Valerian

• How It Works

  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, how long it took to fall asleep, and quantity of sleep per night.
  • 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
    A few studies have shown that valerian may improve hot flashes and insomnia in postmenopausal women.
• 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
• Scientific Name

  Valeriana officinalis, Valeriana jatamansi, Valeriana fauriei, Valeriana wallichii

• 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 improve sleep and anxiety in HIV patients on antiretroviral therapy ⁽⁵³⁾, reduce hot flashes ^(17) (54) 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
• 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⁾.

  In healthy volunteers, valerian was found to modulate intracortical facilitatory circuits ⁽⁵⁵⁾. Valerian iridoids may have choleretic activity and this may increase the risk of gallstone formation, and therefore explain the increased risk for development of acute pancreatitis ⁽²⁷⁾.

• Warnings
  • Valerian should be discontinued at least 1 week before surgery because it may interact with anesthesia ^(40) (41).
  • 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 ⁽⁴⁰⁾.
• 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⁾.
  • 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 ⁽⁴²⁾.
• 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) (43)}.

  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 ⁽⁴²⁾.

• Herb-Drug Interactions

  Barbiturates: Valerian prolonged pentobarbital-induced sleep in animal models ^(40) (44).
  Benzodiazepines: Valerian may have synergistic effects ^(45) (46).
  Haloperidol: Valerian may have an additive effect, causing hepatic damage ⁽⁴⁷⁾.
  Cytochrome P450 (CYP450) substrates: Valerian inhibits CYP2D6 ⁽⁴⁸⁾ and CYP3A4 ^(41) (49), 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) (49)}.
  UGT (Uridine 5’-diphospho-glucuronosyltransferase) substrates: Valerian modulates UGT enzymes in vitro and can increase the side effects of drugs metabolized by them ⁽⁵⁰⁾.

• References

  1. Sudati JH, Fachinetto R, Pereira RP, et al. In vitro antioxidant activity of Valeriana officinalis against different neurotoxic agents. Neurochem Res. Aug 2009;34(8):1372-1379.

  2. de Oliveria DM, Barreto G, De Andrade DV, et al. Cytoprotective effect of Valeriana officinalis extract on an in vitro experimental model of Parkinson disease. Neurochem Res. Feb 2009;34(2):215-220.

  3. Xu J, Guo Y, Xie C, et al. Isolation and neuroprotective activities of acylated iridoids from Valeriana jatamansi. Chem Biodivers. Jul 2012;9(7):1382-1388.

  4. Circosta C, De Pasquale R, Samperi S, et al. Biological and analytical characterization of two extracts from Valeriana officinalis. J Ethnopharmacol. Jun 13 2007;112(2):361-367.

  5. Gilani AH, Khan AU, Jabeen Q, et al. Antispasmodic and blood pressure lowering effects of Valeriana wallichii are mediated through K+ channel activation. J Ethnopharmacol. Sep 14 2005;100(3):347-352.

  6. Murphy K, Kubin ZJ, Shepherd JN, et al. Valeriana officinalis root extracts have potent anxiolytic effects in laboratory rats. Phytomedicine. Jul 2010;17(8-9):674-678.

  7. Liu XG, Gao PY, Wang GS, et al. In vivo antidepressant activity of sesquiterpenes from the roots of Valeriana fauriei Briq. Fitoterapia. Apr 2012;83(3):599-603.

  8. Hattesohl M, Feistel B, Sievers H, et al. Extracts of Valeriana officinalis L. s.l. show anxiolytic and antidepressant effects but neither sedative nor myorelaxant properties. Phytomedicine. Jan 2008;15(1-2):2-15.

  9. Bent S, Padula A, Moore D, et al. Valerian for sleep: a systematic review and meta-analysis. Am J Med. Dec 2006;119(12):1005-1012.

  10. Fernandez-San-Martin MI, Masa-Font R, Palacios-Soler L, et al. Effectiveness of Valerian on insomnia: a meta-analysis of randomized placebo-controlled trials. Sleep Med. Jun 2010;11(6):505-511.

