Drug & supplement interaction

European Mandrake + Methotrexate

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

Moderate Interaction
The bottom line Moderate

European Mandrake has a moderate interaction with Methotrexate. Theoretically, concurrent use might increase absorption of some drugs because of inhibited gastrointestinal (GI) motility caused by European mandrake.

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

European Mandrake and Methotrexate

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

Moderate

ORAL DRUGS

Why this applies to Methotrexate

Methotrexate falls under ORAL DRUGS — the group European Mandrake interacts with.

Theoretically, concurrent use might increase absorption of some drugs because of inhibited gastrointestinal (GI) motility caused by European mandrake.
Severity Moderate Likelihood Probable Evidence D

Interaction 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..

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

First, the most important thing: European mandrake is genuinely poisonous, and we don't recommend taking it at all. Putting that aside, here's the theoretical concern with your methotrexate. Mandrake's tropane alkaloids slow down how fast your gut moves things along. When your gut empties more slowly, an oral medicine can sit there longer and get absorbed more fully, so more of it may end up in your bloodstream.

For methotrexate, that could mean a higher dose effect than expected. This drug already has a narrow safe range, and too much can cause mouth sores, nausea, low blood counts, and liver or kidney strain. This is only a theory based on how these chemicals behave, not proven in studies, but please don't combine them. Talk with your pharmacist or doctor first.

References
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.

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

European Mandrake Also Interacts With Other Medications

European Mandrake has 2,041 moderate known drug interactions in our database — the Methotrexate one above is one of them. If you take anything else, check it against the full list below.

Taking anything else?

Check Another of Your Medications Against European Mandrake

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

From our Q&A

Questions About European Mandrake 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 European Mandrake 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 European Mandrake 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

How much people look this up

Where European Mandrake 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 European Mandrake
Top 25%

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

29 days ago today
Medication Methotrexate
Top 5%

#43 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 European Mandrake

What is European Mandrake?

European Mandrake
  • Insomnia (traditional)
  • Pain relief (historical)
  • Anxiety or depression (folk use)
  • Gout and aches (traditional)
  • Sedation or anesthesia (historical)

European mandrake is a highly toxic plant from the nightshade family that was used in ancient and medieval times as a sedative and pain reliever. It contains powerful poisons that can cause serious harm or death, and there is no proof it safely treats any condition. We strongly recommend you do not consume mandrake in any form.

Read the full European Mandrake 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.

See full Methotrexate drug information
Keep checking

Other Drugs & European Mandrake

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

0Major
2,041Moderate
0Minor
788No known interaction
Moderate

2,041 interactions

Showing 60 of 2,041 moderate interactions — see all 2,041 on the European Mandrake page.

No interaction 788 drugs checked — show the list

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

Showing the 60 most looked-up of 788 medications checked with no known interaction — see the full European Mandrake list.

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

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Pharmacist Counseling Corner

Taking European Mandrake and Methotrexate Together: Common Questions

Can you take European Mandrake with Methotrexate?
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 European Mandrake and Methotrexate 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.