Scientific Name Valeriana angustifolia,  Valeriana edulis, Valeriana jatamansii (synonyms: Valeriana fauriei,  Valeriana sitchensis, Valeriana wallichii), Valeriana officinalis                                          Family Valerianaceae Other Common Names: All-Heal, Amantilla,  Baldrian, Baldrianwurzel, Belgium Valerian, Common Valerian, Fragrant  Valerian, Garden Heliotrope, Garden Valerian,                                                                                                                                                                                                                                    |                                                                                                                                                                          Caution  Valerian should not be confused with Red-Spur Valerian.

Valerian is an herbaceous perennial  plant with feather-like leaves and small flowers that are white to pink  in color. The plant is native to Europe and parts of Asia but has also  been cultivated in North America (81723). Valerian can grow to be just over 6 feet tall and is characterized by a strong odor (81723). Valerian root has a long history of use, dating back to use as a sedative by the ancient Greeks and Romans (56982).                                 

Several  vaping products with labels claiming to contain valerian root have been  found to contain measurable quantities of synthetic cannabinoids (114797).

Likely Safe when  used orally and appropriately, short-term. Valerian 300-600 mg daily has  been safely used in clinical studies in over 12,000 patients for up to 6  weeks (2074, 3484, 3485, 4032, 15018, 17577, 17578, 19409, 96242, 103221)(104010, 105718).                                                             

There is  insufficient reliable information available about the safety of  valerian when used orally for longer than 6 weeks.                                                             

CHILDREN:  Possibly Safe when  used orally and appropriately, short-term. Valerian 160-320 mg has been  used with apparent safety in children under 12 years of age for 4-8  weeks (14416).                                                             

PREGNANCY AND LACTATION: Insufficient reliable information available; avoid using.                                                             

Orally, valerian is generally well-tolerated. 

Orally:  Dizziness, drowsiness, and mental slowness. Other reported side effects  include headache, gastrointestinal upset, excitability, and vivid  dreams. When used chronically and abruptly stopped, symptoms of  withdrawal such as tachycardia, anxiety, irritability, and insomnia  might occur. Advise patients to taper doses slowly after extended use.

Orally:  Several case reports raise concerns about hepatotoxicity after the use  of valerian and valerian-containing multi-ingredient dietary  supplements. Withdrawal from chronic valerian use has been associated  with cases of cardiac failure and hallucinations.

When  used orally in high doses for an extended period of time, valerian  withdrawal has been associated with tachycardia and high output cardiac  failure in one patient with a history of coronary artery disease (3487). Chest tightness has been reported for an 18-year-old female who took 40-50 capsules containing valerian 470 mg/capsule (659).  A case of severe hypotension, suspected to be due to vasodilation,  hypocalcemia, and hypokalemia, has been reported for a patient who  injected an unknown quantity of a crude tap water extract of raw  valerian root (81734).  A case of transient complete atrioventricular block and QT prolongation  was reported in a 25-year-old female following the post-workout use of a  specific product (Muscle Eze Advanced) containing valerian and several  other ingredients. Symptoms of fatigue and lightheadedness started 1  week into use of the product; discontinuation led to restoration of  normal sinus rhythm within 24 hours and normalization of the  electrocardiogram within 2 weeks (112556). It is unclear whether this event was due to valerian, other ingredients, the combination, or other factors.

Orally,  valerian might rarely cause a rash. A case of valerian-related rash  that resolved after valerian root discontinuation was reported in  clinical research (19422).

Orally,  valerian has been associated with increased incidence of  gastrointestinal problems including diarrhea, nausea, vomiting, and  stomach pain (15046, 19406, 19407, 19422, 110712). In one individual, taking 20 times the normal dose caused abdominal cramping (659).

