Valerian
Scientific Name(s): Centranthus ruber L., Valeriana edulis, Valeriana officinalis L., Valeriana sambucifolia Mik., Valeriana wallichi DC.
Common Name(s): Baldrian, Cat's love, Cat's valerian, Garden heliotrope, Garden valerian, Kesso root, Radix valerianae, St. George's herb, Valerian, Valerian fragrant, Vandal root
Medically reviewed by Drugs.com. Last updated on Dec 10, 2024.
Clinical Overview
Use
The evidence to support the common use of valerian in insomnia remains weak. However, as valerian preparations seem to have a wide margin of safety, further trials for insomnia and anxiety may be warranted. Very limited data have been published concerning use for dysmenorrhea and obsessive-compulsive disorder.
Dosing
Insomnia: Valerian extract 400 to 600 mg/day taken 1 hour before bedtime for 2 to 4 weeks has been used in clinical trials.
Contraindications
Contraindications have not been identified.
Pregnancy/Lactation
Information regarding safety and efficacy in pregnancy and lactation is lacking.
Interactions
None well documented.
Adverse Reactions
In general, clinical studies have found valerian to have a wide margin of safety, be devoid of adverse effects, and have fewer adverse reactions than positive control drugs, such as diazepam. Headache and diarrhea have been reported in clinical trials, but hangover is seldom reported. Several cases of hepatotoxicity have been reported.
Toxicology
Valerian has been classified as GRAS (generally recognized as safe) in the United States for food use; extracts and the root oil are used as flavorings in foods and beverages. The observed in vitro cytotoxicity of valepotriate compounds may not be relevant in vivo because of limited absorption.
Scientific Family
- Valerianaceae
Botany
Members of the genus Valeriana are herbaceous perennials widely distributed in the temperate regions of North America, Europe, and Asia. The hollow stemmed plant can grow up to 2 m and is branched at the terminal end with opposite leaves and small white or pink flowers. Fruits are oblong, 4-ridged, and single seeded. Of approximately 200 known species, the Eurasian Vakeruaba officinalis is most often cultivated for medicinal use. The dried rhizome used in valerian extracts has numerous rootlets and one or more stolons and contains a volatile oil with a distinctive, unpleasant odor.1, 2, 3, 4
History
Valerian has been used in Unani, Ayurvedic, and traditional Chinese health systems and for homeopathic uses for cardiotonic and sedative properties, as well as in epilepsy, hysteria, and other conditions.5 Despite its odor, valerian was considered a perfume in 16th-century Europe. The tincture has been used for its sedative properties for centuries; it is still widely used in France, Germany, and Switzerland as a sleep aid.6 Other uses attributed to valerian include a digestive aid, emmenagogue, and antiperspirant.2
Chemistry
Three distinct classes of compounds have been associated with the sedative properties of valerian. These compounds consist of mono- and sesquiterpenes and iridoid triesters (valepotriates). Other compounds identified include flavonoids, triterpenes, lignans, and alkaloids. The composition of the volatile oil varies markedly between cultivars and species, as does the amount and relative proportion of cytotoxic valepotriates, making chemical standardization difficult but highly desirable.
The most important sesquiterpenes include valerenic acid and its congeners, although in Japan, V. officinalis var. latifolia, kessyl alcohols, and esters predominate. Valtrate, acevaltrate, and didrovaltrate are the most important iridoids; European valerian extracts were formerly standardized on these unstable compounds, which have a short shelf life in the tincture.
The alkaloid concentration in roots and rhizomes is low, usually less than 0.2%. The aqueous extract of valerian contains substantial quantities of gamma-aminobutyric acid (GABA); however, it is doubtful whether GABA penetrates the blood-brain barrier.
