The effects of chronic administration of Cannabidiol and Cannabidiol-Selexipag combination on haematological parameters, oxidative stress, BNP, and TNF-α in a rat model of Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by pulmonary vasoconstriction and inflammation, leading to increased pulmonary pressure, right heart failure, and high mortality. Cannabidiol (CBD), a non-psychoactive cannabinoid, exhibits anti-inflammatory and antioxidant properties. This study investigates the therapeutic potential of CBD, alone and in combination with Selexipag, in a rat model of monocrotaline (MCT) -induced PAH.

METHODS: Forty male Sprague-Dawley rats were randomized into five groups: Control, MCT-Control, MCT-Selexipag, MCT-CBD, and MCT-CBD-Selexipag. PAH was induced with MCT (60 mg/kg, intraperitoneally). Treatments (CBD: 10 mg/kg; Selexipag: 3 mg/kg) were administered orally from day 21 to 31. Post-treatment, plasma brain natriuretic peptide (BNP), heart tumour necrosis factor-alpha (TNF-α), and total antioxidant capacity (T-AOC) in heart and plasma were measured, alongside a full haematological profile.

RESULTS: Combination therapy (CBD + Selexipag) significantly increased BNP expression and heart TAOC, while reducing plasma T-AOC, indicating enhanced cardiovascular stress modulation and antioxidant defence. The MCT-CBD group exhibited elevated TNF-α, haemoglobin, and platelet counts, suggesting a proinflammatory response. CBD monotherapy did not effectively reduce inflammation in PAH.

CONCLUSION: CBD, when combined with Selexipag, may enhance BNP modulation and cardiac antioxidant capacity in PAH, supporting its potential as adjunct therapy for oxidative stress management. However, CBD alone may exacerbate inflammation and haematological abnormalities. Further studies are warranted to clarify the mechanisms and clinical relevance of these findings.

ABBREVIATIONS: Cannabidiol Brain (CBD); Natriuretic Peptide (BNP); Pulmonary Arterial Hypertension (PAH); Tumour Necrosis FactorAlpha (TNF-α); Monocrotaline (MCT); Total Antioxidant Capacity (T-AOC).