Overview of Synthetic Cannabinoids ADB-FUBINACA and AMB-FUBINACA: Clinical, Analytical, and Forensic Implications
ADB-FUBINACA and AMB-FUBINACA are two synthetic indazole-derived cannabinoid receptor agonists, up to 140- and 85-fold more potent, respectively, than <i>trans</i>-∆<sup>9</sup>-tetrahydrocannabinol (∆<sup>9</sup>-THC), the main psychoactive compound of cannabis....
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-02-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/14/3/186 |
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| author | Carolina Lobato-Freitas Andreia Machado Brito-da-Costa Ricardo Jorge Dinis-Oliveira Helena Carmo Félix Carvalho João Pedro Silva Diana Dias-da-Silva |
| author_facet | Carolina Lobato-Freitas Andreia Machado Brito-da-Costa Ricardo Jorge Dinis-Oliveira Helena Carmo Félix Carvalho João Pedro Silva Diana Dias-da-Silva |
| author_sort | Carolina Lobato-Freitas |
| collection | DOAJ |
| description | ADB-FUBINACA and AMB-FUBINACA are two synthetic indazole-derived cannabinoid receptor agonists, up to 140- and 85-fold more potent, respectively, than <i>trans</i>-∆<sup>9</sup>-tetrahydrocannabinol (∆<sup>9</sup>-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 <i>O</i>-demethylated metabolite of AMB-FUBINACA, 2-(1-(4-fluorobenzyl)-1<i>H</i>-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. |
| first_indexed | 2024-03-09T00:31:16Z |
| format | Article |
| id | doaj.art-349826da289045ac92e7427f33122c03 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T00:31:16Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-349826da289045ac92e7427f33122c032023-12-11T18:28:08ZengMDPI AGPharmaceuticals1424-82472021-02-0114318610.3390/ph14030186Overview of Synthetic Cannabinoids ADB-FUBINACA and AMB-FUBINACA: Clinical, Analytical, and Forensic ImplicationsCarolina Lobato-Freitas0Andreia Machado Brito-da-Costa1Ricardo Jorge Dinis-Oliveira2Helena Carmo3Félix Carvalho4João Pedro Silva5Diana Dias-da-Silva6UCIBIO-REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, PortugalIINFACTS-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, PortugalUCIBIO-REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, PortugalUCIBIO-REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, PortugalUCIBIO-REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, PortugalUCIBIO-REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, PortugalUCIBIO-REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, PortugalADB-FUBINACA and AMB-FUBINACA are two synthetic indazole-derived cannabinoid receptor agonists, up to 140- and 85-fold more potent, respectively, than <i>trans</i>-∆<sup>9</sup>-tetrahydrocannabinol (∆<sup>9</sup>-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 <i>O</i>-demethylated metabolite of AMB-FUBINACA, 2-(1-(4-fluorobenzyl)-1<i>H</i>-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.https://www.mdpi.com/1424-8247/14/3/186synthetic cannabinoids (SCs)psychoactive substancesmetabolismtoxicityintoxication |
| spellingShingle | Carolina Lobato-Freitas Andreia Machado Brito-da-Costa Ricardo Jorge Dinis-Oliveira Helena Carmo Félix Carvalho João Pedro Silva Diana Dias-da-Silva Overview of Synthetic Cannabinoids ADB-FUBINACA and AMB-FUBINACA: Clinical, Analytical, and Forensic Implications Pharmaceuticals synthetic cannabinoids (SCs) psychoactive substances metabolism toxicity intoxication |
| title | Overview of Synthetic Cannabinoids ADB-FUBINACA and AMB-FUBINACA: Clinical, Analytical, and Forensic Implications |
| title_full | Overview of Synthetic Cannabinoids ADB-FUBINACA and AMB-FUBINACA: Clinical, Analytical, and Forensic Implications |
| title_fullStr | Overview of Synthetic Cannabinoids ADB-FUBINACA and AMB-FUBINACA: Clinical, Analytical, and Forensic Implications |
| title_full_unstemmed | Overview of Synthetic Cannabinoids ADB-FUBINACA and AMB-FUBINACA: Clinical, Analytical, and Forensic Implications |
| title_short | Overview of Synthetic Cannabinoids ADB-FUBINACA and AMB-FUBINACA: Clinical, Analytical, and Forensic Implications |
| title_sort | overview of synthetic cannabinoids adb fubinaca and amb fubinaca clinical analytical and forensic implications |
| topic | synthetic cannabinoids (SCs) psychoactive substances metabolism toxicity intoxication |
| url | https://www.mdpi.com/1424-8247/14/3/186 |
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