Analgesic and toxicological evaluation of cannabidiol-rich Moroccan Cannabis sativa L. (Khardala variety) extract: Evidence from an in vivo and in silico study.

The legalization of cannabis for industrial and medicinal purposes has significantly expanded worldwide. This study delves into the analgesic potential toxicity study of chloroformic extract from the Moroccan Cannabis sativa L. (C. sativa) cultivar, Khardala (KH extract). Our findings reveal that the lethal dose of KH extract is ≥5,000 mg/kg, with mice given 2,000 mg/kg exhibiting neurotoxic symptoms, including piloerection, aggressiveness, and fear, along with marked hepato-renal toxicity indicated by elevated levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, and creatinine in both male and female subjects. Importantly, no toxicity was observed at 250 mg/kg and 500 mg/kg doses. Remarkably, at a dose of 500 mg/kg, the KH extract demonstrated a potent analgesic effect superior to cannabidiol (CBD), suggesting a synergistic interaction among the extract's bioactive compounds, such as CBD, cannabidivarin (CBDV), Delta 9 tetrahydrocannabinol (THC), cannabigerol (CBG), Delta 9 tetrahydrocannabivarin (THCV), and β-caryophyllene. In silico analysis supports these findings, showing the strong binding potential of THC, THCV, CBG, and CBDV to delta opioid receptors, with G-scores >-5.0 kcal/mol, highlighting the promising analgesic efficacy of this cannabis cultivar extract. This study underscores the therapeutic potential of the KH cultivar, positioning it as a promising candidate for pain management therapies.