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Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Fourth Generation of Synthetic Cannabinoid Receptor Agonists: A Review on the Latest Insights

Author(s): Sara Malaca, Francesco P. Busardò*, Giulio Nittari, Ascanio Sirignano and Giovanna Ricci

Volume 28, Issue 32, 2022

Published on: 17 December, 2021

Page: [2603 - 2617] Pages: 15

DOI: 10.2174/1381612827666211115170521

Price: $65

Abstract

Background: Over the past few years, an emerging number of new psychoactive substances (NPSs) entered the illicit market. NPSs are designed to resemble the effects of classical drugs of abuse, reinforcing their effects and duration. Among the most abused NPS, synthetic cannabinoids are cannabinoid receptor agonists (SCRAs) that mimic the effect of the main psychotropic phytocannabinoid Δ9-tetrahydrocannabinol (THC).

Methods: We herein reviewed the international literature to provide available information on the newest SCRAs generation.

Results: Compared to the previous SCRAs generations, the structures of the last generation result in increased affinity for and efficacy at cannabinoid CB1 receptors, which are thought to be mainly responsible for the psychoactive effects of THC and its analogues. Accordingly, these more potent cannabimimetic effects may increase the number of adverse reactions such as neurological disorders (e.g., psychosis, agitation, irritability, paranoia, confusion, and anxiety), psychiatric episodes (e.g., hallucinations, delusions, self-harm), other physical conditions (e.g., tachycardia, hypertension, arrhythmia, chest pain, nausea, vomiting, and fever) and deaths. In the last decade, more than a hundred SCRAs from different chemical classes emerged on the illicit web market. SCRAs have been thoroughly studied: they were physico-chemically characterized, and pharmaco-toxicological characteristics were investigated. The last SCRAs generations include increasingly potent and toxic compounds, posing a potential health threat to consumers.

Conclusion: From November 2017 to February 2021, at least 20 new “fourth-generation” SCRAs were formally reported to international drug agencies. Our understanding of the neurotoxicity of these compounds is still limited due to the lack of global data, but their potency and their toxicity are likely higher than those of the previous generations.

Keywords: Synthetic cannabinoids, new psychoactive substances, receptor agonists, toxicology, THC, fourth generation.

[1]
Wiley JL, Marusich JA, Lefever TW, et al. AB-CHMINACA, AB-PINACA, and FUBIMINA: Affinity and potency of novel synthetic cannabinoids in producing Δ9-Tetrahydrocannabinol-like effects in mice. J Pharmacol Exp Ther 2015; 354(3): 328-39.
[http://dx.doi.org/10.1124/jpet.115.225326] [PMID: 26105953]
[2]
Banister SD, Connor M. The chemistry and pharmacology of synthetic cannabinoid receptor agonists as new psychoactive substances: Origins. In: Handbook of Experimental Pharmacology. New York LLC: Springer 2018; pp. 165-90.
[http://dx.doi.org/10.1007/164_2018_143]
[3]
Banister SD, Adams A, Kevin RC, et al. Synthesis and pharmacology of new psychoactive substance 5F-CUMYL-P7AICA, a scaffold- hopping analog of synthetic cannabinoid receptor agonists 5F-CUMYL-PICA and 5F-CUMYL-PINACA. Drug Test Anal 2019; 11(2): 279-91.
[http://dx.doi.org/10.1002/dta.2491] [PMID: 30151911]
[4]
Cannaert A, Sparkes E, Pike E, et al. Synthesis and in vitro Cannabinoid Receptor 1 Activity of Recently Detected Synthetic Cannabinoids 4F-MDMB-BICA, 5F-MPP-PICA, MMB-4en-PICA, CUMYL-CBMICA, ADB-BINACA, APP-BINACA, 4F-MDMB-BINACA, MDMB-4en-PINACA, A-CHMINACA, 5F-AB-P7AICA, 5F-MDMB-P7AICA, and 5F-AP7AICA. ACS Chem Neurosci 2020; 11(24): 4434-46.
