NutriStack
Buspirone and St. John's Wort, a caution.
A published case report describes serotonin syndrome after combining buspirone with St. John's Wort. St. John's Wort also has broad drug-interaction potential through CYP3A and P-glycoprotein induction, which can make psychiatric drug response less predictable. The combination is especially risky if any other serotonergic drug is present.
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.
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What the row says.
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At a glance
- Substances
- Buspirone and St. John's Wort
- Pair type
- Caution
- Evidence (highest tier)
- Moderate
- Source citations
- 3 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. A published case report describes serotonin syndrome after combining buspirone with St. John's Wort. St. John's Wort also has broad drug-interaction potential through CYP3A and P-glycoprotein induction, which can make psychiatric drug response less predictable. The combination is especially risky if any other serotonergic drug is present.
Mechanism. St. John's Wort contains hyperforin and other constituents that affect monoamine signaling and induce CYP3A/P-glycoprotein through pregnane X receptor activation. Buspirone is a serotonergic 5-HT1A partial agonist and a CYP3A substrate, so the combination can create both pharmacodynamic serotonin-toxicity risk and pharmacokinetic unpredictability.
Recommendation. Avoid St. John's Wort while taking buspirone unless your prescriber specifically directs otherwise. Do not use dose spacing as a workaround because both serotonergic effects and enzyme induction can persist. Seek urgent care for fever, confusion, tremor, sweating, diarrhea, muscle rigidity, or clonus.
Sources (3)
- Dannawi M. Possible serotonin syndrome after combination of buspirone and St John's Wort. J Psychopharmacol. 2002;16(4):401. PMID 12503845
- Nicolussi S, Drewe J, Butterweck V, Meyer Zu Schwabedissen HE. Clinical relevance of St. John's wort drug interactions revisited. Br J Pharmacol. 2020;177(6):1212-1226. PMID 31742659
- Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120. PMID 15784664
Stack Score
How this pair moves the number.
Effect on the composite score
If both Buspirone 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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