Kratom and Esketamine 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 recordEsketamine 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
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 death. 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 suggested1.
Why it happens (mechanism)
Additive CNS depression
Common questions
Can I take Kratom and Esketamine Nasal Spray together?
An increased risk of CNS depression Always confirm with your pharmacist or prescriber before making any change.
How serious is the Kratom and Esketamine 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 "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 Kratom or Esketamine 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 (1)
- 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
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