Many analytical high performance liquid chromatographic methods have been developed for the sesquiterpenes and valepotriates. The seasonal variation in valerenic acids and valepotriates has been studied. Tissue culture of valerian species has focused on the production of valepotriates.2, 7, 8, 9, 10, 11, 12
Uses and Pharmacology
Several in vitro and animal experiments have attempted to elucidate the mechanism of action for various valerian compounds. Many of these experiments provide contradictory evidence, but most attribute the observed actions of valerian extracts to central actions on GABA, serotonin, and adenosine receptors. The sesquiterpene valerenic acid and its derivatives and the valepotriates are generally thought to be the active constituents; however, wide variations in the composition of commercial preparations make interpretation of clinical data difficult.(9, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22)
Anxiolytic effect
Animal data
Another review of clinical trials and in vitro experiments suggests the effect of valerian may be because of anxiolytic action, rather than sedation.(13) This was demonstrated by a laboratory experiment with rodents that found no decrease in spontaneous locomotor activity and no increase in ether-induced anesthesia, but did find a reduction in anxiety using the elevated plus maize test.(25) Older experiments in rodents found conflicting results for spontaneous motor activity.(22, 26)
Clinical data
Both a meta-analysis and systematic review comment on the lack of trials meeting inclusion criteria because of poor methodology, the use of healthy volunteers, and combination therapies.(14, 23) One small, pilot clinical trial meeting inclusion criteria evaluated the effect of valepotriates 150 mg per day in 3 divided doses over 4 weeks in generalized anxiety disorder. No difference was demonstrated for the standardized valerian extract versus placebo or diazepam 20 mg.(24) Until studies with a larger sample size are conducted, the efficacy of valerian remains unclear.(14, 23) In a 2020 systematic review, overall results regarding the effect of valerian for anxiety were positive. Low- and moderate-quality studies, respectively, reported improvements in stress reactivity in healthy subjects (600 mg/day × 1 week standardized extract) and lower anxiety in HIV-positive patients receiving efavirenz (530 mg/day × 4 weeks valerian root/rhizome). Whereas, 3 high-quality trials reported improvements in anxiety prior to dental surgery (100 mg root/rhizome single dose valerian extract 60 minutes preop), prior to menstruation (1,260 mg/day × 7 days for 3 cycles), and in volunteers with non-clinical anxiety and insomnia (6.4 mg, valerenic acid 1% valerian extract × 28 days). In the meta-analysis, pooled data from 7 randomized controlled trials (N=535) with very high heterogeneity, publication bias, and missing negative outcome data showed no statistically significant difference in the anxiolytic effect of valerian compared to controls. Extracts produced more variation in outcomes than did whole root interventions. However, both single-dose and repeat administration of V. officinalis extracts were shown to improve anxiety-associated brain activity.(59)
Dysmenorrhea
Clinical data
One randomized, controlled clinical trial evaluated the use of valerian compared with identical placebo in college-age women for management of dysmenorrhea symptoms. Both valerian and placebo produced significant reductions in pain compared with baseline scores, but the pain reduction seen with valerian was significantly larger compared with placebo. Severity of systemic symptoms was reduced with both valerian and placebo, with valerian’s scores nonsignificantly lower than placebo scores for all symptoms except syncope. Valerian’s reduction of syncope was significantly lower compared with placebo.(57) In another study, premenstrual symptoms were reduced with administration of valerian extract 1,260 mg/day for 7 days given for 3 cycles.(59)
A Cochrane systematic review and meta-analysis of dietary supplements for dysmenorrhea identified only low or very low quality studies with very small sample sizes. Very limited evidence of effectiveness was found for the treatment of primary dysmenorrhea with valerian 255 mg root powder 3 times daily compared to placebo or no treatment (1 randomized clinical trial, n = 100); however, no difference was identified between valerian 250 mg compared to mefenamic acid 250 mg (1 randomized clinical trial, n = 99).(61)
