Objective: HYPER-H21-4 was a randomized, triple-blind, crossover study that demonstrated that 5 week cannabidiol (CBD) supplementation reduces average 24h blood pressure (BP) in patients with arterial hypertension. The aim of this sub-study was to establish whether CBD elicits significant effect on the brain blood flow and memory in these patients. Design and method: The trial was designed as a triple-blind randomized crossover trial. For this prespecified sub-analysis, we included 15 hypertensive patients. Patients were randomized to receive either oral CBD or placebo for the period of 5 weeks. After a 2-week washout, patients were crossed over to alternate therapy (CBD/placebo) (Figure 1). Patients visited the lab at the start and at the end of each dosing period (four times in total). Magnetic resonance imaging (MRI), with specific focus on measurement of the blood flow through internal carotid artery using 4D flow technique. Variables of interest were mean flow (mL/min) and Pulsatility Index (AU). In addition, at each visit, venous blood samples were obtained. Finally, patients fulfilled a Memory Complaint Questionnaire (MAC-Q) at the start at the end of the study (after 12 weeks). Results: After 5 weeks of CBD supplementation, no significant changes in mean flow (time: P = 0.461, group: P = 0.657, interaction: P = 0.285) or Pulsatility Index (time: P = 0.573, group: P = 0.640, interaction: P = 0.970) in internal carotid artery in comparison to 5 weeks of placebo. In addition, significant reduction after in MAC-Q score was observed (25.8 ± 2.4 vs. 22.6 ± 3.8, P = 0.036), indicating reduced complaint on memory loss. Conclusions: The results of the HYPER-H21-4 trial indicate that chronic CBD supplementation leads to BP reduction. However, despite the fact that CBD supplementation improved self-reported memory abilities, no differences in comparison to placebo were noted in terms of blood flow through internal carotid artery, indicating lack of CBD-mediated effect.