Drug & supplement interaction

St. John's Wort + Methotrexate

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

No Known Interaction
The bottom line No known interaction

We found no known interaction between St. John's Wort 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

St. John's Wort 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 St. John's Wort 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.

St. John's Wort safety at a glance

St. John's Wort overall Use caution Generally well tolerated short-term but has many serious drug interactions and can cause sun sensitivity.
Pregnancy Possibly Unsafe When used orally. Preliminary population research has found that taking St. John's wort while pregnant is associated with offspring that develop neural tube, ur... Read the full pregnancy detail
Breastfeeding Possibly Unsafe When used orally. Nursing infants of mothers who take St. John's wort have a greater chance of experiencing colic, drowsiness, and lethargy; avoid using. 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 St. John's Wort? 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. St. John's Wort has documented interactions with 47 drug classes — the most serious being alprazolam (xanax) (major), contraceptive drugs (major) and cyclosporine (neoral, sandimmune) (major) — 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

St. John's Wort Does Interact With Other Medications

St. John's Wort has 755 major, 388 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.

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.

What to actually watch for

No Interaction Found — But Data Suggests St. John's Wort 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. 3 of them are worth acting on rather than waiting out — marked below.

  • Kidney problems Worth acting on Additional detail

    St. John's Wort

    “Orally, St. John's wort has been associated with a case report of acute kidney failure in a 46-year-old female after one dose of homemade St. John's wort tea. Three sessions of hemodialysis were required before there was full recovery. However, causality is unclear since the patient had also been taking diclofenac intermittently for a month prior to developing kidney failure.”

    St. John's Wort · Natural Medicines adverse-effect record, reported in kidney failure.

    1 source cited
    1. 106741. Adibelli Z, Karacay I, Demir M, Duran C. St. John's Wort (Hypericum perforatum)-related acute kidney injury. Blood Purif. 2021 Aug 24:1-3. doi: 10.1159/000518349.

    Methotrexate

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

  • Liver problems Worth acting on Additional detail

    St. John's Wort

    “A case of acute hepatitis with prolonged cholestasis and features of vanishing bile duct syndrome has been reported for a patient who used tibolone and St. John's wort orally for 10 weeks. A case of jaundice with transaminitis and hyperbilirubinemia has been reported for a 79 year-old female who used St. John's wort and copaiba. Laboratory values normalized 7 weeks after discontinuation of both products.”

    St. John's Wort · Natural Medicines adverse-effect record, reported in cholestasis.

    2 sources cited
    1. 76135. Etogo-Asse, F., Boemer, F., Sempoux, C., and Geubel, A. Acute hepatitis with prolonged cholestasis and disappearance of interlobular bile ducts following tibolone and Hypericum perforatum (St. John's wort). Case of drug interaction? Acta Gastroenterol.Be
    2. 95505. Agollo MC, Miszputen SJ, Diament J. Hypericum perforatum-induced hepatotoxicity with possible association with copaiba (copaifera langsdorffii desf): a case report. Einstein (Sao Paulo) 2014;12(3):355-7.

    Methotrexate

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

  • Bleeding or bruising Worth acting on Additional detail

    St. John's Wort

    “Orally, St. John's wort can cause intermenstrual or abnormal menstrual bleeding. However, this effect has occurred in patients who were also taking an oral contraceptive. Changes in menstrual bleeding might be the result of a drug interaction. Also, St. John's wort has been associated with anorgasmia and frequent urination when used orally.

    Sexual dysfunction can occur with St.”

    St. John's Wort · Natural Medicines adverse-effect record, reported in antidepressant-induced sexual dysfunction.

    5 sources cited
    1. 1292. Yue QY, Bergquist C, Gerden B. Safety of St. John's wort (Hypericum perforatum). Lancet 2000;355:576-7. PubMed
    2. 76056. Ratz, A. E., von Moos, M., and Drewe, J. [St. John's wort: a pharmaceutical with potentially dangerous interactions]. Schweiz Rundsch.Med Prax. 5-10-2001;90(19):843-849.
    3. 10843. Hypericum Depression Trial Study Group. Effect of Hypericum perforatum (St. John's wort) in major depressive disorder: a randomized controlled trial. JAMA 2002;287:1807-14. PubMed
    4. 76070. van Gurp, G., Meterissian, G. B., Haiek, L. N., McCusker, J., and Bellavance, F. St John's wort or sertraline? Randomized controlled trial in primary care. Can Fam Physician 2002;48:905-912.
    5. 4836. Assalian P. Sildenafil for SJW-induced sexual dysfunction. J Sex Marital Ther 2000;26:357-8.

    Methotrexate

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

  • A change in sex drive / Chills Additional detail

    St. John's Wort

    “St. John's wort can induce hypomania in depressed patients and mania in depressed patients with occult bipolar disorder. Cases of first-episode psychosis have been reported for females who used St. John's wort orally. In both cases, symptoms resolved following discontinuation of St. John's wort and treatment with antipsychotics for several weeks.”

