The short answer
St. John’s wort can raise a serotonin-related concern with tramadol and should be reviewed before co-use. St. John’s wort may also lower tramadol exposure through enzyme induction; these are separate effects.
What this answer covers
Hypericum perforatum extracts; product composition differs.
- Supplement or preparation
- Hypericum perforatum
- Medication ingredient
- tramadol
The serotonin precaution is relevant
Tramadol affects serotonin signaling, and its labels warn of serotonin syndrome with serotonergic co-medication. Supplement guidance supports reviewing this combination rather than treating it as automatically safe.
Clinical reports are not exact supplement risk estimates
An original report describes serotonin toxicity after tramadol was added to several psychiatric and pain medicines. It supports the medication-level concern but does not establish how often this exact supplement combination causes harm.
Drug handling and product identity matter
The extended-release label specifically names St. John’s wort as an enzyme inducer that can alter tramadol exposure. Starting or stopping it may change effect; this is not proof of reduced intestinal absorption.
Discuss use before a change
Review the product with the prescriber before combining or changing it. A short interval has not been shown to prevent systemic interactions. Agitation with fever, tremor, muscle stiffness or confusion needs urgent assessment.
Evidence and practical considerations
Timing & monitoring
Prescriber review and avoidance of unsupervised co-use warranted for serotonergic and metabolic concerns; no universal supplement prohibition or protective short gap.
- Exact scope
- Hypericum perforatum extracts; product composition differs. with Tramadol10689 IN; oral hydrochloride IR/ER with active M1 and formulation limits.
- Medication form and route
- oral medication; oral supplement
What remains uncertain
- No unmeasured pair incidence, blanket class transfer or arbitrary spacing interval.
Factors that may matter: Preparation; Dose; Other medicines; Organ function.
Read the supporting source summaries
Source 1: current product label
dailymed.nlm.nih.gov · Source check Sep 10, 2026
Population: People prescribed tramadol
Parent tramadol and active M1 metabolite contribute effects; CYP2D6 inhibition can raise parent while lowering M1. Serotonin syndrome, seizures and CNS-depressant risks.
How this applies: Exact tramadol RxCUI 10689 IN, with stated salt/formulation/route bridge.
Not interchangeable with extended-release dosing or combination products; no botanical-specific incidence.
Source 2: current product label
dailymed.nlm.nih.gov · Source check Sep 10, 2026
Population: People prescribed tramadol
CYP3A induction including St John’s wort can alter tramadol exposure; serotonergic and CNS-depressant precautions.
How this applies: Exact tramadol RxCUI 10689 IN, with stated salt/formulation/route bridge.
Once-daily formulation-specific directions and restrictions; not an immediate-release or injectable regimen.
Source 3: federal supplement safety guidance
nccih.nih.gov · Source check Sep 10, 2026
Population: Users of the named oral supplement
Possible serious serotonin-related effects with other serotonin-active drugs.
How this applies: Original source interpreted for tramadol only within the stated preparation and endpoint limits.
Not a direct tramadol combination trial; original preparation, dose and endpoint limits apply. No exact-pair adverse-event rate or protective spacing established.
Source 4: original case report
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: One79-year-old woman.
Serotonin-toxicity features developed after tramadol was introduced.
How this applies: Polypharmacy case, not any requested supplement; no pair-specific incidence.
Polypharmacy case, not any requested supplement; no pair-specific incidence.
Source 5: original transporter experiment
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: Human transporter cell models.
Tramadol inhibited serotonin and noradrenaline transporters in laboratory experiments.
How this applies: Original source interpreted for tramadol only within the stated preparation and endpoint limits.
Mechanistic evidence, not exact botanical co-use incidence.
Research assessment: · Open full citations ↗
Absorption & effectiveness
Exact extended-release label identifies St John’s wort enzyme induction and altered exposure; reduced effectiveness is conditional, while reduced intestinal absorption and net magnitude are unproven.
- Exact scope
- Hypericum perforatum extracts; product composition differs. with Tramadol10689 IN; oral hydrochloride IR/ER with active M1 and formulation limits.
- Medication form and route
- oral medication; oral supplement
What remains uncertain
- No unmeasured pair incidence, blanket class transfer or arbitrary spacing interval.
Factors that may matter: Preparation; Dose; Other medicines; Organ function.
Read the supporting source summaries
Source 1: current product label
dailymed.nlm.nih.gov · Source check Sep 10, 2026
Population: People prescribed tramadol
Parent tramadol and active M1 metabolite contribute effects; CYP2D6 inhibition can raise parent while lowering M1. Serotonin syndrome, seizures and CNS-depressant risks.
How this applies: Exact tramadol RxCUI 10689 IN, with stated salt/formulation/route bridge.
Not interchangeable with extended-release dosing or combination products; no botanical-specific incidence.
