NutriStack
St. John's Wort and Venlafaxine, contraindicated.
Combining venlafaxine with St. John's Wort creates a dangerous risk of serotonin syndrome. Multiple case reports have documented this interaction. St. John's Wort's serotonin reuptake inhibition adds to venlafaxine's, while its CYP induction may unpredictably alter venlafaxine and O-desmethylvenlafaxine levels.
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 Venlafaxine
- Pair type
- Contraindicated
- Evidence (highest tier)
- Strong
- 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 · Strong evidence
Contraindicated
What is happening. Combining venlafaxine with St. John's Wort creates a dangerous risk of serotonin syndrome. Multiple case reports have documented this interaction. St. John's Wort's serotonin reuptake inhibition adds to venlafaxine's, while its CYP induction may unpredictably alter venlafaxine and O-desmethylvenlafaxine levels.
Mechanism. Venlafaxine blocks SERT and NET. St. John's Wort adds serotonin reuptake inhibition (hyperforin) and potential MAO inhibition. CYP2D6 and CYP3A4 induction by St. John's Wort may also alter venlafaxine metabolism, creating unpredictable drug levels alongside pharmacodynamic serotonergic toxicity.
Recommendation. Do not take St. John's Wort with venlafaxine. This is a well-documented dangerous combination. If you are currently using both, contact your prescriber immediately.
Sources (1)
Stack Score
How this pair moves the number.
Effect on the composite score
If both St. John's Wort and Venlafaxine 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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