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 + Zolpidem 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 Zolpidem, a caution.

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

Possibly, but with caution. St. John's Wort and Zolpidem have a documented caution-tier interaction. St. John's Wort can induce CYP3A4 and P-glycoprotein, while zolpidem is partly cleared through CYP3A-mediated metabolism. The combination may reduce zolpidem exposure and make sleep benefit less reliable; stopping St. John's Wort may reverse induction and increase zolpidem effect. Product hyperforin content makes the size of the interaction unpredictable.

Q: How does this affect a NutriStack Stack Score?

-5 to your Stack Score per scored caution row.

St. John's Wort can induce CYP3A4 and P-glycoprotein, while zolpidem is partly cleared through CYP3A-mediated metabolism. The combination may reduce zolpidem exposure and make sleep benefit less reliable; stopping St. John's Wort may reverse induction and increase zolpidem effect. Product hyperforin content makes the size of the interaction unpredictable.

2 primary source citations. Emerging 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 Zolpidem
Pair type: Caution
Evidence (highest tier): Emerging
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 · Emerging evidence

Caution

What is happening. St. John's Wort can induce CYP3A4 and P-glycoprotein, while zolpidem is partly cleared through CYP3A-mediated metabolism. The combination may reduce zolpidem exposure and make sleep benefit less reliable; stopping St. John's Wort may reverse induction and increase zolpidem effect. Product hyperforin content makes the size of the interaction unpredictable.

Mechanism. Hyperforin-containing St. John's Wort induces CYP3A4 through pregnane X receptor activation. Zolpidem undergoes hepatic oxidation that includes CYP3A pathways, so induction can lower hypnotic exposure.

Recommendation. Avoid changing St. John's Wort use while taking zolpidem unless your prescriber agrees. Do not raise zolpidem on your own if it seems weaker after starting the herb. Watch for stronger sedation if the herb is stopped.

Sources (2)

Stack Score

How this pair moves the number.

Effect on the composite score

If both St. John's Wort and Zolpidem 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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