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image of Psychoactive Synthetic Adulterants in Tablets Sold as MDMA after the COVID-19 Pandemic: Implications for Central Effects

Abstract

Introduction

Preclinical and clinical studies reported that 3,4-methylenedioxymeth-amphetamine (MDMA, ‘ecstasy’) can cause adverse effects in the central nervous system (CNS). Recently, preclinical studies have demonstrated that certain psychoactive substances may exacerbate the noxious central effects of MDMA when co-administered, including substances that are contained as adulterants in tablets sold as MDMA in the illegal market. Since the quality and quantity of adulterants in tablets sold as MDMA vary based on factors, such as the year and the geographical region of production, this may result in diverse health risks for people who use MDMA.

Objectives

This review provides a concise overview of: i) composition of tablets sold as MDMA in Continental Europe, UK, USA and Australia in the post COVID-19 pandemic period; ii) recent preclinical and clinical findings about the central effects of the psychoactive adulterants most commonly found in tablets sold as MDMA in the above areas; and iii) the possible adverse CNS effects of these adulterants in humans when taken in combination with MDMA.

Methods

We systematically searched PubMed, Scopus, and Web of Science for studies published between 2020 and 2025 using terms related to “adulterants”, “MDMA tablets composition,” “COVID-19”. Eligible articles were screened for quality, with emphasis on recent, high-impact contributions. Extracted papers included cytotoxicity studies, neurobehavioral outcomes, and mechanistic insights.

Results

Tablets sold as MDMA are frequently and differently adulterated in Continental Europe, the UK, the USA, and Australia.

Discussion

The possible interactions between MDMA and psychoactive adulterants contained in tablets sold as MDMA deserve attention, since they may potentially explain some of the noxious neurological and psychiatric effects that have been described in people who use MDMA.

Conclusion

Ongoing public health efforts and expansion of drug checking are essential to properly inform MDMA users about the risks associated with psychoactive contaminants, first responders, healthcare professionals, and the general public about the possible detrimental consequences for health associated with the use of MDMA obtained from illicit sources and unintended contaminant consumption.

