Synthetic Cannabinoids and Cathinones Cardiotoxicity: Facts and Perspectives

Abstract

New psychoactive substances (NPS) constitute a group of psychotropic substances, designed to mimic the effects of traditional substances like cannabis, cocaine, MDMA, khat, which was not regulated by the 1961 United Nations Convention on Narcotics or the 1971 United Nations Convention on Psychotropic Substances. Illegal laboratories responsible for their production regularly developed new substances and placed them on the market to replace the ones that have been banned; for this reason, during the last decade this class of substances has represented a great challenge for the public health and forensic toxicologists. The spectrum of side effects caused by the intake of these drugs of abuse is very wide since they act on different systems with various mechanisms of action. To date most studies have focused on the neurotoxic effects, very few works focus on cardiotoxicity. Specifically, both synthetic cannabinoids and synthetic cathinones appear to be involved in different cardiac events, including myocardial infarction and sudden cardiac death due to fatal arrhythmias. Synthetic cannabinoids and cathinones cardiotoxicity are mainly mediated through activation of the CB1 receptor present on cardiomyocyte and involved with reactive oxygen species production, ATP depletion and cell death. Concerns with the adrenergic over-stimulation induced by this class of substances and increasing oxidative stress are mainly reported. In this systematic review we aim to summarize the data from all the works analyzing the possible mechanisms through which synthetic cannabinoids and synthetic cathinones damage the myocardial tissue.

Keywords: New psychoactive substances; cardiotoxicity; myocardial damage.; synthetic cannabinoids; synthetic cathinones; toxicity.

Fig. (1)

Synthetic Cannabinoids.

Fig. (2)

Synthetic Cathinones.

Fig. (3)

Mechanisms of cardiotoxicity induced by Synthetic Cannabinoids and Synthetic Cathinones. Through the activation of CB1 and MA T/R receptors of the brain, these molecules determine an intense noradrenergic stimulation. The direct action of synthetic cannabinoids on the heart is realized through the activation of the CB1 and CB2 receptors with both cardiotoxic and cardioprotective effects, while it is not clear which signaling pathway is triggered by synthetic cathinones. (Illustrated by Tina Šinigoj ©, 2020). (A higher resolution / colour version of this figure is available in the electronic copy of the article).