Insomnia and sleep problems
Clinical data
Single-dose studies have consistently found no effect for a single dose of valerian in improving sleep latency or quality.(27, 28, 29)
A meta-analysis of studies published through September, 2008 evaluated data from eighteen randomized controlled trials (>1300 patients). The authors did not find significant benefits for sleep latency time or sleep quality as rated by visual analogue scale. Patients’ subjective rating of sleep quality did significantly favor valerian.(30) Reviews of older trials not included in the meta-analysis found valerian to exert an effect similar to the benzodiazepines, but a number of negative trials are also described.(5, 13) In a 2020 systematic review of 23 studies, overall results regarding the effect of V. officinalis for sleep problems were equivocal. The most consistent, although not necessarily statistically significant, results were seen when sleep studies were categorized based on product type and duration of intervention in which repeat administration of the dried root or rhizome given for 4 or 8 weeks consistently showed improvement in at least 1 sleep subgroup (5 studies; N=435); however, study populations were highly diverse (eg, HIV-positive, postmenopausal, cancer, Hispanic mental health, restless leg syndrome). Data also consistently showed no significant effect on sleep outcomes for the hydroalcoholic extracts given as a single dose. Results were equivocal for aqueous extracts given as a single dose or repeated over 7 days for the hydroalcoholic extracts given in repeated doses for 2 to 6 weeks and for extracts with unspecified extraction methods. In the meta-analysis, pooled data from 10 randomized controlled trials (N=1,065) with high heterogeneity showed no statistically significant difference with V. officinalis on sleep quality compared to controls.(59)
Two additional studies, one in oncology patients, and the other in postmenopausal females, were published in 2011. The study in cancer patients was a phase III trial that found no significant benefit for insomnia, but valerian did provide statistically significant improvements for the patient-rated, secondary outcomes of fatigue and mood.(31) The study in postmenopausal women found a significant improvement in patient-rated sleep quality with valerian compared with placebo.(32)
Various sleep parameters have also been shown to improve with administration of other valerian species, including V. edulis and V. wallichii. These 2 species lack the valerenic acids that are specific to V. officinalis, but do share the valepotriate constituents. Two high-quality studies that used V. edulis noted improvements in sleep latency and sleep quality in children with intellectual deficit (20 mg/kg × 2 weeks) and improved REM sleep with reduced waking in insomnia patients (450 mg single dose hydroalcoholic extract). A moderate-quality study conducted in insomnia patients reported improved sleep quality with administration of V. wallichii valepotriates (300 mg/day x 15 days).(59)
The American Academy of Sleep Medicine clinical practice guideline for the pharmacologic treatment for chronic insomnia (2017) suggests that valerian not be used as a treatment for sleep onset or sleep maintenance insomnia (versus no treatment) in adults. Benefits are considered to be approximately equal to risks (Weak; Low).(54) The Veteran’s Administration and Department of Defense (VA/DoD) clinical practice guideline for the management of chronic insomnia disorder and obstructive sleep apnea (2019) suggest against the use of valerian for the treatment of chronic insomnia disorder (Weak).(155)
Menopause
Clinical data
In a triple-blind, randomized, placebo-controlled study that enrolled 60 postmenopausal Iranian women, administration of valerian 530 mg twice daily for 2 months significantly reduced severity (50% none, 40% mild; P=0.02) and frequency (mean diff, −3/day; P=0.03) of hot flushes compared to placebo (0% none, 30% mild and +0.26/day, respectively). Valerian was well tolerated an no side effects were reported.(63) Similar results were observed in another study with valerian extract 1,060 mg/day given for 8 weeks.(59)
Obsessive-compulsive disorder
Clinical data