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2026-01-09
2026-01-27

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References

  1. World drug report 2024. 2024 Available from: www.unodc.org/unodc/en/data-and-analysis/world-drug-report-2024.html
  2. European drug report 2024. 2024 Available from:https://data.europa.eu/doi/10.2810/91693
  3. Palamar J.J. Le A. Acosta P. Shifts in drug use behavior among electronic dance music partygoers in new york during covid-19 social distancing. Subst. Use Misuse 2021 56 2 238 244 10.1080/10826084.2020.1857408 33317365
    [Google Scholar]
  4. National drug strategy household survey 2022–2023: Ecstasy in the NDSHS 2024 Available from: https://www.aihw.gov.au/reports/illicit-use-of-drugs/ecstasy-ndshs
  5. Syrjanen R. Dutch M. Greene S.L. Lyons T. McKinnon G. Gerostamoulos D. Schumann J.L. Novel harm reduction measures at music festivals in Australia: Pilot implementation of the emerging drugs network of Australia–Victoria toxicosurveillance methodology. Drug Alcohol Rev. 2024 43 7 2045 2054 10.1111/dar.13922 39161236
    [Google Scholar]
  6. Accredited official statistics Seizures of drugs in England and Wales, financial year ending 2023. 2024 Available from: https://www.gov.uk/government/statistics/seizures-of-drugs-in-england-and-wales-financial-year-ending-2023/seizures-of-drugs-in-england-and-wales-financial-year-ending-2023#:~:text=Ecstasy%3A%20the%20number%20of%20ecstasy,the%20year%20ending%20March%202023
  7. Moratalla R. Khairnar A. Simola N. Granado N. García-Montes J.R. Porceddu P.F. Tizabi Y. Costa G. Morelli M. Amphetamine-related drugs neurotoxicity in humans and in experimental animals: Main mechanisms. Prog. Neurobiol. 2017 155 149 170 10.1016/j.pneurobio.2015.09.011 26455459
    [Google Scholar]
  8. Holze F. Vizeli P. Müller F. Ley L. Duerig R. Varghese N. Eckert A. Borgwardt S. Liechti M.E. Distinct acute effects of LSD, MDMA, and d-amphetamine in healthy subjects. Neuropsychopharmacology 2020 45 3 462 471 10.1038/s41386‑019‑0569‑3 31733631
    [Google Scholar]
  9. Hall A.P. Henry J.A. Acute toxic effects of ‘Ecstasy’ (MDMA) and related compounds: Overview of pathophysiology and clinical management. Br. J. Anaesth. 2006 96 6 678 685 10.1093/bja/ael078 16595612
    [Google Scholar]
  10. Brunt T.M. Koeter M.W. Niesink R.J.M. van den Brink W. Linking the pharmacological content of ecstasy tablets to the subjective experiences of drug users. Psychopharmacology 2012 220 4 751 762 10.1007/s00213‑011‑2529‑4 21993879
    [Google Scholar]
  11. Roxburgh A. Lappin J. MDMA-related deaths in Australia 2000 to 2018. Int. J. Drug Policy 2020 76 102630 10.1016/j.drugpo.2019.102630 31865118
    [Google Scholar]
  12. Roxburgh A. Sam B. Kriikku P. Mounteney J. Castanera A. Dias M. Giraudon I. Trends in MDMA‐related mortality across four countries. Addiction 2021 116 11 3094 3103 10.1111/add.15493 33739562
    [Google Scholar]
  13. Green A.R. Mechan A.O. Elliott J.M. O’Shea E. Colado M.I. The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”). Pharmacol. Rev. 2003 55 3 463 508 10.1124/pr.55.3.3 12869661
    [Google Scholar]
  14. Commins D.L. Vosmer G. Virus R.M. Woolverton W.L. Schuster C.R. Seiden L.S. Biochemical and histological evidence that methylenedioxymethylamphetamine (MDMA) is toxic to neurons in the rat brain. J. Pharmacol. Exp. Ther. 1987 241 1 338 345 10.1016/S0022‑5347(25)00317‑9 2883295
    [Google Scholar]