  There  have been several case reports of hepatotoxicity associated with the  use of multi-ingredient oral preparations containing valerian (8243, 96241).  In one case report, a 57-year-old man presented with acute hepatitis  after consuming a cold and flu remedy containing valerian 2 grams for 3  days; the remedy also contained white willow, elderberry, and  horseradish. Although the use of the cold and flu remedy was  discontinued one month prior to symptom presentation, the acute  hepatitis was attributed to valerian root and treated with steroids (96241). It is possible, however, that some of these preparations may have been adulterated with hepatotoxic agents (8243).
Hepatotoxicity involving long-term use of single-ingredient valerian preparations has also been reported (3484, 17578).  Also, a case of a 38-year-old female with liver insufficiency and  cirrhosis of a vascular parenchymal nature who developed hepatotoxic  symptoms following valerian and ethyl-alcohol abuse has been reported (81697).  Symptoms resolved and laboratory values normalized following intense  plasmapheresis treatment. Another case of acute hepatitis characterized  by elevated aminotransferases, mild fibrosis, and liver inflammation has  been reported for a 50-year-old female who consumed valerian root  extract 5 mL three times weekly along with 10 tablets of viamine, a  product containing dry valerian extract 125 mg/tablet, for 2 months (81696).  Because a variety of doses were used in these cases, and many people  have used higher doses safely, these hepatotoxic reactions might have  been idiosyncratic. Tell patients the long-term effect of valerian on  liver function is unknown.

  In  a case report, combined intake of valerian and passionflower caused  throbbing and muscular fatigue when taken concomitantly with lorazepam (19429).

  Orally, valerian might cause dizziness, headaches, fatigue, sleepiness, and mental dullness (3484, 17578, 19411, 19422, 81723, 89407). The severity of adverse effects appears to increase with higher doses (19411).  However, taking valerian extracts in doses up to 1800 mg does not  appear to significantly affect mood or psychomotor performance (10424, 15044). Valerian does not usually have a negative impact on reaction time, alertness, and concentration the morning after intake (2074, 8296).  Clinical research shows that a single dose of valerian root 1600 mg is  not associated with any changes in sleepiness, reaction time, or driving  performance within 1-4 hours after intake (96240).  More serious side effects may occur when valerian is taken at higher  doses. In one individual, 20 times the normal dose caused tremor of the  hand and foot and lightheadedness (659).  In a case report, combined intake of valerian and passionflower caused  shaking of the hands and dizziness when taken concomitantly with  lorazepam (19429).

  Orally, valerian has been associate with reports of restlessness, excitability, uneasiness, agitation, and vivid dreams (3484, 17578, 19411, 19422). Chronic use and rapid cessation can lead to withdrawal syndrome with symptoms of agitation, insomnia, and hallucinations (104003). There appears to be a trend towards increased severity of adverse effects with higher doses (19411).  A case of acute hypomania has been reported for a 21-year-old female  patient who took a valerian decoction in water each night for one month  to treat subclinical anxiety. Symptoms included euphoric mood, rapid  speech, and increased sociability and sexual interest. Following  cessation of valerian use and treatment with quetiapine 100 mg daily for  two weeks, the patient recovered (89405).  In another case report, an 85-year-old male with mild cognitive  impairment, major depression, anxiety, and chronic kidney disease  presented to the emergency department with hallucinations, confusion,  and agitation thought to be due to abrupt cessation after taking  valerian 600 mg daily for about 6 months. The symptoms resolved in about  5 days (104003).

                                                                                                                                                                                                                                                                                                                 Possibly Effective                                                                       

Most  research shows that taking valerian whole root extract 300-600 mg daily  modestly improves subjective sleep quality, although it might take up  to 4 weeks to provide benefit. Valerian does not seem to improve sleep  latency, sleep duration, or insomnia severity.

