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Zebrafish and Artemia salina in vivo evaluation of the recreational 25C-NBOMe drug demonstrates its high toxicity - PubMed

  • ️Fri Jan 01 2021

Zebrafish and Artemia salina in vivo evaluation of the recreational 25C-NBOMe drug demonstrates its high toxicity

Natalie Álvarez-Alarcón et al. Toxicol Rep. 2021.

Abstract

The NBOMe (N-2-methoxybenzyl-phenethylamines) family of compounds are synthetic hallucinogens derived from the 2C series. Although this family of compounds has been responsible for multiple cases of acute toxicity and several deaths around the world, to date there are few studies. These compounds act as potent 5-HT2A receptor agonists, including the hallucinogen 25C-NBOMe (2-(4-chloro-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine). In this study, we first evaluated the toxicity of 25C-NBOMe in two animal models: Artemia salina and zebrafish using the lethality test of Meyer et al. (1982) modified for Artemia salina and the Fish Embryo Toxicity test (FET) for zebrafish (Danio rerio). Subsequently, we determined the behavioral and morphological effects using different concentrations of the 25C-NBOMe. As a result, we found that this substance is highly toxic according to lethality tests in both animal models. We also observe that this hallucinogen induces alterations in swimming and motility patterns in Artemia salina. Similarly, there were alterations in the motor response to a stimulus, as well as abnormal development in the zebrafish. The developmental effects of zebrafish suggest a teratogenic potential for 25C-NBOMe. Therefore, these findings are correlated with side effects, such as motor response abnormalities and muscle deterioration, clinically reported for consumers of this recreational drug. Finally, although recent studies are addressing the neurotoxicity and cardiotoxicity of 25C-NBOMe in cell cultures, to the best of our knowledge, this is the first in vivo report for 25C-NBOMe related to toxicological parameters and their global effects on development. Therefore, it could represent an advance in the study of the substance that contributes to the understanding of the effects on behavior and development in humans.

Keywords: 25C-NBOMe; Artemia salina; Teratogenic effects; Toxicity; Zebrafish.

© 2021 The Authors.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

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Graphical abstract
Fig. 1
Fig. 1

The hallucinogen 25C-NBOMe affects the motor function of Artemia salina. Effects on the behavior of the Artemia salina as a function of 25C-NBOMe concentrations, after 24 and 48 hpi. The hallucinogen 25C-NBOMe effects on motor function are discriminated in 4 categories in grayscale representing the proportion of individuals displaying a particular effect. Exposure to 25C-NBOMe causes a decrease in swimming speed and, in some cases, the movement of antennas without displacement.

Fig. 2
Fig. 2

The hallucinogen 25C-NBOMe affects the motor response in zebrafish. Percentage of fish that do not present a motor response to a stimulus after exposure of 25C-NBOMe as a function of time (hpi). The column color indicates evaluation time (hpi). An average of 10 larvae without morphological defects were tested per concentration of 25C-NBOMe. The error bars represent the sample standard deviation. Asterisks mark significant differences relative to controls in concentrations of 12, 15 and 18 μg/mL of 25C-NBOMe (p < 0.05).

Fig. 3
Fig. 3

The hallucinogen 25C-NBOMe induces morphological changes in zebrafish. Images of most common defects observed in zebrafish embryos exposed to concentrations of 1.5, 3, 12, 15 and 18 μg/mL at 24 hpi (34 hpf), 48 hpi (58 hpf), 72 hpi (82 hpf) and 96 hpi (106 hpf). Asterisk indicates that for 15 μg/mL of 25C-NBOMe at 96 hpi, no photographic record was obtained. Scale bar =1.0 mm.

Fig. 4
Fig. 4

The hallucinogen 25C-NBOMe delays pigmentation pattern in zebrafish. Quantification of the effect of 25C-NBOMe on pigmentation patterns in affected larvae. The error bars represent the data standard deviation. Asterisks mark significant differences in concentrations of 2, 12 and 18 μg/ mL of 25C-NBOMe (p = 0.0300, 0.0201 and 0.0209) relative to controls.

Fig. 5
Fig. 5

25C-NBOMe causes heart defects and circulatory problems in zebrafish. a Effect of 25C-NBOMe on the appearance of pericardial and perivitelline edemas, and alteration in circulation in zebrafish. The error bars represent the data standard deviation. Asterisks show significant differences in the concentrations of 12 and 18 μg/mL of 25C-NBOMe (p = 0.0311 and 0.0438) relative to controls. b Pericardial and perivitelline edemas (blue line) observed in zebrafish exposed to concentrations of 12 and 18 μg/mL of 25C-NBOMe at 72 hpi (p = 0,0041 and 0.0254). Scale bar =1.0 mm (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article).

Fig. 6
Fig. 6

25C-NBOMe causes eye morphogenesis defects. a Normal ocular development in control fish at 60 hpf. b Fish with alteration in the closure of the optic fissure (arrowhead) at 60 hpf exposed to 9 μg/mL of 25C-NBOMe. Scale bar =1.0 mm.

Fig. 7
Fig. 7

The hallucinogen 25C-NBOMe induces lordosis in zebrafish. a Percentage of fish that show lordosis when exposed to 25C-NBOMe. The error bars represent the data standard deviation. Asterisks show significant differences in the concentrations of 1, 1.5, 2, 6, 12, 15 and 18 μg/mL (p = 0.0383, 0.0423, 0.0260, 0.0258, 0.0294, 0.0417 and 0.0383) relative to controls. b Lordosis observed in zebrafish exposed to concentrations of 1, 1.5, 6, 12, 15 and 18 μg/mL of hallucinogen 25C-NBOMe. Scale bar =1.0 mm.

Fig. 8
Fig. 8

The hallucinogen 25C-NBOMe induces yolk deformation in zebrafish. Percentage of fish displaying yolk deformation at 24 hpi per concentration. The error bars represent the data standard deviation. The asterisk shows the significant difference between the vehicle and the concentrations of 6, 12, and 18 μg/mL (p = 0.0037, 0.0121, 0.0048), relative to controls.

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References

    1. Suzuki J. Toxicities associated with NBOMe ingestion-a novel class of potent hallucinogens: a review of the literature. Psychosomatics. 2015;56(2):129–139. doi: 10.1016/j.psym.2014.11.002. - DOI - PMC - PubMed
    1. Bersani F.S. 25C-NBOMe: preliminary data on pharmacology, psychoactive effects, and toxicity of a new potent and dangerous hallucinogenic drug. Biomed. Res. Int. 2014;2014 doi: 10.1155/2014/734749. - DOI - PMC - PubMed
    1. Aguirre R. 2018. NBOMe, la droga que tiene en alerta al país. Medellín, Jan. 08.
    1. Kawahara G., Maeda H., Kikura-Hanajiri R., ichi Yoshida K., Hayashi Y.K. The psychoactive drug 25B-NBOMe recapitulates rhabdomyolysis in zebrafish larvae. Forensic Toxicol. 2017;35(2):369–375. doi: 10.1007/s11419-017-0366-9. - DOI - PMC - PubMed
    1. Braden M.R., Parrish J.C., Naylor J.C., Nichols D.E. Molecular interaction of serotonin 5-HT2A receptor residues Phe339 (6.51) and Phe340 (6.52) with superpotent N-Benzyl phenethylamine agonists. Mol. Pharmacol. 2006;70(6):1956–1964. doi: 10.1124/mol.106.028720.delics. - DOI - PubMed

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