  15. Schmidt C.J. Acute and long-term neurochemical effects of methylenedioxymethamphetamine in the rat. NIDA Res. Monogr. 1989 94 179 195 2575224
    [Google Scholar]
  16. Molliver M. Berger U. Mamounas L.A. Molliver D.C. O’Hearn E. Wilson M.A. Neurotoxicity of MDMA and related compounds: Anatomic studies. Ann. N. Y. Acad. Sci. 1990 600 1 640 661 10.1111/j.1749‑6632.1990.tb16916.x 1979216
    [Google Scholar]
  17. Cox B.M. Shah M.M. Cichon T. Tancer M.E. Galloway M.P. Thomas D.M. Perrine S.A. Behavioral and neurochemical effects of repeated MDMA administration during late adolescence in the rat. Prog. Neuropsychopharmacol. Biol. Psychiatry 2014 48 229 235 10.1016/j.pnpbp.2013.09.021 24121061
    [Google Scholar]
  18. Biezonski D.K. Meyer J.S. Effects of 3,4‐methylenedioxymethamphetamine (MDMA) on serotonin transporter and vesicular monoamine transporter 2 protein and gene expression in rats: Implications for MDMA neurotoxicity. J. Neurochem. 2010 112 4 951 962 10.1111/j.1471‑4159.2009.06515.x 20002520
    [Google Scholar]
  19. De Souza E.B. Battaglia G. Insel T.R. Neurotoxic effect of MDMA on brain serotonin neurons: Evidence from neurochemical and radioligand binding studies. Ann. N. Y. Acad. Sci. 1990 600 1 682 697 10.1111/j.1749‑6632.1990.tb16918.x 1979218
    [Google Scholar]
  20. Müller F. Brändle R. Liechti M.E. Borgwardt S. Neuroimaging of chronic MDMA (“ecstasy”) effects: A meta-analysis. Neurosci. Biobehav. Rev. 2019 96 10 20 10.1016/j.neubiorev.2018.11.004 30439373
    [Google Scholar]
  21. Buchert R. Thomasius R. Petersen K. Wilke F. Obrocki J. Nebeling B. Wartberg L. Zapletalova P. Clausen M. Reversibility of ecstasy-induced reduction in serotonin transporter availability in polydrug ecstasy users. Eur. J. Nucl. Med. Mol. Imaging 2006 33 2 188 199 10.1007/s00259‑005‑1850‑8 16133393
    [Google Scholar]
  22. Iravani MM Asari D Patel J Wieczorek WJ Kruk, ZL Direct effects of 3,4-methylenedioxymethamphetamine (MDMA) on serotonin or dopamine release and uptake in the caudate putamen, nucleus accumbens, substantia nigra pars reticulata, and the dorsal raphé nucleus slices. Synapse 2000 36 4 275 285
    [Google Scholar]
  23. Colado M.I. Camarero J. Mechan A.O. Sanchez V. Esteban B. Elliott J.M. Green A.R. A study of the mechanisms involved in the neurotoxic action of 3,4‐methylenedioxymethamphetamine (MDMA, ‘ecstasy’) on dopamine neurones in mouse brain. Br. J. Pharmacol. 2001 134 8 1711 1723 10.1038/sj.bjp.0704435 11739248
    [Google Scholar]
  24. Camarero J. Sanchez V. O’Shea E. Green A.R. Colado M.I. Studies, using in vivo microdialysis, on the effect of the dopamine uptake inhibitor GBR 12909 on 3,4‐methylenedioxymeth-amphetamine (‘ecstasy’)‐induced dopamine release and free radical formation in the mouse striatum. J. Neurochem. 2002 81 5 961 972 10.1046/j.1471‑4159.2002.00879.x 12065608
    [Google Scholar]
  25. Cadet J.L. Krasnova I.N. Jayanthi S. Lyles J. Neurotoxicity of substituted amphetamines: Molecular and cellular mechanisms. Neurotox. Res. 2007 11 3-4 183 202 10.1007/BF03033567 17449459
    [Google Scholar]
  26. Costa G. Frau L. Wardas J. Pinna A. Plumitallo A. Morelli M. MPTP‐induced dopamine neuron degeneration and glia activation is potentiated in MDMA‐pretreated mice. Mov. Disord. 2013 28 14 1957 1965 10.1002/mds.25646 24108425
    [Google Scholar]
  27. Costa G. Morelli M. Simola N. Progression and persistence of neurotoxicity induced by MDMA in dopaminergic regions of the mouse brain and association with noradrenergic, GABAergic, and serotonergic damage. Neurotox. Res. 2017 32 4 563 574 10.1007/s12640‑017‑9761‑6 28597409