 Although  there is a great deal of conflicting research, overall, taking valerian  300-600 mg before bedtime seems to improve sleep quality when compared  with placebo. In contrast, no consistent benefit has been seen for sleep  latency, sleep duration, or insomnia severity (15046, 17577, 19406, 19409, 104010), although one small clinical trial disagrees (114801).  Older meta-analyses show that valerian root improves sleep quality  regardless of its formulation. However, the most recent meta-analysis  shows that valerian whole root extract improves sleep quality, while  it's unclear whether an unspecified valerian extract is effective (17577, 19406, 104010).  These analyses are limited by significant heterogeneity in valerian  dosage and formulation, treatment duration, and included patient  populations. Some experts claim that valerian does not work acutely for  sleep, and it can take up to 4 weeks for a benefit to be seen (10209, 104010).  Indeed, most short-term studies assessing valerian as a single dose, or  used daily for up to one week, show no benefit for sleep quality when  compared with placebo (19407, 19408, 19411, 19414), although one small study disagrees (114801). However, a meta-analysis of studies lasting 4 weeks or longer also did not find a consistent benefit (104010).
The  benefits of valerian for sleep might vary in different patient  populations. A large post-marketing surveillance study in children with  restlessness or dyssomnia under the age of 12 has found that taking a  specific combination product (Euvegal Forte, Dr. Willmar Schwabe  Pharmaceuticals) containing valerian root extract 160 mg and lemon balm  extract 80 mg 1-2 tablets once or twice daily is associated with  moderate sleep improvement (14416).  Also, one clinical study in postmenopausal adults shows that taking  valerian root extract 530 mg (Sadamine) twice daily for 28 days  moderately improves sleep quality when compared with placebo (19425).  Another clinical study in patients undergoing treatment for cancer  shows that taking valerian 450 mg 1 hour before bedtime for 8 weeks does  not improve objective sleep measures, but might improve subjective  sleep ratings and mood, when compared with placebo (19424).  Small clinical studies in adults on hemodialysis show that taking  valerian 530 mg before bedtime for 1 month improves sleep quality when  compared with baseline or placebo. (105718, 110712). In one of these studies, improvements in sleep quality were similar when compared with gabapentin (110712).
Research  also shows that taking specific combination products containing  valerian and other ingredients can improve sleep quality. These  combination products have combined valerian with hops; lemon balm  (Euvegal Forte); lemon balm and hops (Valerina Natt); or passionflower  and hops (NSF-3, M/s Tablets India) (10423, 15018, 19413, 19417, 19418, 19419, 88193, 89408).
Finally,  limited research has compared valerian to benzodiazepines. A small  clinical study in patients with non-organic insomnia shows that taking  valerian extract (LI 156, Sedonium) 600 mg daily for 6 weeks seems to be  no different for improving sleep quality when compared with taking  low-dose oxazepam 10 mg (19416).  Valerian might also improve sleep quality in patients who are resistant  to chronic benzodiazepine therapy. In one small study, after tapering  the benzodiazepine over two weeks, valerian extract 100 mg three times  daily for 15 days improves sleep quality when compared with placebo (8006).

                                                                   Insufficient Reliable Evidence to Rate                                                                       

It is unclear if valerian is beneficial for anxiety.

 Meta-analyses  of heterogeneous clinical research show that there is insufficient and  contradictory evidence on the use of valerian root for anxiety (104010, 110711). However, one analysis suggests that using whole root preparations seems to have greater efficacy than valerian extracts (104010).  These meta-analyses are limited by significant heterogeneity in  valerian dosage and formulation, treatment duration, and patient  populations and concerns related to publication bias (104010, 110711).

One  small clinical study in patients with generalized anxiety disorder  (GAD) shows that taking valerian extract containing 81.3 mg  valepotriates daily for 4 weeks is no different for reducing anxiety  scores when compared with diazepam 6.5 mg or placebo (9896).  This study was not adequately powered to detect a difference between  groups. Also, a small, quasi-randomized trial in adults with poor sleep  quality who are undergoing hemodialysis shows that taking a specific  valerian root product (Sedamin, Goldaru Company) 530 mg daily for 1  month improves anxiety scores by 2-3.9 times when compared with placebo.  However, not all patients reported anxiety at baseline (105718).

In  contrast, a small clinical study in healthy adults shows that taking a  combination of herbal extracts containing valerian root, passionflower,  ballota, and hawthorn (Euphytose) daily for 14 days reduces subjective  anxiety and objective sympathetic and autonomic nervous system  activation in response to a psychosocial stressor when compared with  placebo (111222). It is unclear if these effects are due to valerian, other ingredients, or the combination.

Oral valerian has only been evaluated in combination with other ingredients; its effect when used alone is unclear.

A  small clinical study in adult intensive care unit (ICU) patients with  agitation and delirium receiving quetiapine 50-200 mg every 12 hours  shows that taking 5 mL of syrup containing valerian root 625 mg and an  extract of lemon balm leaf 50 mg every 12 hours improves agitation from  baseline similarly to placebo. It is unclear if the improvement from  baseline differed between groups (106627).

It is unclear if valerian is beneficial in patients with depression.

A  retrospective case series in patients with mild to moderate depression  and reports of anxiety has found that taking high-dose valerian 1000 mg  with St. John's wort is associated with more rapidly improved depressive  symptoms than low-dose valerian 500 mg with St. John's wort (19402).  The validity of this study is limited by its retrospective nature and  small size. Also, it is unclear if this effect is due to valerian, St.  John's wort, or the combination. One small, quasi-randomized trial in  adults with poor sleep quality who are undergoing hemodialysis shows  that taking a specific valerian root product (Sedamin, Goldaru Company)  530 mg daily for 1 month improves depression scores by 2-3.9 times when  compared with placebo. However, not all patients reported depression at  baseline (105718).

