NutriStack
Bupropion and St. John's Wort, a caution.
Both bupropion and St. John's Wort lower the seizure threshold, and combining them may significantly increase seizure risk. Bupropion already carries a dose-dependent seizure warning, and St. John's Wort's effects on multiple neurotransmitter systems compound this risk.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
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From the interaction database
What the row says.
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At a glance
- Substances
- Bupropion and St. John's Wort
- Pair type
- Caution
- Evidence (highest tier)
- Moderate
- Source citations
- 2 sources
- Stack Score effect
- −5 to your Stack Score (per scored caution row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Caution · Moderate evidence
Caution
What is happening. Both bupropion and St. John's Wort lower the seizure threshold, and combining them may significantly increase seizure risk. Bupropion already carries a dose-dependent seizure warning, and St. John's Wort's effects on multiple neurotransmitter systems compound this risk.
Mechanism. Bupropion inhibits dopamine and norepinephrine reuptake and is known to lower seizure threshold in a dose-dependent manner. St. John's Wort affects multiple neurotransmitter systems including inhibiting serotonin, norepinephrine, and dopamine reuptake. The combined neuroexcitatory effects may further reduce seizure threshold.
Recommendation. Avoid combining St. John's Wort with bupropion due to increased seizure risk. If mood support beyond bupropion is needed, discuss evidence-based augmentation strategies with your prescriber.
Stack Score
How this pair moves the number.
Effect on the composite score
If both Bupropion and St. John's Wort are in the same stack, this pair applies −5 to your Stack Score (per scored caution row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
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