Drug & supplement interaction

Sassafras + Methotrexate

Methotrexate brand names: Rheumatrex, Otrexup, Rasuvo, Reditrex.

No Known Interaction
Medically reviewed by · Updated July 2026 · Pair last verified Sep 13, 2026
The bottom line No known interaction

We found no known interaction between Sassafras and Methotrexate in our sources. Absence of a documented interaction is not the same as proven safety, and does not guarantee one does not exist. Do not start, stop, or change a medication or supplement based on this page; confirm with your pharmacist or doctor first. Additionally, although there is no interaction, the two are separately associated with some of the same side effects, which would make a new symptom harder to attribute to one or the other.

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Interaction report

Sassafras and Methotrexate

We checked these two against our interaction database. Here is what we found.

No Known Interaction Found

We did not find a documented interaction between Methotrexate and Sassafras in our sources. This does not guarantee that the combination is completely free of risk — there is often limited research on supplements and herbal products, especially around drug interactions.

If you decide to take both, the practical routine is simple: add one new thing at a time and note the date you started it. If the combination is going to disagree with you, it usually shows in the first days to a couple of weeks — and a start date turns “I’ve been feeling off” into something a pharmacist can actually work with. Do not stop a prescribed medicine on your own.

Always talk with your pharmacist or doctor before making changes to your medications or supplements, particularly if you take several medications or have an ongoing health condition.

Sassafras safety at a glance

Sassafras overall Avoid Sassafras contains safrole, a compound linked to cancer and liver toxicity, and the FDA has banned it in food.
Pregnancy Likely Unsafe When used orally; avoid using. Sassafras oil has abortifacient effects. Read the full pregnancy detail
Breastfeeding Likely Unsafe When used orally; avoid using. Sassafras oil has abortifacient effects. Read the full breastfeeding detail

Pregnancy & breastfeeding ratings are from Natural Medicines (Therapeutic Research Center) — the full detail is in the Special populations card below. Safety guidance is general; always confirm with your pharmacist or doctor for your situation.

Still wondering about combining Methotrexate and Sassafras? Ask Dr. Brian Staiger, PharmD, BCPS directly ›
How we checked

Why No Interaction Is Listed for Methotrexate

Interactions in our licensed database are recorded against drug classes, not just single drug names. Methotrexate is filed under 6 classifications — including organic anion-transporting polypeptide substrates (oatp), organic anion transporter 3 (oat3) substrates, hepatotoxic drugs. Sassafras has documented interactions with 2 drug classes — the most serious being cns depressants (moderate) and cytochrome p450 1a2 (cyp1a2) inducers (moderate) — and none of Methotrexate’s classifications are among them.

Classification data comes from our licensed Natural Medicines dataset. A medication can belong to classes beyond those recorded there, so this describes how the check was run — it is not a safety guarantee.

Keep it in perspective

Sassafras Does Interact With Other Medications

Sassafras has 275 moderate known drug interactions in our database — Methotrexate isn’t one of them. If you take anything else, check it against the full list below.

Moderate 275 No known interaction 2,555 (incl. Methotrexate)
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.

What to actually watch for

No Interaction Found — But Data Suggests Sassafras and Methotrexate May Share Several of the Same Side Effects

This is not an interaction. Neither one changes how your body handles the other, and nothing here says they react together. What our sources do show is that each has separately been linked to the effects below — so taking both can make those effects more likely to turn up, and harder to pin on one or the other if they do.

  • Sweating Additional detail

    Sassafras

    “Sassafras is generally regarded as unsafe for use in medicinal amounts. Any benefits of therapy may not outweigh the risks of toxicity. Orally, sassafras can cause diaphoresis and hot flashes (11). Consumption of large amounts of sassafras oil can cause hallucinations lasting for several days (4).”

    Sassafras · Natural Medicines adverse-effect record, reported in abortion.

    6 sources cited
    1. 11. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. 2nd ed. New York, NY: John Wiley & Sons, 1996.
    2. 4. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.
    3. 6. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.
    4. 73138. Segelman, A. B., Segelman, F. P., Karliner, J., and Sofia, R. D. Sassafras and herb tea. Potential health hazards. JAMA 8-2-1976;236(5):477. DOI
    5. 73134. Ueng, Y. F., Hsieh, C. H., Don, M. J., Chi, C. W., and Ho, L. K. Identification of the main human cytochrome P450 enzymes involved in safrole 1'-hydroxylation. Chem Res Toxicol 2004;17(8):1151-1156. PubMed
    6. 73137. Kapadia, G. J., Chung, E. B., Ghosh, B., Shukla, Y. N., Basak, S. P., Morton, J. F., and Pradhan, S. N. Carcinogenicity of some folk medicinal herbs in rats. J Natl.Cancer Inst. 1978;60(3):683-686.

