A Systematic Review and Meta-Analysis of the Haemodynamic Effects of Cannabidiol

Salahaden R Sultan, Sophie A Millar, Timothy J England, Saoirse E O'Sullivan, Salahaden R Sultan, Sophie A Millar, Timothy J England, Saoirse E O'Sullivan

Abstract

Despite cannabidiol (CBD) having numerous cardiovascular effects in vitro, its haemodynamic effects in vivo are unclear. Nonetheless, the clinical use of CBD (Epidiolex) is becoming more widespread. The aim of this systematic review was to establish whether CBD is associated with changes in haemodynamics in vivo. Twenty-five studies that assessed the haemodynamic effects of CBD (from PubMed, Medline and EMBASE) were systematically reviewed and meta-analyzed. Data on blood pressure (BP), heart rate (HR), and blood flow (BF) were extracted and analyzed using random effects models. Twenty-two publications assessed BP and HR among 6 species (BP n = 344 and HR n = 395), and 5 publications assessed BF in 3 species (n = 56) after acute dosing of CBD. Chronic dosing was assessed in 4 publications in 3 species (total subjects BP, n = 6; HR, n = 27; BF, n = 3). Acute CBD dosing had no effect on BP or HR under control conditions. Similarly, chronic dosing with CBD had no effect on HR. In models of stress, acute CBD administration significantly reduced the increase in BP and HR induced by stress (BP, mean difference (MD) -3.54, 95% CI -5.19, -1.9, p < 0.0001; HR, MD -16.23, 95% CI -26.44, -6.02, p = 0.002). In mouse models of stroke, CBD significantly increased cerebral blood flow (CBF, standardized mean difference (SMD) 1.62, 95% CI 0.41, 2.83, p = 0.009). Heterogeneity among the studies was present, there was no publication bias except in HR of control and stressful conditions after acute CBD dosing, and median study quality was 5 out of 9 (ranging from 1 to 8). From the limited data available, we conclude that acute and chronic administration of CBD had no effect on BP or HR under control conditions, but reduces BP and HR in stressful conditions, and increases cerebral blood flow (CBF) in mouse models of stroke. Further studies are required to fully understand the potential haemodynamic effects of CBD in humans under normal and pathological conditions.

Keywords: CBD; Epidiolex; blood flow; blood pressure; cannabidiol; cardiovascular system; haemodynamic; heart rate.

Figures

Figure 1
Figure 1
Flow chart for study retrieval and selection. In vitro studies, interaction studies including mixtures of CBD with other cannabis extracts, studies not assessing haemodynamics (BP, HR, or BF), review articles and editorials, or uncontrolled studies were excluded.
Figure 2
Figure 2
Changes in BP (A) and HR (B) induced by acute CBD dosing.
Figure 3
Figure 3
Changes in HR induced by chronic CBD dosing.
Figure 4
Figure 4
Changes in BP (A) and HR (B) induced by acute CBD dosing under stressful conditions.
Figure 5
Figure 5
Changes in regional blood flow induced by acute CBD dosing.
Figure 6
Figure 6
The effect of CBD dose on haemodynamic responses in vivo. The mean difference (MD) in blood pressure (BP, A) or heart rate (HR, B), and standardized mean difference (SMD) in blood flow (BF, C) is plotted against the log dose (mg) for each study. Error bars represent 95% confidence intervals (CI).
Figure 7
Figure 7
Funnel plots for each outcome evaluating publication bias. Standard error (SE) of the mean difference (MD) in blood pressure (BP) and heart rate (HR), or of the standardized mean difference in blood flow (BF, MD, or SMD, y axes) for each study is plotted against its effect size (horizontal axes). There was significant bias in HR after acute dosing (B, HR control p = 0.001; E, HR stress p = 0.049).

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