Health Care Professional Information

Scientific Name
Valeriana officinalis, Valeriana jatamansi, Valeriana fauriei, Valeriana wallichii
Common Name

Garden valerian, Indian valerian, Pacific valerian, Mexican valerian

Clinical Summary

Derived from the root of the plant V. officinalis, valerian is sold as a dietary supplement for calmness, sedation, and to improve sleep quality. Other species including V. jatamansi, V. fauriei, and V. wallichii are also used in traditional medicine to treat insomnia and anxiety. Valerian products are usually available in extracts or teas that have a distinct odor.

In vitro, valerian exhibits antioxidant (1), cytoprotective (2), and neuroprotective (3) effects. In animal models, valerian has demonstrated antihypertensive, antispasmotic (4) (5), anxiolytic (6), and antidepressant (7), but not sedative (8) effects. Human studies show that valerian has modest effects on improving sleep quality (9) (10) (11), but its sleep-inducing properties are not superior to placebo (12) (13) (14) (15). Valerian also failed to improve sleep in a study of cancer patients (16). Other studies suggest that valerian can reduce hot flashes (17) and dysmenorrhea (18), facilitate supervised benzodiazepine withdrawal (19), and relieve symptoms of obsessive-compulsive disorder (20). However, sample sizes in these studies are too small to draw firm conclusions. Reviews of the clinical literature have also concluded the evidence for valerian as an anxiolytic in humans is insufficient (21) (22).

The valerian derivative isovaleroxy-hydroxy dihydrovaltrate showed anticancer effects against human ovarian cancer cells in vitro and in vivo (23). Chlorovaltrates in valerian have shown moderate cytotoxicity against lung, prostate, colon and liver cancer cell lines (24). However, no clinical trials on these effects have been conducted.

Although valerian products are generally safe, cases of liver and pancreatic toxicity have been reported (25) (26) (27). Valerian inhibits CYP3A4 enzymes and P-glycoprotein  transporters and is prone to interact with many drugs (27). Valerian is also thought to have estrogenic activities (17) (28), but this is not observed in vitro (29).

Purported Uses
  • Anxiety
  • Insomnia
  • Menstrual cramps
  • Menopausal symptoms
  • Sedation
  • Spasms
Constituents
  • Alkaloids: actinidine
  • Iridoids: valepotriates, chlorovaltrates
  • Volatile oils: monoterpenes (bornyl acetate), sesquiterpenes (valerenic acid)
  • Phenolic compounds: chlorogenic acid
  • Flavanol glycosides: linarin
  • Gamma-aminobutyric acid (GABA)
    (3) (17) (24) (30) (31) (32) (33)
Mechanism of Action

In vitro, valerian protects against lipid peroxidation, deoxyribose degradation, and reactive oxygen species production (1). Iridoids, germacrane-type sesquiterpenoids, and lignans in valerian are associated with neuroprotective effects (3) (34). Valerian constituents can also bind to various neurotransmitter receptors implicated in circadian rhythms and anxiety such as serotonin receptors (35). In vitro and animal models indicate that anxiolytic activity is due to valerenic acid (VA) which could be inhibited by VA derivatives such as hydroxy-VA that do not modulate gamma-aminobutyric acid type A (GABAA) receptors (36). VA in animals inhibits the enzyme system responsible for central catabolism of GABA, increasing GABA concentration and decreasing CNS activity, and direct binding of this constituent to GABA-receptors has been demonstrated (37). VA interaction with the GABAAergic system has been noted to act in a manner similar to that of benzodiazepines (6). Sesquiterpenes and valepotriates were identified as having varying levels of antidepressant activity (7) (38). Chronic treatment of rodents with valepotriate-rich extract increased norepinephrine and dopamine levels (38). Valerian exhibits antispasmodic and hypotensive effects via potassium channel (KATP) activation, which may be useful in gastrointestinal and cardiovascular disorders (5). Valerian also exhibited a protective effect against vasopressin-induced coronary spasm and pressor response, suggesting coronary and systemic vasodilation (4).

Valerian iridoids may have choleretic activity, based on an early study of other iridoids (39). This may increase the risk of gallstone formation, and therefore explain the increased risk for development of acute pancreatitis (27).

