Drug & supplement interaction

Skullcap + Acetaminophen, Butalbital, Codeine Phosphate

Acetaminophen, Butalbital, Codeine Phosphate brand name: Phrenilin #3.

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

Skullcap has a moderate interaction with Acetaminophen, Butalbital, Codeine Phosphate. Theoretically, skullcap can have additive effects when used with other CNS depressants.

Read the full interaction report
SeverityModerate
LikelihoodPossible
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Skullcap and Acetaminophen, Butalbital, Codeine Phosphate

Here is the interaction we found between these two, with the evidence behind it.

Moderate

CNS DEPRESSANTS

Why this applies to Acetaminophen, Butalbital, Codeine Phosphate

Acetaminophen, Butalbital, Codeine Phosphate falls under CNS DEPRESSANTS — the group Skullcap interacts with.

Theoretically, skullcap can have additive effects when used with other CNS depressants.
Animal and clinical research suggests that skullcap can cause sedation and cognitive impairment.
Severity Moderate Likelihood Possible Evidence D

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 thing to keep in mind with Phrenilin #3: it already carries two ingredients that calm the brain down. Butalbital is a barbiturate sedative, and codeine is an opioid pain reliever. Both can make you drowsy and slow your thinking. Skullcap is thought to nudge the brain's calming GABA system in a similar direction, so stacking it on top could add to that sedating effect.

In plain terms, you might feel more sleepy, foggy, dizzy, or off-balance than usual. To be honest, this concern comes mostly from lab and animal studies, so it's more theoretical than proven. Still, since this medication is already a strong sedative combo, it's worth a quick chat with your pharmacist or doctor before adding skullcap.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Wolfson P, Hoffmann DL. An investigation into the efficacy of Scutellaria lateriflora in healthy volunteers. Altern Ther Health Med 2003;9:74-8.
  2. Awad, R., Arnason, J. T., Trudeau, V., Bergeron, C., Budzinski, J. W., Foster, B. C., and Merali, Z. Phytochemical and biological analysis of skullcap (Scutellaria lateriflora L.): a medicinal plant with anxiolytic properties. Phytomedicine. 2003;10(8):6 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

Skullcap Also Interacts With Other Medications

Skullcap has 247 moderate known drug interactions in our database — the Acetaminophen, Butalbital, Codeine Phosphate one above is one of them. If you take anything else, check it against the full list below.

Moderate 247 No known interaction 2,583 (incl. Acetaminophen, Butalbital, Codeine Phosphate)
Taking anything else?

Check Another of Your Medications Against Skullcap

Covers the 2,830 medications we’ve checked against Skullcap. Pick one to open its full report.

From our Q&A

Questions About Skullcap or Acetaminophen, Butalbital, Codeine Phosphate

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Skullcap or Acetaminophen, Butalbital, Codeine Phosphate, 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 Acetaminophen, Butalbital, Codeine Phosphate

This page covers Skullcap only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Butalbital, Codeine Phosphate page lists 240 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 Gamma-hydroxybutyrate (ghb) (major).

Open the Acetaminophen, Butalbital, Codeine Phosphate interaction page

One more smart check

Taking Skullcap as Part of a Dietary Supplement Product? Check It for Interactions

We hold 926 real supplement products containing Skullcap, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Skullcap. Your product may carry other ingredients that interact with Acetaminophen, Butalbital, Codeine Phosphate too, on top of Skullcap — 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 Skullcap and Acetaminophen, Butalbital, Codeine Phosphate 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 Skullcap
Top 25%

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

29 days ago today
Medication Acetaminophen, Butalbital, Codeine Phosphate
Steady interest

#1,523 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 Skullcap

What is Skullcap?

Skullcap
  • Anxiety and stress
  • Trouble sleeping
  • Nervous tension
  • Muscle spasms
  • General relaxation

American skullcap is an herb traditionally used to calm anxiety and promote relaxation, but solid human evidence is very limited. It is generally considered relatively safe for short-term use in healthy adults, though it should be avoided in pregnancy and breastfeeding and used cautiously because of possible liver concerns and product mislabeling.

Read the full Skullcap monograph & all interactions
Keep checking

Other Drugs & Skullcap

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

0Major
247Moderate
0Minor
2,582No known interaction
247 Moderate 2,582 No interaction
Moderate

247 interactions

Showing 60 of 247 moderate interactions — see all 247 on the Skullcap page.

No interaction 2,582 drugs checked — show the list

We also checked Skullcap against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,582 medications checked with no known interaction — see the full Skullcap list.

See the full Skullcap interactions page
See every supplement checked against Acetaminophen, Butalbital, Codeine Phosphate, 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
Skullcap monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Butalbital, Codeine Phosphate supplement interactions › Every supplement checked against Acetaminophen, Butalbital, Codeine Phosphate, 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 Skullcap and Acetaminophen, Butalbital, Codeine Phosphate Together: Common Questions

Can you take Skullcap with Acetaminophen, Butalbital, Codeine Phosphate?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
How serious is the Skullcap and Acetaminophen, Butalbital, Codeine Phosphate interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

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

Still Have a Question About Acetaminophen, Butalbital, Codeine Phosphate and Skullcap?

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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.