    St. John's Wort · Natural Medicines adverse-effect record, reported in anorexia.

    6 sources cited
    1. 325. O'Breasail AM, Argouarch S. Hypomania and St John's wort. Can J Psychiatry 1998;43:746-7.
    2. 3524. Schneck C. St. John's wort and hypomania. J Clin Psychiatry 1998;59:689. PubMed
    3. 3555. Nierenberg AA, Burt T, Matthews J, et al. Mania associated with St. John's wort. Biol Psychiatry 1999;46:1707-8. PubMed
    4. 3568. Moses EL, Mallinger AG. St. John's wort: Three cases of possible mania induction. J Clin Psychopharmacol 2000;20:115-7. PubMed
    5. 10845. Hammerness P, Basch E, Ulbricht C, et al. St. John's wort: a systematic review of adverse effects and drug interactions for the consultation psychiatrist. Psychosomatics 2003;44:271-82. PubMed
    6. 76047. Barbenel, D. M., Yusufi, B., O'Shea, D., and Bench, C. J. Mania in a patient receiving testosterone replacement postorchidectomy taking St John's wort and sertraline. J Psychopharmacol 2000;14(1):84-86.

    Methotrexate

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

  • Erection problems Additional detail

    St. John's Wort

    Recorded for St. John's Wort in the same Natural Medicines adverse-effect record shown under Bleeding or bruising above.

    Methotrexate

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

  • Sun sensitivity / Hair loss Additional detail

    St. John's Wort

    “Both topical and chronic oral use of St. John's wort can cause photodermatitis. The average threshold dose range for an increased risk of photosensitivity appears to be 1.8-4 grams St. John's wort extract or 5-10 mg hypericin, daily. Lower doses might not cause this effect. For example, a single dose of St.”

    St. John's Wort · Natural Medicines adverse-effect record, reported in alopecia.

    6 sources cited
    1. 206. Gulick RM, McAuliffe V, Holden-Wiltse J, et al. Phase I studies of hypericin, the active compound in St. John's Wort, as an antiretroviral agent in HIV-infected adults. AIDS Clinical Trials Group Protocols 150 and 258. Ann Intern Med 1999;130:510-4. PubMed
    2. 620. Golsch S, Vocks E, Rakoski J, et al. [Reversible increase in photosensitivity to UV-B caused by St. John's wort extract]. Hautarzt 1997;48:249-52.
    3. 758. Upton R, ed. St. John's wort, Hypericum perforatum: Quality control, analytical and therapeutic monograph. Santa Cruz, CA: American Herbal Pharmacopoeia 1997;1-32.
    4. 4628. Schempp CM, Ludtke R, Winghofer B, Simon JC. Effect of topical application of hypericum perforatum extract on skin sensitivity to solar simulated radiation. Photodermatol Photoimmunol Photomed 2000;16:125-8.
    5. 4631. Jacobson JM, Feinman L, Liebes L, et al. Pharmacokinetics, safety, and antiviral effects of hypericin, a derivative of St. John's Wort plant, in patients with chronic hepatitis C virus infection. Antimicrob Agents Chemother 2001;45:517-24. PubMed
    6. 6477. Lane-Brown MM. Photosensitivity associated with herbal preparations of St. John's wort (Hypericum perforatum). Med J Aust 2000;172:302.

    Methotrexate

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

  • Sore throat / Sweating Additional detail

    St. John's Wort

    “Orally, St. John's wort may cause sore throat, swollen glands, laryngitis, sinus ache, sweating, and hot flashes, although the frequency of these events appears to be similar to placebo.”

    St. John's Wort · Natural Medicines adverse-effect record, reported in pharyngitis.

    1 source cited
    1. 76150. Canning, S., Waterman, M., Orsi, N., Ayres, J., Simpson, N., and Dye, L. The efficacy of Hypericum perforatum (St John's wort) for the treatment of premenstrual syndrome: a randomized, double-blind, placebo-controlled trial. CNS.Drugs 2010;24(3):207-225. PubMed

    Methotrexate

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

Showing the 10 most notable of 23 shared effects — ranked by how unusual each one is, not just whether both lists mention it.

Reported for St. John's Wort but not commonly for Methotrexate: dependence or withdrawal symptoms, serotonin syndrome, passing urine more often and thoughts of self-harm.

Effects for Methotrexate come from the ADVERSE REACTIONS section of its FDA label; effects for St. John's Wort 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

St. John's Wort in Pregnancy & Breastfeeding

Pregnancy Possibly Unsafe

When used orally. Preliminary population research has found that taking St. John's wort while pregnant is associated with offspring that develop neural tube, urinary, and cardiovascular malformations. Subgroup analyses suggest that these risks may be higher when taking St. John's wort during the first trimester when compared with the second or third trimester. However, more research is needed to confirm these findings. Animal-model research also shows that constituents of St. John's wort might have teratogenic effects. Until more is known, St. John's wort should not be taken during pregnancy.

