Skullcap and Midazolam Injection: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Midazolam Injection
Skullcap
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
Increased central nervous system depression
Interaction Deep Dive
In vitro studies demonstrate that several constituents of skullcap have affinity for the benzodiazepine binding site of the GABA-A receptor, and appear to compete with benzodiazepines for the site12. Theoretically, skullcap may have additive effects when administered with a benzodiazepine, yet if the binding is competitive in nature, skullcap may displace the benzodiazepine from the receptor and reduce its effectiveness. Caution is advised with concomitant use of skullcap and benzodiazepines until this potential interaction is better characterized.
Why it happens (mechanism)
Several constituents of skullcap have demonstrated binding affinity for the benzodiazepine site of the GABA-A receptor
Literature reports
2 reports — tap to read
a) Constituents isolated from the organic solvent extract of skullcap root demonstrated binding affinity for the benzodiazepine (BZD) site of the GABA-A receptor. Wogonin and baicalein had the strongest affinity, scutellarein had moderate activity, and baicalin had weakest activity. All of these constituents contain the flavonoid phenylbenzopyrone nucleus, which binds to the benzodiazepine site. The concentrations at which 50 percent inhibition (IC50) of (3H)flunitrazepam binding occurred were as follows, wogonin 3.62 micromolar (mcM); baicalein 10.11 mcM; scutellarein 20.96 mcM; and baicalin 137.07 mcM, whereas the IC50 of diazepam was 0.029 mcM 1.
b) Constituents isolated from the water extract of skullcap root demonstrated activity on the dopamine D1, D2, 5-hydroxytryptamine, and benzodiazepine (BDZ) binding sites of gamma-amino butyric acid (GABA) receptors, but not on muscarinic acetylcholine M1, 5-HT2 receptors or the GABA binding site of GABA receptors in vitro. Baicalein, oroxylin A and wogonin, flavone constituents of skullcap, showed weak binding to the BDZ sites while skullcapflavone II demonstrated binding comparable to that of chlordiazepoxide but 100-fold less than flurazepam 2.
Common questions
Can I take Skullcap and Midazolam Injection together?
Increased central nervous system depression Always confirm with your pharmacist or prescriber before making any change.
How serious is the Skullcap and Midazolam Injection interaction?
It is rated minor. Usually limited clinical impact.
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 Skullcap or Midazolam Injection 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 (2)
- Hui KM, Wang XH, & Xue H: Interaction of flavones from the roots of Scutellaria baicalensis with the benzodiazepine site. Planta Med 2000; 66(1):91-93.
- Liao JF, Wang HH, Chen MC, et al: Benzodiazepine binding site-interactive flavones from Scutellaria baicalensis root. Planta Med 1998; 64(6):571-572.
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