Abstract
Psychedelic and stimulating phenethylamines belong to the family of new psychoactive substances (NPS). The acute toxicity framework has begun to be investigated, while studies showing genotoxic potential are very limited or not available. Therefore, in order to fill this gap, the aim of the present work was to evaluate the genotoxicity by treating TK6 cells with 2C-H, 2C-I, 2C-B, 25B-NBOMe, and the popular 3,4-Methylenedioxymethylamphetamine (MDMA). On the basis of cytotoxicity and cytostasis results, we selected the concentrations (6.25–35 µM) to be used in genotoxicity analysis. We used the micronucleus (MN) as indicator of genetic damage and analyzed the MNi frequency fold increase by an automated flow cytometric protocol. All substances, except MDMA, resulted genotoxic; therefore, we evaluated reactive oxygen species (ROS) induction as a possible mechanism at the basis of the demonstrated genotoxicity. The obtained results showed a statistically significant increase in ROS levels for all genotoxic phenethylamines confirming this hypothesis. Our results highlight the importance of genotoxicity evaluation for a complete assessment of the risk associated also with NPS exposure. Indeed, the subjects who do not have hazardous behaviors or require hospitalization by using active but still “safe” doses could run into genotoxicity and in the well-known long-term effects associated.
Highlights
Psychoactive phenethylamines were among the first new psychoactive substances (NPS) to appear on the market in the late 1980s [1].NPS are defined as “new narcotic or psychotropic drugs, in pure form or in preparation, that are not controlled by the United Nations drug conventions, but which may pose a public health threat comparable to that posed by substances listed in these conventions” [2]
In the preliminary phase of the research, we determined the concentrations to be used in the subsequent experiments aimed at evaluating the potential genotoxicity of different molecules under study
Our automated cytofluorimetric protocol was able to demonstrate a statistically significant increase in MNi frequency for all four psychedelics phenethylamines, in particular for 2C-H and 2C-I at the highest concentration tested (35 μM), and for 2C-B and 25B-NBOMe at both tested concentrations (6.25 and 12.5 μM)
Summary
Psychoactive phenethylamines were among the first new psychoactive substances (NPS) to appear on the market in the late 1980s [1]. NPS are defined as “new narcotic or psychotropic drugs, in pure form or in preparation, that are not controlled by the United Nations drug conventions, but which may pose a public health threat comparable to that posed by substances listed in these conventions” [2]. The term “new” refers to substances which have recently become available on the illegal market which are not controlled by international drug laws and not necessarily developed by new inventions. NPS involve a large number of substances that are conventionally grouped into different classes according to their psychoactive effects. They include synthetic cannabinoids, stimulants, benzodiazepines, opioids, hallucinogens, and dissociatives [4,5]
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