Lactation Possibly Unsafe

When used orally. Nursing infants of mothers who take St. John's wort have a greater chance of experiencing colic, drowsiness, and lethargy; avoid using.

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 St. John's Wort 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 St. John's Wort 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 St. John's Wort 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 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. Even though St. John's Wort 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 St. John's Wort 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 St. John's Wort
Top 25%

#157 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 St. John's Wort reference on this page ↓
  • Freshness: we automatically re-check this combination every week — this pair was last verified September 13, 2026. The St. John's Wort and Methotrexate records this page draws on were last updated July 11, 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 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.

Hypericum perforatum · Hypericaceae · Flowering tops and aerial parts (leaves and flowers) · Capsules, tablets, standardized extracts, teas, tinctures, and topical oils

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

St. John's Wort: dosing

There is no single official dose for St. John's wort. Products vary widely in strength, and many studies use extracts standardized to a set amount of hypericin or hyperforin. Because of this, the right dose depends on the specific product.The safest approach is to follow the directions on the product label and to choose a standardized extract from a reputable brand. Effects on mood, if any, may take several weeks to appear.

From our St. John's Wort monograph — the full record covers uses, side effects and every documented interaction.

Read the full St. John's Wort 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 & 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.

755Major
388Moderate
0Minor
1,686No known interaction
Major

755 interactions

Showing 60 of 755 major interactions — see all 755 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 1,686 drugs checked — show the list
Evidence & sources

St. John's Wort References

The 152 references that drive our St. John's Wort 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. Miller LG. Herbal Medicinals: Selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med 1998;158:2200-11.
  2. Gulick RM, McAuliffe V, Holden-Wiltse J, et al. Phase I studies of hypericin, the active compound in St. John's Wort, as an antiretroviral agent in HIV-infected adults. AIDS Clinical Trials Group Protocols 150 and 258. Ann Intern Med 1999;130:510-4. PubMed
  3. O'Breasail AM, Argouarch S. Hypomania and St John's wort. Can J Psychiatry 1998;43:746-7.
  4. Johne A, Brockmoller J, Bauer S, et al. Pharmacokinetic interaction of digoxin with an herbal extract from St John's wort (Hypericum perforatum). Clin Pharmacol Ther 1999;66:338-45.
  5. Gordon JB. SSRIs and St. John's Wort: possible toxicity? Am Fam Physician 1998;57:950, 953.
  6. Golsch S, Vocks E, Rakoski J, et al. [Reversible increase in photosensitivity to UV-B caused by St. John's wort extract]. Hautarzt 1997;48:249-52.
  7. Bove GM. Acute neuropathy after exposure to sun in a patient treated with St. John's Wort. Lancet 1998;352:1121-2. PubMed
  8. Brockmoller J, Reum T, Bauer S, et al. Hypericin and pseudohypericin: pharmacokinetics and effects on photosensitivity in humans. Pharmacopsychiatry 1997;30:94-101. PubMed
  9. Upton R, ed. St. John's wort, Hypericum perforatum: Quality control, analytical and therapeutic monograph. Santa Cruz, CA: American Herbal Pharmacopoeia 1997;1-32.
  10. Muller WE, Singer A, Wonnemann M, et al. Hyperforin represents the neurotransmitter reuptake inhibiting constituent of hypericum extract. Pharmacopsychiatry 1998;31:16-21.
  11. Abul-Ezz SR, Barone GW, Gurley BJ, et al. Effect of herbal supplements on cyclosporine blood levels and associated acute rejection. Am Soc of Nephrol Ann Mtg, Toronto, CAN 2000;Oct. 11-16:abstract A3754.
  12. Piscitelli SC, Burstein AH, Chaitt D, et al. Indinavir concentrations and St John's wort. Lancet 2000;355:547-8. PubMed
  13. Yue QY, Bergquist C, Gerden B. Safety of St. John's wort (Hypericum perforatum). Lancet 2000;355:576-7. PubMed
  14. Ruschitzka F, Meier PJ, Turina M, et al. Acute heart transplant rejection due to Saint John's wort. Lancet 2000;355:548-9. PubMed
  15. Roberts JE, Wang RH, Tan IP, et al. Hypericin (active ingredient in St. John's wort) photo-oxidation of lens proteins. Photochem Photobiol 1999;69:42S.

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 St. John's Wort and Methotrexate Together: Common Questions

Is it safe to take St. John's Wort with Methotrexate?
We do not list a known interaction between St. John's Wort 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 St. John's Wort and Methotrexate have any of the same side effects?
Yes — our sources link each of them separately to 10 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 St. John's Wort and Methotrexate combination checked?
Interactions in our licensed database are recorded against drug classes. Methotrexate is filed under 6 classifications, and St. John's Wort has documented interactions with 47 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 St. John's Wort interact with any other medications?
Yes. St. John's Wort has 1,143 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 — St. John's Wort 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

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

Our pharmacists answer your medication & supplement questions — free.

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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.