OBJECTIVES: Recent evidence has demonstrated the potential benefits of cannabis in various indications. However, serious cardiovascular (CV) events have been reported with recreational use but little is known about safety issues with medical use. This study aims to investigate the extent of cannabis-associated CV events reported among randomized controlled trials (RCT).

METHODS: A two-stage systematic review (SR) approach was undertaken. First, we searched for SRs of cannabis in PubMed, EMBASE, CENTRAL, and AMED until June 2019. Second, RCTs identified from SRs were included if they were RCT assessing medical cannabis and reporting CV events. The outcomes of interest were all types of CV events. Data were extracted by two independent reviewers. Study quality was assessed using the Cochrane risk of bias. A statistical test of heterogeneity was performed. The summary risk ratios and 95% Confidence Intervals (Cis) were calculated using a random-effects model.

RESULTS: A total of 142 SRs including 897 RCTs met the first-stage review. In the second stage, 51 studies involving 5,087 patients were included. The median duration of cannabis use was 1.3 weeks (range 0.1 to 46) and 47% of studies excluded patients with underlying cardiovascular diseases. Cannabis use was significantly associated with increased risks of orthostatic hypotension (RR 3.16; 95% CI 2.27 to 4.40; I2 = 2.3%), and hypotension (RR 3.55; 95% CI 1.45 to 8.71; I2 = 31.8%) with a trend of increased risk of tachycardia (RR 2.08; 95% CI 0.90 to 4.81; I2 = 46%). No study reported sudden cardiac arrest, acute coronary syndrome, or heart failure.

CONCLUSIONS: There is a paucity of evidence of serious CV events among medical cannabis users. This might be due to the low CV risk population or short study duration. This warrants future studies to investigate CV risk among medical cannabis users especially those with CV diseases.