Valerian

Metadata

Approved Indications

Commission E (Germany)

• Approved: Restlessness, sleep disorders based on nervous conditions

ESCOP

• Approved: Tenseness, restlessness, irritability with difficulty in falling asleep

EMA/HMPC (2016 revision)

• Well-established use: Relief of mild nervous tension and sleep disorders (specific dry ethanol extracts with demonstrated clinical evidence)
• Traditional use: Relief of mild symptoms of mental stress and to aid sleep (other preparations including teas, tinctures, comminuted herbal substance, expressed juice, essential oil)

Agreement/Disagreement

All three bodies agree on the core dual indication: nervous tension/restlessness AND sleep disorders. The EMA is most precise in distinguishing which preparation types qualify for which level of evidence. Commission E and ESCOP do not differentiate as granularly between extract types.

Conditions Treated

Primary (Moderate Evidence)

• Sleep disorders / Insomnia — Particularly difficulty falling asleep (sleep onset latency) and subjective sleep quality
• Mild nervous tension / Restlessness — Both as standalone and as contributor to sleep difficulties

Secondary (Emerging Evidence)

• Anxiety symptoms — 6 of 7 studies examining anxiolytic potential showed positive outcomes; 600 mg/day reduced stress reactivity in healthy adults
• Menopausal sleep disturbance — Some evidence for benefit in perimenopausal women

Commonly Used In Combination

• Valerian + Hops — The most widely used combination; EMA has a separate monograph for this combination
• Valerian + Lemon Balm — Traditional combination
• Valerian + Passionflower — Traditional combination

Mechanism of Action

Primary Mechanism: GABA-A Receptor Modulation

• Valerenic acid is a positive allosteric modulator of GABA-A receptors
• A specific binding site on GABA-A receptors has been identified with nanomolar affinity for valerenic acid and valerenol
• The binding involves the beta2 and beta3 subunits (point mutation N265M strongly reduces the drug response)
• Both valerenic acid and valerenol enhance the response to GABA at multiple types of recombinant GABA-A receptors
• This mechanism is analogous to (but distinct from) benzodiazepine binding

Secondary Mechanisms

1. GABA reuptake inhibition and metabolism: Valerian extract components may block GABA reuptake and inhibit GABA metabolism (via GABA transaminase inhibition), increasing synaptic GABA availability
2. Adenosine A1 receptor modulation: Valerenic acid and pinoresinol have been identified as positive allosteric modulators (PAMs) of adenosine A1 receptors (A1ARs). Adenosine accumulates during wakefulness and promotes sleep via A1AR activation — this is a recently discovered mechanism that helps explain valerian’s sleep-promoting effects [Source: PubMed 40509231]
3. 5-HT1A receptor affinity: Valerian shows some affinity for serotonin 5-HT1A receptors, which play a role in both sleep induction and anxiety
4. Lower affinity at other receptors: GABA-A benzodiazepine site, mu-opioid receptors (lower affinity than primary targets)

Why the Delayed Onset?

Unlike benzodiazepines, valerian does not produce immediate sedation. The 2-4 week onset period may reflect:

• Gradual accumulation of active metabolites
• Receptor-level adaptations (similar to SSRI onset delay)
• Indirect mechanisms (e.g., GABA transaminase inhibition leading to gradual GABA accumulation)

Clinical Evidence Summary

Sleep Disorders

Systematic Reviews and Meta-Analyses

• Shinjyo et al. (2020) — PMC7585905: Systematic review and meta-analysis of 23 studies addressing valerian for sleep problems. 13 of 23 studies found valerian effective as a sleep aid. Effects were most consistent for subjective sleep quality rather than objective polysomnographic measures.
• Bent et al. (2006): Meta-analysis of 16 RCTs found valerian improved subjective sleep quality but not sleep latency or total sleep time by objective measures.
• Fernandez-San-Martin et al. (2010): Meta-analysis found a statistically significant benefit for subjective sleep quality (OR 1.37, 95% CI 1.05-1.78).

Key Findings Across Trials

• Subjective sleep quality: Most consistently improved outcome
• Sleep onset latency: Some reduction reported, but inconsistent across trials
• Sleep architecture: Some studies report decreased time in Stages 1-2, increased REM and slow-wave sleep
• Effect size: Generally modest — clinically meaningful for some patients but not comparable to benzodiazepines or Z-drugs
• Onset: Benefits typically emerge after 2-4 weeks of regular use, not after single doses

Anxiety

• Andreatini et al. (2002): 36 patients with GAD; valerian 81.3 mg/day valerenic acid vs. diazepam 6.5 mg/day vs. placebo for 4 weeks. Valerian showed significant reduction in psychic cluster of HAMA (Hamilton Anxiety Rating Scale).
• In a stress-reactivity study, valerian standardized extract 600 mg/day for 1 week reduced psychological and physiological stress responses in healthy adults.
• Overall: 6 of 7 studies examining anxiolytic potential showed positive outcomes, but these studies are generally small.

