Methotrexate

For an informed discussion with your doctor or pharmacist. This information collection is not a clinically validated interaction checker. Missing data do not establish safety. Do not change or stop prescribed medicines on the basis of this information. The findings apply to the specific conditions studied; laboratory and animal studies cannot be directly extrapolated to humans.

Active substance: Methotrexate

Examples of brand names: Lantarel [DE]; Metex [DE]

ATC code: L04AX03

Main use (for orientation): Autoimmune diseases; oncology

Documented research summary

A mouse experiment examined CBD and methotrexate together. It generates hypotheses; it does not establish human benefits/safety or proven pharmacological synergy.

Uncertainties and limitations

No evidence of synergy or hepatoprotection in humans; do not equate weekly low-dose use with high-dose oncology treatment.

Research is limited to the specified date and protocol; it is not globally exhaustive. Brand names and authorisations do not constitute a complete current market overview.

Structured assessment

Category: Direct pair finding

Cannabinoid scope: 28 register names in the documented search family; neither 28 individual clinical trials nor a blanket assessment of all cannabinoids.

Evidence status: Pair-specific evidence, distinguished in the individual findings

Mechanism / drug context: Preclinical combination effects on inflammatory signals; no clinically determined methotrexate pharmacokinetics with CBD.

Type of supporting material: See the separate original findings

Clinical interpretation: Requires individual assessment by a doctor or pharmacist. Lack of evidence does not establish safety; no dosage or discontinuation advice is provided.

Context: Methotrexate is an active folate antagonist with active intracellular polyglutamates; not a classical CYP-activated prodrug; oral Trexall label.

Drug context and gaps in search results are not measured interactions. The source role below describes which statement the source actually supports.

Source role [CA_L_D0026]: Drug context

Statement supported: Supports dosage form, metabolism and/or known risks; alone, it does not substantiate a cannabinoid–drug pair finding.

Source: TREXALL (METHOTREXATE) TABLET, FILM COATED [TEVA WOMEN'S HEALTH LLC] [CA_L_D0026]

Source role [CA_P_41955700]: Pair finding

Statement supported: The combination altered inflammatory and tissue characteristics compared with methotrexate alone.

Source: Cannabidiol synergizes with methotrexate to attenuate rheumatoid arthritis via STAT3/NF-κB signalling-mediated M1 macrophage polarization. [CA_P_41955700]

Source role [CA_P_42462478]: Commentary critically examining methodology

Statement supported: Commentary on the methodological assessment of the CBD/methotrexate work; not a second independent animal study.

Source: Comment on "cannabidiol synergizes with methotrexate to attenuate rheumatoid arthritis via STAT3/NF-κB signalling-mediated M1 macrophage polarization". [CA_P_42462478]

Scope of review: Individual research with documented title/abstract screening and targeted review of original sections. This is not exhaustive evidence that interactions are absent.

Unresolved source question: The complete stored individual review, label review, literature screening, conclusion and uncertainties were read. Targeted sections of original information were rechecked; no claim is made that all product information or full texts were completely revalidated.

Separately recorded findings

1 separately recorded finding. Each statement applies to its documented study context.

CBD – laboratory and animal studies

Finding ID: V6_D0026_1

Type of result: Finding within the documented study context

Observation: The combination altered inflammatory and tissue characteristics compared with methotrexate alone.

Mechanism: Inflammatory signals/macrophages in a mouse arthritis model

Study type: Mouse experiment

Context studied: Xu et al. 2026; n=5 per group.

Clinical interpretation: No assurance of clinical benefit or safety.

Limitations and uncertainties: Formal synergy, pharmacokinetics and long-term safety remain unresolved; methodological criticism taken into account.

Original sources for this finding: Cannabidiol synergizes with methotrexate to attenuate rheumatoid arthritis via STAT3/NF-κB signalling-mediated M1 macrophage polarization. [CA_P_41955700]; Comment on "cannabidiol synergizes with methotrexate to attenuate rheumatoid arthritis via STAT3/NF-κB signalling-mediated M1 macrophage polarization". [CA_P_42462478]

References and access status

[CA_L_D0026] TREXALL (METHOTREXATE) TABLET, FILM COATED [TEVA WOMEN'S HEALTH LLC]

Original source / bibliographic reference

Authors: Teva Women's Health LLC

Year: 2026

Source type: Current published human-use SPL / product information

Source access – 23 October 2026: Source destination was accessible when checked.

Bibliographic attribution or source identity cross-checked.

[CA_P_41955700] Cannabidiol synergizes with methotrexate to attenuate rheumatoid arthritis via STAT3/NF-κB signalling-mediated M1 macrophage polarization.