A randomized, double-blind, placebo-controlled pilot study evaluated valerian in a small group of patients who qualified for inclusion according to DSM-IV-TR criteria for obsessive-compulsive disorder, and Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores 21 or higher. The valerian group had significantly lower Y-BOCS scores beginning 4 weeks after study initiation, and this significant difference continued through the end of study at week 8. Somnolence was reported more frequently in the valerian group.(58)
Postoperative cognitive dysfunction
Clinical data
Cognitive dysfunction has become a common complication after cardiac surgery since the introduction of cardiopulmonary bypass (CPB) in the 1950s and leads to increased length of hospital stay, costs, risk of dementia, and mortality. Mechanisms involved include acute inflammation and decreased serotonin levels. A double-blind, randomized, placebo-controlled trial enrolled 61 adult Iranians who were candidates for coronary artery bypass surgery using CPB to evaluate the effect of V. officinalis (530 mg root extract every 12 hours × 8 weeks) on the prevention of postoperative cognitive dysfunction. Cognitive function was assessed using the Mini-Mental State Examination at baseline, 10 days postoperation, and 60 days postoperation. Patients receiving valerian had reduced odds of cognitive dysfunction compared to placebo based on a generalized estimation equation (estimate, −2.2; odds ratio, 0.108; 95% confidence interval, 0.022 to 0.545).(60)
Restless legs syndrome
Clinical data
Guidelines have been published regarding the use of valerian in restless legs syndrome (RLS). A joint European task force developed evidence-based guidelines on the management of RLS (2012) and stated that a low quality study with valerian failed to demonstrate efficacy in the treatment of RLS symptoms or sleep.(55) Likewise, an American Academy of Sleep Medicine evidence-based guideline (2012) determined there is insufficient evidence at present to evaluate the use of valerian for RLS based on one small controlled trial.(56)
Other uses
The valepotriates, isovaltrate, and valtrate, along with valerenone, had antispasmodic effects in isolated guinea pig ileum and other smooth muscle preparations.(33)
Valerian had no effect on haloperidol-induced orofacial dyskinesia in rats.(34)
Oral administration of valerian root extracts was protective against vasopressin-induced coronary spasms and pressor response in guinea pigs.(7) In the same experiment, bronchial resistance was reduced in both histamine- and antigen-induced bronchospasm.(7)
In a low-quality trial, cognition in hemodialysis patients was reported to improve with 530 mg/day of valerian root/rhizome given for 1 month.(59)
Dosing
A dose of a commercial preparations of valerian extract 600 mg in healthy subjects peaked at 30 minutes to 2 hours, with an elimination half-life of 1.1 ± 0.6 hours, and the marker valerenic acid was in the serum for at least 5 hours after dosing.(35)
Insomnia
Valerian extract 400 to 600 mg taken 1 hour before bedtime for 2 to 4 weeks has been used in clinical trials evaluating valerian in insomnia.(32)
Pregnancy / Lactation
Despite common use without apparent harm during pregnancy, the use of valerian preparations in pregnancy and lactation cannot be supported without evidence of safety. Widespread differences in dosages, duration, and preparations exist, and the stage of pregnancy may be a factor.37 Valerian is reported in the Complete German Commission E Monographs to stimulate uterine contractions.38 Information regarding safety and efficacy in pregnancy and lactation is lacking.
Interactions
Alcohol (ethyl): CNS depressants may enhance the CNS depressant effect of alcohol (ethyl). Monitor therapy.(65)
Azelastine (nasal): CNS depressants may enhance the CNS depressant effect of azelastine (nasal). Avoid combination.(66, 67, 68)
Benzodiazepines: Valerian may enhance the adverse/toxic effect of benzodiazepines. Monitor therapy.(48, 49, 50, 51, 52, 53)
Blonanserin: CNS depressants may enhance the CNS depressant effect of blonanserin. Consider therapy modification.(69)
Brimonidine (topical): Brimonidine (topical) may enhance the CNS depressant effect of CNS depressants. Monitor therapy.(70, 71, 72, 73, 74)
Bromopride: Bromopride may enhance the CNS depressant effect of CNS depressants. Monitor therapy.(75)
Bromperidol: Bromperidol may enhance the CNS depressant effect of CNS depressants. Avoid combination.(76)