Pharmacokinetics

After intravenous administration of valerenic acid (VA) in animal studies, plasma VA was characterized by rapid distribution (T1/2: 6–12 min) and slow elimination (T1/2: 6–46 h), indicating possible large-tissue binding (40). After oral administration, extent of absorption was estimated to be 33.7%, with T1/2 of 2.7–5 h. Dose and AUC were proportional, suggesting linear pharmacokinetics at the levels studied in rats.

Warnings
  • Valerian should be discontinued at least 1 week before surgery because it may interact with anesthesia (41) (42).
  • Patients should not drive or operate dangerous machinery after taking valerian as it could disrupt information processing, task performance, and vigilance (35).
  • Abrupt discontinuation of valerian in those who may have developed a dependency may cause benzodiazepine-like withdrawal (41).
Contraindications
  • Patients with liver or pancreatic disease should avoid valerian as there have been case reports of hepatotoxicity (25) (26) as well as a possible association of valerian iridoids with an increased risk for development of acute pancreatitis (27) (39).
  • Patients should not drive or operate dangerous machinery when taking valerian as early studies indicate that single-dose valerian could disrupt information processing, task performance, and vigilance in humans 1–2 hours post-administration (35).
  • Individuals who are pregnant or nursing should avoid valerian, as it has not adequately been studied and preliminary animal models indicate some adverse effects on fetal brain development (43).
Adverse Reactions

Occasional, anecdotal, or possibly related: Headache, diarrhea and other gastrointestinal complaints, daytime sedation/dullness, impaired alertness, depression, irritability, dizziness, sweating, heart palpitations, bitter taste, benzodiazepine-like withdrawal symptoms with supplement cessation (10) (16) (35) (44).

Case Reports
Hepatotoxicity:
Two separate cases in women with the use of valerian products, with eventual symptom resolution after discontinuation (25) (26).
Risk of acute pancreatitis: A case-control study identified valerian use as a potential contributor to cases of idiopathic acute pancreatitis (27).
Fetal development: Valerian administration in pregnant mice significantly reduced zinc levels in the fetal brain (43).

Herb-Drug Interactions

Barbiturates: Valerian prolonged pentobarbital-induced sleep in animal models (41) (45).
Benzodiazepines: Valerian may have synergistic effects (46) (47).
Haloperidol: Valerian may have an additive effect, causing hepatic damage (48).
Cytochrome P450 (CYP450) substrates: Valerian inhibits CYP2D6 (49) and CYP3A4 (42) (50), and can affect the serum concentration of drugs metabolized by these enzymes.
P-glycoprotein (P-gp)substrates: Valerian inhibits P-gp transporters and can increase the intracellular concentration of substrate drugs (17) (28) (50).
UGT (Uridine 5'-diphospho-glucuronosyltransferase) substrates: Valerian modulates UGT enzymes in vitro and can increase the side effects of drugs metabolized by them (51).

Literature Summary and Critique

Barton DL, et al. The use of Valeriana officinalis (Valerian) in improving sleep in patients who are undergoing treatment for cancer: a phase III randomized, placebo-controlled, double-blind study (NCCTG Trial, N01C5). J Support Oncol. 2011;9:24-31.
In this RCT, a total of 227 patients with various cancers who reported difficulty sleeping were randomized to receive either valerian 450 mg or placebo 1 hour prior to bedtime for 8 weeks. Although single doses in studies have ranged from 400–900 mg at bedtime, investigators chose to evaluate 450 mg because of older dose-finding trials that suggested 900 mg was not significantly better than 450 mg (52) (53). The primary endpoint was the averaged area under the curve (AUC) of the overall Pittsburgh Sleep Quality Index (PSQI) score. Secondary endpoints included the Functional Outcomes of Sleep Questionnaire, the Brief Fatigue Inventory (BFI), and the Profile of Mood States (POMS). Toxicity was evaluated with self-reported numeric analogue scale questions and the Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Questionnaires were completed at baseline and 4 and 8 weeks. In 119 patients evaluable for the primary endpoint over 8 weeks, valerian AUC was nonsignificant compared with placebo (51.4 vs 49.7; P=.6957). However, BFI and POMS analysis indicated that several secondary endpoints were significantly better for those taking valerian vs placebo including fatigue, sleep problems, sleep latency, and amount of sleep per night. The intervention group also reported less drowsiness. There were no significant differences in toxicities except for mild alkaline phosphatase increases, which were slightly more common in the placebo group. Although this study does not support that nighttime valerian 450 mg could improve sleep as measured by the PSQI, secondary endpoint results using other validated scales did indicate some beneficial effects, and only 52% of initial participants were fully evaluable. Further research to evaluate the possible physiologic effects and safety of valerian in oncology symptom management may be warranted.

