Nadar, Anand.Gunpath, Chayil.2026-04-302026-04-3020242024https://hdl.handle.net/10413/24371Masters Degree. University of KwaZulu-Natal Durban.Background: Pulmonary arterial hypertension (PAH) is a severe condition characterized by elevated pulmonary artery pressure, leading to progressive cardiovascular impairment and high mortality rates. Current therapies often fall short of providing adequate symptom relief and disease management. This study evaluates the combined therapeutic potential of Cannabidiol (CBD) and Selexipag, assessing their effects on key biomarkers and haematological parameters associated with PAH. Methods: In a preclinical model, PAH was induced in rats using monocrotaline (MCT), followed by treatment with CBD, Selexipag, or their combination. Biomarkers including B-type natriuretic peptide (BNP), total antioxidant capacity (T-AOC), and tumour necrosis factor-alpha (TNF-α) were measured to evaluate cardiovascular and inflammatory responses. Additionally, haematological parameters such as platelet count, and haemoglobin levels were assessed. Statistical analysis was conducted using Welch’s ANOVA and unpaired Welch’s T-Tests to determine the significance of treatment effects. Results: The combination therapy of CBD and Selexipag was found to be significantly more effective in normalizing BNP and T-AOC levels compared to the individual treatments. This suggests that adjunctive therapy might enhance cardiovascular function and reduce oxidative stress. Despite CBD’s established anti-inflammatory properties, elevated TNF-α levels in the MCT-CBD group indicated a potential exacerbation of inflammation. This finding is at odds with previous literature on CBD’s effects, which may be influenced by specific experimental conditions or dosages. Haematological analysis revealed elevated platelet counts and haemoglobin levels, with increased platelet activation noted, which correlates with findings linking these parameters to PAH progression. Discussion: The study underscores the potential of combining CBD with Selexipag as a promising approach for PAH management, showing improved biomarker profiles indicative of better cardiovascular function and oxidative stress mitigation. However, the unexpected rise in TNF-α levels with CBD treatment highlights the complexity of its anti-inflammatory effects and suggests that its therapeutic benefits may vary based on the disease context. Furthermore, changes in haematological parameters support existing literature linking elevated haemoglobin and platelet activation to PAH, emphasizing the need for careful monitoring of these parameters in clinical settings. Conclusion: The combination of CBD and Selexipag demonstrates enhanced therapeutic potential for PAH compared to monotherapy, with promising improvements in key biomarkers. Nevertheless, the paradoxical increase in TNF-α and associated haematological changes necessitate further research to elucidate the mechanisms behind CBD’s effects and optimize therapeutic strategies for PAH. Future studies should focus on understanding these complex interactions and exploring the full therapeutic potential of CBD and Selexipag in cardiovascular disease management. Keywords: Pulmonary Arterial Hypertension, Cannabidiol, Selexipag, Brain Natriuretic Peptide, Total antioxidant capacity, Tumour Necrosis Factor Alpha, Monocrotaline, Platelet count, Haemoglobin levelsenCannabidiol.Total Antioxidant Capacity.Pulmonary Arterial Hypertension.Tumour Necrosis Factor.Brain Natriuretic PeptideThesis