Buprenorphine and Kratom: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Buprenorphine
Kratom
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.
Let's talk about taking buprenorphine (like Belbuca, Suboxone, or BuTrans) together with kratom. Both of these can slow down your breathing and make you very sleepy. When you use them together, that effect can stack up and become dangerous, in rare cases even leading to trouble breathing or worse.
On top of that, kratom can slow down how your body breaks buprenorphine down, so more of it can build up in your system. Kratom also touches the same brain chemicals as some antidepressants, which raises the risk of a reaction called serotonin syndrome. The good news is your care team can manage this safely. Please talk with your pharmacist or doctor before combining these, and never adjust your medicine on your own.
Effect: Additive CNS and respiratory depression, increased serotonin syndrome risk, and increased buprenorphine exposure. Evidence: probable; severity: major.
- Mechanism: Kratom (mitragynine) inhibits CYP3A, reducing buprenorphine metabolism and raising exposure; additive opioid/CNS depression; additive serotonergic activity via kratom's multi-receptor profile.
- Direction: Increased buprenorphine effect and toxicity risk (neither is a prodrug requiring activation here).
- Magnitude: Greater with higher kratom doses or chronic use; unpredictable due to variable alkaloid content.
- Management: Avoid or minimize concurrent use. If combined, monitor closely for sedation, respiratory depression, and serotonin syndrome. FAERS documents hospitalizations and fatalities with kratom-opioid combinations.
What happens
Increased CYP3A substrate exposure, increased risk of CNS depression and serotonin syndrome
Interaction Deep Dive
Taking kratom together with a CNS depressant and a serotonergic agent can produce serious consequences, including respiratory depression, serotonin syndrome, or death1. Kratom also acts as a CYP3A inhibitor and can raise the exposure of CYP3A substrates, an effect that is more pronounced with larger kratom doses or long-term use2. Between June 2008 and 2024, the FDA Adverse Event Reporting System (FAERS) database recorded 1223 adverse events tied to kratom, a large number of which reflected interactions between kratom and other agents (particularly opioids and CNS drugs) and encompassed serious outcomes such as hospitalizations, life threatening conditions, and deaths. Because kratom engages multiple receptors (opioid, adrenergic, and serotonergic) and its alkaloid content differs across formulations, predicting drug interactions is difficult. Close monitoring is advised1.
Why it happens (mechanism)
Inhibition of CYP3A-mediated metabolism by kratom; additive CNS depression; additive serotonergic effects
How to manage this interaction
The safest approach here is caution, because both substances depress breathing and the nervous system, and kratom can raise buprenorphine levels in your body.
- Keep taking your buprenorphine as prescribed and do not stop or change it on your own.
- Tell your pharmacist or prescriber if you use kratom (any form), since products vary a lot in strength.
- Your care team may watch you more closely for heavy sedation, slowed or shallow breathing, confusion, and signs of serotonin syndrome (agitation, fast heartbeat, sweating, shivering, muscle twitching).
- Get emergency help right away for very slow breathing, extreme drowsiness, or unresponsiveness.
Bring this up at your next visit so your team can individualize the plan.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) An open-label crossover study in healthy adults (N=12) assessed the intake of a single, low dose of kratom tea (2 g) alongside oral midazolam (a CYP3A probe substrate; 2.5 mg) and oral dextromethorphan (a CYP2D6 probe substrate; 30 mg). Kratom produced a modest rise in the midazolam geometric mean AUC (1.39; 90% CI, 1.23 to 1.57) and Cmax (1.5; 90% CI, 1.32 to 1.7); there was no observed effect on the AUC or Cmax of dextromethorphan. The half life of midazolam was not significantly changed by concurrent kratom use, which points to inhibition of first-pass metabolism, mainly CYP3A within the intestine. The participants (median age, 30 years) had prior kratom exposure and were willing to refrain from concomitant medications and botanical or other natural products (including kratom) for the duration of the study 2.
Common questions
Can I take Buprenorphine and Kratom together?
Combining buprenorphine and kratom can dangerously stack up sedation and breathing suppression and raise buprenorphine levels, so talk to your pharmacist or doctor before using both and never adjust your medicine yourself. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Buprenorphine and Kratom 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 is the Buprenorphine and Kratom interaction managed?
The safest approach here is caution, because both substances depress breathing and the nervous system, and kratom can raise buprenorphine levels in your body. Keep taking your buprenorphine as prescribed and do not stop or change it on your own. Tell your pharmacist or prescriber if you use kratom (any form), since products vary a lot in strength. Your care team may watch you more closely for heav… Management is individual — always follow your own care team's guidance.
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 Buprenorphine or Kratom 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. PubMed
Keep reading about Buprenorphine
Keep reading about Kratom
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Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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