25X-NBOMe compounds – chemistry, pharmacology and toxicology. A comprehensive review

Abstract

Recently, a growing number of reports have indicated a positive effect of hallucinogenic-based therapies in different neuropsychiatric disorders. However, hallucinogens belonging to the group of new psychoactive substances (NPS) may produce high toxicity. NPS, due to their multi-receptors affinity, are extremely dangerous for the human body and mental health. An example of hallucinogens that have been lately responsible for many severe intoxications and deaths are 25X-NBOMes – N-(2-methoxybenzyl)-2,5-dimethoxy-4-substituted phenethylamines, synthetic compounds with strong hallucinogenic properties. 25X-NBOMes exhibit a high binding affinity to serotonin receptors but also to dopamine, adrenergic and histamine receptors. Apart from their influence on perception, many case reports point out systemic and neurological poisoning with these compounds. In humans, the most frequent side effects are tachycardia, anxiety, hypertension and seizures. Moreover, preclinical studies confirm that 25X-NBOMes cause developmental impairments, cytotoxicity, cardiovascular toxicity and changes in behavior of animals. Metabolism of NBOMes seems to be very complex and involves many metabolic pathways. This fact may explain the observed high toxicity. In addition, many analytical methods have been applied in order to identify these compounds and their metabolites. The presented review summarized the current knowledge about 25X-NBOMes, especially in the context of toxicity.

Graphical abstract (created in BioRender.com)

Keywords:

• N-benzyl-phenethylamines
• new psychoactive substances
• 5-HT_2A receptor
• hallucinogen
• toxicity
• NBOMe

Acknowledgements

The authors would like to thank Mrs. Anna Dudek-Kowalska (English language editor), Dr. Bolesław Banach (Department of Physiology, Pomeranian Medical University in Szczecin, Poland) and a senior colleague for the proofreading of this manuscript. Moreover, the authors would like to express gratitude for valuable comments received from the Reviewers that improved the quality of the presented review. The graphical abstract has been created in BioRender.com.

Declaration of interest

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors declare no conflict of interest.

Authors contribution

MH was responsible for conceptualization, search of the data related to the pharmacological properties and the effect of 25X-NBOMe on experimental models. PŚ was in charge of gathering data related to chemistry and identification of 25X-NBOMe by analytical techniques. MH and PŚ were involved in writing the original draft, developing the final manuscript and contributed to the preparation of figures and tables. All authors have approved the final manuscript.