Passionflower and Midazolam Nasal Spray: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Midazolam Nasal Spray
Passionflower
No brand names on record
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
Interaction Deep Dive
In one case report, valerian and passionflower used concurrently with lorazepam resulted in additive CNS depressive effects. 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 . It is recommended that patients be asked about herbal product use during intake of personal history1. Monitor for increased CNS depressive adverse effects if passionflower is coadministered with a benzodiazepine.
Why it happens (mechanism)
Additive effects on the benzodiazepine receptor
Literature reports
2 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) Chrysin (5,7-di-OH-flavone), a flavonoid in Passiflora coerulea, was identified as a naturally-occurring benzodiazepine receptor ligand in plants obtained from local sources at the Universidad de Buenos Aires 2. However, in a high performance liquid chromatography analysis sensitive to a detection limit of 1 part per million (ppm), chrysin could not be detected in an ethanolic extract of aerial parts of Passiflora coerulea obtained from the botanical garden of the University of Bologna or in a Passiflora incarnata fluid extract prepared according to the Italian Pharmacopoeia, IX edition 3. Passiflora coerulea collected in the wild is sometimes adulterated or substituted with the spurious species Cucurbitella asperata 4.
Common questions
Can I take Passionflower and Midazolam Nasal Spray together?
Additive CNS depression Always confirm with your pharmacist or prescriber before making any change.
How serious is the Passionflower 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 Passionflower 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 (4)
- 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.
- Medina JH, Paladini RC, Wolfman C, et al: Chrysin (5,7,-di-OH-flavone), a naturally-occurring ligand for benzodiazepine receptors with anticonvulsant properties. Biochem Pharmacol 1990; 40(10):2227-2231. PubMed
- Speroni E, Billi R, Crespi Perellino N, et al: Role of chrysin in the sedative effects of Passiflora incarnata L. Phytother Res 1996; 10:S98-S100.
- Gattuso S, Di Sapio O, McCargo J, et al: Passiflora caerulea (sic) and its adulterator Cucurbitella asperata. Fitoterapia 1996; 67(6):535-544.
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