European vs. US/Anglophone Consensus

Safety Profile

Contraindications

• Known hypersensitivity to valerian preparations
• No absolute contraindications in current monographs
• EMA/HMPC: Not recommended for children under 12 years due to lack of data

Drug Interactions

• Generally minimal: Valerian has a favorable drug interaction profile
• Theoretical additive sedation: With benzodiazepines, Z-drugs, barbiturates, alcohol, and other CNS depressants. Clinical significance is uncertain; no serious cases well-documented.
• CYP450: In vitro studies suggest minor CYP3A4 inhibition, but clinical pharmacokinetic studies have not found clinically relevant interactions
• No known significant pharmacokinetic interactions in clinical use

Side Effects

• Reported: Nausea, abdominal cramps (infrequent)
• Headache, dizziness: Occasionally reported
• Morning drowsiness: Uncommon at recommended doses but possible
• Paradoxical stimulation: Rare reports of insomnia or restlessness
• Overall: Side effects in clinical trials have been comparable to placebo. No severe adverse events in subjects aged 7-80 years across reviewed trials.

Pregnancy and Lactation

• Pregnancy: Insufficient human data. Animal studies have not shown teratogenicity. Valepotriates (iridoids) showed mutagenicity in Ames test in vitro, but these are present in very low concentrations in finished products and are unstable. EMA/HMPC: Not recommended during pregnancy due to lack of adequate data.
• Lactation: No data available. EMA/HMPC: Not recommended during lactation.

Special Safety Notes

• No habituation or withdrawal: Unlike benzodiazepines, valerian does not appear to cause dependence, tolerance, or rebound insomnia
• Elderly patients: Well-tolerated in elderly populations
• Driving/machinery: At recommended doses, no significant impairment of cognitive or psychomotor function demonstrated in clinical studies (in contrast to benzodiazepines)

Clinical Dosage

For Sleep Disorders

• Dried ethanol extract: 400-600 mg taken 30-60 minutes before bedtime
• Some protocols: 300-600 mg 2-3 times daily for daytime anxiolysis, with a larger evening dose for sleep
• Crude drug (tea): 2-3 g of dried root, 1-2 times daily

EMA/HMPC Recommended Doses

• Well-established use (dry ethanol extract, DER 3-7.4:1):
  • Single dose: 600 mg, 0.5-1 hour before bedtime
  • If needed: additional 600 mg dose earlier in the evening
• Traditional use (various preparations):
  • Comminuted herb for tea: 1-3 g, 1-4 times daily
  • Tincture (1:5, ethanol 70%): 1-3 mL, 1-3 times daily
  • Expressed juice: 15 mL, 1-4 times daily

Duration

• Minimum 2-4 weeks for assessment of benefit
• Can be used for extended periods; no maximum duration specified in monographs
• If symptoms persist after 2 weeks (traditional use) or 4 weeks (well-established use), consult a physician

Sources

• EMA/HMPC Final Assessment Report on Valeriana officinalis L., radix (February 2016, EMA/HMPC/150846/2015)
• EMA/HMPC Final European Union Herbal Monograph on Valeriana officinalis L., radix
• EMA Herbal Summary for the Public: Valerian Root (April 2016)
• ESCOP Monograph: Valerianae radix
• Commission E Monograph: Valerian root
• Shinjyo N et al. Valerian Root in Treating Sleep Problems and Associated Disorders — A Systematic Review and Meta-Analysis. J Evid Based Integr Med. 2020;25. PMC7585905
• Andreatini R et al. Effect of valerenic acid on HAMA. Phytother Res. 2002
• Valerenic acid and GABA-A receptors: PubMed 17585957
• Valerenic acid and adenosine A1 receptors: PubMed 40509231

Connections

• Combination with hops: see Hops
• Compare with other sedative herbs: Passionflower, Lemon Balm
• GABA mechanism shared with kava: see Kava
• The valerian + hops combination has its own EMA monograph — see Hops
• For stronger anxiolytic evidence, see Lavender (Silexan) and Kava