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Valeriana officinalis

Valeriana officinalis, commonly referred to as Valerian root, is a medicinal herb found in North America, Asia, and Europe that has been traditionally used to treat sleep and anxiety disorders. Valerian contains more than 150 phytochemicals, and valerian extracts are most often standardized by their valeric acid content. However, it is not fully known which constituents are primarily responsible for its effects. (26)(31)(54)

Valerian’s mechanism of action is not completely understood but may be due to its stimulation of GABA transmission via positive modulation of GABA-A receptors, (7)(33) similarly to benzodiazepines (a class of sedatives). (31) However, valerian may possess certain advantages over benzodiazepines and other conventional sedatives, including lower rates of adverse events. (18)(27)(59) For example, valerian may not impair alertness, concentration, or reaction time upon awakening, (35) impair machine operation and driving ability, (22)(57) or exhibit the same extent of clinically relevant interactions with other pharmaceuticals. It is important to note, however, that valerian may theoretically have additive effects if administered in combination with other sedatives. (26)(31)

Main uses

Anxiety and stress
Behavioral and nervous system regulation
Insomnia and sleep disturbance
Premenstrual, menstrual, and postmenopausal symptoms

Formulations

Formulation	Characteristics
Dormeasan ®	Tincture containing 460 mg valerian root at a drug extract ratio (DER) of 1:10 and 460 mg of Humulus lupulus at a DER of 1:12, both of which are dissolved in 61% ethanol (15)
LI 156 (Sedonium®)	Contains 300 mg dry root extract of at a DER of 3-6:1 (14)
NSF-3	Contains 300 mg valerian standardized to 0.8% valerenic acid, 30 mg Humulus lupulus standardized to 0.35% rutin, and 80 mg Passiflora incarnata standardized to 4% isovitexin in a 410 mg tablet (38)
Songha Night™	Contains 120 mg of valerian extract at a DER of 4.5:1 and 80 mg of Melissa officinalis extract at a DER of 5:1 (32)
Valdispert ® forte	Contains 135 mg of aqueous alkaline dried valerian root extract with DER of 5-6:1 (52)
Ze 185 (Relaxane®)	Contains 90 mg of a 55% methanolic valerian root extract at a DER of 5-8:1, 90 mg of a 90% ethanolic Petasites hybridus root extract at a DER of 7-14:1, 90 mg of a 50% ethanolic Passiflora incarnata herbal extract at a DER of 3-6:1, and 60 mg of a 20% ethanolic Melissa officinalis leaf extract at a DER of 3.5-5.5:1 (40)
Ze 91019	Contains 250 mg of a 45% methanolic valerian root extract at a DER of 4-6:1 and 60 mg of Humulus lupulus extract at a DER of 5-7:1 (34)(58)

Dosing & administration

Anxiety & stress
General outcomes from A-level evidence	Note: evidence does not consistently report benefit in the treatment of anxiety (44)
Dosing & administration	90 mg (in Ze 185) per day for four days or 600 mg (as LI 156, Sedonium®) per day for seven days prior to a stressful event to healthy adults
Outcomes	↓ systolic blood pressure and heart rate Attenuated self-reported anxiety due to stress (10)(9)
Class of evidence	B
Dosing & administration	530 mg per day one hour before sleep for four weeks to Px with HIV using efavirenz
Outcomes	Improves anxiety score (reduced Hamilton Anxiety Rating Scale) and sleep score (reduced Pittsburgh Sleep Quality Index) (1)
Class of evidence	B
Dosing & administration	1,500 mg single dose with mefenamic acid therapy to infertile women undergoing hysterosalpingography
Outcomes	↓ anxiety score compared with mefenamic therapy alone (23)
Class of evidence	B
Dosing & administration	100 mg (standardized to 0.8% valeric acid; 70% ethanolic extract) or 50 mg (valepotriates) three times per day for four weeks to adults with psychological stress or generalized anxiety disorder (GAD)
Outcomes	↓ psychic factor subscale on the Hamilton Anxiety scale to a similar extent to diazepam in Px with GAD ↑ alpha coherence (negatively correlated with improvement in anxiety scores) and theta coherence in Px with psychological stress Indicates brain connectivity alteration as a possible cause of anxiolysis (4)(49)
Class of evidence	C
Dosing & administration	100 mg valerian extract single administration one hour prior to mandibular molar extraction to Px with anxiety
Outcomes	↓ anxiety to a similar extent as midazolam without sedation or somnolence (19)
Class of evidence	C
Dosing & administration	360 mg (as Songha Night™) with 240 mg lemon balm extract single administration prior to lab-induced stress
Outcomes	Attenuates negative effects of stressor test on anxiety Note: higher doses increased anxiety (32)
Class of evidence	C

