Evaluation of Efficacy and Safety of Aqueous Root Extract of <i>Cannabis sativa</i> for Alcohol Use Disorder (AUD) in Wistar Albino Rats

Background: Alcohol Use Disorder (AUD) significantly impacts physical and neurological health. Existing pharmacotherapies face limitations due to adverse effects, high relapse rates, and poor patient adherence, driving interest in plant-based therapies with better safety profiles. Despite Cannabis sativa’s historical medical use, limited research exists on its root extract, which may offer neuroprotective and hepatoprotective benefits. Aim: To evaluate the efficacy, safety and neuroprotective effect of aqueous root extract of C. sativa in a rat model of AUD. Methods: 30 Wistar rats were divided into five groups (n=6): normal control, AUD control, C. sativa extract (low dose-25mg/kg and high dose-50mg/kg), and standard (acamprosate). Over 21 days, a 24-hour two-bottle choice paradigm was employed. From day 1-7, both bottles were filled with drinking water. From day 8-21, one bottle was filled with Ethanol and the other with drinking water, along with the respective treatments. Ethanol intake and preference were measured daily in all the groups. Haematological, biochemical tests and behavioural assessments were performed on day 21, following which the rats were sacrificed, and histopathological analysis of vital organs was performed. Phytochemical analysis of the extract were done using chemical tests and GC-MS. In vitro antioxidant and anti-inflammatory effects were assessed using the DPPH reduction assay and Egg albumin denaturation assay. Results: C. sativa significantly decreased ethanol intake and preference, and alleviated the neurological symptoms of AUD, with a good safety profile. The high-dose extract exhibited comparable efficacy with acamprosate. Histopathological analyses revealed reduced organ damage, with near-normal architecture in the high-dose group. The extract demonstrated promising antioxidant and anti-inflammatory effects. Conclusion: The findings of this research show that C. sativa is a potential therapeutic option in AUD, demonstrating notable hepatoprotective and neuroprotective effects in the rat model of AUD, which can be further explored in clinical studies. Major Findings: High-dose C. sativa reduced ethanol intake/preference and improved behavioural outcomes comparable to acamprosate. It also mitigated AUD-related organ damage and showed in vitro antioxidant and anti-inflammatory activity.