Oral Administration of Moroccan Cannabis sativa L. Extract and Cannabidiol: A Comparative Study in Acute Pain Models

Background and objectives The therapeutic properties of local Cannabis sativa varieties remain underexplored. This study aimed to evaluate the antinociceptive effects of a Moroccan C. sativa ethanolic extract (CEE) in acute pain models. Methods Phytochemical analysis of CEE was conducted using HPLC, and antioxidant activity was assessed via DPPH and FRAP assays. Antinociceptive effects were evaluated using writhing and formalin tests after a single oral administration. Mice treated with CEE (30 mg/kg) or cannabidiol (CBD; 30 mg/kg) were compared to a diclofenac-treated group (10 mg/kg). Both treatments were tested for cannabinoid receptor-1 effects known as the cannabinoid tetrad. Results Of several polyphenolic compounds identified from CEE, kaempferol formed the main component. In vitro, CEE exhibited antioxidant activity, with IC 50 values of 289.01 ± 0.003 μg/mL in the DPPH assay and 57.29 ± 6.7 μg/mL in the FRAP assay. Both CEE and CBD significantly reduced writhing responses, paw licking/biting time, and paw swelling, indicating antinociceptive and anti-inflammatory effects. The histopathological analysis supported these findings. Neither CEE nor CBD induced cannabinoid tetrad-related effects. Conclusions CEE exhibited significant antinociceptive and anti-inflammatory activities comparable to CBD and diclofenac, without cannabinoid tetrad-associated symptoms. Moroccan C. sativa extract shows promise for developing novel anti-inflammatory drugs.