Abstract
ADB-FUBINACA and AMB-FUBINACA are two synthetic indazole-derived cannabinoid receptor agonists, up to 140- and 85-fold more potent, respectively, than trans-∆9-tetrahydrocannabinol (∆9-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 O-demethylated metabolite of AMB-FUBINACA, 2-(1-(4-fluorobenzyl)-1H-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.
Highlights
Synthetic cannabinoids (SCs), known as synthetic cannabinoid receptor agonists (SCRAs), represent the largest group of new psychoactive substances (NPS) currently monitored by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA)through the EU Early Warning System [1]
This review summarises the available information on ADB-FUBINACA and AMBFUBINACA regarding their physicochemical properties and detection methods, abuse and prevalence patterns, legal status, biological and clinical effects, mechanisms of toxicity and treatment of intoxications, focusing on their pharmacodynamics and pharmacokinetics
10 mg of the herbal matrix crushed to powder were extracted with 1 mL methanol under ultrasonication for 10 min
Summary
Synthetic cannabinoids (SCs), known as synthetic cannabinoid receptor agonists (SCRAs), represent the largest group of new psychoactive substances (NPS) currently monitored by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA)through the EU Early Warning System [1]. Pharmaceuticals 2021, 14, 186 involved in numerous cases of poisonings and deaths [2,3,4,5] Most of these recreational substances were originally synthesised for biomedical and therapeutic research, but currently there are several laboratories, mainly in China, that produce and export them in bulk powder to Europe [6,7]. In 2013, ADB-FUBINACA was first identified in Japan in mixtures of herbs and other NPS (e.g., α-pyrrolidinopentiothiophenone and AH-7921) for recreational use [9] That same year, this substance was first detected in Europe, in Hungary, both in pills labelled with a Facebook logo, and in biological samples of consumers [10]. In 2014, the ADB-FUBINACA analogue methyl (S)-2[1-(4-fluorobenzyl)-1H-indazole-3-carboxamido]-3-methylbutanoate (AMB-FUBINACA), known as FUB-AMB and MMB-FUBINACA, was first detected in the state of Louisiana, USA, and in Sweden; emerging in the city of Auckland, New Zealand, in 2017, and having recently gained great notoriety in different parts of the world [1,2,11,12]
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