Cardiovascular Complications of Marijuana and Related Substances: A Review

Abstract

The recreational use of cannabis has sharply increased in recent years in parallel with its legalization and decriminalization in several countries. Commonly, the traditional cannabis has been replaced by potent synthetic cannabinoids and cannabimimetics in various forms. Despite overwhelming public perception of the safety of these substances, an increasing number of serious cardiovascular adverse events have been reported in temporal relation to recreational cannabis use. These have included sudden cardiac death, vascular (coronary, cerebral and peripheral) events, arrhythmias and stress cardiomyopathy among others. Many of the victims of these events are relatively young men with few if any cardiovascular risk factors. However, there are reasons to believe that older individuals and those with risk factors for or established cardiovascular disease are at even higher danger of such events following exposure to cannabis. The pathophysiological basis of these events is not fully understood and likely encompasses a complex interaction between the active ingredients (particularly the major cannabinoid, Δ9-tetrahydrocannabinol), and the endo-cannabinoid system, autonomic nervous system, as well as other receptor and non-receptor mediated pathways. Other complicating factors include opposing physiologic effects of other cannabinoids (predominantly cannabidiol), presence of regulatory proteins that act as metabolizing enzymes, binding molecules, or ligands, as well as functional polymorphisms of target receptors. Tolerance to the effects of cannabis may also develop on repeated exposures at least in part due to receptor downregulation or desensitization. Moreover, effects of cannabis may be enhanced or altered by concomitant use of other illicit drugs or medications used for treatment of established cardiovascular diseases. Regardless of these considerations, it is expected that the current cannabis epidemic would add significantly to the universal burden of cardiovascular diseases.Electronic supplementary materialThe online version of this article (10.1007/s40119-017-0102-x) contains supplementary material, which is available to authorized users.

Genome-wide DNA methylation analysis of heavy cannabis exposure in a New Zealand longitudinal cohort

“…Pathway enrichment revealed that hypermethylation in cannabis-only users was overrepresented in genes associated with cardiomyopathies and neural signalling. This is consistent with the literature which raises clinical concerns around cardiac complications potentially associated with cannabis use 100–103 . The enrichment of genes associated with neural signalling pathways is also consistent with the literature, including previous analyses of the CHDS cohort, which report associations between cannabis exposure and brain related biology such as mood disorders 7; 12; 48; 49; 51–54; 104; 105 .…”

Cannabis Use Is an Independent Predictor for Acute Myocardial Infarction Related Hospitalization in Younger Population

“…Although a meta-analysis of epidemiologic studies published between 1960 and 2010 showed that risk of AMI in cannabis user is low [31], a recent systemic literature review shows that the younger patients presenting with AMI following cannabis use had no preexisting coronary artery disease have had normal coronary angiograms [32], had toxicology positive for cannabis only, suggesting there may be a presence of potent synthetic cannabis increasing the overall risk of AMI attributable to cannabis [33]. There are studies that have shown that immediate risk of AMI increases fivefold within an hour of cannabis exposure compared with nonusers [15], and the annual risk of AMI in daily cannabis users may increase by 3% per year [34]. Our study, along with past literature [1,15,31e33,35], shows the magnitude of cannabis abuse/dependence to be at a higher scale as a causative factor for AMI, compared with other drugs.…”

“…Recreational drugs tend to have varying harmful effects on the cardiovascular system. Reported adverse cardiovascular events associated with cannabis, synthetic cannabinoids, and cannabimimetics include, but are not limited to, acute coronary syndrome, cerebrovascular diseases including stroke and vasospasm, rhythm disturbances, vasculopathy, and rhabdomyolysis [15]. While considering the mechanisms that are involved with cannabis and related drugs, it is vital to note that the molecules present in cannabis can change the metabolism of other drugs because of their natural tendency to clear metabolic pathways such as cytochromes CYP450 [16].…”

Recurrent STEMI Precipitated by Marijuana Use: Case Report and Literature Review

“…Oxygen demand-supply mismatch contributing to myocardial ischemia is due to decreased oxygen supply from elevated levels of carboxyhemolgobin, nearly five times higher than seen in tobacco cigarettes, generated from inhalation of combustion products [8,9,21,27]. Cannabis derived reactive oxygen species, CBR1 mediated endothelial dysfunction, and regional arterial vasospasm cause ischemia and increase the risk for subtotal to total arterial occlusion and downstream infarction [28,29]. The cannabinoid vasoactive effect ranges from vasoconstriction to vasodilatation in different vascular beds, with the coronary arterial bed likewise demonstrating both vasoconstriction and vasodilation [7,30].…”