St John's Wort and Buprenorphine: 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
St John's Wort
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.
St. John's wort can weaken your buprenorphine. St. John's wort is an herbal supplement that speeds up the liver enzyme (CYP3A4) that breaks down buprenorphine. That means your body clears the buprenorphine faster, so there is less of it working. You might notice it isn't controlling pain as well, or you could feel opioid withdrawal symptoms like chills, sweating, stomach upset, or restlessness.
There is also a second concern. Both can raise a brain chemical called serotonin, so together they can rarely trigger serotonin syndrome (agitation, fast heartbeat, shivering, muscle twitching). The good news: your care team can manage this by tailoring your dose and watching you closely. Please don't stop or change either one on your own, just talk with your pharmacist or doctor first.
Effect: St. John's wort (CYP3A4 inducer) increases buprenorphine metabolism, reducing buprenorphine exposure (AUC/Cmax) and efficacy, with risk of opioid withdrawal. Buprenorphine is active drug, not a prodrug, so induction lowers effect. Additive serotonergic activity also raises serotonin syndrome risk.
Evidence: Probable. Onset: unspecified (induction develops over days to weeks). Severity: major.
Management:
- If St. John's wort is needed, titrate buprenorphine to stable effect; monitor for withdrawal.
- On St. John's wort discontinuation, anticipate rising levels; reduce dose and monitor for respiratory depression.
- Prefer formulations allowing precise titration if dose cannot be adjusted.
- Monitor for serotonin syndrome during initiation/titration; discontinue buprenorphine if suspected.
What happens
Reduced buprenorphine exposure, reduced efficacy of buprenorphine and an increased risk of serotonin syndrome
Interaction Deep Dive
Taking buprenorphine together with St. John's wort (a serotonergic inducer of CYP3A4) can lower buprenorphine exposure and precipitate opioid withdrawal symptoms. When a patient on buprenorphine must also use St. John's wort, consider raising the buprenorphine dose until stable drug effects are reached, while watching for withdrawal. Conversely, upon stopping St. John's wort in a buprenorphine-treated patient, consider reducing the buprenorphine dose and monitor for respiratory depression2. Should dose adjustment prove impossible once the CYP3A4 inducer is gone, switch the patient back to a buprenorphine formulation that allows finer dose titration. For patients transitioned off a regimen of transmucosal buprenorphine given with St. John's wort, verify that the plasma buprenorphine level achieved by subQ buprenorphine is sufficient. For those already receiving subQ buprenorphine who need to add St. John's wort, monitor for withdrawal. If the buprenorphine dose is inadequate while the concomitant drug is present and that drug cannot be lowered or stopped, adjust the buprenorphine dose. When dose adjustment is not feasible, treat the patient with a buprenorphine formulation that permits more precise dose adjustments. In addition, watch the patient for signs and symptoms of serotonin syndrome, particularly at the start of therapy and during dose changes; discontinue buprenorphine if serotonin syndrome is suspected 1.
Why it happens (mechanism)
Induction of CYP3A4-mediated metabolism of buprenorphine; additive serotonergic effects
How to manage this interaction
Keep taking both exactly as prescribed and let your care team know you use St. John's wort so they can plan around it. Here is what teams typically do:
- Adjust and individualize your buprenorphine dose so it stays effective, since your dose may need to change and be tailored to you.
- Watch for opioid withdrawal (chills, sweating, cramps, restlessness), especially while starting.
- If you stop the St. John's wort, expect your team may lower the buprenorphine dose and monitor you more closely for very slow or shallow breathing.
- Report agitation, fast heartbeat, shivering, or muscle twitching right away (possible serotonin syndrome).
Ask your pharmacist before starting or stopping any supplement.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) The impact of a concurrently administered CYP3A4 inducer on buprenorphine exposure in patients receiving subQ buprenorphine has not been investigated; nevertheless, interactions of this kind have been demonstrated in studies employing transmucosal buprenorphine. The effects of buprenorphine may vary according to the route of administration 1.
Common questions
Can I take St John's Wort and Buprenorphine together?
St. John's wort can lower your buprenorphine levels and cause withdrawal or reduced pain control, plus a small added risk of serotonin syndrome. Don't start or stop either on your own; your care team can manage this by adjusting your dose and monitoring you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the St John's Wort and Buprenorphine 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 St John's Wort and Buprenorphine interaction managed?
Keep taking both exactly as prescribed and let your care team know you use St. John's wort so they can plan around it. Here is what teams typically do: Adjust and individualize your buprenorphine dose so it stays effective, since your dose may need to change and be tailored to you. Watch for opioid withdrawal (chills, sweating, cramps, restlessness), especially while starting. If you stop the St.… 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.
Questions for your pharmacist
- Does my dose of St John's Wort or Buprenorphine 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)
- Product Information: BRIXADI(TM) subcutaneous extended-release injection, buprenorphine subcutaneous extended-release injection. Braeburn Inc (per FDA), Plymouth Meeting, PA, 2023. DailyMed
- Product Information: ZUBSOLV(R) sublingual tablets, buprenorphine naloxone sublingual tablets. Orexo US Inc (per FDA), Morristown, NJ, 2023. DailyMed
Keep reading about Buprenorphine
Keep reading about St John's Wort
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