One small study suggests that oral valerian may reduce symptoms of dysmenorrhea.

A  small clinical study shows that taking powdered valerian root 255 mg  three times daily for two menstrual cycles reduces pain severity  associated with menstruation when compared with placebo (19342).

Small studies suggest that oral valerian may reduce menopausal symptoms.

Two  small clinical studies in postmenopausal adults show that taking  valerian root (Zardband or Goldaroo Co.) 225 mg three times daily or 530  mg twice daily for 2 months moderately reduces hot flash frequency and  severity when compared with placebo (89407, 96243).  Another small study in adults with menopausal symptoms shows that  taking a combination of valerian and fennel extracts 500 mg twice daily  for 8 weeks reduces the severity of hot flashes and improves sleep  quality but does not reduce the duration or frequency of hot flashes  when compared with control (112369).  It is unclear if these effects are due to valerian, fennel, or the  combination. All 3 studies were conducted in Iran, so it is unclear if  these results are generalizable to other geographic locations.

One small study suggests that oral valerian may reduce PMS symptoms.

A  small clinical study in young adults with PMS shows that taking  valerian root extract (Goldaroo Co.) 530 mg twice daily on the last 7  days of the menstrual cycle for 3 cycles moderately reduces the severity  of self-reported PMS symptoms when compared with placebo (96239).

Two small studies suggests that oral valerian may reduce anxiety during wisdom tooth extraction.

A  small crossover study in adults undergoing impacted mandibular molar  extraction shows that taking valerian extract (Dermatologica Ltda.) 100  mg one hour prior to the extraction reduces physiological responses to  anxiety to a satisfactory but lesser degree than midazolam 15 mg.  Patients expressed no clear preference for either valerian or midazolam  for reducing perioperative anxiety (102242).  The validity of these findings is limited by the use of subjective  outcome measures. Another small clinical trial in adults undergoing  tooth extraction shows that taking valerian 400 mg orally one hour prior  to the procedure reduces anxiety scores when compared to baseline. The  placebo group did not exhibit a reduction from baseline anxiety scores;  however, there was no direct comparison between groups, limiting the  interpretability of this finding (114800).

It is unclear if oral valerian is beneficial in patients with RLS.

A  small clinical study in patients with RLS shows that taking valerian  (Pharmavite, LLC) 800 mg daily for 8 weeks does not improve RLS symptoms  or sleep latency when compared with placebo (19422).  However, this study was not adequately powered to detect a difference  in RLS symptoms between groups. Conversely, another small clinical study  in adults with RLS on hemodialysis shows that taking valerian 530 mg  nightly before bed for 1 month reduces symptoms of RLS when compared to  baseline; however, valerian's effects were weaker when compared with  gabapentin 100 mg nightly (110712). The validity of this study is limited by a lack of a placebo group and a small sample size.

Two  small studies suggest that oral valerian may reduce the stress response  in healthy adults who are performing a stressful mental task or a  verbal presentation.

Two  small clinical studies in healthy volunteers shows that taking valerian  100 mg once or 600 mg daily for 7 days prior to participating in a  mental stress task or public verbal test reduces physiologic responses  to stress and feelings of anxiety when compared to baseline (9893, 9895).  The validity of these findings is limited by the lack of statistical  comparison to the control group. Another small study in healthy  volunteers shows that taking a specific combination product containing  valerian 360 mg and lemon balm 240 mg (Songha Night, Pharmaton Natural  Health Products) reduces anxiety associated with laboratory-induced  stress. However increasing the dose to valerian 1080 mg and lemon balm  720 mg seems to increase anxiety (19405).

One small study suggests that oral valerian may reduce tension headache.

A  small clinical study in patients with frequent tension headaches shows  that taking valerian root extract (Sedamin, Goldaru Pharmaceutical  Company) 1060 mg daily after dinner for one month modestly reduces  headache severity and disability when compared with placebo (103221).

More evidence is needed to rate valerian for these uses.

Valerian  has been used in daily divided doses of 1215 mg for up to 7 days.  Valerian has most often been used in doses of 300-600 mg daily for up to  6 weeks. It is frequently found in combination products with other  sedative herbs such as hops, passionflower, and lemon balm. Prolonged  use might result in dependence, and withdrawal symptoms upon  discontinuation (17577, 103221, 104010). See Effectiveness section for condition-specific information.

