A single dose of cannabidiol reduces blood pressure in healthy volunteers in a randomized crossover study

Khalid A. Jadoon, Garry D. Tan, and Saoirse E. O’Sullivan

JCI Insight, 2017, 2, (11), e93760

Doi : 10.1172/jci.insight.93760

 

BACKGROUND. Cannabidiol (CBD) is a nonpsychoactive phytocannabinoid used in multiple sclerosis and intractable epilepsies. Preclinical studies show CBD has numerous cardiovascular benefits, including a reduced blood pressure (BP) response to stress. The aim of this study was to investigate if CBD reduces BP in humans.

METHODS. Nine healthy male volunteers were given 600 mg of CBD or placebo in a randomized, placebo-controlled, double-blind, crossover study. Cardiovascular parameters were monitored using a finometer and laser Doppler.

RESULTS. CBD reduced resting systolic BP (–6 mmHg; P < 0.05) and stroke volume (–8 ml; P < 0.05), with increased heart rate (HR) and maintained cardiac output. Subjects who had taken CBD had lower BP (–5 mmHg; P < 0.05, especially before and after stress), increased HR (+10 bpm; P < 0.01), decreased stroke volume (–13 ml; P < 0.01), and a blunted forearm skin blood flow response to isometric exercise. In response to cold stress, subjects who had taken CBD had blunted BP (–6 mmHg; P < 0.01) and increased HR (+7 bpm; P < 0.05), with lower total peripheral resistance.

CONCLUSIONS. This data shows that acute administration of CBD reduces resting BP and the BP increase to stress in humans, associated with increased HR. These hemodynamic changes should be considered for people taking CBD. Further research is required to establish whether CBD has a role in the treatment of cardiovascular disorders.

Introduction

Epidemiological studies have shown a positive relationship between long-term stress and the development of cardiovascular disease (1). Factors like social isolation, low socioeconomic status, depression, stressful family and work life, and anxiety are associated with an increased risk of the development and accelerated progression of existing cardiovascular disease. Current European guidelines on the prevention of cardiovascular disease have emphasized the importance of tackling these factors (2). Mental stress induces myocardial ischaemia in patients with stable coronary artery disease, and this appears to be mediated by adrenal release of catecholamines (3).

Cannabinoids (CBs) are compounds that bind to CB receptors or are structurally similar to compounds that bind to CB receptors. They include endogenously produced compounds (called endocannabinoids), synthetic compounds and phytocannabinoids obtained from the Cannabis sativa plant. There are over 80 known types of phytocannabinoids, the most widely studied of which is Δ9 tetrahydrocannabinol (Δ9 THC or THC), which is responsible for the psychoactive properties of cannabis (4). The other major phytocannabinoid is cannabidiol (CBD), which does not have psychoactive properties. CBD is currently the focus of much research due to its potential in a number of therapeutic areas, as it has been shown to have antiinflammatory, anticonvulsant, antioxidant, anxiolytic, antinausea, and antipsychotic properties (5). A number of preclinical studies have also shown beneficial effects of CBD in a range of disorders of the cardiovascular system (6). A CBD/THC combination (Sativex/Nabiximols, GW Pharmaceuticals) is licensed for the treatment of spasticity in multiple sclerosis, and CBD alone (Epidiolex, GW Pharmaceuticals) has entered an expanded access program in children with intractable epilepsies (Dravet syndrome and Lennox-Gastaut syndrome). Epidiolex has also received orphan designation status for the treatment of neonatal hypoxia-ischaemic encephalopathy.

CBD has multiple desirable effects on the cardiovascular system. It attenuates high glucose– induced proinflammatory changes in human coronary artery endothelial cells (7) and myocardial dysfunction associated with animal models of diabetes (8), and it preserves endothelial integrity in diabetic retinal microvasculature (9). In vivo administration of CBD before cardiac ischemia and reperfusion also reduces ventricular arrhythmias and infarct size. CBD also causes both acute and time-dependent vasorelaxation in isolated arteries in rats and humans (10–12). There is also evidence from animal studies that CBD modulates the cardiovascular response to stress. Resstel and colleagues (13) showed in rats that i.p. injection of CBD (10 and 20 mg/kg, –30 min) reduced restraint stress–induced cardiovascular response and behavior. Both these effects were blocked by preadministration of WAY100635 (0.1 mg/kg), a 5-hydroxytryptamine 1A (5HT1A) antagonist. These effects appear to be mediated centrally and involve the bed nucleus of the stria terminalis (BNST), a limbic structure that modulates neuroendocrine responses to acute stress (14).

Our recent systematic review showed us that there are no dedicated studies in humans to date, to our knowledge, looking at the effect of CBD on either resting cardiovascular measurement or on the responses to stress, with continuous monitoring of CV parameters (15). Therefore, the aim of the present study was to investigate whether CBD decreases the cardiovascular response to stress after the administration of a single dose of CBD (600 mg) in healthy volunteers, with the hypothesis that blood pressure would be reduced by CBD. Noninvasive cardiovascular measurements were used along with stress tests in the form of mental arithmetic, isometric exercise, and the cold pressor test.

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