Kratom and Midazolam Nasal Spray: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Kratom
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
Increased CYP3A substrate exposure and an increased risk of CNS depression
Interaction Deep Dive
Concomitant use of kratom and a CNS depressant may lead to serious effects, such as respiratory depression or death1. Additionally, kratom is a CYP3A inhibitor and may increase exposure of CYP3A substrates, especially with higher kratom doses or chronic use 2. In the FDA Adverse Event Reporting System (FAERS) database, 1223 adverse events involving kratom were reported between June 2008 to 2024, many of which involved drug interactions between kratom and other drugs (especially opioids and CNS agents) and included serious events such as hospitalizations, life threatening conditions and fatalities. Kratom's multi-receptor mechanism of action (including opioid, adrenergic, and serotonergic receptors) and variable alkaloid content in different formulations makes drug interactions challenging to predict. Close monitoring is suggested 1.
Why it happens (mechanism)
Inhibition of CYP3A-mediated metabolism by kratom; additive CNS depression
Literature reports
1 report — tap to read
a) Consumption of a single, low dose of kratom tea (2 g) together with oral midazolam (CYP3A probe substrate; 2.5 mg) and oral dextromethorphan (CYP2D6 probe substrate; 30 mg) was evaluated in an open-label crossover study of healthy adults (N=12). Kratom modestly increased midazolam geometric mean AUC (1.39; 90% CI, 1.23 to 1.57) and Cmax (1.5; 90% CI, 1.32 to 1.7); no effect on dextromethorphan AUC or Cmax was observed. Midazolam half life was not significantly altered with concomitant use of kratom which suggests inhibition of first-pass metabolism, primarily CYP3A in the intestine. Participants (median age, 30 years) were previously exposed to kratom and willing to abstain from concomitant medications and botanical or other natural products (including kratom) during the study 2.
Common questions
Can I take Kratom and Midazolam Nasal Spray together?
Increased CYP3A substrate exposure and an increased risk of CNS depression Always confirm with your pharmacist or prescriber before making any change.
How serious is the Kratom and Midazolam Nasal Spray interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Kratom 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 a safer alternative to one of these medications for me?
References (2)
- Dhoble LR, Gour A, McCurdy CR, et al: Evaluating the drug interactions in kratom usage: clinical application. Expert Opin Drug Metab Toxicol 2025; 21(8):949-959. PubMed
- Tanna RS, Nguyen JT, Hadi DL, et al: Clinical assessment of the drug interaction potential of the psychotropic natural product kratom. Clin Pharmacol Ther 2023; 113(6):1315-1325. DOI
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