NutriStack
Lamotrigine and St. John's Wort, a conflict.
St. John's Wort can induce UGT glucuronidation enzymes responsible for lamotrigine metabolism, potentially reducing lamotrigine blood levels and risking loss of seizure control or mood stabilization. Lamotrigine is primarily metabolized by UGT1A4 and UGT2B7 to its N2-glucuronide metabolite (approximately 90% of the excreted dose). Reduced lamotrigine levels can lead to breakthrough seizures or bipolar mood episodes.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
Same shape as the other 1,729 pairs in the public database.
From the interaction database
What the row says.
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At a glance
- Substances
- Lamotrigine and St. John's Wort
- Pair type
- Conflict
- Evidence (highest tier)
- Moderate
- Source citations
- 1 source
- Stack Score effect
- −10 to your Stack Score (per scored conflict row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Conflict · Moderate evidence
Conflict
What is happening. St. John's Wort can induce UGT glucuronidation enzymes responsible for lamotrigine metabolism, potentially reducing lamotrigine blood levels and risking loss of seizure control or mood stabilization. Lamotrigine is primarily metabolized by UGT1A4 and UGT2B7 to its N2-glucuronide metabolite (approximately 90% of the excreted dose). Reduced lamotrigine levels can lead to breakthrough seizures or bipolar mood episodes.
Mechanism. St. John's Wort induces hepatic UGT enzymes (including UGT1A4) through PXR and other nuclear receptor activation. This accelerates lamotrigine's glucuronidation to its inactive N2-glucuronide metabolite, increasing clearance and reducing therapeutic plasma concentrations. The induction effect is dose-dependent on hyperforin content.
Recommendation. Avoid St. John's Wort while taking lamotrigine. Loss of seizure control or mood stabilization can have severe consequences including status epilepticus. If already taking both, consult your prescriber immediately before making changes. Do not abruptly stop St. John's Wort as lamotrigine levels may rise.
Stack Score
How this pair moves the number.
Effect on the composite score
If both Lamotrigine and St. John's Wort are in the same stack, this pair applies −10 to your Stack Score (per scored conflict row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
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