NutriStack
Oxycodone and St. John's Wort, a caution.
St. John's Wort can induce CYP3A activity, and oxycodone exposure is clinically sensitive to CYP3A induction and inhibition. Using them together may reduce oxycodone levels and analgesia; stopping St. John's Wort can then raise oxycodone exposure again. This can cause unstable pain control, withdrawal symptoms, or unexpected sedation if oxycodone is adjusted during the interaction.
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.
Every entry follows the same shape: what is happening, the mechanism, the recommendation, and the primary literature.
At a glance
- Substances
- Oxycodone 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. St. John's Wort can induce CYP3A activity, and oxycodone exposure is clinically sensitive to CYP3A induction and inhibition. Using them together may reduce oxycodone levels and analgesia; stopping St. John's Wort can then raise oxycodone exposure again. This can cause unstable pain control, withdrawal symptoms, or unexpected sedation if oxycodone is adjusted during the interaction.
Mechanism. St. John's Wort induces intestinal and hepatic CYP3A activity in humans. Oxycodone is metabolized mainly by CYP3A to noroxycodone and is affected by CYP3A inducers and inhibitors, so induction can lower oxycodone exposure and discontinuation can reverse that effect.
Recommendation. Avoid starting or stopping St. John's Wort while taking oxycodone unless your prescriber is managing the change. Do not increase oxycodone on your own if pain worsens after adding St. John's Wort. Watch for withdrawal or loss of pain control when starting it, and for sedation or slow breathing after stopping it.
Sources (2)
- Wang Z, Gorski JC, Hamman MA, Huang SM, Lesko LJ, Hall SD. The effects of St John's wort (Hypericum perforatum) on human cytochrome P450 activity. Clin Pharmacol Ther. 2001;70(4):317-326. PMID 11673747
- Kinnunen M, Piirainen P, Kokki H, Lammi P, Kokki M. Updated Clinical Pharmacokinetics and Pharmacodynamics of Oxycodone. Clin Pharmacokinet. 2019;58(6):705-725. PMID 30652261
Stack Score
How this pair moves the number.
Effect on the composite score
If both Oxycodone 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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