Valerenic acid

Other Names

(2E)-3-[(4S,7R,7aR)-2,4,5,6,7,7a-Hexadydro-3,7-dimethyl-1H-inden-4-yl]-2-methyl-2-propenoic acid(2E)-3-[(4S,7R,7aR)-2,4,5,6,7,7a-hexahydro-3,7-dimethyl-1H-inden-4-yl]-2-methyl-2-propenoic acid(2E)-3-[(4S,7R,7aR)-3,7-dimethyl-2,4,5,6,7,7a-hexahydro-1H-inden-4-yl]-2-methylacrylic acid(2E)-3-[(4S,7R,7aR)-3,7-dimethyl-2,4,5,6,7,7a-hexahydro-1H-inden-4-yl]-2-methylprop-2-enoic acid(E)-3-((4S,7R,7aR)-3,7-Dimethyl-2,4,5,6,7,7a-hexahydro-1H-inden-4-yl)-2-methylacrylic acid(E)-3-[(4S,7R,7aR)-3,7-dimethyl-2,4,5,6,7,7a-hexahydro-1H-inden-4-yl]-2-methylprop-2-enoic acid2-Propenoic acid, 3-(2,4,5,6,7,7a-hexahydro-3,7-dimethyl-1H-inden-4-yl)-2-methyl-, [4S-[4α(E),7β,7aα]]-2-Propenoic acid, 3-[(4S,7R,7aR)-2,4,5,6,7,7a-hexahydro-3,7-dimethyl-1H-inden-4-yl]-2-methyl-, (2E)-Indene-4-acrylic acid, 2,4,5,6,7,7a-hexahydro-α,3,7-trimethyl-ValerenicacidValerian AcidValeric acid

Synopsis

Valerenic Acid: A Comprehensive Reference

1. Identity and Chemical Characterization

Chemical Names and Classification

Valerenic acid (CAS 3569-10-6) is a monocarboxylic acid and a bicyclic sesquiterpenoid phytochemical. Its molecular formula is C₁₅H₂₂O₂. It is a sesquiterpenoid constituent of the essential oil of the valerian plant. Within systematic phytochemistry it belongs to the class of sesquiterpenic acids — carboxylic-acid-bearing terpenoids composed of three isoprene units.

Botanical Source

Valerenic acid is recognized as a key active compound in valerian preparations, which are derived primarily from the roots of Valeriana officinalis and contain a variety of chemicals with central nervous system activity, including sesquiterpenes, valepotriates, and alkaloids in unknown proportions. It is naturally occurring in valerian (Valeriana officinalis), with the highest concentration in the root.

Highest amounts of valerenic acids were detected in V. officinalis L., trace amounts in V. sitchensis, and none in the other species analyzed. Valeriana officinalis, a member of the Valerianaceae family, is a perennial plant native to Europe and Asia and naturalized in North America. It has a distinctive odor that many find unpleasant. Other names for the plant include setwall (English), Valerianae radix (Latin), Baldrianwurzel (German), and phu (Greek).

The genus Valeriana comprises over 250 species, with Valeriana officinalis being the most extensively studied and utilized for medicinal purposes. Different species or varieties of Valeriana yielded 11.65–0.15 mg/g of valerenic acid derivatives. The variation between individuals of one commercial cultivar of V. officinalis ranged from 12.34 to 3.01 mg/g of valerenic acid derivatives.

Naturally Occurring Derivatives

Valerenic acid may be at least partly responsible for valerian's sedative effects, in addition to the other valerenic acids hydroxyvalerenic acid and acetoxyvalerenic acid. Between this compound and its two naturally occurring derivatives (acetoxyvalerenic acid and hydroxyvalerenic acid), valerenic acid occurs at a significantly higher concentration.