Research is limited; typical dosing is unavailable.

Some  valerian products are standardized based on the valerenic acid  constituent. Most clinical studies do not specify the valerenic acid  content of the valerian extracts used. However, some products containing  valerian root extract have been standardized to contain 0.683% to 1%  valerenic acid (10424, 15046). Similarly, some products containing ground valerian root have been standardized to contain 0.15% to 0.8% valerenic acid (19422, 19424).

Specific products containing valerian root or valerian root extract  that have been used in clinical research include: Sedamin 530 mg (19425, 105718); Valerina Forte (Cederroth International AB) 200 mg (19409); Valdispert forte (19415); a valerian root extract called Li 156 (Sedonium, Lichtwer Pharma) 300 mg or 600 mg (6249, 19411, 19416); and Valmane (Whitehall Pharmaceutical) 100 mg (8006).

  Interaction Rating Moderate Be cautious with this combination.     Severity HIGH   Occurrence POSSIBLE   Level of Evidence B (Lower quality RCT)    

Valerian can have additive sedative effects when used concomitantly with alcohol.
 

Valerian has sedative effects (9894).  Theoretically, valerian might have an additive sedative effect when  combined with alcohol. Excessive sedation has been reported in an  alcohol-abusing individual who took valerian and Gingko biloba (19426).  However, the potential interaction between valerian and alcohol has  been disputed in other research. Limited evidence suggests that a  combination of valerian 160 mg and lemon balm 80 mg (Euvegal) does not  cause further deterioration in reaction ability and reaction rate when  taken with alcohol as compared to the effects of alcohol alone (19427).

  Interaction Rating Moderate Be cautious with this combination.     Severity HIGH   Occurrence POSSIBLE   Level of Evidence B (Nonrandomized clinical trial)    

Valerian  can have additive sedative effects when used with alprazolam. Also,  valerian in high doses might modestly increase alprazolam levels, though  this is not likely to be clinically significant.

Valerian has sedative effects (9894).  Theoretically, valerian might cause additive sedation when combined  with alprazolam. Also, a small pharmacokinetic study shows that taking  valerian extract 1000 mg daily (providing 11 mg valerenic acid) might  increase alprazolam levels by about 19%. This might be due to valerian's  mild inhibition of cytochrome P450 3A4 (CYP3A4) (13014). Despite being statistically significant, this increase is not likely to be clinically significant.

  Interaction Rating Moderate Be cautious with this combination.     Severity HIGH   Occurrence POSSIBLE   Level of Evidence D (In vitro or animal study)    

Valerian can have additive sedative effects when used concomitantly with CNS depressant drugs.

Theoretically,  concomitant use of valerian and drugs with sedative and anesthetic  properties may cause additive therapeutic and adverse effects (3486, 12720, 19429).

  Interaction Rating Minor Be watchful with this combination.     Severity MILD   Occurrence UNLIKELY   Level of Evidence B (Nonrandomized clinical trial)    Valerian does not seem to have a clinically relevant effect on levels of drugs metabolized by CYP2D6.
 

Although  some in vitro evidence suggests that valerian affects CYP2D6, clinical  pharmacokinetic (PK) studies show that valerian is unlikely to affect  the CYP2D6 enzyme (13014, 13536, 19430, 19431).  In one PK study, taking valerian 1000 mg (providing about 11 mg  valerenic acid) nightly for 14 days did not affect the metabolism of  dextromethorphan, a CYP2D6 substrate. In another PK study, taking  valerian 125 mg three times daily for 28 days did not affect metabolism  of debrisoquine, an accepted CYP2D6 probe-substrate (13014, 13536).

  Interaction Rating Minor Be watchful with this combination.     Severity MILD   Occurrence POSSIBLE   Level of Evidence B (Nonrandomized clinical trial)    Valerian does not seem to have a clinically relevant effect on levels of drugs metabolized by CYP3A4.
 

Although  some in vitro and animal evidence suggests that valerian extract might  inhibit or induce CYP3A4, clinical pharmacokinetic (PK) studies show  that valerian does not have a clinically significant effect on the  CYP3A4 enzyme (6450, 12214, 13014, 13536, 19431, 111404, 114799).  In one PK study, taking valerian 125 mg three times daily for 28 days  did not affect metabolism of midazolam, an accepted CYP3A4  probe-substrate. In another PK study, taking valerian 1000 mg (providing  about 11 mg valerenic acid) nightly for 14 days modestly increases  levels of alprazolam, a CYP3A4 substrate, suggesting mild inhibition of  CYP3A4 (13014, 13536). However, this mild inhibition is unlikely to be clinically relevant.

