomized placebo-controlled clinical trial. Sleep 2005;28:1465-1471.View Abstract
  • 30.Strandell J, Neil A, Carlin G. An approach to the in vitro evaluation of potential for cytochrome P450 enzyme inhibition from herbals and other natural remedies. Phytomedicine 2004;11:98-104.View Abstract
  • 31.Lefebvre T, Foster BC, Drouin CE et al. In vitro activity of commercial valerian root extracts against human cytochrome P450 3A4. J Pharm Pharm Sci 2004;7:265-273.View Abstract
  • 32.Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 2000;7:273-282.View Abstract
  • 33.Gurley BJ, Gardner SF, Williams DK et al. Effect of goldenseal, black cohosh, kava kava, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4 phenotypes. Clin Pharmacol Ther 2005;77:P36.
  • 34.Gurley BJ, Gardner SF, Hubbard MA et al. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther 2005;77:415-426.View Abstract
  • 35.Donovan JL, DeVane CL, Chavin KD et al. 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 2004;32:1333-1336.
  • 36.Andreatini R, Leite JR. Effect of valepotriates on the behavior of rats in the elevated plus-maze during diazepam withdrawal. Eur J Pharmacol 1994;260:233-235.
  • 37.Garges HP, Varia I, Doraiswamy PM. Cardiac complications and delirium associated with valerian root withdrawal. JAMA 1998;280:1566-1567.View Abstract
  • 38.Leuschner J, Muller J, Rudmann M. Characterisation of the central nervous depressant activity of a commercially available valerian root extract. Arzneimittelforschung 1993;43:638-641.View Abstract
  • 39.Hendriks H, Bos R, Woerdenbag HJ, Koster AS. Central nervous depressant activity of valerenic acid in the mouse. Planta Med 1985:28-31.View Abstract
  • 40.Hiller K, Zetler G. Neuropharmacological studies on ethanol extracts of Valeriana officinalis L.: behavioural and anticonvulsant properties. Phytother Res 1996;10:145-151.
  • 41.Kohnen R, Oswald WD. The effects of valerian, propranolol, and their combination on activation, performance, and mood of healthy volunteers under social stress conditions. Pharmacopsychiatry 1988;21:447-448.View Abstract
  • 42.Ugalde M, Reza V, Gonzalez-Trujano ME et al. Isobolographic analysis of the sedative interaction between six central nervous system depressant drugs and Valeriana edulis hydroalcoholic extract in mice. J Pharm Pharmacol 2005;57:631-639.
  • 43.Berenbaum MC. What is synergy? Pharmacol Rev 1989;41:93-141.
  • 44.Tallarida RJ, Raffa RB. Testing for synergism over a range of fixed ratio drug combinations: replacing the isobologram. Life Sci 1996;58:PL 23-28.View Abstract
  • 45.Williamson EM. Interactions between herbal and conventional medicines. Expert Opin Drug Saf 2005;4:355-378.