    [Google Scholar]
  28. Halpin L.E. Collins S.A. Yamamoto B.K. Neurotoxicity of methamphetamine and 3,4-methylenedioxymethamphetamine. Life Sci. 2014 97 1 37 44 10.1016/j.lfs.2013.07.014 23892199
    [Google Scholar]
  29. Granado N. O’Shea E. Bove J. Vila M. Colado M.I. Moratalla R. Persistent MDMA‐induced dopaminergic neurotoxicity in the striatum and substantia nigra of mice. J. Neurochem. 2008 107 4 1102 1112 10.1111/j.1471‑4159.2008.05705.x 18823368
    [Google Scholar]
  30. Cadoni C. Pisanu A. Simola N. Frau L. Porceddu P.F. Corongiu S. Dessì C. Sil A. Plumitallo A. Wardas J. Di Chiara G. Widespread reduction of dopamine cell bodies and terminals in adult rats exposed to a low dose regimen of MDMA during adolescence. Neuropharmacology 2017 123 385 394 10.1016/j.neuropharm.2017.06.008 28603026
    [Google Scholar]
  31. Millot M. Saga Y. Duperrier S. Météreau E. Beaudoin-Gobert M. Sgambato V. Prior MDMA administration aggravates MPTP-induced Parkinsonism in macaque monkeys. Neurobiol. Dis. 2020 134 104643 10.1016/j.nbd.2019.104643 31689516
    [Google Scholar]
  32. Boxler M.I. Streun G.L. Liechti M.E. Schmid Y. Kraemer T. Steuer A.E. Human metabolome changes after a single dose of 3,4-Methylenedioxymethamphetamine (MDMA) with special focus on steroid metabolism and inflammation processes. J. Proteome Res. 2018 17 8 2900 2907 10.1021/acs.jproteome.8b00438 29947220
    [Google Scholar]
  33. Costa G. Gołembiowska K. Neurotoxicity of MDMA: Main effects and mechanisms. Exp. Neurol. 2022 347 113894 10.1016/j.expneurol.2021.113894 34655576
    [Google Scholar]
  34. Serra M. Simola N. Pollack A.E. Costa G. Brain dysfunctions and neurotoxicity induced by psychostimulants in experimental models and humans: An overview of recent findings. Neural Regen. Res. 2024 19 9 1908 1918 10.4103/1673‑5374.390971 38227515
    [Google Scholar]
  35. Zimmermann J. Zölch N. Coray R. Bavato F. Friedli N. Baumgartner M.R. Steuer A.E. Opitz A. Werner A. Oeltzschner G. Seifritz E. Stock A.K. Beste C. Cole D.M. Quednow B.B. Chronic 3,4-methylenedioxymethamphetamine (MDMA) use is related to glutamate and gaba concentrations in the striatum but not the anterior cingulate cortex. Int. J. Neuropsychopharmacol. 2023 26 6 438 450 10.1093/ijnp/pyad023 37235749
    [Google Scholar]
  36. Coray R.C. Berberat J. Zimmermann J. Seifritz E. Stock A.K. Beste C. Cole D.M. Unschuld P.G. Quednow B.B. Striatal iron deposition in recreational MDMA (Ecstasy) users. Biol. Psychiatry Cogn. Neurosci. Neuroimaging 2023 8 9 956 966 10.1016/j.bpsc.2023.02.005 36848948
    [Google Scholar]
  37. Byrska B. Stanaszek R. Chemical composition of Ecstasy tablets seized in Poland between 2005 and 2020. Forensic Toxicol. 2024 39017813
    [Google Scholar]
  38. Mj P. S, R.; Htd, S.; F, M. The cathinone hydra: Increased cathinone and caffeine adulteration in the english mdma market after brexit and COVID-19 lockdowns. Drug Sci. Policy Law 2022 8 20503245221099209 10.1177/20503245221099209
    [Google Scholar]
  39. Frau L. Costa G. Porceddu P.F. Khairnar A. Castelli M.P. Ennas M.G. Madeddu C. Wardas J. Morelli M. Influence of caffeine on 3,4‐methylenedioxymethamphetamine‐induced dopaminergic neuron degeneration and neuroinflammation is age‐dependent. J. Neurochem. 2016 136 1 148 162 10.1111/jnc.13377 26442661
    [Google Scholar]
