INTRODUCTION

One out of 7 adults used marijuana in 2017.1 The concentration of tetrahydrocannabinol (THC), the primary psychoactive component of marijuana is increasing in commercially available products.2 However, there is little safety data available on the acute effects of cannabis outside of its psychoactive effects. One area of interest is the acute cardiovascular effects of marijuana given the ubiquitous presence of endocannabinoid receptors in the myocardium, coronary endothelium, and vascular endothelial and smooth muscle cells.3 We conducted a systematic review to examine the acute cardiovascular effects of marijuana use.

METHODS

We searched PubMed, MEDLINE, EMBASE, PsychINFO, and Cochrane Library for all English-language experimental studies examining marijuana use and acute cardiovascular effects between January 1, 1975, and March 31, 2018. Our search using MeSH terms outlined in Figure 1 yielded 1791 articles. We exclude articles with less than 20 participants. Two reviewers (M.G. and D.R.) selected 997 abstracts for review of which 80 met inclusion criteria and were selected for full text review. Two papers were added via author and reference tracking. Inter-rater reliability for the abstract selection process and the concurrent decision to include the article was excellent (Cohen kappa 0.87). We discussed the overall strength of evidence as a group for each outcome and graded it as insufficient, low, moderate, or high risk of bias (ROB) using methods outlined by the AHRQ.4 The protocol was registered on Prospero at the start of our review (No. CRD42016051297).

Figure 1
figure 1

Flow of articles in the review. MeSH terms: (Marijuana OR Marihuana OR Tetrahydrocannabinol OR Cannabinoid) AND (Hypertension OR Hypotension OR Blood pressure OR Heart Rate OR Bradycardia OR Tachycardia OR Arrhythmia OR Hemodynamics OR Syncope OR Cerebrovascular Constriction). An asterisk indicates that some studies were assigned more than one outcome label and are counted twice.

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RESULTS

Article Characteristics

Fourteen articles focused on change of heart rate (HR), 6 on blood pressure (BP), and 2 on cerebrovascular circulation in response to marijuana administration. Among these, 7 were randomized clinical trials (RCT) and 7 were non-randomized experimental studies. Twelve out of 14 studies employed inhalation/smoking as the route of exposure. THC content in smoke ranged from 1.5 to 3.6% per cigarette (equal to 14 to 35 mg). The highest dose of THC administered as edible or an injection was 17.5 and 5 mg, respectively. Half the articles were rated as high ROB (Table 1).

Table 1 Summary of Experimental Studies that Examined Exposure to Marijuana and Acute Cardiovascular Changes
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Heart Rate

All 14 studies (7 RCTs and 7 non-randomized experimental) rated as low to high ROB reported marijuana use was associated with tachycardia. The 2 low ROB RCT studies reported increase in HR after exposure to 3.55% smoke, 8 mg oral, or 4 mg injection THC. Two moderate ROB RCTs found an increase in HR in a dose-dependent manner. Two non-randomized studies (moderate ROB) found a linear association between use and tachycardia. The last moderate ROB (non-randomized experimental) study reported all forms of marijuana (1.83% smoked, 17.5 mg oral THC, and 2 mg synthetic nabilone) increased HR.

Blood Pressure

Six studies examined BP as an outcome (2 RCTs, and 4 non-randomized experimental studies). Findings were mixed. In one study (RCT, low ROB) exposure to 3.55% THC per cigarette or 4 mg THC per injection showed a drop in systolic BP (p < 0.01). The non-randomized study (moderate ROB) reported a linear association between marijuana dose (1.75 to 3.55%) and decreasing systolic BP. The remaining 4 high ROB studies had mixed findings with 3 studies showing no effect and one study reporting an increase in BP.

Cerebrovascular Circulation

Exposure to 3.55% THC per cigarette or 4 mg THC injection (RCT, low ROB) showed drop in cerebral blood velocity (p < 0.007) while administration of 20 mg THC per cigarette (equal to 2.08% THC) in a second study (non-randomized study, high ROB) showed no association with change in global cerebral blood flow (Table 1).

DISCUSSION

Low strength evidence suggests that marijuana use is associated with tachycardia. There was insufficient evidence on the relationship between marijuana use and acute changes in blood pressure and cerebrovascular circulation.

While the psychoactive effects of THC are well known,5 our review suggests that low concentrations of THC can cause tachycardia which may have health implications for older adults with vascular disease. The studies included this review had lower concentration of THC compared with products currently on the market. The highest dose of THC used in experimental studies in our review was 3.6% per cigarette. Pre-rolled cannabis cigarettes available for purchase in cannabis dispensaries contain THC concentrations often exceeding 18% and reaching as high as 35%.2, 6 This is particularly concerning in older population with existing cardiovascular disease where acute hemodynamic changes may precipitate adverse outcomes.

Our study has several limitations. We may have overlooked relevant studies published outside of our predefined timeline. In addition, studies were conducted in young health populations limiting generalizability.

In conclusion, low concentrations of THC are associated with tachycardia among largely healthy and young populations. More safety data on use of high concentrations of THC and in clinically diverse populations are needed.