Mirabi P, Mojab F. The effects of valerian root on hot flashes in menopausal women. Iran J Pharm Res. 2013;12:217-222.
In this randomized double-blind study, 68 menopausal women with the main complaint of hot flashes received either valerian capsules 255 mg 3 times daily for 8 weeks or placebo. Severity and frequency of hot flashes were measured and recorded through questionnaires and information forms at 3 time points: 2 weeks pre-intervention and 4 and 8 weeks post-intervention. There was a statistically significant reduction in severity of hot flashes post-valerian treatment (P<.001) with significant between-group differences (P<.001). Valerian also reduced the number of hot flashes at 4 and 8 weeks post-treatment (P<.001) with no between-group difference in side effects. Investigators concluded that valerian may be useful to treat hot flashes in menopausal women and as a potential alternative to hormone therapy.

Taavoni S, et al. Effect of valerian on sleep quality in postmenopausal women: a randomized placebo-controlled clinical trial. Menopause. 2011;18:951-955.
This randomized, triple-blind, controlled trial evaluated valerian extract on the improvement of sleep quality in 100 postmenopausal women experiencing insomnia. Women aged 50–60 years received either valerian extract 530 mg or placebo twice daily for 4 weeks. Demographic data and the Pittsburgh Sleep Quality Index were used in evaluation. Change in sleep quality with valerian versus placebo was statistically significant (P<.001), with approximately 30% of intervention participants showing an improvement. Investigators concluded that valerian may be useful in the clinical management of insomnia in postmenopausal women.

Oxman AD, et al. A televised, web-based randomised trial of an herbal remedy (valerian) for insomnia. PLoS One. 2007;2:e1040.
In this randomized double-blind placebo-controlled study, 405 participants with insomnia were recruited via television and the internet. Participants were mailed valerian 200-mg tablets or placebo and instructed to take 3 tablets 1 hour before bedtime for 2 weeks. Although no differences in self-reported sleep quality were detected, participants using the intervention reported better outcomes on the global self-assessment question. Trends toward improved sleep duration and reduced night awakening were also observed. The authors concluded that valerian had modest effects on sleep quality compared with placebo. Because the optimal dose of valerian is unknown, whether larger dosages could safely increase benefits also requires further study.