Biosynthesis

These sesquiterpenes retain an isobutenyl side chain whose biosynthetic origin has long been considered enigmatic. Using recently developed metabolomic and transcriptomic resources, researchers identified seven V. officinalis terpene synthase genes (VoTPSs), two functionally characterized as monoterpene synthases and three that preferred farnesyl diphosphate, the substrate for sesquiterpene synthases. VoTPS1 catalyzes the conversion of farnesyl diphosphate to valerena-1,10-diene, which is an early precursor in the sesquiterpene acid pathway leading to valerenic acid.

Common Preparations and Standardization

Dried roots are prepared as teas or tinctures, and dried plant materials and extracts are put into capsules or incorporated into tablets. The chemical composition of these preparations, including the proportion of valerenic acid, varies depending on the specific valerian species used, the extraction method (aqueous versus ethanolic), and the presence of other herbs or agents such as hops.

Valerian supplements are often standardized to contain a particular amount of valerenic acid by weight (often 0.8%). Valerian is available as whole powdered root and an aqueous or ethanolic extract standardized to 0.8% valerenic acids. The most commonly used valerian preparations include aqueous and hydroalcoholic extracts, such as tinctures, intended for oral administration. Ammoniated valerian tinctures were used medicinally in the English-speaking world since at least the beginning of the seventeenth century.

2. Traditional and Historical Use

Ancient Greece and Rome

Valerian has been used in traditional herbal medicine since at least the times of ancient Greece and Rome. Valerian root is native to Europe and western Asia, where it's been historically incorporated into daily routines for wellness and vitality by emperors, saints, and even the "father of medicine," Hippocrates. Classical physicians of antiquity employed the root primarily as a carminative (to ease gastrointestinal complaints), as an emmenagogue, and to ease tremors and nausea. The name 'valerian' is derived from the Latin verb 'valere', meaning 'to be strong' or 'to be healthy', which reflects the plant's historical reputation as a powerful medicinal herb.

Medieval European and Monastic Traditions

Benedictine infirmarers catalogued valerian — often under the Anglo-Saxon name setwall — as a chief ingredient in tonics for "night restlessness." Hildegard of Bingen praised the root for easing "stormy thoughts," reflecting a shift toward spiritual well-being alongside physical relief. Scribes standardised recipes: one typical sleep draft combined grated valerian, warm ale, and honey — an early forerunner of the modern valerian-hops bedtime preparation.

Community records from the 14th–16th centuries cite valerian for headaches, trembling, and convulsions, suggesting broad acceptance well before pharmacopoeias codified dosage.

Early Modern and 19th-Century Western Medicine

Industrial-scale distilleries refined alcohol extraction. Fluid extracts, ammoniated tinctures, and concentrated "compound drops" appeared in medical compendia on both sides of the Atlantic. Civil-War-era formularies documented doses ranging from ½ to 4 fluidrachms, taken up to four times daily for hysteria, restlessness, and sleeplessness.

Use Across Cultures

In traditional herbal medicine, valerian root has been used for centuries across various cultures, including ancient Greek, Roman, and Chinese medical practices, to treat a wide range of conditions from sleep disorders to anxiety and nervous system imbalances. The roots of Nardostachys jatamansi have been used as a substitute for valerian in Iranian traditions. In alternative medicine, extracts from valerian have served to treat various ailments for over 2,000 years.

3. Key Constituents of Valeriana officinalis and Their Roles

There is no scientific agreement as to the active constituents of valerian, and its activity may result from interactions among multiple constituents. Nonetheless, researchers have identified several pharmacologically relevant classes of compounds. Valerian's effects on the central nervous system have been attributed to many of its active compounds: valepotriates, baldrinals, valerenic acid, valerenal, and valeranone, and other constituents in the essential oils.

