The effects of cannabidiol against Methotrexate-induced lung damage

Basic Clin Pharmacol Toxicol. 2024 May;134(5):695-703. doi: 10.1111/bcpt.13992. Epub 2024 Feb 22.


Methotrexate (MTX) is a widely used medication for various cancers, yet its use is associated with adverse effects on organs, notably the lungs. Cannabidiol (CBD), known for its antioxidant and anti-inflammatory properties, was investigated for its potential protective effects against MTX-induced lung injury. Thirty-two female Wistar Albino rats were divided into four groups: control, MTX (single 20 mg/kg intraperitoneal dose), MTX + CBD (single 20 mg/kg MTX with 0.1 ml of 5 mg/kg CBD for 7 days intraperitoneally) and CBD only (for 7 days). Lung tissues were analysed using histopathological, immunohistochemical and PCR methods after the study. Histopathological assessment of the MTX group revealed lung lesions like hyperemia, edema, inflammatory cell infiltration and epithelial cell loss. Immunohistochemical examination showed significant increases in Cas-3, tumour necrosis factor-alpha (TNF-α) and nuclear factor-kappa B (NF-κB) expressions. PCR analysis indicated elevated expressions of apoptotic peptidase activating factor 1 (Apaf 1), glucose-regulated protein 78 (GRP 78), CCAAT-enhancer-binding protein homologous protein (CHOP) and cytochrome C (Cyt C), along with reduced B-cell lymphoma-2 (BCL 2) expressions in the MTX group, though not statistically significant. Remarkably, CBD treatment reversed these findings. This study highlights CBD's potential in mitigating MTX-induced lung damage, suggesting its therapeutic promise.

Keywords: cannabidiol; immunohistochemistry; lung; pathology.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Antioxidants / pharmacology
  • Cannabidiol* / pharmacology
  • Female
  • Lung / metabolism
  • Methotrexate* / toxicity
  • Oxidative Stress
  • Rats
  • Rats, Wistar


  • Methotrexate
  • Cannabidiol
  • Antioxidants