Drug & supplement interaction

St. John's Wort + Aspirin, Codeine Phosphate, Phenobarbital

Aspirin, Codeine Phosphate, Phenobarbital brand name: Phenaphen.

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

Aspirin, Codeine Phosphate, 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 Aspirin, Codeine Phosphate, 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. Aspirin, Codeine Phosphate, 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)

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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

This combo pill packs three medicines, and the one that matters most here is the phenobarbital. St. John's wort revs up the liver enzymes that break phenobarbital down, so your body clears it faster and blood levels can drop. For a seizure or sedative medicine, that's a real concern: weaker control could mean breakthrough seizures or the drug simply not working as well as expected.

This isn't a guess, there's decent evidence behind it, which is why it's rated as a major, likely interaction. The tricky part is that levels can swing both ways: lower while you're taking the herb, then climbing again if you stop it, which risks extra drowsiness. Please don't start or stop either one on your own. Talk with your pharmacist or doctor first so they can monitor you safely.

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

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Why this applies to Aspirin, Codeine Phosphate, Phenobarbital

Aspirin, Codeine Phosphate, 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 piece that matters for this combo pill. St. John's wort tends to speed up a liver enzyme called CYP2B6, and the phenobarbital part of this product is one of the medicines that enzyme helps break down. So in theory, taking the herb regularly could lower your phenobarbital levels and make it work less well, which matters a lot since phenobarbital is a seizure and sedative drug with a narrow safe range.

On top of that, St. John's wort revs up other enzymes too, so it can nudge the codeine and even general drug handling around. The study we have was on a different drug (bupropion) and showed only a modest drop, so the effect here is possible, not certain. Please don't start or stop anything on your own. Check with your pharmacist or doctor first.

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 Aspirin, Codeine Phosphate, 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. Aspirin, Codeine Phosphate, 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 Aspirin, Codeine Phosphate, 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 Aspirin, Codeine Phosphate, 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 Aspirin, Codeine Phosphate, Phenobarbital

This page covers St. John's Wort only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Aspirin, Codeine Phosphate, Phenobarbital page lists 352 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), Asarabacca (major), Beer (major) and Danshen (major).

By severity: 12 major · 304 moderate · 36 minor.

From our pharmacist’s overview on the Aspirin, Codeine Phosphate, Phenobarbital page

“Alcohol is the entry I would flag first with Phenaphen (aspirin, codeine phosphate, phenobarbital): beer or wine layered onto codeine and phenobarbital can deepen sedation and, at worst, slow breathing. This medication deserves real caution with supplements.”

Reviewed by 2 · Jul 18, 2026

Open the Aspirin, Codeine Phosphate, 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 Aspirin, Codeine Phosphate, 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 Aspirin, Codeine Phosphate, 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%

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

29 days ago today
Medication Aspirin, Codeine Phosphate, Phenobarbital
Top 10%

#260 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
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 Aspirin, Codeine Phosphate, 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 Aspirin, Codeine Phosphate, Phenobarbital supplement interactions › Every supplement checked against Aspirin, Codeine Phosphate, Phenobarbital, ranked by severity 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 Aspirin, Codeine Phosphate, Phenobarbital Together: Common Questions

Can you take St. John's Wort with Aspirin, Codeine Phosphate, 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 Aspirin, Codeine Phosphate, Phenobarbital?
Aspirin, Codeine Phosphate, 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 Aspirin, Codeine Phosphate, 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 Aspirin, Codeine Phosphate, 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.