    Methotrexate

    Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate. Read the label on DailyMed ›

  • A skin rash Additional detail

    Sassafras

    “Topically, sassafras can cause contact dermatitis (6).”

    Sassafras · Natural Medicines adverse-effect record, reported in dermatitis.

    1 source cited
    1. 6. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.

    Methotrexate

    Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate. Read the label on DailyMed ›

  • Vomiting Additional detail

    Sassafras

    “Orally, consuming 5 mL sassafras oil can cause vomiting (4,6).”

    Sassafras · Natural Medicines adverse-effect record, reported in nausea and vomiting.

    2 sources cited
    1. 4. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.
    2. 6. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.

    Methotrexate

    Listed in the ADVERSE REACTIONS section of the FDA label for Methotrexate. Read the label on DailyMed ›

Reported for Sassafras but not commonly for Methotrexate: hallucinations, raised blood pressure, a fast or pounding heartbeat and flushing.

Effects for Methotrexate come from the ADVERSE REACTIONS section of its FDA label; effects for Sassafras come from the Natural Medicines adverse-effect record, quoted above. Where a percentage is shown, it is the share of 489,806 voluntary FDA FAERS reports for Methotrexate that mention that effect — a reporting proportion, not an incidence rate and not evidence the drug caused it. Wording is matched across sources by our own clinical vocabulary, so treat this as a prompt to pay attention, not a diagnosis.

Special populations

Sassafras in Pregnancy & Breastfeeding

Pregnancy And Lactation Likely Unsafe

When used orally; avoid using. Sassafras oil has abortifacient effects.

DISCLAIMER: This tool is intended for informational purposes only, and should not be interpreted as specific medical advice. Patients should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.© 2026 Therapeutic Research Center

From our Q&A

Questions About Sassafras or Methotrexate

These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers Sassafras or Methotrexate, 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 Methotrexate

This page covers Sassafras only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Methotrexate page lists 82 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: Activated Charcoal (major), Apple (major), Beer (major), Grapefruit (major) and Siberian Cocklebur (major).

By severity: 7 major · 60 moderate · 15 minor.

From our pharmacist’s overview on the Methotrexate page

“The liver is where methotrexate and supplements clash most. Methotrexate (Rheumatrex, Otrexup, Rasuvo), used for rheumatoid arthritis, psoriasis, and certain cancers, can strain the liver on its own, and 38 of the 82 interacting ingredients on this list add liver risk of their own, alcohol included, which makes this a list to approach…”

Reviewed by 2 · Jul 18, 2026

Open the Methotrexate 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. Even though Sassafras itself has no known interaction with Methotrexate, another ingredient on your label might. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Sassafras and Methotrexate 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
Steady interest

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

29 days ago today
Medication Methotrexate
Top 5%

#49 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.

Where does our data come from?
  • Source: the Natural Medicines (TRC Healthcare) clinical database — the evidence-graded professional reference for herb & supplement interactions.
  • Citation library: 103,510 references behind our interaction content, 65,311 of them resolved to verified PubMed/DOI sources. See every Sassafras reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 13, 2026. The Sassafras and Methotrexate records this page draws on were last updated July 10, 2026.
  • What “no known interaction” means: no documented interaction in the sources above — not a guarantee of safety. Supplements are studied far less than prescription drugs, so we say exactly what the evidence supports, and nothing more.
Data structure & sourcing designed and verified by .
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.

Sassafras albidum · Lauraceae · Root bark, bark, and essential oil · Tea, dried root bark, essential oil, capsules, and as a flavoring

An interaction check asks whether these two react with each other — it does not ask whether Sassafras is a good idea for someone in your situation. Here is what our Sassafras record says about it on its own.

Sassafras: dosing

There is no established safe dose for sassafras, and most experts recommend not taking it internally at all because of safrole. There is no standardized medical dosing.If you use a commercial flavoring product that is labeled safrole-free, follow the directions on the label. Do not use whole sassafras root, bark, or essential oil as a home remedy.

From our Sassafras monograph — the full record covers uses, side effects and every documented interaction.

Read the full Sassafras monograph & all interactions
Medication

About Methotrexate

What Is Methotrexate Used For?

