Why Do Marijuana and Synthetic Cannabimimetics Induce Acute Myocardial Infarction in Healthy Young People?

Abstract

The use of cannabis preparations has steadily increased. Although cannabis was traditionally assumed to only have mild vegetative side effects, it has become evident in recent years that severe cardiovascular complications can occur. Cannabis use has recently even been added to the risk factors for myocardial infarction. This review is dedicated to pathogenetic factors contributing to cannabis-related myocardial infarction. Tachycardia is highly important in this respect, and we provide evidence that activation of CB₁ receptors in brain regions important for cardiovascular regulation and of presynaptic CB₁ receptors on sympathetic and/or parasympathetic nerve fibers are involved. The prototypical factors for myocardial infarction, i.e., thrombus formation and coronary constriction, have also been considered, but there is little evidence that they play a decisive role. On the other hand, an increase in the formation of carboxyhemoglobin, impaired mitochondrial respiration, cardiotoxic reactions and tachyarrhythmias associated with the increased sympathetic tone are factors possibly intensifying myocardial infarction. A particularly important factor is that cannabis use is frequently accompanied by tobacco smoking. In conclusion, additional research is warranted to decipher the mechanisms involved, since cannabis use is being legalized increasingly and Δ⁹-tetrahydrocannabinol and its synthetic analogue nabilone are indicated for the treatment of various disease states.

Keywords: THC; cannabinoid receptor; cannabinoids; heart; marijuana; myocardial infarction; oxygen consumption; sympathetic system; tachycardia; thrombus.

Figure 1

Cannabinoids and their affinities to the classical cannabinoid CB₁ and CB₂ receptors and to other receptors sensitive to cannabinoids, as well as to inhibitors of enzymes involved in the synthesis and/or degradation of AEA and 2-AG. Note that the numbers in the superscript indicate the appropriate reference [15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38]. The figure presents only phytocannabinoids (green font), synthetic cannabinoids and other compounds discussed in this article (black font), endogenous cannabinoids (pink font) and inhibitors of the endocannabinoid synthesis and degradation (blue font) that have been considered in this review. ECS, endocannabinoid system; the “plus sign” indicates agonism and the “minus sign” antagonism, inverse agonism or inhibition versus the respective receptors/enzymes. The intensity of blue color next to the compound is higher the lower the values of K_i, IC₅₀ or EC₅₀ are (expressed in nM). Based on Pertwee et al. [39] unless stated otherwise (superscript). WIN55212-3, inactive S(–)enantiomer of WIN55212-2 [40]; AM404, an inhibitor of anandamide transport [41]. Abbreviations: Δ⁹-THC, Δ⁹-tetrahydrocannabinol; 2-AG, 2-arachidonoylglycerol; abn-CBD, abnormal cannabidiol; ACEA, arachidonoyl-2’-chlorethylamide; ACPA, arachidonylcyclopropylamide; AEA, anandamide; CB₁, cannabinoid CB₁ receptor; CB₂, cannabinoid CB₂ receptor; CBD, cannabidiol; DAGL, diacylglycerol lipase; ECS, endocannabinoid system; FAAH, fatty-acid amide hydrolase; GPR18, G protein-coupled receptor 18; GPR55, G protein-coupled receptor 55; LPI, L-alpha-lysophosphatidylinositol; MethAEA, methanandamide; n.d., not determined; OEA, oleoylethanolamide; PEA, palmitoylethanolamide; TRPV1 transient receptor-potential cation-channel subfamily V member 1; URB597, inhibitor of fatty-acid amide hydrolase.

Figure 2

Effects of cannabinoids on the heart possibly implicated in myocardial infarction. ?, pathophysiological relevance plausible but not supported by appropriate studies; CB₁-R, cannabinoid CB₁ receptor; MI, myocardial infarction.