Valerian and Midazolam Nasal Spray: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Valerian
No brand names on recordMidazolam Nasal Spray
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Additive CNS depression or reduced effectiveness of the benzodiazepine
Interaction Deep Dive
In one case report, valerian and passionflower used concurrently with lorazepam resulted in additive CNS depressive effects1. Valerian extracts have shown affinity for central and peripheral benzodiazepine receptors as well as barbiturate and GABA-A receptors 72. Valerian extract displaced the benzodiazepine fluorodiazepam from the receptor 2. The clinical effect may be additive or reduced effectiveness of benzodiazepines depending on the nature of the binding. It is recommended that patients be asked about herbal product use during intake of personal history 1. Monitoring for altered effectiveness of the benzodiazepine should be considered with concurrent use.
Why it happens (mechanism)
Additive effects on the benzodiazepine receptor, possible displacement of the benzodiazepine from its receptor
Literature reports
3 reports — tap to read
a) A case report describes a potentiated CNS depressive effect in a 40-year-old man following concomitant use of lorazepam with valerian and passionflower. The patient, who had been treating with lorazepam 2 mg/day for 2 months with no adverse effects, self-administered an infusion of valerian subterranean parts (estimated dose, 300 mg). 2 hours before going to bed for 2 consecutive days. On day 3, he instead ingested 3 oral tablets of dry extract from valerian rhizomes (300 mg/tablet) plus roots and aerial parts of passionflower (380 mg/tablet) at 1 hour intervals before bedtime. Nervousness and mild shaking dissipated after going to bed followed by extreme somnolence. After taking the same dose of the valerian root/passionflower product on day 4, he experienced more severe symptoms including substantial hand shaking, dizziness, and palpitations before bedtime followed by profound somnolence. Upon presentation after 32 hours of experiencing these CNS symptoms, he was observed to have nervousness while speaking and demonstrated anxious behavior without shaking. He had a history of general anxiety disorders and dream disorders. His family history was negative for essential tremor and there were no metabolic, renal, or hepatic disorders, high blood pressure, or drug allergies. Because a drug interaction was suspected, the patient was continued on lorazepam but withdrawn from valerian and passionflower and symptoms resolved. It is postulated that the valerian root and passionflower have additive or synergistic effects on the inhibitory activity of benzodiazepines binding to the gamma-aminobutyric acid (GABA) receptors 1.
b) The amount of the amino acid gamma-aminobutyric acid (GABA) in aqueous and hydroalcoholic extracts of valerian is sufficient to explain its (3H)muscimol displacement effect at GABA receptor sites during in vitro tests. The GABA content of the aqueous extract is also sufficient to cause release of (3H)GABA in synaptosomes through homologous exchange, accounting for this in vitro effect as well. Since GABA cannot effectively cross the blood-brain barrier when given in the amounts available in the extracts, it appears unlikely that the influence of valerian on GABA neurotransmission contributes to central nervous system sedation 34. Valeriana officinalis extracts significantly displaced fluorodiazepam from benzodiazepine receptors, and a fraction containing sesquiterpene alcohols and ketones showed 80% inhibition at concentrations of 1.5 x 10(-3) moles/liter. A fraction containing valepotriates also produced significant displacement. Statistical values were not provided 2. In local cerebral glucose utilization, valerian extracts reacted in a way analogous to that observed with the GABA agonist, progabide. Therefore, the interaction at the GABA-A-benzodiazepine receptor complex may differ from that of diazepam 5. Valerian extracts inhibit (3H)flunitrazepam binding to benzodiazepine receptors; however, the amount of benzodiazepine-like molecules present in the plants is below pharmacologically-active doses 6.
c) Hydroalcoholic and aqueous extracts of Valeriana officinalis roots showed affinity for the GABA-A receptors with lesser affinity for the peripheral benzodiazepine receptors in vitro. Inhibition of 3H-PK 11195 binding to benzodiazepine and GABA-A receptors was measured and expressed as IC50 values. IC50 values for the hydroalcoholic extract were 0.04 milligrams/milliliter (mg/ml) and 3.9 x 10(-3) mg/ml for peripheral and central benzodiazepine receptors and GABA-A receptors, respectively. The lipophilic fraction of the hydroalcoholic extract showed affinity for the barbiturate receptor and to some extent for peripheral benzodiazepine receptors. The aqueous total extract A, the aqueous fraction B derived from the hydroalcoholic extracts, as well as the hydroalcoholic extracts demonstrated affinity for GABA-A receptors. This interaction at the receptor level could represent the molecular basis for the sedative effect noted with Valeriana officinalis 7.
Common questions
Can I take Valerian and Midazolam Nasal Spray together?
Additive CNS depression or reduced effectiveness of the benzodiazepine Always confirm with your pharmacist or prescriber before making any change.
How serious is the Valerian and Midazolam Nasal Spray interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Valerian or Midazolam Nasal Spray need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there anything you'd monitor while I'm on both?
References (7)
- Carrasco MC, Vallejo JR, Pardo-de-Santayana M, et al: Interactions of Valeriana officinalis L. and Passiflora incarnata L. in a patient treated with lorazepam. Phytother Res 2009; 23(12):1795-1796.
- Holzl J & Godau P: Receptor binding studies with Valeriana officinalis on the benzodiazepine receptor. Planta Med 1989; 55:642.
- Cavadas C, Araujo I, Cotrim MD, et al: In vitro study on the interaction of Valeriana officinalis L. extracts and their amino acids on GABA-A receptor in rat brain. Arzneim-Forsch/Drug Res 1995; 45(7):753-755.
- Santos MS, Ferreira F, Faro C, et al: The amount of GABA present in aqueous extracts of valerian is sufficient to account for (3H)GABA release in synaptosomes. Planta Med 1994; 60(5):475-476.
- Kriegelstein VJ & Grusla D: Central dampfende Ihaltsstoffe im Baldrian: Valepotriate, Valeransaure, Valeranon und atherisches Ol sind jedoch umwirksam. Deutsche Apothekar Zeitung 1988; 40:2041-2046.
- Medina JH, Pena C, deStein ML, et al: Benzodiazepine-like molecules, as well as other ligands for the brain benzodiazepine receptors are relatively common constituents of plants. Biochem Biophys Res Comm 1989; 165:547-553. PubMed
- Mennini T, Bernasconi P, Bombardelli F, et al: In vitro study on the interaction of extracts and pure compounds from Valeriana officinalis roots with GABA, benzodiazepine and barbiturate receptors in rat brain. Fitoterapia 1993; 64:291-300.
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