[http://dx.doi.org/10.1021/acschemneuro.0c00644] [PMID: 33253529]
[5]
Banister SD, Moir M, Stuart J, et al. The pharmacology of indole and indazole synthetic cannabinoid designer drugs AB-FUBINACA, ADB-FUBINACA, AB-PINACA, ADB-PINACA, 5F-AB- PINACA, 5F-ADB-PINACA, ADBICA and 5F-ADBICA. ACS Chem Neurosci 2013; 6(9): 2522-31.
[http://dx.doi.org/10.1021/acschemneuro.6b00137] [PMID: 27421060]
[6]
Antonides LH, Cannaert A, Norman C. Shape matters: The application of activity-based in vitro bioassays and chiral profiling to the pharmacological evaluation of synthetic cannabinoid receptor agonists in drug-infused papers seized in prisons. Drug Test Anal 2020; 13(3): 628-43.
[http://dx.doi.org/10.1002/dta.2965] [PMID: 33161649]
[7]
Mackie K. Cannabinoid receptors as therapeutic targets. Annu Rev Pharmacol Toxicol 2006; 46: 101-22.
[http://dx.doi.org/10.1146/annurev.pharmtox.46.120604.141254] [PMID: 16402900]
[8]
Hess C, Schoeder CT, Pillaiyar T, Madea B, Müller CE. Pharmacological evaluation of synthetic cannabinoids identified as constituents of spice. Forensic Toxicol 2016; 34(2): 329-43.
[http://dx.doi.org/10.1007/s11419-016-0320-2] [PMID: 27429655]
[9]
Pertwee RG, Howlett AC, Abood ME, et al. International union of basic and clinical pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB1 and CB2. Pharmacol Rev 2010; 62(4): 588-631.
[http://dx.doi.org/10.1124/pr.110.003004] [PMID: 21079038]
[10]
Mechoulam R, Parker LA. The endocannabinoid system and the brain. Annu Rev Psychol 2013; 64: 21-47.
[http://dx.doi.org/10.1146/annurev-psych-113011-143739] [PMID: 22804774]
[11]
Longworth M, Banister SD, Boyd R, et al. Pharmacology of cumyl-carboxamide synthetic cannabinoid new psychoactive substances (NPS) CUMYL-BICA, CUMYL-PICA, CUMYL-5F-PICA, CUMYL-5F-PINACA, and their analogues. ACS Chem Neurosci 2017; 8(10): 2159-67.
[http://dx.doi.org/10.1021/acschemneuro.7b00267] [PMID: 28792725]
[12]
Abouchedid R, Hudson S, Thurtle N, et al. Analytical confirmation of synthetic cannabinoids in a cohort of 179 presentations with acute recreational drug toxicity to an Emergency Department in London, UK in the first half of 2015. Clin Toxicol (Phila) 2017; 55(5): 338-45.
[http://dx.doi.org/10.1080/15563650.2017.1287373] [PMID: 28421836]
[13]
Longworth M, Banister SD, Mack JBC, Glass M, Connor M, Kassiou M. The 2-alkyl-2H-indazole regioisomers of synthetic cannabinoids AB-CHMINACA, AB-FUBINACA, AB-PINACA, and 5F-AB-PINACA are possible manufacturing impurities with cannabimimetic activities. Forensic Toxicol 2016; 34(2): 286-303.
[http://dx.doi.org/10.1007/s11419-016-0316-y] [PMID: 27547266]
[14]
Boczek T, Zylinska L. Receptor-dependent and independent regulation of voltage-gated Ca2+ channels and Ca2+-permeable channels by endocannabinoids in the brain. Int J Mol Sci 2021; 22(15): 8168.
[http://dx.doi.org/10.3390/ijms22158168] [PMID: 34360934]
[15]
Storozhuk MV, Zholos AV. TRP channels as novel targets for endogenous ligands: focus on endocannabinoids and nociceptive signalling. Curr Neuropharmacol 2018; 16(2): 137-50.
[http://dx.doi.org/10.2174/1570159X15666170424120802] [PMID: 28440188]
[16]
Abdulrahim D, Bowden-Jones O. Novel psychoactive treatment UK network harms of synthetic cannabinoid receptor agonists (SCRAs) and their management 2016. [cited 2021 Mar 29]. Available from: www.neptune-clinical-guidance.co.uk
[17]
Ashton JC. Synthetic cannabinoids as drugs of abuse. Curr Drug Abuse Rev 2012; 5(2): 158-68.