Valerenic acid and derivatives: Valerenic acid and acetoxyvalerenic acid are bicyclic sesquiterpenoid phytochemicals present in various plant species of Valeriana. These phytoconstituents have been found to produce various pharmacological activities including sedative, antidepressant, anxiolytic, with roles in brain-derived neurotrophic factor (BDNF) and gastrointestinal motility.
Valepotriates: Valepotriates, a group of unstable iridoids, have been shown to possess sedative activity, as have some valepotriate degradation products. The constituent valepotriate has been shown to increase norepinephrine and dopamine levels in rodents.
Flavonoids (6-methylapigenin, linarin, hesperidin): Valerenol, 6-methylapigenin, and linarin — other components of valerian extract — also demonstrate activity at the GABA channel, though these results were obtained from in vitro experiments and confirmation from in vivo studies is still lacking.
Pinoresinol (lignan): Valerenic acid and pinoresinol, key constituents of the valerian extract Ze 911, were identified as positive allosteric modulators (PAMs) of adenosine A1 receptors.
Valeranone: Valeranone isolated from the essential oil of valerian root revealed sedative and muscle relaxant activity. In addition, valerenic acid and valeranone were found to prolong barbiturate-induced sleeping time.

4. Mechanisms of Action

4.1 GABA_A Receptor Positive Allosteric Modulation

The most extensively investigated mechanism of valerenic acid concerns the gamma-aminobutyric acid type A (GABA_A) receptor system. Valerenic acid acts as a subtype-selective GABA_A receptor positive allosteric modulator via a binding site in the transmembrane domain at the β+α− interface.

Researchers reported the stimulation of chloride currents through GABA_A receptors by valerenic acid. To analyse the molecular basis of action, GABA_A receptors with 13 different subunit compositions were expressed in Xenopus oocytes and currents measured using the two-microelectrode voltage-clamp technique. Only channels incorporating β2 or β3 subunits were stimulated by valerenic acid; replacing β2/3 by β1 drastically reduced the sensitivity of the resulting GABA_A channels.

Valerenic acid exhibited a positive allosteric modulatory effect at concentrations ≥1 μM by enhancing GABA-induced chloride currents (I_GABA). The effect was dose-dependent, and the averaged concentration–response curve showed that maximum stimulation of α1β2γ2S receptors occurred at approximately 100 μM. Importantly, only valerenic acid (but neither acetoxyvalerenic acid nor hydroxyvalerenic acid) acts as a positive allosteric modulator of GABA_A receptors.

Valerenic acid was identified as a subunit-specific allosteric modulator of GABA_A receptors, and research investigated the relation between modulation of GABA_A receptors by valerian extracts of different polarity and the content of sesquiterpenic acids (valerenic acid, acetoxyvalerenic acid).

In addition to direct receptor modulation, valerenic acid 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. Valerian extracts have been demonstrated to exert a variety of effects on GABAergic neurons in laboratory animals, including increased release of GABA, decreased GABA reuptake, and decreased GABA degradation.

4.2 Adenosine A1 Receptor Modulation

The sleep-promoting effects of valerian are also associated with the adenosine A1 receptor (A1AR), a key regulator of sleep through neural activity inhibition. Adenosine, a neuromodulator that accumulates during wakefulness, activates A1ARs to facilitate sleep transitions. Valerenic acid and pinoresinol were identified as positive allosteric modulators (PAMs) of A1ARs. Valerenic acid exhibited strong PAM activity, with high cooperativity (αβ = 4.79 for adenosine) and intrinsic efficacy (τB = 5.98 for adenosine).

4.3 Serotonin (5-HT5a) Receptor Partial Agonism

Valerian extracts showed high binding affinity for the 5-HT5a receptor. Binding of valerian extracts to the 5-HT5a receptor had not been previously reported, and thus may represent a new mechanism of action. Valerenic acid is the primary active compound responsible. The 5-HT5a receptor is distributed in the suprachiasmatic nucleus of the brain, which is implicated in the sleep–wake cycle, lending biological plausibility to this mechanism in the context of sleep regulation. This activity has been characterized in vitro only; clinical significance has not been established.

