Drug & supplement interaction

Sassafras + Aspirin, Codeine Phosphate, Phenobarbital

Aspirin, Codeine Phosphate, Phenobarbital brand name: Phenaphen.

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

Aspirin, Codeine Phosphate, Phenobarbital falls into 2 drug categories that Sassafras can interact with; the most serious is rated moderate. Theoretically, concomitant use of sassafras with drugs with sedative properties may cause additive sedative effects.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Sassafras and Aspirin, Codeine Phosphate, Phenobarbital

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

Why Are There 2 Interactions?

Sassafras interacts with whole categories of medication. Aspirin, Codeine Phosphate, Phenobarbital falls into 2 of those categories, so it can interact with Sassafras in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CNS DEPRESSANTS

1 of 2

Why this applies to Aspirin, Codeine Phosphate, Phenobarbital

Aspirin, Codeine Phosphate, Phenobarbital falls under CNS DEPRESSANTS — the group Sassafras interacts with.

Theoretically, concomitant use of sassafras with drugs with sedative properties may cause additive sedative effects.
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

This combination pill pairs aspirin with two ingredients that can make you sleepy: codeine (a narcotic pain reliever) and phenobarbital (a barbiturate sedative). Sassafras has been reported to have a calming, sedative quality of its own. So the concern here is simple addition: taking sassafras alongside this medicine could pile drowsiness on top of drowsiness. You might feel more groggy, lightheaded, or mentally foggy than usual, and in heavier cases slowed breathing is a worry with codeine and phenobarbital together.

To be fair, this caution is theoretical, based on how the ingredients work rather than solid human studies. Even so, since sassafras carries real liver and cancer concerns of its own, I'd steer clear of it and check with your pharmacist or doctor first.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications, 1998.
Moderate

CYTOCHROME P450 1A2 (CYP1A2) INDUCERS

2 of 2

Aspirin, Codeine Phosphate, Phenobarbital also falls under CYTOCHROME P450 1A2 (CYP1A2) INDUCERS.

In vitro research suggests that cytochrome P450 1A2 (CYP1A2) inducers might increase the cytotoxicity of safrole. So far, this interaction has not been reported in humans. Also, it is not known if CYP1A2 inducers increase the toxicity of sassafras. Inducers of CYP1A2 include omeprazole (Prilosec).
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 angle to focus on with this combo pill (aspirin, codeine, and phenobarbital). The phenobarbital part is a known liver enzyme booster, and it can rev up CYP1A2. The concern on file is that speeding up that enzyme might turn more of sassafras's safrole into harmful, liver-damaging byproducts. In plain terms, taking sassafras alongside this medicine could, in theory, raise the risk of liver injury from the sassafras itself.

I'll be honest, this comes only from lab and animal work, not from real people, so it's more of a caution than a proven problem. The bigger point: safrole is banned from foods because it can damage the liver and may cause cancer, so internal use of sassafras isn't worth the risk. Choose safrole-free products and check with your pharmacist.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Hu L, Wu F, He J, Zhong L, Song Y, Shao H. Cytotoxicity of safrole in HepaRG cells: studies on the role of CYP1A2-mediated ortho-quinone metabolic activation. Xenobiotica. 2019;49(12):1504-1515. 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

Sassafras Also Interacts With Other Medications

Sassafras has 274 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.

Moderate 274 No known interaction 2,556 (incl. Aspirin, Codeine Phosphate, Phenobarbital)
Taking anything else?

Check Another of Your Medications Against Sassafras

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

Everything else you take

See Every Supplement That Interacts With Aspirin, Codeine Phosphate, Phenobarbital

This page covers Sassafras 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 Sassafras as Part of a Dietary Supplement Product? Check It for Interactions

We hold 11 real supplement products containing Sassafras, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Sassafras. Your product may carry other ingredients that interact with Aspirin, Codeine Phosphate, Phenobarbital too, on top of Sassafras — 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 Sassafras 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 Sassafras
Top half

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

29 days ago today
Medication Aspirin, Codeine Phosphate, Phenobarbital
Top 25%

#377 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 Sassafras

What is Sassafras?

  • Digestive complaints
  • Cold and flu symptoms
  • Joint and muscle aches
  • Skin conditions (topical folk use)
  • As a flavoring agent (traditional root beer)

Sassafras is an aromatic North American tree whose root bark and oil were once popular in teas and as a flavoring, but it contains safrole, a compound the FDA has banned in foods because it can cause cancer and liver damage. There is no good evidence it safely treats any health condition, and most experts recommend avoiding internal use. If you want the flavor, choose products that are labeled safrole-free.

Read the full Sassafras monograph & all interactions
Keep checking

Other Drugs & Sassafras

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

0Major
274Moderate
0Minor
2,555No known interaction
274 Moderate 2,555 No interaction
Moderate

274 interactions

Showing 60 of 274 moderate interactions — see all 274 on the Sassafras page.

No interaction 2,555 drugs checked — show the list

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

Showing the 60 most looked-up of 2,555 medications checked with no known interaction — see the full Sassafras list.

See the full Sassafras 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
Sassafras 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 Sassafras and Aspirin, Codeine Phosphate, Phenobarbital Together: Common Questions

Can you take Sassafras with Aspirin, Codeine Phosphate, Phenobarbital?
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.
Why are there 2 interactions listed for Sassafras and Aspirin, Codeine Phosphate, Phenobarbital?
Aspirin, Codeine Phosphate, Phenobarbital belongs to more than one drug category, and Sassafras 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 Sassafras and Aspirin, Codeine Phosphate, Phenobarbital 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

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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.