Brand names: Rheumatrex, Otrexup, Rasuvo, Reditrex

Methotrexate treats a wide range of serious conditions. In cancer care, it is used for acute lymphoblastic leukemia, non-Hodgkin lymphoma, osteosarcoma, breast cancer, head and neck cancer, and gestational trophoblastic neoplasia (a rare tumor related to pregnancy). It is also used to prevent and treat meningeal leukemia (cancer affecting the lining of the brain and spinal cord).

Outside of cancer, methotrexate is prescribed for adults with rheumatoid arthritis (RA), children with polyarticular juvenile idiopathic arthritis (a form of childhood arthritis), and adults with severe psoriasis that hasn't responded well to other treatments.

Most-Reported Side Effects for Methotrexate

From FAERS, the FDA’s public side-effect reporting system (489,806 reports, all brands). Reports are voluntary and are not proof the drug caused the effect.

Rheumatoid arthritis 42,798 reports
Arthralgia 40,830 reports
Fatigue 33,049 reports
Nausea 28,999 reports
Joint swelling 25,026 reports
See full Methotrexate drug information
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
275Moderate
0Minor
2,554No known interaction
275 Moderate 2,554 No interaction
Moderate

275 interactions

Showing 60 of 275 moderate interactions — see all 275 on the Sassafras page.

No interaction 2,554 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 2,554 medications checked with no known interaction — see the full Sassafras list.

See the full Sassafras interactions page
See every supplement checked against Methotrexate, ranked by severity
Evidence & sources

Sassafras References

The 9 references that drive our Sassafras monograph and interaction data, from the evidence-graded Natural Medicines (TRC Healthcare) database. Citations with a link open the study on PubMed or the publisher’s site.

  1. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.
  2. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.
  3. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. 2nd ed. New York, NY: John Wiley & Sons, 1996.
  4. McGuffin M, Hobbs C, Upton R, Goldberg A, eds. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press, LLC 1997.
  5. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications, 1998.
  6. Ueng, Y. F., Hsieh, C. H., Don, M. J., Chi, C. W., and Ho, L. K. Identification of the main human cytochrome P450 enzymes involved in safrole 1'-hydroxylation. Chem Res Toxicol 2004;17(8):1151-1156. PubMed
  7. Kapadia, G. J., Chung, E. B., Ghosh, B., Shukla, Y. N., Basak, S. P., Morton, J. F., and Pradhan, S. N. Carcinogenicity of some folk medicinal herbs in rats. J Natl.Cancer Inst. 1978;60(3):683-686.
  8. Segelman, A. B., Segelman, F. P., Karliner, J., and Sofia, R. D. Sassafras and herb tea. Potential health hazards. JAMA 8-2-1976;236(5):477. DOI
  9. 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

Medication overviews come from MedlinePlus (NIH); supplement label data from the NIH Dietary Supplement Label Database. Content is written and reviewed by licensed HelloPharmacist pharmacists — see our data sources and editorial standards.

Pharmacist Counseling Corner

Taking Sassafras and Methotrexate Together: Common Questions

Is it safe to take Sassafras with Methotrexate?
We do not list a known interaction between Sassafras and Methotrexate. That does not guarantee the combination is risk-free, so confirm with your pharmacist or doctor — especially if you take other medications or have a health condition.
Do Sassafras and Methotrexate have any of the same side effects?
Yes — our sources link each of them separately to 3 of the same effects. That is not an interaction: neither changes how your body handles the other. It does mean that if one of those effects turns up, it can be harder to tell which one is behind it. They are listed on this page with the source behind each.
How was the Sassafras and Methotrexate combination checked?
Interactions in our licensed database are recorded against drug classes. Methotrexate is filed under 6 classifications, and Sassafras has documented interactions with 2 drug classes — none of Methotrexate's classifications are among them. A medication can belong to classes beyond those recorded in our dataset, so this describes how the check was run rather than guaranteeing safety.
Does Sassafras interact with any other medications?
Yes. Sassafras has 275 documented drug interactions in our database — Methotrexate is simply not one of them. If you take anything else, it is worth checking each one; they are all listed on this page.
Does Methotrexate interact with any supplements?
Yes. Methotrexate has documented interactions with 82 supplements in our database — Sassafras is not one of them. The Methotrexate interaction page linked on this page lists every one, ranked by severity.

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

Where next

Keep Exploring

Sassafras monograph Uses, safety profile, and every drug interaction in one place Methotrexate drug information The full plain-English guide to this medication Methotrexate supplement interactions Every supplement checked against Methotrexate, 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 References The 9 citations behind this page Ask a pharmacist Free, personal answer from our licensed team

Still Have a Question About Methotrexate and Sassafras?

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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.