[http://dx.doi.org/10.2174/1874473711205020158] [PMID: 22530798]
[18]
CFSRE. Positivity of New Synthetic Cannabinoid 4F - MDMB - BICA Increasing in U.S. as Prevalence of 5F - MDMB - PICA Wanes. 2021. [cited 2021 Mar 29]. Available from: https://www.npsdiscovery.org/wp-content/uploads/2021/02/Public-Alert_4F-MDMB-BICA_NPS-Discovery_020921.pdf?mc_cid=10c03dcc2a&mc_eid=0872426f82
[19]
Adams AJ, Banister SD, Irizarry L, Trecki J, Schwartz M, Gerona R. “Zombie” outbreak caused by the synthetic cannabinoid AMB-FUBINACA in New York. N Engl J Med 2017; 376(3): 235-42.
[http://dx.doi.org/10.1056/NEJMoa1610300] [PMID: 27973993]
[20]
Castaneto MS, Gorelick DA, Desrosiers NA, Hartman RL, Pirard S, Huestis MA. Synthetic cannabinoids: epidemiology, pharmacodynamics, and clinical implications. Drug Alcohol Depend 2014; 144: 12-41.
[http://dx.doi.org/10.1016/j.drugalcdep.2014.08.005] [PMID: 25220897]
[21]
Seely KA, Lapoint J, Moran JH, Fattore L. Spice drugs are more than harmless herbal blends: a review of the pharmacology and toxicology of synthetic cannabinoids. Prog Neuropsychopharmacol Biol Psychiatry 2012; 39(2): 234-43.
[http://dx.doi.org/10.1016/j.pnpbp.2012.04.017] [PMID: 22561602]
[22]
Rosado T, Gonçalves J, Luís Â, et al. Synthetic cannabinoids in biological specimens: a review of current analytical methods and sample preparation techniques. Bioanalysis 2018; 10(19): 1609-23.
[http://dx.doi.org/10.4155/bio-2018-0150] [PMID: 30226077]
[23]
Hruba L, McMahon LR. Apparent affinity estimates and reversal of the effects of synthetic cannabinoids AM-2201, CP-47,497, JWH-122, and JWH-250 by rimonabant in rhesus monkeys. J Pharmacol Exp Ther 2017; 362(2): 278-86.
[http://dx.doi.org/10.1124/jpet.117.240572] [PMID: 28533288]
[24]
Synthetic cannabinoids in Europe. European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) 2017. [cited 2021 Mar 29]. Available from: https://www.emcdda.europa.eu/topics/pods/synthetic-cannabinoids
[25]
Ogata J, Uchiyama N, Kikura-Hanajiri R, Goda Y. DNA sequence analyses of blended herbal products including synthetic cannabinoids as designer drugs. Forensic Sci Int 2013; 227(1-3): 33-41.
[http://dx.doi.org/10.1016/j.forsciint.2012.09.006] [PMID: 23092848]
[26]
Norman C, Walker G, McKirdy B, et al. Detection and quantitation of synthetic cannabinoid receptor agonists in infused papers from prisons in a constantly evolving illicit market. Drug Test Anal 2020; 12(4): 538-54.
[http://dx.doi.org/10.1002/dta.2767] [PMID: 31944624]
[27]
HM Inspectorate of Prisons. Changing patterns of substance misuse in adult prisons and service responses A thematic review by HM Inspectorate of Prisons Changing patterns of substance misuse in adult prisons and service responses 2015. [cited 2021 Mar 29]. Available from: http://www.justiceinspectorates.gov.uk/ hmiprisons/about-our-inspections/http://www.justiceinspectorates.gov.uk/hmiprisons/
[28]
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Results from an EMCDDA trendspotter study New psychoactive substances in prison. 2018. [cited 2021 Mar 29]. Available from: https://www.drugsandalcohol.ie/29145/1/nps-in-prison.pdf
[29]
Ralphs R, Williams L, Askew R, Norton A. Adding Spice to the Porridge: The development of a synthetic cannabinoid market in an English prison. Int J Drug Policy 2017; 40: 57-69.
