Drug & supplement interaction

St. John's Wort + Phenobarbital

Phenobarbital brand names: Phenobarbital, Solfoton, Luminal.

Major Interaction
Medically reviewed by · Updated September 2026
The bottom line Major

Phenobarbital falls into 2 drug categories that St. John's Wort can interact with; the most serious is rated major. St. John's wort decreases the levels and clinical effects of phenobarbital.

Read the full interaction report
SeverityMajor
LikelihoodLikely
Interactions2
EvidenceB
What do Severity, Likelihood & Evidence mean?
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Interaction report

St. John's Wort and Phenobarbital

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

St. John's Wort interacts with whole categories of medication. Phenobarbital falls into 2 of those categories, so it can interact with St. John's Wort in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Major).

Major

PHENOBARBITAL (Luminal)

1 of 2
St. John's wort decreases the levels and clinical effects of phenobarbital.
St. John's wort may increase the metabolism of phenobarbital. Plasma concentrations of phenobarbital should be monitored carefully. The dose of phenobarbital may need to be increased when St. John's wort is started and decreased when it is stopped.
Severity Major Likelihood Likely Evidence B

Well-controlled human studies have demonstrated the likely existence of this interaction.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the concern with pairing these two. St. John's wort revs up the liver enzymes that break down many medicines, and phenobarbital is one of them. When the herb speeds up that clearance, your phenobarbital levels can drop, which means it may not control your seizures as well. For someone relying on it to stay seizure-free, that's a real worry, since breakthrough seizures can happen if levels fall too low.

Phenobarbital is also a drug where the right blood level matters a lot, so even modest changes can tip the balance. Please don't start or stop St. John's wort on your own. Talk with your doctor or pharmacist first, since your phenobarbital dose and blood levels would need to be watched closely if anything changes.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Henderson L, Yue QY, Bergquist C, et al. St John's wort (Hypericum perforatum): drug interactions and clinical outcomes. Br J Clin Pharmacol 2002;54:349-56..
Moderate

CYTOCHROME P450 2B6 (CYP2B6) SUBSTRATES

2 of 2

Why this applies to Phenobarbital

Phenobarbital falls under CYTOCHROME P450 2B6 (CYP2B6) SUBSTRATES — the group St. John's Wort interacts with.

St. John's wort may increase the metabolism and reduce the levels of CYP2B6 substrates.
Clinical research shows that taking St. John's wort 325 mg three times daily for 14 days along with bupropion, a CYP2B6 substrate, reduces the area under the concentration-time curve by approximately 14% and increases the clearance of bupropion by approximately 20%.
Severity Moderate Likelihood Possible Evidence B

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the gist: St. John's wort tends to rev up certain liver enzymes (in this case CYP2B6), and phenobarbital is partly cleared by that same pathway. So pairing them could nudge your body into breaking phenobarbital down a little faster, which may lower its levels over time. Since phenobarbital is a seizure medicine where steady, reliable blood levels really matter, even a modest drop is worth taking seriously, as it could mean less seizure protection.

I'll be honest, the direct evidence here is limited (the clearest study used bupropion, not phenobarbital), so this is more of a reasonable caution than a proven, dramatic effect. Please don't start or stop anything on your own. Loop in your doctor or pharmacist first so they can keep an eye on your levels and seizure control.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Lei HP, Yu XY, Xie HT, et al. Effect of St. John's wort supplementation on the pharmacokinetics of bupropion in healthy male Chinese volunteers. Xenobiotica 2010;40(4):275-81. PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

St. John's Wort Also Interacts With Other Medications

St. John's Wort has 754 major, 388 moderate known drug interactions in our database — the Phenobarbital one above is among them. If you take anything else, check it against the full list below.

Major 754 Moderate 388 No known interaction 1,688 (incl. Phenobarbital)
Taking anything else?

Check Another of Your Medications Against St. John's Wort

Covers the 2,830 medications we’ve checked against St. John's Wort. Pick one to open its full report.

From our Q&A

Questions About St. John's Wort or Phenobarbital

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers St. John's Wort or Phenobarbital, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:

Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.

Everything else you take

See Every Supplement That Interacts With Phenobarbital

This page covers St. John's Wort only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Phenobarbital page lists 174 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Beer (major), Gamma-hydroxybutyrate (ghb) (major) and Henbane (major).

By severity: 10 major · 143 moderate · 21 minor.

Open the Phenobarbital interaction page

One more smart check

Taking St. John's Wort as Part of a Dietary Supplement Product? Check It for Interactions

We hold 1,159 real supplement products containing St. John's Wort, each one broken down to its full ingredient list — and combination products often carry several ingredients besides St. John's Wort. Your product may carry other ingredients that interact with Phenobarbital too, on top of St. John's Wort — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where St. John's Wort and Phenobarbital Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement St. John's Wort
Top 25%

#156 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Phenobarbital
Top half

#1,104 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About St. John's Wort

What is St. John's Wort?

St. John's Wort
  • Mild to moderate depression
  • Anxiety and stress
  • Sleep problems
  • Menopausal symptoms
  • Wound healing (topical)

St. John's wort is a well-studied herb most often used for mild to moderate depression, and some research suggests it may help with this. However, it has many serious interactions with prescription medicines and is not safe for everyone, so always talk to your pharmacist or doctor before taking it.

Read the full St. John's Wort monograph & all interactions
Medication

About Phenobarbital

What Is Phenobarbital Used For?

Brand names: Phenobarbital, Solfoton, Luminal

Phenobarbital tablets and oral solutions are used to treat generalized and partial seizures and as a sedative. Phenobarbital Sodium injection is used as a long-term anticonvulsant for generalized tonic-clonic and focal seizures, for emergency control of acute convulsive episodes (including status epilepticus), for sedation, short-term treatment of insomnia, and as a preanesthetic. It is also used in pediatric patients as an anticonvulsant and sedative, including before and after surgery.

Sezaby (phenobarbital injection, intravenous) is specifically indicated for the treatment of neonatal seizures in term and preterm infants. It is not approved for use in adolescents or adults.

See full Phenobarbital drug information
Keep checking

Other Drugs & St. John's Wort

Browse every other medication we’ve checked against St. John's Wort — both the ones with a known interaction and the ones without. Select any drug for the full detail.

754Major
388Moderate
0Minor
1,687No known interaction
754 Major 388 Moderate 1,687 No interaction
Major

754 interactions

Showing 60 of 754 major interactions — see all 754 on the St. John's Wort page.

Moderate

388 interactions

Showing 60 of 388 moderate interactions — see all 388 on the St. John's Wort page.

No interaction 1,687 drugs checked — show the list

We also checked St. John's Wort against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 1,687 medications checked with no known interaction — see the full St. John's Wort list.

See the full St. John's Wort interactions page
See every supplement checked against Phenobarbital, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
St. John's Wort monograph › Uses, safety, and every drug interaction in one place Phenobarbital supplement interactions › Every supplement checked against Phenobarbital, ranked by severity Phenobarbital drug information › The full plain-English guide to this medication Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking St. John's Wort and Phenobarbital Together: Common Questions

Can you take St. John's Wort with Phenobarbital?
This is rated a major interaction, so the combination is best avoided unless your doctor or pharmacist has specifically told you otherwise. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for St. John's Wort and Phenobarbital?
Phenobarbital belongs to more than one drug category, and St. John's Wort interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the St. John's Wort and Phenobarbital interaction?
We rate it Major. This is a clinically significant combination that is generally best avoided, or used only under the direct supervision of your physician or pharmacist.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

Still Have a Question About Phenobarbital and St. John's Wort?

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.