NutriStack
Alprazolam and St. John's Wort, a caution.
St. John's Wort can induce CYP3A4, the main enzyme clearing alprazolam. High-hyperforin St. John's Wort products may lower alprazolam exposure and reduce anxiety control; stopping the herb can then allow alprazolam levels to rise again. Low-hyperforin products may have little effect, so product variability is a major issue.
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At a glance
- Substances
- Alprazolam 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 CYP3A4, the main enzyme clearing alprazolam. High-hyperforin St. John's Wort products may lower alprazolam exposure and reduce anxiety control; stopping the herb can then allow alprazolam levels to rise again. Low-hyperforin products may have little effect, so product variability is a major issue.
Mechanism. Hyperforin in St. John's Wort activates pregnane X receptor signaling and induces CYP3A4. Alprazolam is a CYP3A substrate, so induction can increase clearance and lower active exposure.
Recommendation. Avoid starting or stopping St. John's Wort while taking alprazolam unless your prescriber is managing the change. Do not increase alprazolam on your own if anxiety worsens after starting the herb. Watch for oversedation if St. John's Wort is stopped after an alprazolam dose increase.
Sources (2)
- Markowitz JS, Donovan JL, DeVane CL, Taylor RM, Ruan Y, Wang JS, et al. Effect of St John's wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. JAMA. 2003;290(11):1500-1504. PMID 13129991
- Arold G, Donath F, Maurer A, Diefenbach K, Bauer S, Henneicke-von Zepelin HH, et al. No relevant interaction with alprazolam, caffeine, tolbutamide, and digoxin by treatment with a low-hyperforin St John's wort extract. Planta Med. 2005;71(4):331-337. PMID 15856409
Stack Score
How this pair moves the number.
Effect on the composite score
If both Alprazolam 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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