Associations Between Marijuana Use and Cardiovascular Risk Factors and Outcomes : A Systematic Review, Divya Ravi et al., 2018

Associations Between Marijuana Use and Cardiovascular Risk Factors and Outcomes : A Systematic Review

Divya Ravi, MD, MPH; Mehrnaz Ghasemiesfe, MD; Deborah Korenstein, MD; Thomas Cascino, MD;
and Salomeh Keyhani, MD, MPH

Annals of Internal Medicine, 2018, 168, (3), 187-194.

doi : 10.7326/M17-1548


Background : Marijuana use is increasing in the United States, and its effect on cardiovascular health is unknown.

Purpose : To review harms and benefits of marijuana use in relation to cardiovascular risk factors and clinical outcomes.

Data Sources : PubMed, MEDLINE, EMBASE, PsycINFO, and the Cochrane Library between 1 January 1975 and 30 September 2017.

Study Selection : Observational studies that were published in English, enrolled adults using any form of marijuana, and reported on vascular risk factors (hyperglycemia, diabetes, dyslipidemia, and obesity) or on outcomes (stroke, myocardial infarction, cardiovascular mortality, and all-cause mortality in cardiovascular cohorts).

Data Extraction : Study characteristics and quality were assessed by 4 reviewers independently; strength of evidence for each outcome was graded by consensus.

Data Synthesis : 13 and 11 studies examined associations between marijuana use and cardiovascular risk factors and clinical outcomes, respectively. Although 6 studies suggested a metabolic benefit from marijuana use, they were based on crosssectional designs and were not supported by prospective studies. Evidence examining the effect of marijuana on diabetes, dyslipidemia, acute myocardial infarction, stroke, or cardiovascular and all-cause mortality was insufficient. Although the current literature includes several long-term prospective studies, they are limited by recall bias, inadequate exposure assessment, minimal marijuana exposure, and a predominance of low-risk cohorts.

Limitation : Poor- or moderate-quality data, inadequate assessment of marijuana exposure and minimal exposure in the populations studied, and variation in study design.

Conclusion : Evidence examining the effect of marijuana on cardiovascular risk factors and outcomes, including stroke and myocardial infarction, is insufficient.

Primary Funding Source : National Heart, Lung, and Blood Institute. (PROSPERO: CRD42016051297)

As more states legalize the sale and consumption of marijuana, the number of Americans using it continues to rise (1, 2). This increase in the use of marijuana highlights the need for a better understanding of its risks and benefits. One area of importance is its effect on cardiovascular disease, the number one cause of morbidity and mortality worldwide (3).

Marijuana may affect cardiovascular health in several ways. Like other psychoactive drugs, it may have hemodynamic effects that can precipitate events (4). The active ingredient in marijuana is Δ9- tetrahydrocannabinol (THC) (5), which is responsible for the psychoactive effects of marijuana through its interaction with cannabinoid receptors. These receptors are ubiquitous in the brain and its vasculature and present throughout the body, including the myocardium, coronary endothelium, and smooth muscle cells (6, 7). In vitro and animal studies have reported that THC can modulate cannabinoid receptors on human cardiomyocytes and vascular smooth muscles, resulting in ischemia (7, 8). In vitro studies also have demonstrated that THC influences the regulation of glucose and lipid metabolism, suggesting a possible effect on vascular risk factors (9, 10). At the cellular level, THC may cause inflammatory cytokine release, alteration in lipid metabolism (11, 12), and reactive oxygen species formation (13). These effects may potentiate the progression of vascular disease. Marijuana smoking, the predominant method of use, causes a 5-fold increase in the blood carboxy-hemoglobin level and a 3-fold increment in the quantity of tar inhaled compared with tobacco (14). Studies on secondhand marijuana smoke have found endothelial dysfunction in rats after exposure (15).

Given the myriad ways in which marijuana might potentiate vascular disease, we conducted a systematic review to assess the effect of regular marijuana use on cardiovascular outcomes and their associated risk factors.