Department of Excellence Biomedical Sciences and Public Health, Marche Polytechnic University, 60121 Ancona, Italy.
Dipartimento di Anestesia, Rianimazione e Emergenza-Urgenza, Fondazione IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.
Int J Mol Sci. 2023 Mar 25;24(7):6230. doi: 10.3390/ijms24076230.
According to the EU Early Warning System (EWS), synthetic cathinones (SCs) are the second largest new psychoactive substances (NPS) class, with 162 synthetic cathinones monitored by the EU EWS. They have a similar structure to cathinone, principally found in Catha Edulis; they have a phenethylamine related structure but also exhibit amphetamine-like stimulant effects. Illegal laboratories regularly develop new substances and place them on the market. For this reason, during the last decade this class of substances has presented a great challenge for public health and forensic toxicologists. Acting on different systems and with various mechanisms of action, the spectrum of side effects caused by the intake of these drugs of abuse is very broad. To date, most studies have focused on the substances' cardiac effects, and very few on their associated neurotoxicity. Specifically, synthetic cathinones appear to be involved in different neurological events, including increased alertness, mild agitation, severe psychosis, hyperthermia and death. A systematic literature search in PubMed and Scopus databases according to PRISMA guidelines was performed. A total of 515 studies published from 2005 to 2022 (350 articles from PubMed and 165 from Scopus) were initially screened for eligibility. The papers excluded, according to the criteria described in the Method Section (n = 401) and after full text analyses (n = 82), were 483 in total. The remaining 76 were included in the present review, as they met fully the inclusion criteria. The present work provides a comprehensive review on neurotoxic mechanisms of synthetic cathinones highlighting intoxication cases and fatalities in humans, as well as the toxic effects on animals (in particular rats, mice and zebrafish larvae). The reviewed studies showed brain-related adverse effects, including encephalopathy, coma and convulsions, and sympathomimetic and hallucinogenic toxidromes, together with the risk of developing excited/agitated delirium syndrome and serotonin syndrome.
根据欧盟早期预警系统 (EWS)，合成卡西酮类物质 (SCs) 是第二大类新精神活性物质 (NPS)，欧盟 EWS 监测到 162 种合成卡西酮类物质。它们的结构与主要存在于卡他柯植物中的卡西酮类似；它们具有苯乙胺的相关结构，但也表现出安非他命样的刺激作用。非法实验室经常开发新物质并将其投放市场。因此，在过去十年中，这一类物质对公共卫生和法医毒理学家构成了巨大挑战。这些滥用药物通过不同的作用机制作用于不同的系统，其引起的副作用范围非常广泛。迄今为止，大多数研究都集中在这些物质的心脏效应上，而很少关注其相关的神经毒性。具体来说，合成卡西酮类物质似乎与不同的神经事件有关，包括警觉性增加、轻度激动、严重精神病、体温过高和死亡。根据 PRISMA 指南，在 PubMed 和 Scopus 数据库中进行了系统的文献检索。最初筛选了 2005 年至 2022 年发表的 515 项研究（来自 PubMed 的 350 篇文章和 Scopus 的 165 篇文章），以确定其是否符合资格。根据方法部分中描述的标准（n = 401）和全文分析（n = 82）排除了不符合条件的论文，共排除了 483 篇。其余 76 篇论文完全符合纳入标准，因此被纳入本综述。本研究全面综述了合成卡西酮类物质的神经毒性机制，重点介绍了人类中毒和死亡病例，以及对动物（特别是大鼠、小鼠和斑马鱼幼虫）的毒性作用。综述研究显示，合成卡西酮类物质具有与大脑相关的不良反应，包括脑病、昏迷和抽搐，以及拟交感神经和致幻毒理学综合征，同时还存在发生兴奋/激动性谵妄综合征和血清素综合征的风险。