  40. Górska A.M. Kamińska K. Wawrzczak-Bargieła A. Costa G. Morelli M. Przewłocki R. Kreiner G. Gołembiowska K. Neurochemical and neurotoxic effects of MDMA (Ecstasy) and caffeine after chronic combined administration in mice. Neurotox. Res. 2018 33 3 532 548 10.1007/s12640‑017‑9831‑9 29134560
    [Google Scholar]
  41. Simola N. Cauli O. Morelli M. Sensitization to caffeine and cross-sensitization to amphetamine: Influence of individual response to caffeine. Behav. Brain Res. 2006 172 1 72 79 10.1016/j.bbr.2006.04.019 16740323
    [Google Scholar]
  42. Tronci E. Simola N. Carta A.R. De Luca M.A. Morelli M. Potentiation of amphetamine‐mediated responses in caffeine‐sensitized rats involves modifications in A 2A receptors and zif‐268 mRNAs in striatal neurons. J. Neurochem. 2006 98 4 1078 1089 10.1111/j.1471‑4159.2006.03943.x 16771831
    [Google Scholar]
  43. European monitoring centre for drugs and drug addiction 2023 Available from: https://data.europa.eu/doi/10.2810/161905
  44. Drug misuse in england and wales: Year ending march. 2020 Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/crimeandjustice/articles/drugmisuseinenglandandwales/yearendingmarch2020#overall-trends-in-drug-misuse.
  45. Couchman L. Frinculescu A. Sobreira C. Shine T. Ramsey J. Hecht M. Kipper K. Holt D. Johnston A. Variability in content and dissolution profiles of MDMA tablets collected in the UK between 2001 and 2018 – A potential risk to users? Drug Test. Anal. 2019 11 8 1172 1182 10.1002/dta.2605 31009168
    [Google Scholar]
  46. WEDINOS - reports & publications. 2024 Available from: https://www.wedinos.org/reports-publications
  47. Arillotta D. Guirguis A. Corkery J.M. Scherbaum N. Schifano F. COVID-19 pandemic impact on substance misuse: A social media listening, mixed method analysis. Brain Sci. 2021 11 7 907 10.3390/brainsci11070907 34356142
    [Google Scholar]
  48. Drug misuse in england and wales - Office for national statistics. 2025 Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/crimeandjustice/articles/drugmisuseinenglandandwales/yearendingmarch2020#overall-trends-indrug-misuse.
  49. Deaths by drug poisoning where MDMA or ecstasy were mentioned on the death certificate: Local authorities in England and Wales. 2017 Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/adhocs/010140numberofdeathsbydrugpoisoningwheremdmaorecstasywerementionedonthedeathcertificatelocalauthoritiesinenglandandwalesdeathsregisteredin2017.
  50. Drug seizure statistics. 2025 Available from: https://www.cbp.gov/newsroom/stats/drug-seizure-statistics
  51. Palamar J.J. Le A. Cleland C.M. Keyes K.M. Trends in drug use among nightclub and festival attendees in New York City, 2017-2022. Int. J. Drug Policy 2023 115 104001 10.1016/j.drugpo.2023.104001 36934660
    [Google Scholar]
  52. NFLIS-Drug forensic laboratories with drug chemistry sections. 2024 Available from: https://www.nflis.deadiversion.usdoj.gov/drug.xhtml.
  53. Palamar J.J. Salomone A. Shifts in unintentional exposure to drugs among people who use ecstasy in the electronic dance music scene, 2016‐2019. Am. J. Addict. 2021 30 1 49 54 10.1111/ajad.13086 32813326
    [Google Scholar]
  54. Palamar J.J. Salomone A. Vincenti M. Cleland C.M. Detection of “bath salts” and other novel psychoactive substances in hair samples of ecstasy/MDMA/“Molly” users. Drug Alcohol Depend. 2016 161 200 205 10.1016/j.drugalcdep.2016.02.001 26883685
    [Google Scholar]