  Interaction Rating Moderate Be cautious with this combination.     Severity MODERATE   Occurrence POSSIBLE   Level of Evidence D (In vitro or animal study)    

Valerian might weakly inhibit glucuronidation and increase concentrations of drugs metabolized by UGT1A1 and UGT2B7.
 

In  vitro research shows that methanolic valerian extract and valerenic  acid might competitively inhibit UDP-glucuronosyltransferase (UGT) 1A1  (UGT1A1) and UGT2B7 (81685).

Theoretically, valerian might have additive sedative effects when used with herbs with these properties.
Use of valerian with other herbs and supplements with sedative properties might enhance therapeutic and adverse effects (3486). See other natural products with sedative properties here.

 Valerian  has sedative effects which might cause additive CNS depression when  combined with anesthesia and other medications used perioperatively (3486). Tell patients to discontinue valerian at least 2 weeks before elective surgical procedures.

 Presentation

One  case report describes a middle-aged female, previously diagnosed with  bipolar disorder, and currently noncompliant with prescribed psychiatric  medications, presenting with altered mental status, hypertension,  tachycardia, mydriasis, tremors, and diaphoresis following  self-treatment with valerian root 2000 mg nightly and an unspecified  product containing gamma-aminobutyric acid (GABA) for an unknown  duration. A psychiatric consultation revealed agitation and paranoia,  delayed thinking, and mostly normal cognition; the patient was diagnosed  with encephalitis due to accidental overdose. Self-treatment was  discontinued and the patient was restarted on carbamazepine, with mental  status returning to baseline by the third day (108064). 

There is insufficient reliable information available about the treatment of overdose with valerian.

Following  a 600 mg oral dose of a specific valerian extract (Sedonium, Lichtwer  Pharma) in healthy volunteers, maximum valerenic acid serum  concentrations of 0.9-2.3 ng/mL usually occur within 1-2 hours (14405)

Following  a 600 mg oral dose of a specific valerian extract (Sedonium, Lichtwer  Pharma) in healthy volunteers, the elimination half-life of valerenic  acid is about 1.1 hours (14405).

The  applicable part of valerian is the root and rhizome. The pharmacological  effects of valerian have primarily been attributed to valepotriates  (iridoid esters such as valtrate), baldrinals, volatile oils,  monoterpenes, and sesquiterpenes constituents (3486, 81704, 81705, 81706, 81707, 81709, 81715). The primary monoterpene is borneol and the primary sesquiterpenes are valerenic acid, valeranone, and kessel glycol (3484, 3486, 15043). Other potentially active constituents include the flavonoids 6-methylapigenin, hesperidin, and linarin (15043, 54810, 81677). The valepotriates decompose to other potentially active compounds, notably baldrinal and homobaldrinal (3486, 81709, 81715). The characteristic unpleasant odor of valerian has been attributed to isovaleric acid.

Valerenic  acid and valepotriate constituents have received the most attention.  Some valerian extracts are standardized based on the valerenic acid  constituent. These extracts can be standardized to contain from 0.25% to  1% valerenic acid.

The roots and rhizomes of valerian can have  wide variation in the composition of these constituents, and different  species of valerian can also have a different constituent profile.

Valeriana  officinalis primarily contains valerenic acid and its derivatives as  well as the valepotriates. Valeriana wallichii and Valeriana edulis do  not contain valerenic acid (15043).  Because valerian extracts without some of these constituents can still  have similar effects, it is likely that multiple constituents are  responsible for its pharmacological effects.

Valepotriates  are highly unstable and rapidly decompose in acid or alkaline  environments and at high temperatures. Although there are published  reports of toxicity due to the valepotriate constituents, these  constituents are poorly absorbed and quickly degraded to less toxic  metabolites and are not likely to cause acute adverse reactions (3486). The presence of an epoxide group on the valepotriates has raised concern about possible cytotoxicity and carcinogenicity (3485, 3486); however, in vivo studies to date have failed to show any carcinogenic effects (3486).  In fact, some evidence from in vitro research has shown that various  acylated iridoids and valepotriates derived from the roots of valerian  weakly to moderately inhibit the growth of A549 (lung adenocarcinoma),  HCT116 (colon carcinoma), HepG2 (hepatoma), and SK-BR-3 (breast  carcinoma), PC-3M (metastatic prostate cancer), HCT-8 (colon cancer),  and Bel 7402 (hepatoma) cell lines (81706, 81707).  Also evidence from animal research shows that valepotriates exert  cytotoxic effects on hepatoma cell lines and inhibit DNA and protein  synthesis; didrovaltrate prolonged survival in mice bearing ascitic  tumors (81712, 81714).