4.4 Glutamate Receptor Interactions

Although GABA neurotransmission has been suggested as a mechanism for Valeriana officinalis effects, CNS depression can also be evoked by inhibition of ionotropic and metabotropic glutamate receptors. In vitro research examined whether aqueous valerian extract interacted with glutamatergic receptors. Valerenic acid interacted selectively with Group I metabotropic glutamate receptors. The selective interactions of valerian extract and valerenic acid with Group I and Group II mGluR may represent an alternative explanation for the anxiolytic properties of this plant.

4.5 Serotonin and Norepinephrine Turnover Modulation

Valerenic acid administration at 0.5 mg/kg can mitigate the physical and psychological stress response by decreasing the turnover of serotonin (5-HT) to 5-hydroxyindoleacetic acid and norepinephrine to 3-methoxy-4-hydroxyphenylethyleneglycol sulfate in the hippocampus and amygdala. This was demonstrated in animal models and has not yet been assessed in human subjects.

4.6 Spasmolytic and Muscle Relaxant Effects

Valerenic acid exhibits spasmolytic and muscle relaxant properties, further supporting its use in managing nervous tension and muscle spasms. Valerenic acid and the esters of eugenyl and isoeugenyl are spasmolytic.

4.7 Blood–Brain Barrier Permeability

A key pharmacokinetic consideration for the central nervous system activity of valerenic acid concerns its ability to cross the blood–brain barrier. To interact with GABA_A receptors in the brain, valerenic acid and its derivatives have to cross the blood–brain barrier (BBB). Transport of these compounds was compared with the permeability of the GABA_A modulator diazepam, which penetrates into the CNS transcellularly by passive diffusion. Results indicated clearly that all three acids permeated significantly slower than diazepam. Valerenic acid (1.06 ± 0.29 μm/min, factor 0.03 related to diazepam) was the slowest to permeate, suggesting it likely requires an active transport mechanism rather than simple passive diffusion across the BBB.

5. Scientific Evidence by Area of Use

5.1 Sleep Disorders and Insomnia

Background and human evidence: Evidence from clinical studies of the efficacy of valerian in treating sleep disorders such as insomnia is inconclusive. Constituents of valerian have been shown to have sedative effects in animals, but there is no scientific agreement on valerian's mechanisms of action.

Systematic reviews and meta-analyses: Multiple systematic reviews have been conducted, with overall findings that are mixed but cautiously positive for subjective sleep outcomes.

A systematic review published in 2000, which analyzed 9 randomized clinical trials, found contradictory results and significant inconsistency in terms of patients, experimental design, and methodology among the trials.
An extensive literature search identified 16 eligible studies examining a total of 1,093 patients. Most studies had significant methodologic problems, and the valerian doses, preparations, and length of treatment varied considerably. A dichotomous outcome of sleep quality (improved or not) was reported by 6 studies and showed a statistically significant benefit (relative risk of improved sleep = 1.8, 95% CI 1.2–2.9), but there was evidence of publication bias in this summary measure.
One review concluded that the evidence suggested that valerian would be effective for a subjective improvement of insomnia, although its effectiveness was not demonstrated with quantitative or objective measurements.
A meta-analysis of 18 randomized placebo-controlled trials, published in 2010, concluded that valerian's effectiveness had not been demonstrated with quantitative or objective measures, although valerian could improve subjective sleep quality.
Of the studies investigating responses to single doses, three reported positive results whilst three showed no difference between valerian and placebo; the latter three were all conducted in healthy volunteers without documented sleep problems. Few adverse events of valerian were reported, and those that were reported were mild and similar to those experienced with placebo. The evidence for valerian as a treatment for insomnia was described as promising but not conclusive.

Dosage specifics in trials: In the trials reviewed, doses ranged from 60 to 1,215 mg/day. Only 2 of the 16 studies specifically stated that the herb was standardized to a specific amount of valerenic acid, which is believed to be one of the most biologically active components of the herb.

