| 003P London, UK
8th European Workshop on Cannabinoid Research
A systematic review and meta-analysis of the haemodynamic effects of Δ9-Tetrahydrocannabinol in vivo in animals and humans
Introduction: The effects of ∆9-Tetrahydrocannabinol (THC) on the cardiovascular system are complex. The aim of the present study was to systematically review and analyse in vivo studies evaluating the effects of THC on haemodynamics.
Methods: PubMed, Medline and EMBASE were systematically reviewed for studies assessing the haemodynamic effects of THC. Pre-specified inclusion criteria was used to prevent bias: studies had to be in vivo; assess at least one of blood pressure (BP), heart rate (HR) or blood flow (BF); be an original article and a controlled study; and include cannabis naďve subjects. Changes in BP (mmHg), HR (beats per minute, bpm) and BF (percentage change or mL/min) at 2 hours post-single (acute) dose, or after repeated (chronic) dosing, were extracted and analysed using Cochrane Review Manager software.
Results: Thirty-one studies assessing the haemodynamic effects of THC met the eligibility criteria. Fourteen publications assessed BP (n=541) and twenty-two assessed HR (n=567) among six species. Three publications assessed BF in two species (n=45). Acute THC dosing significantly reduced BP and HR in anaesthetised animals (BP, mean difference (MD) -19.7 mmHg, 95% CI -26.16, -13.25, p<0.00001; HR, MD −53.49 bpm, 95% CI -65.9, -41.07, p<0.00001), conscious animals (BP, MD -12.3 mmHg, 95% CI -19.42, -5.18, p=0.0007; HR, MD −30.05 bpm, 95% CI -38.47, -21.64, p < 0.00001), animal models of stress or hypertension (BP, MD -61.37 mmHg, 95% CI -117.56, -5.17, p=0.03), and significantly increased cerebral blood flow (CBF) in murine stroke models (MD 32.35%, 95% CI 23.81, 40.88, p<0.00001). Chronic dosing increased BF (MD 21.95 mL/min, 95% CI -0.38, 44.29, p=0.05) in anaesthetised animals and reduced BP in animal models of stress or hypertension (MD -22.09 mmHg, 95% CI -30.61 mmHg, -13.58, p<0.00001). In humans, acute THC dosing significantly increased HR (MD 8.16 bpm, 95% CI 4.99, 11.33, p<0.00001). Species, experimental conditions (anaesthetised, conscious, stress or hypertensive) and dose all affected haemodynamic responses to THC. Statistical heterogeneity was present among analyses of BP and HR post-acute THC dosing in animals and humans (p<0.00001), and in BP post-chronic THC dosing in anaesthetised animals (p=0.03).
Conclusion: Haemodynamic responses to THC varied according to species (tachycardia in humans; bradycardia, hypotension and increased BF in animals), experimental conditions and dose. Data in humans are largely limited to responses in HR warranting further investigation.