Buprenorphine: Depressants may enhance the CNS depressant effect of buprenorphine.(77, 78, 79, 80, 81)
Cannabis: Cannabis may enhance the CNS depressant effect of CNS depressants. Monitor therapy. This interaction is only expected when physiologically significant amounts of tetrahydrocannabinol (THC, the major known psychoactive component of cannabis) are introduced systemically. While this encompasses the vast majority of medical and recreational cannabis use, some cannabis strains, products, and routes of administration specifically (and often intentionally) minimize systemic THC exposure.(82, 83, 84, 85, 86, 87, 88, 89)
Chlormethiazole: Chlormethiazole may enhance the CNS depressant effect of CNS depressants. Consider therapy modification.(90)
Chlorphenesin carbamate: Chlorphenesin carbamate may enhance the adverse/toxic effect of CNS depressants. Monitor therapy.(153)
CNS depressants: Valerian may enhance the CNS depressant effect of CNS depressants. Monitor therapy.(28, 29, 43, 48, 49, 51, 157, 158, 159, 160, 161)
Dimethindene (topical): Dimethindene (topical) may enhance the CNS depressant effect of CNS depressants. Monitor therapy. This interaction is mentioned only in dimethindene nasal product labeling. It is not mentioned in dimethindene topical gel product information.(154)
Doxylamine: Doxylamine may enhance the CNS depressant effect of CNS Depressants. Monitor therapy. Use of Diclegis (doxylamine/pyridoxine) with other CNS depressants is not recommended and should be avoided.(91)
Dronabinol: Dronabinol may enhance the CNS depressant effect of CNS depressants. Monitor therapy.(83, 84, 86, 87, 88, 93, 94)
Droperidol: Droperidol may enhance the CNS depressant effect of CNS depressants. Consider therapy modification.(95)
Flunitrazepam: CNS depressants may enhance the CNS depressant effect of flunitrazepam. Consider therapy modification.(96, 97)
Hydrocodone: CNS depressants may enhance the CNS depressant effect of hydrocodone. Consider therapy modification.(98, 99, 100, 101, 102, 103)
Hydroxyzine: Hydroxyzine may enhance the CNS depressant effect of CNS depressants. Monitor therapy.(104)
Kava kava: Kava kava may enhance the adverse/toxic effect of CNS depressants. Monitor therapy.(105, 106, 107, 108, 109)
Lofexidine: Lofexidine may enhance the CNS depressant effect of CNS depressants. Monitor therapy.(110, 111)
Magnesium sulfate: Magnesium sulfate may enhance the CNS depressant effect of CNS depressants. Monitor therapy. The significance of this interaction is likely considerably greater with higher magnesium sulfate doses. Similarly, the use of injectable magnesium sulfate appears to increase the significance of this potential interaction.(112, 113, 114, 115, 116, 117, 118)
Methotrimeprazine: CNS depressants may enhance the CNS depressant effect of methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS depressants. Consider therapy modification.(119)
Metyrosine: CNS depressants may enhance the sedative effect of metyrosine. Monitor therapy.(120)
Minocycline: Minocycline may enhance the CNS depressant effect of CNS depressants. Monitor therapy. This interaction only applies to the intravenous administration of minocycline.(112, 113, 114, 115, 116, 117, 118, 121)
Mirtazapine: CNS depressants may enhance the CNS depressant effect of mirtazapine. Monitor therapy.(122)
Nabilone: Nabilone may enhance the CNS depressant effect of CNS depressants. Monitor therapy.(123)
Opioid analgesics: CNS depressants may enhance the CNS depressant effect of opioid analgesics. Consider therapy modification.(80, 81, 103, 104, 105, 106, 107, 124)
Orphenadrine: CNS depressants may enhance the CNS depressant effect of orphenadrine. Avoid combination.(125)
Oxomemazine: Oxomemazine may enhance the CNS depressant effect of CNS depressants. Avoid combination.(126)
Oxycodone: CNS depressants may enhance the CNS depressant effect of oxycodone. Consider therapy modification.(81, 98, 99, 100, 101, 102, 127, 128, 129)
Paraldehyde: CNS depressants may enhance the CNS depressant effect of paraldehyde. Avoid combination.(130)
Perampanel: Perampanel may enhance the CNS depressant effect of CNS depressants. Consider therapy modification.(131)
Piribedil: CNS depressants may enhance the CNS depressant effect of piribedil. Monitor therapy.(132)
Pramipexole: CNS depressants may enhance the sedative effect of pramipexole. Monitor therapy.(133)