[http://dx.doi.org/10.1016/j.drugpo.2016.10.003] [PMID: 27955961]
[30]
Adamowicz P. Blood concentrations of synthetic cannabinoids. Clin Toxicol (Phila) 2021; 59(3): 246-51.
[http://dx.doi.org/10.1080/15563650.2020.1787429] [PMID: 32615814]
[31]
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Understanding the “Spice” phenomenon. 2017. [cited 2021 Mar 29]. Available from: https://www.emcdda.europa.eu/ publications/thematic-papers/understanding-spice-phenomenon_en
[32]
Huffman JW, Szklennik PV, Almond A, et al. 1-Pentyl-3-phenylacetylindoles, a new class of cannabimimetic indoles. Bioorg Med Chem Lett 2005; 15(18): 4110-3.
[http://dx.doi.org/10.1016/j.bmcl.2005.06.008] [PMID: 16005223]
[33]
Auwärter V, Dresen S, Weinmann W, Müller M, Pütz M, Ferreirós N. ‘Spice’ and other herbal blends: harmless incense or cannabinoid designer drugs? J Mass Spectrom 2009; 44(5): 832-7.
[http://dx.doi.org/10.1002/jms.1558] [PMID: 19189348]
[34]
Teske J, Weller JP, Fieguth A, Rothämel T, Schulz Y, Tröger HD. Sensitive and rapid quantification of the cannabinoid receptor agonist naphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-018) in human serum by liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2010; 878(27): 2659-63.
[http://dx.doi.org/10.1016/j.jchromb.2010.03.016] [PMID: 20378423]
[35]
Huffman JW. Cannabimimetic indoles, pyrroles, and indenes: structure–activity relationships and receptor interactions. In: Reggio PH, Ed. The Cannabinoid Receptors. Humana Press 2009; pp. 49-94.
[http://dx.doi.org/10.1007/978-1-59745-503-9_3]
[36]
Lapoint J, James LP, Moran CL, Nelson LS, Hoffman RS, Moran JH. Severe toxicity following synthetic cannabinoid ingestion. Clin Toxicol (Phila) 2011; 49(8): 760-4.
[http://dx.doi.org/10.3109/15563650.2011.609822] [PMID: 21970775]
[37]
Debruyne D, Le Boisselier R. Emerging drugs of abuse: current perspectives on synthetic cannabinoids. Subst Abuse Rehabil 2015; 6: 113-29.
[http://dx.doi.org/10.2147/SAR.S73586] [PMID: 26543389]
[38]
Coppola M, Mondola R. JWH-122 consumption adverse effects: a case of hallucinogen persisting perception disorder five-year follow-up. J Psychoactive Drugs 2017; 49(3): 262-5.
[http://dx.doi.org/10.1080/02791072.2017.1316431] [PMID: 28441106]
[39]
Tait RJ, Caldicott D, Mountain D, Hill SL, Lenton S. A systematic review of adverse events arising from the use of synthetic cannabinoids and their associated treatment. Clin Toxicol (Phila) 2016; 54(1): 1-13.
[http://dx.doi.org/10.3109/15563650.2015.1110590] [PMID: 26567470]
[40]
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Guidance note 2 Formal notification of a new psychoactive substance. EMCDDA operating guidelines for the European Union Early Warning System on new psychoactive substances. 2020. [cited 2021 Mar 29]. Available from: https://www.emcdda.europa.eu/system/files/publications/12213/downloads/Guidance%20Note%202-%20Formal%20notification%20of%20a%20new%20psychoactive%20substance.pdf_no
[41]
ACMD (Advisory Council on the Misuse of Drugs). Further consideration of the Synthetic cannabinoids. 2012. [cited 2021 Mar 29]. Available from: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/119042/synthetic-cannabinoids-2012.pdf
[42]
McQuade D, Hudson S, Dargan PI, Wood DM. First European case of convulsions related to analytically confirmed use of the synthetic cannabinoid receptor agonist AM-2201. Eur J Clin Pharmacol 2013; 69(3): 373-6.
