The Toxicology of New Psychoactive Substances: Synthetic Cathinones and Phenylethylamines

New psychoactive substances (NPSs) are substitutes for classical drugs of abuse and there are now compounds available from all groups of classical drugs of abuse. During 2014, the number of synthetic cathinones increased dramatically and, together with phenylethylamines, they dominate the NPS markets in the European Union. In total, 31 cathinones and 9 phenylethylamines were encountered in 2014. The aim of this article was to summarize the existing knowledge about the basic pharmacology, metabolism, and human toxicology of relevant synthetic cathinones and phenylethylamines. Compared with existing reviews, we have also compiled the existing case reports from both fatal and nonfatal intoxications.

We performed a comprehensive literature search using bibliographic databases PubMed and Web of Science, complemented with Google Scholar. The focus of the literature search was on original articles, case reports, and previously published review articles published in 2014 or earlier.

The rapid increase of NPSs is a growing concern and sets new challenges not only for societies in drug prevention and legislation but also in clinical and forensic toxicology. In vivo and in vitro studies have demonstrated that the pharmacodynamic profile of cathinones is similar to that of other psychomotor stimulants. Metabolism studies show that cathinones and phenylethylamines are extensively metabolized; however, the parent compound is usually detectable in human urine. In vitro studies have shown that many cathinones and phenylethylamines are metabolized by CYP2D6 enzymes. This indicates that these drugs may have many possible drug-drug interactions and that genetic polymorphism may influence their toxicity. However, the clinical and toxicological relevance of CYP2D6 in adverse effects of cathinones and phenylethylamines is questionable, because these compounds are metabolized by other enzymes as well. The toxidromes commonly encountered after ingestion of cathinones and phenylethylamines are mainly of sympathomimetic and hallucinogenic character with a risk of excited delirium and life-threatening cardiovascular effects.

The acute and chronic toxicity of many NPSs is unknown or very sparsely investigated. There is a need for evidence-based-treatment recommendations for acute intoxications and a demand for new strategies to analyze these compounds in clinical and forensic cases.