  55. Gladden R.M. Chavez-Gray V. O’Donnell J. Goldberger B.A. Notes From the Field: overdose deaths involving eutylone (Psychoactive Bath Salts) — United states, 2020. MMWR Morb. Mortal. Wkly. Rep. 2022 71 32 1032 1034 10.15585/mmwr.mm7132a3 35951491
    [Google Scholar]
  56. Krotulski A.J. Papsun D.M. Kacinko S.L. Logan B.K. Isotonitazene quantitation and metabolite discovery in authentic forensic casework. J. Anal. Toxicol. 2020 44 6 521 530 10.1093/jat/bkaa016 32091095
    [Google Scholar]
  57. Haridy R. Australia to prescribe MDMA and psilocybin for PTSD and depression in world first. Nature 2023 619 7969 227 228 10.1038/d41586‑023‑02093‑8 37386185
    [Google Scholar]
  58. Test results. 2025 Available from: https://cantest.com.au/results/
  59. Kolovos B. Victoria’s pill testing service to become permanent after 18-month trial. The guardian. 2024 Available from: https://www.theguardian.com/australia-news/article/2024/jun/25/victorias-pill-testing-service-to-become-permanent-after-18-month-trial
  60. Highly potent MDMA pill prompts call for drug testing services. 2025 Available from: https://www.coronerscourt.vic.gov.au/highly-potent-mdma-pill-prompts-call-drug-testing-services.
  61. Red Bull' logo red/orange rectangular tablets sold as MDMA (ecstasy) found to contain a nitazene (potent opioid) and no MDMA. 2021 Available from: https://www.health.nsw.gov.au/aod/publicdrug-alerts/Pages/nitazenes-mdma-red-bull-Jan24.aspx.
  62. MDMA adulterated with PMMA. 2025 Available from: https://www.health.vic.gov.au/alcohol-and-drugs/mdma-adulterated-with-pmma
  63. Grifell M. Ventura M. Carbón X. Quintana P. Galindo L. Palma Á. Fornis I. Gil C. Farre M. Torrens M. Patterns of use and toxicity of new para‐halogenated substituted cathinones: 4‐ CMC (clephedrone), 4‐ CEC (4‐chloroethcatinone) and 4‐ BMC (brephedrone). Hum. Psychopharmacol. 2017 32 3 2621 10.1002/hup.2621 28657185
    [Google Scholar]
  64. Zwartsen A. Olijhoek M.E. Westerink R.H.S. Hondebrink L. Hazard characterization of synthetic cathinones using viability, monoamine reuptake, and neuronal activity assays. Front. Neurosci. 2020 14 9 10.3389/fnins.2020.00009 32063828
    [Google Scholar]
  65. Daziani G. Lo Faro A.F. Montana V. Goteri G. Pesaresi M. Bambagiotti G. Montanari E. Giorgetti R. Montana A. Synthetic cathinones and neurotoxicity risks: A systematic review. Int. J. Mol. Sci. 2023 24 7 6230 10.3390/ijms24076230 37047201
    [Google Scholar]
  66. Novel stimulants sold as MDMA, cocaine or speed. 2024 Available from: https://www.health.vic.gov.au/drug-alerts/novel-stimulants-sold-as-mdma-cocaine-or-speed
  67. Wojcieszak J. Kuczyńska K. Zawilska J.B. Four synthetic cathinones: 3-chloromethcathinone, 4-chloromethcathinone, 4-fluoro-α-pyrrolidinopentiophenone, and 4-methoxy-α-pyrrolidinopentio-phenone produce changes in the spontaneous locomotor activity and motor performance in mice with varied profiles. Neurotox. Res. 2020 38 2 536 551 10.1007/s12640‑020‑00227‑8 32506339
    [Google Scholar]
  68. Zhou X. Bouitbir J. Liechti M.E. Krähenbühl S. Mancuso R.V. Hyperthermia increases neurotoxicity associated with novel methcathinones. Cells 2020 9 4 965 10.3390/cells9040965 32295288
    [Google Scholar]
  69. Gatch M.B. Dolan S.B. Forster M.J. Locomotor activity and discriminative stimulus effects of five novel synthetic cathinone analogs in mice and rats. Drug Alcohol Depend. 2019 199 50 58 10.1016/j.drugalcdep.2019.02.016 30986635
    [Google Scholar]