[http://dx.doi.org/10.1007/s00228-012-1379-2] [PMID: 22936123]
[43]
Breivogel CS, Wells JR, Jonas A, et al. Comparison of the neurotoxic and seizure-inducing effects of synthetic and endogenous cannabinoids with Δ9-tetrahydrocannabinol. Cannabis Cannabinoid Res 2020; 5(1): 32-41.
[http://dx.doi.org/10.1089/can.2019.0003] [PMID: 32322674]
[44]
Kacinko SL, Xu A, Homan JW, McMullin MM, Warrington DM, Logan BK. Development and validation of a liquid chromatography-tandem mass spectrometry method for the identification and quantification of JWH-018, JWH-073, JWH-019, and JWH-250 in human whole blood. J Anal Toxicol 2011; 35(7): 386-93.
[http://dx.doi.org/10.1093/anatox/35.7.386] [PMID: 21871146]
[45]
Circular 009/2019: third generation synthetic cannabinoids update - GOV.UK 2021. [cited 2021 Mar 30]. Available from: https://www.gov.uk/government/publications/circular-0092019-third-generation-synthetic-cannabinoids-update/circular-0092019-third-generation-synthetic-cannabinoids-update
[46]
De Luca MA, Castelli MP, Loi B, et al. Native CB1 receptor affinity, intrinsic activity and accumbens shell dopamine stimulant properties of third generation SPICE/K2 cannabinoids: BB-22, 5F-PB-22, 5F-AKB-48 and STS-135. Neuropharmacology 2016; 105: 630-8.
[http://dx.doi.org/10.1016/j.neuropharm.2015.11.017] [PMID: 26686391]
[47]
Miliano C, Serpelloni G, Rimondo C, Mereu M, Marti M, De Luca MA. Neuropharmacology of New psychoactive substances (NPS): Focus on the rewarding and reinforcing properties of cannabimimetics and amphetamine-like stimulants. Front Neurosci 2016; 10: 153.
[http://dx.doi.org/10.3389/fnins.2016.00153] [PMID: 27147945]
[48]
De Luca MA, Fattore L. Therapeutic use of synthetic cannabinoids: still an openIssue? Clin Ther 2018; 40(9): 1457-66.
[http://dx.doi.org/10.1016/j.clinthera.2018.08.002] [PMID: 30180974]
[49]
Banister SD, Longworth M, Kevin R, et al. Pharmacology of valinate and tert-leucinate synthetic cannabinoids 5F-AMBICA, 5F-AMB, 5F-ADB, AMB-FUBINACA, MDMB-FUBINACA, MDMB-CHMICA, and their analogues. ACS Chem Neurosci 2016; 7(9): 1241-54.
[http://dx.doi.org/10.1021/acschemneuro.6b00137] [PMID: 27421060]
[50]
Canazza I, Ossato A, Vincenzi F, et al. Pharmaco-toxicological effects of the novel third-generation fluorinate synthetic cannabinoids, 5F-ADBINACA, AB-FUBINACA, and STS-135 in mice. in vitro and in vivo studies. Hum Psychopharmacol 2017; 32(3): 1-27.
[http://dx.doi.org/10.1002/hup.2601] [PMID: 28597570]
[51]
Barceló B, Pichini S, López-Corominas V, et al. Acute intoxication caused by synthetic cannabinoids 5F-ADB and MMB-2201: A case series. Forensic Sci Int 2017; 273(273): e10-4.
[http://dx.doi.org/10.1016/j.forsciint.2017.01.020] [PMID: 28190538]
[52]
Trecki J, Gerona RR, Schwartz MD. Synthetic cannabinoid-related illnesses and deaths. N Engl J Med 2015; 373(2): 103-7.
[http://dx.doi.org/10.1056/NEJMp1505328] [PMID: 26154784]
[53]
Giorgetti A, Busardò FP, Tittarelli R, et al. Post-mortem toxicology: a systematic review of death cases involving synthetic cannabinoid receptor agonists. Front Psychiatry 2020; 11: 464. https://dx.doi.org/10.3389%2Ffpsyt.2020.00464.
