NutriStack
St. John's Wort and Tramadol, contraindicated.
Combining tramadol with St. John's Wort creates dual risks: serotonin syndrome from additive serotonergic effects, and potential loss of tramadol's analgesic efficacy from CYP3A4/CYP2D6 induction that may reduce active metabolite formation or increase clearance.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
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At a glance
- Substances
- St. John's Wort and Tramadol
- Pair type
- Contraindicated
- Evidence (highest tier)
- Moderate
- Source citations
- 1 source
- Stack Score effect
- −25 to your Stack Score (per scored contraindication row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Contraindicated · Moderate evidence
Contraindicated
What is happening. Combining tramadol with St. John's Wort creates dual risks: serotonin syndrome from additive serotonergic effects, and potential loss of tramadol's analgesic efficacy from CYP3A4/CYP2D6 induction that may reduce active metabolite formation or increase clearance.
Mechanism. Both tramadol and St. John's Wort inhibit serotonin reuptake, creating additive serotonergic toxicity risk. Additionally, St. John's Wort induces CYP2D6 (which converts tramadol to its active M1 metabolite) and CYP3A4, potentially causing unpredictable changes in tramadol and M1 levels.
Recommendation. Do not take St. John's Wort with tramadol. This combination poses both serotonin syndrome risk and potential loss of pain control. Seek alternative mood support from your prescriber.
Stack Score
How this pair moves the number.
Effect on the composite score
If both St. John's Wort and Tramadol are in the same stack, this pair applies −25 to your Stack Score (per scored contraindication row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
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