A recent RCT (2023): Among 72 men and women (average age 34) with mild-to-moderate sleep difficulty, 200 mg of valerian root powder extract standardized to 2% valerenic acid (4 mg valerenic acid per nightly dose) taken one hour before bedtime for two months significantly decreased sleep latency by 36 minutes and increased total sleep time by 11 minutes compared to placebo. However, sleep quality improvement was only slight versus placebo. The study was funded by the extract manufacturer.

Evidence strength: Overall, the evidence that valerenic acid specifically — as opposed to whole valerian preparations — improves sleep in humans is indirect and preliminary. Human trials have used whole valerian extracts rather than isolated valerenic acid. Methodological heterogeneity, publication bias, lack of standardization across studies, and the wide variation in preparations make definitive conclusions difficult. The evidence base supports a possible modest benefit on subjective sleep quality, particularly with repeated use, but does not robustly support improvements in objective measures such as polysomnography.

5.2 Anxiety

Animal evidence: Valerian extracts allosterically modulate GABA_A receptors and induce anxiolytic activity. This activity is closely related to valerenic acid. The determining compound for the observed anxiolytic effect of the valerian extract is its content of valerenic acid, as demonstrated in rodent studies using the elevated plus maze. Valerenic acid treatment effectively reduced multiple anxiety-related behaviors measured in the elevated plus maze (EPM). At a dose of 12 mg/kg, the anxiolytic effect of valerenic acid was just as robust as that of diazepam — though this was in a female mouse model.

Human evidence: The anxiolytic properties of valerian have been demonstrated in animals; however, there are no sufficient studies in humans. Consequently, the therapeutic properties of Valeriana officinalis for anxiety have yet to be conclusively demonstrated. A 2020 systematic review found overall positive results regarding the effect of valerian for anxiety. Low- and moderate-quality studies reported improvements in stress reactivity in healthy subjects (600 mg/day for 1 week of standardized extract) and lower anxiety in HIV-positive patients receiving efavirenz (530 mg/day for 4 weeks of valerian root/rhizome).

Evidence strength: The human clinical evidence for anxiety is sparse, methodologically weak, and largely indirect (i.e., based on whole valerian extract studies rather than isolated valerenic acid). Preclinical animal data are more robust and mechanistically plausible. This area requires well-designed clinical trials before any definitive conclusions can be drawn.

5.3 Stress and Neuroendocrine Effects

In an animal experiment, mice received valerenic acid at a dose of 0.5 mg/kg orally once daily for 3 weeks before being subjected to physical or psychological stress for 3 days, followed by estimation of levels of monoamines and their metabolites in the hippocampus-amygdala region. Administration of valerenic acid at 0.5 mg/kg was found to mitigate the physical and psychological stress response by decreasing the turnover of serotonin to its metabolite and norepinephrine to its metabolite in the hippocampus and amygdala. These findings are preclinical (rodent) only and have not been replicated in human trials.

5.4 Anti-inflammatory Activity

Valerenic acid has anti-inflammatory benefit via inhibiting the transcription of NF-κB, one essential transcription factor controlling the expression of numerous inflammation-related genes. This mechanism has been characterized in vitro and in cell-based models. No human clinical evidence has been published specifically for valerenic acid's anti-inflammatory activity.

5.5 Anticonvulsant Activity

Valerenic acid and Valeriana officinalis extracts delayed the onset of pentylenetetrazole (PTZ)-induced seizures in adult zebrafish. Valeriana also demonstrated anticonvulsant activity and even increased the efficacy of phenytoin and clonazepam, used to treat epilepsy. There are no relevant clinical studies or case reports, and the clinical relevance of these findings is unclear.

5.6 Antispasmodic and Gastrointestinal Effects

Valerian also demonstrated antispasmodic and hypotensive effects via potassium channel activation, which may be useful for patients with gastrointestinal and cardiovascular disorders — though these results are from preclinical models. Based on review of published data, in low dosages valerian acts thymoleptic–sedatively; in higher dosages, anticonvulsive–spasmolytic effects will be additionally observed, and these different effects can probably be attributed to the different active components found in valerian.