[54]
Solimini R, Busardò FP, Rotolo MC, et al. Hepatotoxicity associated to synthetic cannabinoids use. Eur Rev Med Pharmacol Sci 2017; 21(1)(Suppl.): 1-6.
[PMID: 28379600]
[55]
Giorgetti A, Mogler L, Halter S, et al. Four cases of death involving the novel synthetic cannabinoid 5F-Cumyl-PEGACLONE. Forensic Toxicol 2020; 38(2): 314-26.
[http://dx.doi.org/10.1007/s11419-019-00514-w]
[56]
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). European Drug Report Trends and developments. 2020. [cited 2021 Mar 29]. Available from: https://www.emcdda.europa.eu/system/files/publications/13236/TDAT20001ENN_web.pdf
[57]
World Health Organization. Single Convention on Narcotic Drugs. 1961. [cited 2021 Sep 3]. Available from: https://www.unodc.org/pdf/convention_1961_en.pdf
[58]
World Health Organization. Critical Review Report: 4F-MDMB-BINACA WHO Expert Committe on Drug Dependance 2019. Available from: https://papers3://publication/uuid/ C0F2D662-7151-4F7C-834D-F3C6631A8B20
[59]
Yeter O. Simultaneous determination of 4F-MDMB binaca, a new synthetic cannabinoid, and its metabolites in human blood samples by LC-MS/MS. J Turkish Chem Soc Sect. Chem 2020; 7(3): 827-32.
[http://dx.doi.org/10.18596/jotcsa.770427]
[60]
Leong HS, Watanabe S, Kuzhiumparambil U, et al. Monitoring metabolism of synthetic cannabinoid 4F-MDMB-BINACA via high-resolution mass spectrometry assessed in cultured hepatoma cell line, fungus, liver microsomes and confirmed using urine samples. Forensic Toxicol 2021; 39(1): 198-212.
[http://dx.doi.org/10.1007/s11419-020-00562-7]
[61]
Krotulski AJ, Mohr ALA, Kacinko SL, et al. 4F-MDMB-BINACA: a new synthetic cannabinoid widely implicated in forensic casework. J Forensic Sci 2019; 64(5): 1451-61.
[http://dx.doi.org/10.1111/1556-4029.14101] [PMID: 31260580]
[62]
Haschimi B, Mogler L, Halter S, et al. Detection of the recently emerged synthetic cannabinoid 4F-MDMB-BINACA in “legal high” products and human urine specimens. Drug Test Anal 2019; 11(9): 1377-86.
[http://dx.doi.org/10.1002/dta.2666] [PMID: 31228224]
[63]
Lie W, Cheong EJY, Goh EML, et al. Diagnosing intake and rationalizing toxicities associated with 5F-MDMB-PINACA and 4F-MDMB-BINACA abuse. Arch Toxicol 2020; 95((2)(0123456789)): 489-508.
[http://dx.doi.org/10.1007/s00204-020-02948-3]
[64]
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Report on the risk assessment of methyl 2-{[1-(5-fluoropentyl)-1H-indazole-3- carbonyl]amino}-3,3-dimethylbutanoate in the framework of the Council Decision on new psychoactive substances. 2018. [cited 2021 Mar 29]. Available from: https://www.emcdda.europa.eu/system/files/publications/9122/Risk%20assessment%205F-MDMB-PINACA.pdf
[65]
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). EMCDDA initial report on the new psychoactive substance methyl 2-({[1-(4-fluorobutyl)-1H-indol-3-yl]carbonyl}amino)-3,3-dimethylbutanoate (4F-MDMB-BICA). 2006. [cited 2021 Mar 29]. Available from: https://www.emcdda.europa.eu/system/files/publications/13362/emcdda-initial-report-4F-MDMB-BICA.pdf
[66]
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). New psychoactive substances: global markets, glocal threats and the COVID-19 pandemic. 2020. [cited 2021 Sep 3]. Available from: https://www.emcdda.europa.eu/system/files/publications/13464/20205648_TD0320796ENN_PDF_rev.pdf
[67]
Tai S, Fantegrossi WE. Pharmacological and toxicological effects of synthetic cannabinoids and their metabolites. Curr Top Behav Neurosci 2017; 32: 249-62.
