Abstract
High doses of nicotine in rodents are known to induce anxiety, dysregulate brain-derived neu-rotrophic factor (BDNF) levels, contribute to oxidative stress, and promote the secretion of cytokines. Conversely, at lower doses, nicotine exhibits anxiolytic effects. The endocannabinoids and nicotine modu-late several central nervous system processes via their specific receptors, impacting locomotion, anxiety, memory, nociception, and reward. Cannabidiol (CBD), a non-psychoactive active ingredient of Cannabis sativa L., has garnered scientific attention primarily due to its recognized effects, including anxiolytic, an-tioxidant, and anti-inflammatory properties. This work aims to explore the potential anxiety-reducing properties of CBD in a well-established experimental mouse model of anxiety-like behavior induced by high doses of nicotine. In this context, the open field behavioral test was specially conducted to assess CBD’s effects on anxiety-like behavior and locomotion. Brain neuronal plasticity, modulated by brain-derived neurotrophic factor (BDNF), along with a diverse array of blood’s metabolic markers, was examined as a means of evaluating systemic toxicity under various treatments. Finally, oxidative stress was evaluated through the measurement of GSH, SOD, and MDA, while pro-inflammatory cytokine assessments were conducted to evaluate redox status and immune system function. Our findings indicate that CBD holds promise in alleviating high-dose nicotine-induced anxiety-like behaviors by targeting specific liver en-zymes, maintaining tissue’s systemic toxicity (i.e., renal, kidney, and pancreatic), balancing redox reactions (SOD, GSH, and MDA), promoting secretion of pro-inflammatory cytokines (TNF-alpha and IL-6), and mitigating changes in BDNF protein levels.