What kind of interaction is it?

Caution: an interaction that may reduce efficacy or raise side-effect risk and warrants monitoring.

Is this interaction backed by published research?

Yes. NutriStack lists 2 citation rows for the St. John's Wort + Trazodone pair, each linking to PubMed by PMID where available. Full sourcing methodology at https://nutristackapp.com/methodology/interactions.

Interaction databaseSupplement × PrescriptionReviewed May 2026

St. John's Wort and Trazodone, a caution.

Q: Can I take St. John's Wort and Trazodone together?

Possibly, but with caution. St. John's Wort and Trazodone have a documented caution-tier interaction. St. John's Wort has SSRI-like activity and induces CYP3A4, which is the primary enzyme that metabolizes trazodone. The combination both adds serotonergic load (risking serotonin syndrome) and accelerates trazodone clearance, potentially undercutting its sleep and mood benefit.

Q: How does this affect a NutriStack Stack Score?

-5 to your Stack Score per scored caution row.

St. John's Wort has SSRI-like activity and induces CYP3A4, which is the primary enzyme that metabolizes trazodone. The combination both adds serotonergic load (risking serotonin syndrome) and accelerates trazodone clearance, potentially undercutting its sleep and mood benefit.

2 primary source citations. Moderate evidence. Last verified May 30, 2026.

Open the interaction checker →Read the methodology

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.

Sourcing standards·Evidence tiers

From the interaction database

What the row says.

Every entry follows the same shape: what is happening, the mechanism, the recommendation, and the primary literature.

At a glance

Substances: St. John's Wort and Trazodone
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. St. John's Wort has SSRI-like activity and induces CYP3A4, which is the primary enzyme that metabolizes trazodone. The combination both adds serotonergic load (risking serotonin syndrome) and accelerates trazodone clearance, potentially undercutting its sleep and mood benefit.

Mechanism. St. John's Wort constituents inhibit monoamine reuptake (serotonergic activity) and induce CYP3A4. Trazodone is metabolized to mCPP by CYP3A4; induction raises mCPP levels, which is itself a serotonin receptor agonist, while clearing parent drug faster.

Recommendation. Avoid St. John's Wort with trazodone. If you have been taking it, allow a 2-week washout before starting trazodone and avoid restarting it during treatment.

Sources (2)

Stack Score

How this pair moves the number.

Effect on the composite score

If both St. John's Wort and Trazodone 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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