[http://dx.doi.org/10.1007/7854_2016_60] [PMID: 28012093]
[68]
Körmöczi T, Sija É, Institóris L, Kereszty ÉM, Ilisz I, Berkecz R. Analytical methodologies for the characterization and analysis of the parent compound and phase I metabolites of 4F-MDMB-BICA in human microsome, urine, and blood samples. J Anal Toxicol 2021; 1-11.
[http://dx.doi.org/10.1093/jat/bkab004] [PMID: 33404059]
[69]
Angerer V, Mogler L, Steitz JP, et al. Structural characterization and pharmacological evaluation of the new synthetic cannabinoid CUMYL-PEGACLONE. Drug Test Anal 2018; 10(3): 597-603.
[http://dx.doi.org/10.1002/dta.2237] [PMID: 28670781]
[70]
Mogler L, Halter S, Wilde M, Franz F, Auwärter V. Human phase I metabolism of the novel synthetic cannabinoid 5F-CUMYL-PEGACLONE. Forensic Toxicol 2019; 37(1): 154-63.
[http://dx.doi.org/10.1007/s11419-018-0447-4] [PMID: 30636984]
[71]
NPS Discovery. 5F-EMB-PICA. 2020. [cited 2021 Sep 3]. Available from: https://www.npsdiscovery.org/wp-content/uploads/2020/06/5F-EMB-PICA_061520_NMSLabs_Report.pdf
[72]
World Health Organization (WHO). 43rd WHO ECDD Summary assessment and recommendations. 2020. [cited 2021 Sep 3]. Available from: https://www.who.int/docs/default-source/medicines/43ecdd-unsg-annex1-to-letter-30nov20.pdf?sfvrsn=1cc00192_5
[73]
5CL-adb-a aka. (MDMB-4en-PINACA) review. : researchchemicals 2020. [cited 2021 Mar 30]. Available from: https://www.reddit.com/r/researchchemicals/comments/d106p1/5cladba_aka_mdmb4enpinaca_review/
[74]
Erol Ozturk Y, Yeter O. In vitro phase I metabolism of the recently emerged synthetic MDMB-4en-PINACA and its detection in human urine samples. J Anal Toxicol 2021; 44(9): 976-84.
[http://dx.doi.org/10.1093/jat/bkaa017] [PMID: 32091101]
[75]
Watanabe S, Vikingsson S, Åstrand A, Gréen H, Kronstrand R. Biotransformation of the new synthetic cannabinoid with an alkene, MDMB-4en-PINACA, by human hepatocytes, human liver microsomes, and human urine and blood. AAPS J 2019; 22(1): 13.
[http://dx.doi.org/10.1208/s12248-019-0381-3] [PMID: 31848852]
[76]
Krotulski AJ, Cannaert A, Stove C, Logan BK. The next generation of synthetic cannabinoids: Detection, activity, and potential toxicity of pent-4en and but-3en analogues including MDMB-4en-PINACA. Drug Test Anal 2020; 13(2): 427-8.
[http://dx.doi.org/10.1002/dta.2935]
[77]
Norman C, Halter S, Haschimi B, et al. A transnational perspective on the evolution of the synthetic cannabinoid receptor agonists market: Comparing prison and general populations. Drug Test Anal 2021; 13(4): 841-52.
[http://dx.doi.org/10.1002/dta.3002] [PMID: 33463894]
[78]
Drug Enforcement Administration Toxicology Testing Program (DEA TOX). Announcement of a Newly Identified Synthetic Cannabinoid 4CN-AB-BUTICA. 2021. [cited 2021 Mar 29]. Available from: https://www.deadiversion.usdoj.gov/dea_tox/4CN-AB-BUTICA.pdf
[79]
Åstrand A, Vikingsson S, Lindstedt D, et al. Metabolism study for CUMYL-4CN-BINACA in human hepatocytes and authentic urine specimens: Free cyanide is formed during the main metabolic pathway. Drug Test Anal 2018; 10(8): 1270-9.
