Sultan, Salahaden
(2020)
Characterisation of the haemodynamic effects of cannabidiol in humans using duplex ultrasound and other techniques.
PhD thesis, University of Nottingham.
Abstract
The two main phytocannabinoids, ∆9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD) are agents already licensed for clinical use (i.e. Sativex®and Epidiolex®). THC and CBD have numerous cardiovascular effects in vitro; however, their effects on haemodynamics in vivoin humans remain unclear.
Two systematic reviews and meta-analysis were established to evaluate the effects of THC and CBD on the haemodynamics in vivoin animals and humans. Our analysis showed that THC acts differently according to species and experimental conditions, causing bradycardia, hypotension and increased blood flow (BF) in animals, and increased heart rate (HR) in humans. However, CBD has no effect on blood pressure (BP) or HR under control conditions, but reduces BP and HR in stressful conditions, and increases cerebral BF in mouse models of stroke. Both systematic reviews and meta-analysis highlighted the limited data available in humans and further studies should be considered.
Our group’s recent study in healthy men showed that acute oral administration of CBD (600 mg) causes a reduction in BP at rest and in response to stress. Because of this, three human studies were conducted to see if the findings from our previous study are reproducible, as well as if tolerance develops and if other vascular endpoints were affected post-CBD. Continuous beat-to-beat haemodynamics was assessed at rest and in response to stress (isometric exercise) using Finometer®. Arterial stiffness and aortic blood pressure were assessed using Vicorder®.Duplex ultrasound was used to assess changes in cerebral blood flow, extra-cranial arterial diameter, and brachial artery endothelial function after CBD administration.
In the first human study, 26 healthy men were given 600 mg of CBD or placebo orally for seven days in a randomised, placebo-controlled, double-blind, parallel trial (n=13 per group). Cardiovascular parameters were assessed after single (acute) and repeated (chronic) dosing for seven days. CBD reduced mean arterial pressure after acute dosing at rest and reduced systolic BP after acute and chronic dosing in response to stress. Repeated CBD dosing reduced arterial stiffness, induced vasodilation and augmented BF volume in the internal carotid artery and improved endothelial function compared to single CBD dosing.
Based on these findings, the second study was conducted to investigate the effect of a single dose of CBD in healthy men on arterial stiffness and cerebral BF to determine whether the effects seen after repeated dosing of CBD can also be seen after a single dose compared to baseline. Ten healthy men were given a single dose of placebo and CBD (600 mg) orally with a washout period of at least a week between the two treatments in a randomised, placebo-controlled, double-blind, crossover trial. The cardiovascular system was assessed before and after receiving the treatment. No effect was seen on arterial stiffness or cerebral BF following acute CBD administration.
Due to the lack of studies assessing the effects of CBD on the cardiovascular system in women, a third study was conducted to establish the acute effect of CBD on the haemodynamics in women. Thirteen healthy females were given a single dose of placebo and CBD (600 mg) orally with a washout period of at least a week between the two treatments in a randomised, placebo-controlled, double-blind, crossover trial. The cardiovascular system was assessed after receiving the treatment. No effects wereseen following acute CBD administration.
The findings of this thesis indicate that CBD may induce positive effects on human haemodynamics and on vascular function following chronic administration, and that sex-difference could impact its effects and should be considered in future studies investigating the effect of CBD on the human cardiovascular system. Further research is needed with larger sample sizes in dose-escalation trials and patient populations with vascular diseases.
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