Antihypertensive effects of CBD are mediated by altered inflammatory response: A sub-study of the HYPER-H21-4 trial

Despite the abundance of preclinical data, cardiovascular effects of cannabidiol (CBD) in humans remain controversial. HYPER-H21-4 trial was designed as a randomized, placebo-controlled, crossover trial aimed to explore the effects of chronic CBD dosing on ambulatory blood pressure (BP) and vascular stiffness in hypertensive individuals. In this pre-specified analysis of the trial we aimed to elucidate the anti-inflammatory effects of CBD by measuring the dynamic of serum cytokines. Specifically, interleukin 1 beta (IL-1 beta), IL-8, IL-6, IL-10, IL-18, Plasminogen activator inhibitor-1 (PAI-1), tumor necrosis factor alpha (TNF-alpha) and lectin-type oxidized LDL receptor 1 (LOX-1) were measured. A total of 65 patients with primary hypertension were included. After five weeks of oral CBD administration, but not of placebo, serum concentrations of IL-8, IL-10 and IL-18 were significantly lower in comparison to baseline concentrations (p = 0.044, p < 0.001 and p < 0.001, respectively). Serum levels of other cytokines showed no CBD-associated dynamic. Higher IL-8 and IL-10 baseline levels heralded higher diastolic BP reduction (r = -0.478, p < 0.001 and r = -0.265, p = 0.034, respectively), whereas the extent of reduction in IL-8 and IL-10 serum levels correlated with the extent of reduction in diastolic BP (r = 0.434, p < 0.001 and r = 0.594, p < 0.001, respectively). Overall, the results of the present analysis imply that the antihypertensive effects of CBD in patients with primary hypertension are accompanied by changes in serum concentrations of multiple cytokines.