Source 2: current product label
dailymed.nlm.nih.gov · Source check Sep 10, 2026
Population: People prescribed tramadol
CYP3A induction including St John’s wort can alter tramadol exposure; serotonergic and CNS-depressant precautions.
How this applies: Exact tramadol RxCUI 10689 IN, with stated salt/formulation/route bridge.
Once-daily formulation-specific directions and restrictions; not an immediate-release or injectable regimen.
Source 3: federal supplement safety guidance
nccih.nih.gov · Source check Sep 10, 2026
Population: Users of the named oral supplement
Possible serious serotonin-related effects with other serotonin-active drugs.
How this applies: Original source interpreted for tramadol only within the stated preparation and endpoint limits.
Not a direct tramadol combination trial; original preparation, dose and endpoint limits apply. No exact-pair adverse-event rate or protective spacing established.
Source 4: original case report
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: One79-year-old woman.
Serotonin-toxicity features developed after tramadol was introduced.
How this applies: Polypharmacy case, not any requested supplement; no pair-specific incidence.
Polypharmacy case, not any requested supplement; no pair-specific incidence.
Source 5: original transporter experiment
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: Human transporter cell models.
Tramadol inhibited serotonin and noradrenaline transporters in laboratory experiments.
How this applies: Original source interpreted for tramadol only within the stated preparation and endpoint limits.
Mechanistic evidence, not exact botanical co-use incidence.
Research assessment: · Open full citations ↗
Side effects & toxicity
Conditional serotonergic precaution from exact tramadol label, transporter activity and supplement guidance; clinical case is other-drug polypharmacy, not exact-pair incidence.
- Exact scope
- Hypericum perforatum extracts; product composition differs. with Tramadol10689 IN; oral hydrochloride IR/ER with active M1 and formulation limits.
- Medication form and route
- oral medication; oral supplement
What remains uncertain
- No unmeasured pair incidence, blanket class transfer or arbitrary spacing interval.
Factors that may matter: Preparation; Dose; Other medicines; Organ function.
Read the supporting source summaries
Source 1: current product label
dailymed.nlm.nih.gov · Source check Sep 10, 2026
Population: People prescribed tramadol
Parent tramadol and active M1 metabolite contribute effects; CYP2D6 inhibition can raise parent while lowering M1. Serotonin syndrome, seizures and CNS-depressant risks.
How this applies: Exact tramadol RxCUI 10689 IN, with stated salt/formulation/route bridge.
Not interchangeable with extended-release dosing or combination products; no botanical-specific incidence.
Source 2: current product label
dailymed.nlm.nih.gov · Source check Sep 10, 2026
Population: People prescribed tramadol
CYP3A induction including St John’s wort can alter tramadol exposure; serotonergic and CNS-depressant precautions.
How this applies: Exact tramadol RxCUI 10689 IN, with stated salt/formulation/route bridge.
Once-daily formulation-specific directions and restrictions; not an immediate-release or injectable regimen.
Source 3: federal supplement safety guidance
nccih.nih.gov · Source check Sep 10, 2026
Population: Users of the named oral supplement
Possible serious serotonin-related effects with other serotonin-active drugs.
How this applies: Original source interpreted for tramadol only within the stated preparation and endpoint limits.
Not a direct tramadol combination trial; original preparation, dose and endpoint limits apply. No exact-pair adverse-event rate or protective spacing established.
Source 4: original case report
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: One79-year-old woman.
Serotonin-toxicity features developed after tramadol was introduced.
How this applies: Polypharmacy case, not any requested supplement; no pair-specific incidence.
Polypharmacy case, not any requested supplement; no pair-specific incidence.
Source 5: original transporter experiment
pubmed.ncbi.nlm.nih.gov · Source check Sep 10, 2026
Population: Human transporter cell models.
Tramadol inhibited serotonin and noradrenaline transporters in laboratory experiments.
How this applies: Original source interpreted for tramadol only within the stated preparation and endpoint limits.
Mechanistic evidence, not exact botanical co-use incidence.
Research assessment: · Open full citations ↗
Review and change history
- Publication status
- Published research summary
- Clinical review
- Not yet recorded
| Date | Update |
|---|---|
| Article prepared | |
| Prepared exact tramadol article with formulation-specific evidence and uncertainty. | |
| Research summary published |
Article revision: fb2911874f02fd09
This guide brings together the evidence records used by our interaction checker. Each finding retains its own preparation limits, research date, and source summaries.
Full citations require verification. Reading this answer and the source summaries does not.
Taking other supplements or medications?
Use the checker to explore your other combinations. Ask a pharmacist to review the exact products, amounts and medical conditions in your complete list.
Open the interaction checkerInformation, not medical advice. Do not change prescribed treatment based on this guide.