There  is contradictory evidence about the effects of valerian on cytochrome  P450 3A4 (CYP3A4). In vitro, valerian extract seems to inhibit the  cytochrome P450 3A4 (CYP3A4) enzyme (6450, 12214);  however, clinical research suggests valerian does not significantly  affect CYP3A4 when used at a relatively low dose of 375 mg/day, but  modestly inhibits CYP3A4 at a higher dose of 1000 mg/day (13014, 13536).  It does not seem to significantly affect cytochrome P450 1A2 (CYP1A2),  cytochrome P450 2D6 (CYP2D6), or (CYP2E1) cytochrome P450 2E1 (13014).

Animal  research suggests that valerian extract may reduce gastric mucosal  damage, inhibit intestinal spasm, and improve intestinal peristalsis in  the setting of gastrointestinal disease. Valerian is theorized to  mitigate gastric damage and reduce gastric lesions induced by ethanol  and nonsteroidal anti-inflammatory agents through antioxidant,  anti-inflammatory, and cytoprotective effects (111221).

In  anesthetized guinea pigs, orally administered valerian root extracts  (50, 100, and 200 mg/kg) demonstrated significant anticoronaryspastic  and antihypertensive effects against pitressin-induced coronary spasm  and pressor response, which were similar to those exhibited by  nifedipine (19428).

There  is concern that valerian may alter the composition of breast milk. In  rats receiving valerian extract at doses two- to four-fold greater than  the lowest dose recommendations from reproductive toxicity trials, milk  had lower protein content and greater lactose content, with unchanged  cholesterol or triglyceride content, when compared with the milk of rats  receiving control (106628).

Valerians  anxiolytic, anticonvulsant, and sedative properties may be due to the  effects of its constituents on gamma-aminobutyric acid (GABA), adenosine  A1, and serotonin (5HT) receptors. Valerenic acid and other  constituents of valerian are GABA agonists. Valerian constituents may  inhibit the enzyme system responsible for the central catabolism of  GABA, increasing GABA concentrations and decreasing CNS activity.  Valerian may also bind directly to GABA-A receptors and stimulate the  release and reuptake of GABA (3486, 12720, 56982, 81666, 81688, 81718, 81720, 81739, 81740, 81741)(81742).  However, other research suggests that the presence of small quantities  of GABA in valerian extracts may have confounded these results by  directly elevating measured GABA levels in the synaptic cleft (81719, 81722). In addition to the effects on GABA, valerian might affect sleep regulation via activity on adenosine and serotonin (5-HT1) receptors (12720, 81679, 81682, 81683, 81687, 81692).  One study in female mice shows that valerenic acid improves multiple  anxiety-related behaviors, with an overall anxiolytic effect similar to  that of diazepam (114802).

Some evidence in animals and human subjects also suggests that valerian may have some antidepressant effects (81673, 81702, 81717).  While the activity in depression is unclear, these effects may be  mediated via GABA-related mechanisms and/or the binding of valerian  constituents to serotonin (5HT1A) receptors (19405).

Animal  research shows that female offspring of rats that received valerian  extract during the postnatal period demonstrate behavior indicative of  memory impairment as adults (106628). The clinical implications of this finding are unclear.

Evidence  from animal models suggests that valerian extract may reduce cold  allodynia, a symptom commonly associated with neuropathic pain, when  compared with placebo (108063).

Research  in male rats with induced neuropathic pain shows that taking valerian  extract for 3 weeks increases the density and frequency of sleep  spindles and may extend the time spent in non-rapid eye movement (REM)  sleep when compared with placebo. Valerian also increased the length of  REM sleep, but this was subsequently reduced following the introduction  of a neuropathic pain condition (108063).

Cytochrome P450 3A4 (CYP3A4) Inhibitors,                                     Sedative-Hypnotic Agents  

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Literature Review Current Through: 3/23/2026, Last Updated: 7/5/2026

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