[http://dx.doi.org/10.1002/dta.2373] [PMID: 29577658]
[80]
Kevin RC, Anderson L, McGregor IS, et al. CuMyl-4CN-BINACA is an efficacious and potent pro-convulsant synthetic cannabinoid receptor agonist. Front Pharmacol 2019; 10: 595.
[http://dx.doi.org/10.3389/fphar.2019.00595] [PMID: 31191320]
[81]
El Zahran T, Gerona R, Morgan BW, Pomerleau AC. A novel synthetic cannabinoid (Cumyl-4-cyano-BINACA) resulting in hyperthermia, rhabdomyolysis, and renal failure in a 29-year-old patient: it’s not meningitis. Clin Toxicol (Phila) 2019; 57(6): 421-2.
[http://dx.doi.org/10.1080/15563650.2018.1534241] [PMID: 30442067]
[82]
Öztürk YE, Yeter O, Öztürk S, et al. Detection of metabolites of the new synthetic cannabinoid CUMYL-4CN-BINACA in authentic urine samples and human liver microsomes using high-resolution mass spectrometry. Drug Test Anal 2018; 10(3): 449-59.
[http://dx.doi.org/10.1002/dta.2248] [PMID: 28691766]
[83]
Drug Enforcement Administration Toxicology Testing Program (DEA TOX). Announcement of a Newly Identified Synthetic Cannabinoid 4-CN-AMB-BUTINACA. 2021. [cited 2021 Mar 29]. Available from: https://www.deadiversion.usdoj.gov/dea_tox/4CN-AMB-BUTINACA.pdf
[84]
Drug Enforcement Administration (DEA), Department of Justice. Federal Register. 2021. [cited 2021 Sep 3]. Available from: https://www.govinfo.gov/content/pkg/FR-2021-03-30/pdf/2021-06553.pdf
[85]
Ellison R, Sparkes E, Ametovski A, Chen S, Glass M, Banister S. Announcement of a Newly Identified Synthetic Cannabinoid ADB-P7AICA. 2021. [cited 2021 Mar 29]. Available from: https://www.deadiversion.usdoj.gov/dea_tox/ADB-P7AICA.pdf
[86]
Krotulski AJ, Mohr ALA, Diamond FX, Logan BK. Detection and characterization of the new synthetic cannabinoid APP-BINACA in forensic casework. Drug Test Anal 2020; 12(1): 136-44.
[http://dx.doi.org/10.1002/dta.2698] [PMID: 31788963]
[87]
Zawilska JB, Andrzejczak D. Next generation of novel psychoactive substances on the horizon - A complex problem to face. Drug Alcohol Depend 2015; 157: 1-17.
[http://dx.doi.org/10.1016/j.drugalcdep.2015.09.030] [PMID: 26482089]
[88]
Odoardi S, Romolo FS, Strano-Rossi S. A snapshot on NPS in Italy: Distribution of drugs in seized materials analysed in an Italian forensic laboratory in the period 2013-2015. Forensic Sci Int 2016; 265: 116-20.
[http://dx.doi.org/10.1016/j.forsciint.2016.01.037] [PMID: 26874736]
[89]
Carlier J, Diao X, Sempio C, Huestis MA. Identification of New Synthetic Cannabinoid ADB-CHMINACA (MAB-CHMINACA) Metabolites in Human Hepatocytes. AAPS J 2017; 19(2): 568-77.
[http://dx.doi.org/10.1208/s12248-016-0037-5] [PMID: 28070717]
[90]
Carlier J, Diao X, Scheidweiler KB, Huestis MA. Distinguishing intake of new synthetic cannabinoids ADB-PINACA and 5F-ADB-PINACA with human hepatocyte metabolites and high-resolution mass spectrometry. Clin Chem 2017; 63(5): 1008-21.
[http://dx.doi.org/10.1373/clinchem.2016.267575] [PMID: 28302730]
[91]
Carlier J, Diao X, Wohlfarth A, Scheidweiler K, Huestis MA. In vitro metabolite profiling of ADB-FUBINACA, a new synthetic cannabinoid. Curr Neuropharmacol 2017; 2017: 682-91.
[http://dx.doi.org/10.2174/1570159X15666161108123419]

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