6. Body Systems and Health Areas

Valerenic acid and its parent plant extract have been associated with the following body systems in published research:

Central nervous system (CNS): Sedative, hypnotic, anxiolytic, and anticonvulsant activities via GABA_A, adenosine A1, serotonin 5-HT5a, and metabotropic glutamate receptors.
Neuroendocrine system: Modulation of corticosterone levels and monoamine turnover (serotonin, norepinephrine) in hippocampus and amygdala in animal stress models.
Musculoskeletal/smooth muscle: Valerenic acid exhibits spasmolytic and muscle relaxant properties.
Gastrointestinal system: Valerenic acid and acetoxyvalerenic acid have roles in gastrointestinal motility.
Cardiovascular system: Preclinical evidence of antihypertensive and antispasmodic effects via potassium channel activation, though human data are lacking.
Neurological (Alzheimer's disease): Valerenic acid could affect the condition of Alzheimer's disease, as assumed through an increase in BDNF expression. This remains a hypothesis supported only by preclinical and mechanistic data.

7. Dosage Forms and Reported Dosages

Forms

Valerian is available as whole powdered root and as an aqueous or ethanolic extract standardized to 0.8% valerenic acids. Capsules, tablets, tinctures, and herbal teas are all commercially available delivery formats. High-quality products have an unpleasant odor, which confirms potency.

Dosages Reported in Clinical Studies and Monographs

Standardized extract (sleep): For adults, clinical studies have used 300–900 mg standardized extract of 0.8% valerenic acid, taken 30–120 minutes before bedtime for 2–4 weeks to assess effectiveness.
Standardized extract (anxiety, daytime): Valerian is also considered useful as an anxiolytic when administered during the daytime at doses up to 250 mg three times per day.
Herbal tea: As a tea prepared from 2–3 g of dried root steeped for 10–15 minutes, taken 30–120 minutes before bedtime.
EMA monograph range: Clinical monographs from the European Medicines Agency cite 400–600 mg of standardized extract, or 0.3–3 g of powdered root, up to three times daily for adults.
Range across reviewed trials: In reviewed placebo-controlled trials, doses ranged from 60 to 1,215 mg/day.
Specific RCT dosage: A 2023 study used 200 mg of valerian root powder extract standardized to 2% valerenic acid (4 mg valerenic acid per nightly dose) taken one hour before bedtime for two months.
NCCIH-reported safety range: The U.S. National Center for Complementary and Integrative Health reports that 300–600 mg daily has been used with apparent safety for six weeks.

Standardization Note

Only 2 of 16 studies in a major systematic review specifically stated that the herb was standardized to a specific amount of valerenic acid, which is believed to be one of the most biologically active components of the herb. Although there is clearly not enough evidence to define the optimum amount of valerenic acid that should be present in a given dose, the use of standardized products in clinical trials might improve the reproducibility and clinical relevance of results.

Pharmacokinetics

Valerenic acid is used as a marker for quantitative analysis of valerian products with evidence of pharmacological activity relevant to the hypnotic effects of valerian. One pharmacokinetic study determined the pharmacokinetics of valerenic acid in elderly women after receiving a single nightly valerian dose and after 2 weeks of dosing. There was not a statistically significant difference in the average peak concentration, time to maximum concentration, area under the time curve, elimination half-life, and oral clearance between single and multiple dosing. There was considerable inter- and intra-subject variability in the pharmacokinetic parameters. Large variability in the pharmacokinetics of valerenic acid may contribute to the inconsistencies in the effect of valerian as a sleep aid. The elimination half-life of valerenic acid, a major component, is about 1.1 hours.

8. Safety Considerations and Drug Interactions

General Tolerability

Although few adverse events have been reported, long-term safety data are not available. Few adverse events of valerian were reported in clinical trials, and those that were reported were mild and similar to those experienced with placebo.