  11. Taavoni S, Ekbatani N, Kashaniyan M, et al. Effect of valerian on sleep quality in postmenopausal women: a randomized placebo-controlled clinical trial. Menopause. Sep 2011;18(9):951-955.

  12. Diaper A, Hindmarch I. A double-blind, placebo-controlled investigation of the effects of two doses of a valerian preparation on the sleep, cognitive and psychomotor function of sleep-disturbed older adults. Phytother Res. Oct 2004;18(10):831-836.

  13. Jacobs BP, Bent S, Tice JA, et al. An internet-based randomized, placebo-controlled trial of kava and valerian for anxiety and insomnia. Medicine (Baltimore). Jul 2005;84(4):197-207.

  14. Oxman AD, Flottorp S, Havelsrud K, et al. A televised, web-based randomised trial of an herbal remedy (valerian) for insomnia. PLoS One. 2007;2(10):e1040.

  15. Taibi DM, Vitiello MV, Barsness S, et al. A randomized clinical trial of valerian fails to improve self-reported, polysomnographic, and actigraphic sleep in older women with insomnia. Sleep Med. Mar 2009;10(3):319-328.

  16. Barton DL, Atherton PJ, Bauer BA, 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. Jan-Feb 2011;9(1):24-31.

  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.

  21. Sarris J, McIntyre E, Camfield DA. Plant-based medicines for anxiety disorders, part 2: a review of clinical studies with supporting preclinical evidence. CNS Drugs. Apr 2013;27(4):301-319.

  22. Miyasaka LS, Atallah AN, Soares BG. Valerian for anxiety disorders. Cochrane Database Syst Rev. 2006(4):CD004515.

  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. 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.

  40. Ang-Lee MK, Moss J, Yuan CS. Herbal medicines and perioperative care. JAMA. Jul 11 2001;286(2):208-216.

  41. Mooiman KD, Maas-Bakker RF, Hendrikx JJ, et al. The effect of complementary and alternative medicines on CYP3A4-mediated metabolism of three different substrates: 7-benzyloxy-4-trifluoromethyl-coumarin, midazolam and docetaxel. J Pharm Pharmacol. 2014 Jun;66(6):865-874.

  42. 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.

  43. 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.

  44. 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.

  45. 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.

  46. 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.

  47. 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.

  48. Hellum BH, Nilsen OG. The in vitro inhibitory potential of trade herbal products on human CYP2D6-mediated metabolism and the influence of ethanol. Basic Clin Pharmacol Toxicol. Nov 2007;101(5):350-358.

  49. Hellum BH, Nilsen OG. In vitro inhibition of CYP3A4 metabolism and P-glycoprotein-mediated transport by trade herbal products. Basic Clin Pharmacol Toxicol. May 2008;102(5):466-475.

  50. Mohamed ME, Frye RF. Effects of herbal supplements on drug glucuronidation. Review of clinical, animal, and in vitro studies. Planta Med. Mar 2011;77(4):311-321.

  51. Leathwood PD, Chauffard F. Aqueous extract of valerian reduces latency to fall asleep in man. Planta Med. Apr 1985(2):144-148.

  52. Balderer G, Borbely AA. Effect of valerian on human sleep. Psychopharmacology (Berl). 1985;87(4):406-409.

  53. Ahmadi M, Khalili H, Abbasian L, et al. Effect of Valerian in Preventing Neuropsychiatric Adverse Effects of Efavirenz in HIV-Positive Patients: A Pilot Randomized, Placebo-Controlled Clinical Trial. Ann Pharmacother. Jun 2017;51(6):457-464.

  54. Jenabi E, Shobeiri F, Hazavehei SMM, et al. The effect of Valerian on the severity and frequency of hot flashes: A triple-blind randomized clinical trial. Women Health. Mar 2018;58(3):297-304.

  55. Mineo L, Concerto C, Patel D, et al. Valeriana officinalis Root Extract Modulates Cortical Excitatory Circuits in Humans. Neuropsychobiology. 2017;75(1):46-51.