Lobato-Freitas Carolina, Brito-da-Costa Andreia Machado, Dinis-Oliveira Ricardo Jorge, Carmo Helena, Carvalho Félix, Silva João Pedro, Dias-da-Silva Diana
UCIBIO-REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal.
IINFACTS-Institute of Research and Advanced Training in Health Sciences and Technologies, Department of Sciences, University Institute of Health Sciences (IUCS), CESPU, CRL, 4585-116 Gandra, Portugal;
Pharmaceuticals (Basel). 2021 Feb 25;14(3):186. doi: 10.3390/ph14030186.
ADB-FUBINACA and AMB-FUBINACA are two synthetic indazole-derived cannabinoid receptor agonists, up to 140- and 85-fold more potent, respectively, than -∆-tetrahydrocannabinol (∆-THC), the main psychoactive compound of cannabis. Synthesised in 2009 as a pharmaceutical drug candidate, the recreational use of ADB-FUBINACA was first reported in 2013 in Japan, with fatal cases being described in 2015. ADB-FUBINACA is one of the most apprehended and consumed synthetic cannabinoid (SC), following AMB-FUBINACA, which emerged in 2014 as a drug of abuse and has since been responsible for several intoxication and death outbreaks. Here, we critically review the physicochemical properties, detection methods, prevalence, biological effects, pharmacodynamics and pharmacokinetics of both drugs. When smoked, these SCs produce almost immediate effects (about 10 to 15 s after use) that last up to 60 min. They are rapidly and extensively metabolised, being the -demethylated metabolite of AMB-FUBINACA, 2-(1-(4-fluorobenzyl)-1-indazole-3-carboxamide)-3-methylbutanoic acid, the main excreted in urine, while for ADB-FUBINACA the main biomarkers are the hydroxdimethylpropyl ADB-FUBINACA, hydroxydehydrodimethylpropyl ADB-FUBINACA and hydroxylindazole ADB-FUBINACA. ADB-FUBINACA and AMB-FUBINACA display full agonism of the CB1 receptor, this being responsible for their cardiovascular and neurological effects (e.g., altered perception, agitation, anxiety, paranoia, hallucinations, loss of consciousness and memory, chest pain, hypertension, tachycardia, seizures). This review highlights the urgent requirement for additional studies on the toxicokinetic properties of AMB-FUBINACA and ADB-FUBINACA, as this is imperative to improve the methods for detecting and quantifying these drugs and to determine the best exposure markers in the various biological matrices. Furthermore, it stresses the need for clinicians and pathologists involved in the management of these intoxications to describe their findings in the scientific literature, thus assisting in the risk assessment and treatment of the harmful effects of these drugs in future medical and forensic investigations.
ADB - FUBINACA和AMB - FUBINACA是两种合成的吲唑衍生的大麻素受体激动剂，效力分别比大麻的主要精神活性化合物 - ∆ - 四氢大麻酚（∆ - THC）高140倍和85倍。ADB - FUBINACA于2009年作为候选药物合成，其娱乐性使用于2013年首次在日本被报道，2015年出现了致命病例。ADB - FUBINACA是继AMB - FUBINACA之后被查获和使用最多的合成大麻素之一，AMB - FUBINACA于2014年作为滥用药物出现，此后导致了多起中毒和死亡事件。在此，我们对这两种药物的物理化学性质、检测方法、流行情况、生物学效应、药效学和药代动力学进行批判性综述。吸食这些合成大麻素后几乎立即产生效果（使用后约10至15秒），持续长达60分钟。它们迅速且广泛地代谢，AMB - FUBINACA的去甲基化代谢产物2 - (1 - (4 - 氟苄基)-1 - 吲唑 - 3 - 甲酰胺)-3 - 甲基丁酸是尿液中主要的排泄产物，而ADB - FUBINACA的主要生物标志物是羟基二甲基丙基ADB - FUBINACA、羟基脱氢二甲基丙基ADB - FUBINACA和羟基吲唑ADB - FUBINACA。ADB - FUBINACA和AMB - FUBINACA对CB1受体表现出完全激动作用，这导致了它们的心血管和神经学效应（例如，感知改变、激动、焦虑、偏执、幻觉、意识和记忆丧失、胸痛、高血压、心动过速、癫痫发作）。本综述强调迫切需要对AMB - FUBINACA和ADB - FUBINACA的毒代动力学性质进行更多研究，因为这对于改进这些药物的检测和定量方法以及确定各种生物基质中的最佳暴露标志物至关重要。此外，它强调参与这些中毒事件管理的临床医生和病理学家需要在科学文献中描述他们的发现，从而有助于未来医学和法医调查中对这些药物有害影响的风险评估和治疗。