Ropinirole: CNS depressants may enhance the sedative effect of ropinirole. Monitor therapy.(134)
Rotigotine: CNS depressants may enhance the sedative effect of rotigotine. Monitor therapy.(135)
Rufinamide: Rufinamide may enhance the adverse/toxic effect of CNS depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy.(136)
Selective serotonin reuptake inhibitors: CNS depressants may enhance the adverse/toxic effect of selective serotonin reuptake inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy.(137, 138, 139, 140, 141, 142, 143)
Sodium oxybate: Sodium oxybate may enhance the CNS depressant effect of CNS depressants. Consider therapy modification.(144)
Suvorexant: CNS depressants may enhance the CNS depressant effect of suvorexant. Consider therapy modification.(145)
Tapentadol: Tapentadol may enhance the CNS depressant effect of CNS depressants. Consider therapy modification.(98, 99, 100, 101, 102, 146)
Tetrahydrocannabinol: Tetrahydrocannabinol may enhance the CNS depressant effect of CNS depressants. Monitor therapy.(83, 84, 85, 86, 87, 147)
Thalidomide: CNS depressants may enhance the CNS depressant effect of thalidomide. Avoid combination.(148)
Thiopental: Valerian may enhance the CNS depressant effect of thiopental.(19, 64)
Trimeprazine: Trimeprazine may enhance the CNS depressant effect of CNS depressants. Monitor therapy.(149)
Zolpidem: CNS depressants may enhance the CNS depressant effect of zolpidem. Consider therapy modification. A dose reduction is recommended for Intermezzo brand sublingual zolpidem (applies to men only) but is not applicable to the other zolpidem products.(150, 151, 152)
Adverse Reactions
Valerian has been classified as GRAS in the United States for food use; extracts and the root oil are used as flavorings in foods and beverages.(13)
Generally, clinical studies have found that valerian has a wide margin of safety, is devoid of adverse effects, and has fewer adverse reactions than positive control drugs, such as diazepam. Headache and diarrhea have been reported in clinical trials, but hangover is seldom reported.(5, 6, 13, 24, 30, 31, 32)
An intentional overdose has been reported, in which 20 times the recommended dose was ingested; the patient experienced mild symptoms that resolved within 24 hours.(42) A case of withdrawal after chronic use of valerian has been reported; however, the complex nature of the patient's medical history provides weak evidence of valerian's role.(43) Valerian withdrawal was suspected as the etiology of acute delirium in an elderly male with multiple risk factors for developing delirium (eg, mild neurocognitive disorder, older age, history of mood disorders).(156) Farmers growing valerian were evaluated for adverse reactions, with few notable effects observed.(44)
Hepatotoxicity associated with valerian use was first reported in 1989. Six cases have been reported in women, all of whom reported marked improvement or normalization of liver function tests over 1 to 19 months after valerian discontinuation. However, one case of severe acute hepatitis refractory to improvement subsequent to valerian discontinuation was reported in a 57-year-old man. He had taken 2 g/day of valerian for 3 days and developed worsening liver function over the following 4 weeks. He was successfully treated with oral prednisolone 50 mg daily.(62)
Toxicology
Concern was raised following the discovery that valepotriates are mutagenic in the Ames assay; however, their poor bioavailability and hepatic detoxification makes them a dubious source of toxicity for patients.2, 45 The cytotoxicity of baldrinal compounds (metabolites of the valepotriates) is higher in vivo than in vitro because they are more readily absorbed, and these metabolites have been detected in commercial preparations.2
No teratogenicity or overt toxicity of valepotriate compounds was found in rodents in 2 different studies.2, 13, 46 Mice receiving doses of valerian more than 1 g/kg by oral and intraperitoneal routes have experienced ataxia, muscle relaxation, and hypothermia.47
No evidence of hepatitis was observed following consumption of oral valerian at average dosages of 2.5 g/day for 4 years.46
Index Terms
- Vakeruaba officinalis
References
Disclaimer
This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.
This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.
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