Giorgetti Arianna, Pascali Jennifer P, Fais Paolo, Pelletti Guido, Gabbin Andrea, Franchetti Giorgia, Cecchetto Giovanni, Viel Guido
Unit of Legal Medicine, Department of Medical and Surgical Sciences, University of Bologna, Via Irnerio 49, 40126 Bologna, Italy.
Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Via Falloppio 50, 35121 Padova, Italy.
Life (Basel). 2021 May 14;11(5):440. doi: 10.3390/life11050440.
Novel psychoactive substances (NPS) represent a severe health risk for drug users. Even though the phenomenon has been growing since the early 2000s, the mechanisms of action of NPS at the receptors and beyond them are still scarcely understood. The aim of the present study was to provide a systematic review of the updated knowledge regarding the molecular mechanisms underlying the toxicity of synthetic opioids, cannabinoids, cathinones, and stimulants. The study was conducted on the PubMed database. Study eligibility criteria included relevance to the topic, English language, and time of publication (2010-2020). A combined Mesh and free-text protocols search was performed. Study selection was performed on the title/abstract and, in doubtful cases, on the full texts of papers. Of the 580 records identified through PubMed searching and reference checking, 307 were excluded by title/abstract and 78 additional papers were excluded after full-text reading, leaving a total of 155 included papers. Molecular mechanisms of synthetic opioids, synthetic cannabinoids, stimulants, psychedelics, and hallucinogens were reviewed and mostly involved both a receptor-mediated and non-receptor mediated cellular modulation with multiple neurotransmitters interactions. The molecular mechanisms underlying the action of NPS are more complex than expected, with a wide range of overlap among activated receptors and neurotransmitter systems. The peculiar action profile of single compounds does not necessarily reflect that of the structural class to which they belong, accounting for possible unexpected toxic reactions.
新型精神活性物质（NPS）对吸毒者构成严重的健康风险。尽管自21世纪初以来这一现象一直在增加，但人们对NPS在受体及其以外的作用机制仍知之甚少。本研究的目的是对合成阿片类药物、大麻素、卡西酮和兴奋剂毒性的分子机制的最新知识进行系统综述。该研究在PubMed数据库上进行。研究纳入标准包括与主题的相关性、英文语言以及发表时间（2010 - 2020年）。进行了主题词和自由文本协议的联合检索。研究选择基于标题/摘要进行，在有疑问的情况下，基于论文全文进行。通过PubMed检索和参考文献核对确定的580条记录中，307条因标题/摘要被排除，全文阅读后又排除了78篇论文，最终共纳入155篇论文。对合成阿片类药物、合成大麻素、兴奋剂、致幻剂和幻觉剂的分子机制进行了综述，其大多涉及受体介导和非受体介导的细胞调节以及多种神经递质相互作用。NPS作用的分子机制比预期更复杂，激活的受体和神经递质系统之间存在广泛重叠。单一化合物的独特作用模式不一定反映其所属结构类别的作用模式，这解释了可能出现的意外毒性反应。