Dosage (Inside MSKCC Only)
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References
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  17. Mirabi P, Mojab F. The effects of valerian root on hot flashes in menopausal women. Iran J Pharm Res. Winter 2013;12(1):217-222.
  18. Mirabi P, Dolatian M, Mojab F, et al. Effects of valerian on the severity and systemic manifestations of dysmenorrhea. Int J Gynaecol Obstet. Dec 2011;115(3):285-288.
  19. Lopez-Peig C, Mundet X, Casabella B, et al. Analysis of benzodiazepine withdrawal program managed by primary care nurses in Spain. BMC Res Notes. 2012;5:684.
  20. Pakseresht S, Boostani H, Sayyah M. Extract of valerian root (Valeriana officinalis L.) vs. placebo in treatment of obsessive-compulsive disorder: a randomized double-blind study. J Complement Integr Med. Jan 2011;8.
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  23. Li X, Chen T, Lin S, et al. Valeriana jatamansi constituent IVHD-valtrate as a novel therapeutic agent to human ovarian cancer: in vitro and in vivo activities and mechanisms. Curr Cancer Drug Targets. May 2013;13(4):472-483.
  24. Lin S, Zhang ZX, Chen T, et al. Characterization of chlorinated valepotriates from Valeriana jatamansi. Phytochemistry. Jan 2013;85:185-193.
  25. Cohen DL, Del Toro Y. A case of valerian-associated hepatotoxicity. J Clin Gastroenterol. Sep 2008;42(8):961-962.
  26. Vassiliadis T, Anagnostis P, Patsiaoura K, et al. Valeriana hepatotoxicity. Sleep Med. Sep 2009;10(8):935.
  27. Douros A, Bronder E, Andersohn F, et al. Drug-induced acute pancreatitis: results from the hospital-based Berlin case-control surveillance study of 102 cases. Aliment Pharmacol Ther. Oct 2013;38(7):825-834.
  28. Malekzadeh F, Rose C, Ingvar C, et al. [Natural remedies and hormone preparations—potential risk for breast cancer patients. A study surveys the use of agents which possibly counteract with the treatment]. Lakartidningen. Oct 31-Nov 6 2005;102(44):3226-3228, 3230-3221.
  29. Zava DT, Dollbaum CM, Blen M. Estrogen and progestin bioactivity of foods, herbs, and spices. Proc Soc Exp Biol Med. Mar 1998;217(3):369-378.
  30. Houghton PJ. The scientific basis for the reputed activity of Valerian. J Pharm Pharmacol. May 1999;51(5):505-512.
  31. Navarrete A, Avula B, Choi YW, et al. Chemical fingerprinting of valeriana species: simultaneous determination of valerenic acids, flavonoids, and phenylpropanoids using liquid chromatography with ultraviolet detection. J AOAC Int. Jan-Feb 2006;89(1):8-15.
  32. Muller LG, Salles LA, Stein AC, et al. Antidepressant-like effect of Valeriana glechomifolia Meyer (Valerianaceae) in mice. Prog Neuropsychopharmacol Biol Psychiatry. Jan 10 2012;36(1):101-109.
  33. Pyle BW, Tran HT, Pickel B, et al. Enzymatic synthesis of valerena-4,7(11)-diene by a unique sesquiterpene synthase from the valerian plant (Valeriana officinalis). FEBS J. Sep 2012;279(17):3136-3146.
  34. Wang Q, Wang C, Zuo Y, et al. Compounds from the roots and rhizomes of Valeriana amurensis protect against neurotoxicity in PC12 cells. Molecules. 2012;17(12):15013-15021.
  35. Kennedy DO, Wightman EL. Herbal extracts and phytochemicals: plant secondary metabolites and the enhancement of human brain function. Adv Nutr. Jan 2011;2(1):32-50.
  36. Felgentreff F, Becker A, Meier B, et al. Valerian extract characterized by high valerenic acid and low acetoxy valerenic acid contents demonstrates anxiolytic activity. Phytomedicine. Oct 15 2012;19(13):1216-1222.
  37. Benke D, Barberis A, Kopp S, et al. GABA A receptors as in vivo substrate for the anxiolytic action of valerenic acid, a major constituent of valerian root extracts. Neuropharmacology. Jan 2009;56(1):174-181.
  38. Sah SP, Mathela CS, Chopra K. Antidepressant effect of Valeriana wallichii patchouli alcohol chemotype in mice: Behavioural and biochemical evidence. J Ethnopharmacol. Apr 26 2011;135(1):197-200.
  39. Miyagoshi M, Amagaya S, Ogihara Y. Choleretic actions of iridoid compounds. J Pharmacobiodyn. Mar 1988;11(3):186-190.
  40. Sampath C, Haug K, Thanei S, et al. Pharmacokinetics of valerenic acid in rats after intravenous and oral administrations. Planta Med. Apr 2012;78(6):575-581.
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  43. Mahmoudian A, Rajaei Z, Haghir H, et al. Effects of valerian consumption during pregnancy on cortical volume and the levels of zinc and copper in the brain tissue of mouse fetus. Zhong Xi Yi Jie He Xue Bao. Apr 2012;10(4):424-429.
  44. Taibi DM, Landis CA, Petry H, et al. A systematic review of valerian as a sleep aid: safe but not effective. Sleep Med Rev. Jun 2007;11(3):209-230.
  45. Komori T, Matsumoto T, Motomura E, et al. The sleep-enhancing effect of valerian inhalation and sleep-shortening effect of lemon inhalation. Chem Senses. Oct 2006;31(8):731-737.
  46. Carrasco MC, Vallejo JR, Pardo-de-Santayana M, et al. Interactions of Valeriana officinalis L. and Passiflora incarnata L. in a patient treated with lorazepam. Phytother Res. Dec 2009;23(12):1795-1796.
  47. Bhatt C, Kanaki N, Nayak R, et al. Synergistic potentiation of anti-anxiety activity of valerian and alprazolam by liquorice. Indian J Pharmacol. Mar-Apr 2013;45(2):202-203.
  48. Dalla Corte CL, Fachinetto R, Colle D, et al. Potentially adverse interactions between haloperidol and valerian. Food Chem Toxicol. Jul 2008;46(7):2369-2375.
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Consumer Information