Occasionally reported adverse effects include: headache, diarrhea and other GI complaints, daytime sedation/dullness, impaired alertness, depression, irritability, dizziness, sweating, heart palpitations, bitter taste, and benzodiazepine-like withdrawal symptoms with supplement cessation.

Hepatotoxicity

Valerian has been implicated in a small number of cases of clinically apparent liver injury, but usually in combination with other botanicals such as skullcap or black cohosh. In view of its wide-scale use, valerian has to be considered a very rare cause of hepatic injury. In published cases, the latency to onset ranged from 3 to 12 weeks and the pattern of enzyme elevations was usually hepatocellular or mixed hepatocellular-cholestatic. The liver injury was usually mild-to-moderate in severity with recovery within 2 to 4 months of stopping. The likelihood score is C (probable rare cause of clinically apparent liver injury). The cause of the liver injury associated with valerian use is not known. Valerian extracts contain multiple ingredients, but none have been shown to be specifically hepatotoxic.

Pregnancy

Because of uncertainty in composition and the potential for toxicity in the fetus and hepatotoxicity in the mother, valerian use is discouraged during pregnancy. Pregnant or nursing women should avoid valerian, as it has not adequately been studied and preliminary animal models indicate some adverse effects on fetal brain development.

Driving and Psychomotor Performance

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.

Withdrawal

Chronic use might lead to withdrawal symptoms upon discontinuation, such as anxiety and insomnia. This is consistent with the compound's GABAergic mechanism, which overlaps with the pharmacology of benzodiazepines.

Drug–Drug Interactions

CNS depressants: Valerian can enhance the sedative effects of alcohol and drugs that depress the central nervous system. It can also have additive sedative effects when used with substances like alprazolam.

Benzodiazepines: An animal study and case report suggest valerian may have synergistic effects with benzodiazepines, though clinical relevance has yet to be determined.

CYP450 enzyme interactions: Valerian may inhibit CYP2D6 and CYP3A4, although other studies in vivo and in humans suggest CYP-mediated interactions with valerian are unlikely. A specific human pharmacokinetic study found that multiple night-time doses of valerian had minimal effects on CYP3A4 activity and no effect on CYP2D6 activity in healthy volunteers. Oral nightly administration of 1 gram of Valeriana extract (at a concentration of 1.1% valerenic acids) for two weeks led to a 20% increase in the Cmax of 2 mg alprazolam via CYP3A4 inhibition (p < 0.05) without affecting other metabolism parameters, and it was therefore concluded that valerian had no significant effect on CYP3A4 activity.

P-glycoprotein: Valerian may inhibit P-glycoprotein transporters and affect the intracellular concentration of substrate drugs, although another study suggests an in vivo P-gp interaction is less probable.

Haloperidol: An animal study suggests valerian may have an additive effect with haloperidol, causing hepatic damage. Clinical relevance has not been established.

Product quality and variability: As an unregulated product, the concentration, contents, and potential contaminants in valerian preparations cannot be easily determined. Hydroxyvalerenic acid, acetoxyvalerenic acid, and valerenic acid content showed wide variation between samples compared to the concentrations noted on product labels. Valerian extracts from commercial products also exhibited a marked capacity to inhibit cytochrome P450 3A4-mediated metabolism and P-glycoprotein transport based upon in vitro assays. There is wide variation between commercially available samples of valerian root.

References

Health Conditions

Health conditions that Valerenic acid may help support.

Sleep Maintenance (Staying Asleep)Scientific
Valerenic acid is the primary bioactive marker compound in Valeriana officinalis root, responsible for its sleep-maintenance effects via partial GABA-A receptor allosteric modulation (beta-subunit) and 5-HT5A receptor partial agonism. It is the compound measured for valerian extract standardization. Multiple meta-analyses of valerian RCTs show significantly improved subjective sleep quality and sleep efficiency relevant to maintenance insomnia.

Body Systems

Body systems that Valerenic acid may help support.

No body systems available.