Original source / bibliographic reference

Authors: Xu J, Wang Z, Geng Q, Wen C, Jiao Y, Deng T, Shi T, Wang Y, Deng T, Xiao C.

Year: 2026

Source type: Journal Article

DOI: 10.1016/j.intimp.2026.116627

PMID: 41955700

Source access – 23 October 2026: Source destination was accessible when checked.

Bibliographic attribution or source identity cross-checked.

DOI – publisher access (access restrictions may apply)

[CA_P_42462478] Comment on "cannabidiol synergizes with methotrexate to attenuate rheumatoid arthritis via STAT3/NF-κB signalling-mediated M1 macrophage polarization".

Original source / bibliographic reference

Authors: Qu X, Huang T, Chen B.

Year: 2026

Source type: Journal Article

DOI: 10.1016/j.intimp.2026.117138

PMID: 42462478

Source access – 23 October 2026: Direct retrieval could not be fully verified; availability remains unresolved.

Bibliographic attribution or source identity cross-checked.

DOI – publisher access (access restrictions may apply)

[CA_P_39603835] Cannabidiol mitigates methotrexate-induced hepatic injury via SIRT-1/p53 signaling and mitochondrial pathways: reduces oxidative stress and inflammation.

Original source / bibliographic reference

Authors: Ilhan I, Asci H, Candan IA, Savran M, Imeci OB, Sevuk MA.

Year: 2025

Source type: Journal Article

DOI: 10.1080/01480545.2024.2425994

PMID: 39603835

Source access – 23 October 2026: Source destination was accessible when checked.

Bibliographic attribution or source identity cross-checked.

DOI – publisher access (access restrictions may apply)

[CA_P_38388876] The effects of cannabidiol against Methotrexate-induced lung damage.

Original source / bibliographic reference

Authors: Ozmen O, Milletsever A, Tasan S, Selcuk E, Savran M.

Year: 2024

Source type: Journal Article

DOI: 10.1111/bcpt.13992

PMID: 38388876

Source access – 23 October 2026: Direct retrieval could not be fully verified; availability remains unresolved.

Bibliographic attribution or source identity cross-checked.

DOI – publisher access (access restrictions may apply)

[CA_P_37927177] The ameliorative effects of cannabidiol on methotrexate-induced neuroinflammation and neuronal apoptosis via inhibiting endoplasmic reticulum and mitochondrial stress.

Original source / bibliographic reference

Authors: Unlu MD, Asci H, Yusuf Tepebasi M, Arlioglu M, Huseynov I, Ozmen O, Sezer S, Demirci S.

Year: 2024

Source type: Journal Article

DOI: 10.1002/jbt.23571

PMID: 37927177

Source access – 23 October 2026: Direct retrieval could not be fully verified; availability remains unresolved.

Bibliographic attribution or source identity cross-checked.

DOI – publisher access (access restrictions may apply)

[CA_P_293141] Delata-9-tetrahydrocannabinol as an antiemetic in cancer patients receiving high-dose methotrexate. A prospective, randomized evaluation.

Original source / bibliographic reference

Authors: Chang AE, Shiling DJ, Stillman RC, Goldberg NH, Seipp CA, Barofsky I, Simon RM, Rosenberg SA.

Year: 1979

Source type: Clinical Trial; Randomized Controlled Trial; Journal Article

DOI: 10.7326/0003-4819-91-6-819

PMID: 293141

Source access – 23 October 2026: Source destination was accessible when checked.

Bibliographic attribution or source identity cross-checked.

DOI – publisher access (access restrictions may apply)

[CA_P_26033282] Cannabidiol for the Prevention of Graft-versus-Host-Disease after Allogeneic Hematopoietic Cell Transplantation: Results of a Phase II Study.

Original source / bibliographic reference

Authors: Yeshurun M, Shpilberg O, Herscovici C, Shargian L, Dreyer J, Peck A, Israeli M, Levy-Assaraf M, Gruenewald T, Mechoulam R, Raanani P, Ram R.

Year: 2015

Source type: Clinical Trial, Phase II; Journal Article

DOI: 10.1016/j.bbmt.2015.05.018

PMID: 26033282

Source access – 23 October 2026: Direct retrieval could not be fully verified; availability remains unresolved.

Bibliographic attribution or source identity cross-checked.

DOI – publisher access (access restrictions may apply)

Research as of 23 October 2026. Not all original full texts could be reviewed in full. Source accessibility and the strength of scientific evidence must be assessed separately. An accessible link does not establish medical approval; a bibliographic record with an abstract does not replace the original full text.

Drug search and explanation of the evidence · Guide: cannabinoids and medicines · Author and responsibility