How It Works

Bottom Line: Valerian may provide modest improvements in sleep, but study results are mixed.

In laboratory experiments, valerian extract prevents the breakdown of an important inhibitory neurotransmitter chemical in the nervous system, causing a calming effect. Human studies suggest valerian products have a modest effect to improve sleep quality. Valerian supplements often have a distinct odor that some may find unpleasant, and these products might interact with a number of drugs or health conditions. More research is needed to determine the benefits and safety of this botanical.

Purported Uses
  • To treat anxiety
    Several analyses have determined there is not enough evidence to determine whether valerian can treat anxiety.
  • To treat insomnia
    It is possible that valerian may provide modest improvements in sleep quality. Although a study in cancer patients did not find this to be true, valerian did appear to improve other symptoms such as fatigue.
  • To calm muscle spasms
    Laboratory studies suggest positive effects, and an initial study indicates that valerian may be helpful for menstrual cramps.
  • To treat menopausal symptoms
    Two studies have shown that valerian may improve hot flashes and insomnia in postmenopausal women.
Research Evidence

Insomnia
Several studies in humans suggest that valerian is no better than placebo in promoting sleep. Although a study in cancer patients also did not find valerian to improve sleep when using specific tests, it did appear to improve symptoms such as fatigue, sleep problems, the amount of time it took to fall asleep, and quantity of sleep per night. A few large analyses looking at groups of trials and a large randomized trial concluded that valerian might produce modest improvements in sleep quality.

Menopause
A small study conducted over 8 weeks in 68 postmenopausal women found that valerian may reduce both the number of hot flashes and their severity, with no noticeable differences in side effects compared with placebo. A 4-week study of 100 postmenopausal women who had insomnia also noticed a change in sleep quality. However, larger studies would be needed to confirm results and to see whether valerian is safe for long-term use.

Patient Warnings
  • Valerian should be stopped at least 1 week before surgery because it can interfere with general anesthesia.
  • Patients should not drive or operate dangerous machinery after taking valerian because it could disrupt the ability to process information, perform tasks, or be alert.
  • Withdrawal symptoms may occur in those taking valerian for a period of time, if valerian is discontinued abruptly.
Do Not Take If
  • You are taking barbiturates, benzodiazepines, or other central nervous system drugs used to treat conditions such as anxiety, insomnia, seizures, or psychiatric disorders: Valerian lengthens the sedation time caused by these drugs and may have other added effects.
  • You are taking haloperidol: Valerian may increase effects and cause liver damage.
  • You are taking drugs that are substrates of P-glycoprotein: Valerian may increase the risk of side effects of these drugs.
  • You are taking drugs that are substrates of cytochrome P450: Valerian may increase the risk of side effects of these drugs.
  • You have pancreatic, liver, or gall bladder disease: Valerian usage has been associated with cases of liver damage and acute infection of the pancreas.
  • You are driving or operating machinery: Valerian may affect your performance or functioning.
  • You are pregnant or nursing: Animal experiments have shown reduced levels of essential micronutrients in fetal mouse brain tissue.
Side Effects

Occasional, anecdotal, or possibly related symptoms include:

  • Bitter taste
  • Daytime drowsiness/dullness
  • Depression
  • Diarrhea
  • Dizziness
  • Headache
  • Heart palpitations
  • Impaired alertness
  • Irritability
  • Liver toxicity
  • Sweating
E-mail your questions and comments to aboutherbs@mskcc.org.