“Ethnopharmacological relevance: Cannabis sativa has been traditionally used in Moroccan medicine for centuries, either for its psychoactive or therapeutic effects. However, the safety profile of extracts from macerated leaves remains poorly documented in the scientific literature.
Aim of the study: This study, for the first time, evaluates the phytochemical composition and the toxicological profile of an ethanolic extract of Cannabis sativa (CEE) leaves in mice, focusing on behavioral effects, oxidative stress markers, and histopathological examination.
Materials and methods: The CEE was evaluated using HPLC analysis, secondary metabolites quantification, and in vitro antioxidant assays. Acute oral toxicity was assessed in female mice at doses from 500 to 3000 mg/kg, while oral subacute toxicity was evaluated over 7 days in male mice receiving 10, 30, or 50 mg/kg of CEE. Behavioral assessments included the open field, rotarod, and elevated plus maze tests. Additionally, body weight gain, organ coefficients, organ edema, oxidative stress markers, and histopathology of the brain, liver, kidneys, spleen, and testes were examined.
Results: CEE exhibited substantial amounts of polyphenols, flavonoids, tannins, and saponins, with notable antioxidant activity (DPPH IC50: 289.01 ± 0.003 μg/mL; FRAP IC50: 57.29 ± 6.7 μg/mL). No mortality was observed in the acute toxicity study. The 7-day treatment caused no sedation or motor impairment, rather, it showed anxiolytic effects. A significant increase in body weight gain was noted, particularly at 10 mg/kg, while no changes in organ coefficients or signs of organ edema were detected. However, MDA and catalase activity increased in the liver and brain at 50 mg/kg. Histopathological examination revealed signs of cellular stress without severe tissue damage.
Conclusions: CEE appears to be safe at moderate doses, with an LD50 above 3000 mg/kg. Further studies are needed to assess long-term effects.”
https://pubmed.ncbi.nlm.nih.gov/40436124/
https://www.sciencedirect.com/science/article/abs/pii/S0378874125007457?via%3Dihub