Cognitive function
General outcomes from A-level evidence	No data currently available.
Dosing & administration	530 mg valerian root extract twice per day for eight weeks in patients who underwent coronary artery bypass graft surgery
Outcomes	Prevents disturbance of mini-mental state examination scores by 10 days of use and reduced odds of cognitive dysfunction by ~11% (28)
Class of evidence	B
Dosing & administration	530 mg per day one hour before bed for one month to Px on hemodialysis
Outcomes	↑ mini-mental state examination total score (50)
Class of evidence	C

Insomnia/sleep disturbances
General outcomes from A-level evidence	↑ chance of self-reported improvement in sleep quality by 37-80% (8)(20) ↓ sleep latency and wake time after sleep onset to improve sleep duration (24) Note: evidence does not consistently report improvement in objective measures of sleep quality such as sleep onset latency, sleep duration, sleep efficiency, or wake times. (8)(20)(36)(51)(53)(56) Inconsistency in the formulation of the valerian extract (e.g., ethanolic, aqueous, etc.) and the presence of additional ingredients such as hops may partially explain inconsistent effects (8)(12)
Dosing & administration	400-1,060 mg extract per day one hour before bed for 1-4 weeks to healthy adults or adults with insomnia
Outcomes	↑ self-assessed sleep quality and number of Px reporting improvement in sleep quality ↓ sleep latency Effects may be particularly apparent in individuals who perceive themselves as poor sleepers (37)(46)(55)
Class of evidence	B
Dosing & administration	120-375 mg (45% methanolic standardized extract, or Hova®) with 60-84 mg hops per night for 1-4 weeks to healthy adults or adults with mild insomnia
Outcomes	↓ self-rated insomnia severity within two weeks in adults with insomnia ↑ sleep quality within one week & QoL score by 4th week Effects may be particularly apparent in individuals who perceive themselves as poor sleepers (37)(43)
Class of evidence	B
Dosing & administration	90 mg (in Ze 185) three times per day for two weeks to adults diagnosed with somatoform disorder
Outcomes	↓ anxiety score (measured by visual analog scale) & depression score (Beck’s Depression inventory) Improves the Clinician’s Global Impression score (40)
Class of evidence	B
Dosing & administration	450 mg (standardized to 0.8% valerenic acid) per day one hour before bedtime for eight weeks to Px undergoing cancer therapy
Outcomes	↓ fatigue, reports of sleep disturbance, & drowsiness (5)
Class of evidence	B
Dosing & administration	600 mg (as LI 156, Sedonium®) once or twice for 2-6 weeks to adults with primary or non-organic/non-psychiatric insomnia
Outcomes	↓ slow-wave sleep latency ↑ percentage of slow-wave sleep time Improves sleep quality score similarly to oxazepam with fewer adverse events (16)(18)(59)
Class of evidence	C
Dosing & administration	300 mg (in NSF-3) per day at bedtime for two weeks to adults with insomnia
Outcomes	Improves total sleep time, sleep latency, number of nightly awakenings, & insomnia severity scores to a similar extent as zolpidem (38)
Class of evidence	C
Dosing & administration	500 mg (in Ze 91019) per day for four weeks to adults with primary insomnia
Outcomes	↓ sleep latency (34)
Class of evidence	C
Dosing & administration	800 mg dry root (containing 106 mg valeric acid) per day one hour before bed for eight weeks to adults with restless leg syndrome
Outcomes	↓ sleepiness and restless leg syndrome symptom severity in Px with higher Epworth sleepiness scale scores (11)
Class of evidence	C
Dosing & administration	500 mg (as Valeriana edulis containing 5.52 mg valtrate/isovaltrate) one hour before bed for two weeks to children aged 7-14 with intellectual deficits and sleep difficulty
Outcomes	↓ sleep latency & nocturnal wake times ↑ duration of sleep & sleep quality (21)
Class of evidence	C
Dosing & administration	405 mg (as Valdispert ® Forte) three times per day for one week to healthy elderly adults
Outcomes	↓ sleep stage 1 ↑ slow-wave sleep & density of K-complexes (52)
Class of evidence	C
Dosing & administration	460 mg (as Dormeasan® tincture) single dose to healthy adults with self-reported poor sleep
Outcomes	↑ sleep duration and time spent in deep sleep (15)
Class of evidence	C
Dosing & administration	100 mg (as Valeriana wallichii root combination with 80% didrovaltrate, 15% valerate, and 5% acelvaltrate) three times per day for two weeks to Px with insomnia previously using chronic benzodiazepines
Outcomes	↑ subjective sleep quality ↓ wake time after sleep onset May also increase sleep latency and alpha counts in slow-wave sleep (48)
Class of evidence	C

Obsessive-compulsive disorder
General outcomes from A-level evidence	No data currently available.
Dosing & administration	765 mg extract per day for eight weeks to adults
Outcomes	↓ obsessive-compulsive behavior (47)
Class of evidence	C

Premenstrual, menstrual or postmenopausal symptoms
General outcomes from A-level evidence	No data currently available.
Dosing & administration	530 mg valerian extract twice per day for the last seven days of the menstrual cycle for three consecutive cycles, or every day for two months to women with premenstrual syndrome
Outcomes	↓ severity of emotional, behavioral, & physical PMS symptoms (6)(30)
Class of evidence	B
Dosing & administration	765-1,060 mg in two or three divided doses, respectively, for two months to postmenopausal women
Outcomes	↓ severity of hot flashes within one month & frequency within two months (29)(41)
Class of evidence	B
Dosing & administration	255 mg three times per day for three days at the start of menstruation for two consecutive cycles to women with dysmenorrhea
Outcomes	↓ severity of menstrual pain & syncope score (41)
Class of evidence	B

Adverse effects

Reported side effects may include headaches, gastrointestinal distress, nausea, diarrhea, sweating, dizziness, drowsiness, or other psychological effects such as feelings of isolation, brain fog, depression, or irritability. Valerian does not appear to have an increased risk of any severe side effects compared to other pharmaceutical treatments or placebo groups. (8)(56) However, the likelihood of experiencing multiple adverse events per patient may be greater than placebo. (36)

Pharmacokinetics

Absorption

Valerenic acid max serum concentration occurs between 1-2 hours in healthy adults with large interindividual variability (range 0.5-4 hours) (2)(3)
Similar absorption speed occurs with single- or multiple-doses (3)

Distribution

Valerenic acid in serum measurable for at least five hours in healthy adults (2)

Metabolism

Low doses (125 mg three times per day) did not inhibit CYP2D6, CYP1A2, CYP3A4/5, or CYP2E1 in humans (25)
High doses (500 mg twice per day) mildly inhibited CYP2D6, but not likely in a clinically relevant fashion and had no effect on CYP3A4 in humans (17)

Excretion

Valerenic acid’s half-life was approximately one hour in healthy adults (2)(3)
Similar elimination rate occurs with single- or multiple-doses, but elimination rate may be positively correlated with body weight indicating that higher range doses may be required for individuals with increased body weight (3)