  70. Gatch M.B. Shetty R.A. Sumien N. Forster M.J. Behavioral effects of four novel synthetic cathinone analogs in rodents. Addict. Biol. 2021 26 4 12987 10.1111/adb.12987 33155384
    [Google Scholar]
  71. Jo C. Joo H. Lim N.Y. Park S.J. Choi S.O. Withdrawal from 3‐Fluoroethamphetamine induces hyperactivity and depression‐like behaviors in male mice. J. Neurosci. Res. 2024 102 1 25251 10.1002/jnr.25251 37818759
    [Google Scholar]
  72. Kelečević I. Vejnović A.M. Javorac J. Gvozdenović N. Janjić N. Mijatović Jovin V. Metaphedrone (3-Methylmethcathinone): Pharmacological, clinical, and toxicological profile. Medicina 2024 60 3 466 10.3390/medicina60030466 38541192
    [Google Scholar]
  73. Dams R. De Letter E.A. Mortier K.A. Cordonnier J.A. Lambert W.E. Piette M.H.A. Van Calenbergh S. De Leenheer A.P. Fatality due to combined use of the designer drugs MDMA and PMA: A distribution study. J. Anal. Toxicol. 2003 27 5 318 323 10.1093/jat/27.5.318 12908947
    [Google Scholar]
  74. Gołembiowska K. Jurczak A. Kamińska K. Noworyta-Sokołowska K. Górska A. Effect of some psychoactive drugs used as ‘Legal Highs’ on brain neurotransmitters. Neurotox. Res. 2016 29 3 394 407 10.1007/s12640‑015‑9569‑1 26501352
    [Google Scholar]
  75. Luethi D. Liechti M.E. Designer drugs: Mechanism of action and adverse effects. Arch. Toxicol. 2020 94 4 1085 1133 10.1007/s00204‑020‑02693‑7 32249347
    [Google Scholar]
  76. Páleníček T. Fujáková M. Brunovský M. Horáček J. Gorman I. Balíková M. Rambousek L. Syslová K. Kačer P. Zach P. Bubeníková-Valešová V. Tylš F. Kubešová A. Puskarčíková J. Höschl C. Behavioral, neurochemical and pharmaco-EEG] profiles of the psychedelic drug 4-bromo-2,5-dimethoxy-phenethylamine (2C-B) in rats. Psychopharmacology 2013 225 1 75 93 10.1007/s00213‑012‑2797‑7 22842791
    [Google Scholar]
  77. Montgomery T. Buon C. Eibauer S. Guiry P.J. Keenan A.K. McBean G.J. Comparative potencies of 3,4‐methylenedioxymeth-amphetamine (MDMA) analogues as inhibitors of [3H]] noradrenaline and [3H]5‐HT transport in mammalian cell lines. Br. J. Pharmacol. 2007 152 7 1121 1130 10.1038/sj.bjp.0707473 17891159
    [Google Scholar]
  78. Rickli A. Luethi D. Reinisch J. Buchy D. Hoener M.C. Liechti M.E. Receptor interaction profiles of novel N-2-methoxybenzyl (NBOMe) derivatives of 2,5-dimethoxy-substituted phenethylamines (2C drugs). Neuropharmacology 2015 99 546 553 10.1016/j.neuropharm.2015.08.034 26318099
    [Google Scholar]
  79. Luethi D. Walter M. Zhou X. Rudin D. Krähenbühl S. Liechti M.E. Para-Halogenation affects monoamine transporter inhibition properties and hepatocellular toxicity of amphetamines and methcathinones. Front. Pharmacol. 2019 10 438 10.3389/fphar.2019.00438 31068823
    [Google Scholar]
  80. Villalobos C.A. Bull P. Sáez P. Cassels B.K. Huidobro-Toro J.P. 4‐Bromo‐2,5‐dimethoxyphenethylamine (2C‐B) and structurally related phenylethylamines are potent 5‐HT 2A receptor antagonists in Xenopus laevis oocytes. Br. J. Pharmacol. 2004 141 7 1167 1174 10.1038/sj.bjp.0705722 15006903
    [Google Scholar]
  81. Sleigh J. Harvey M. Voss L. Denny B. Ketamine – More mechanisms of action than just NMDA blockade. Trends Anaesth. Crit. Care 2014 4 2-3 76 81 10.1016/j.tacc.2014.03.002
    [Google Scholar]
  82. Sachkova A. Doetsch D.A. Jensen O. Brockmöller J. Ansari S. How do psychostimulants enter the human brain? Analysis of the role of the proton-organic cation antiporter. Biochem. Pharmacol. 2021 192 114751 10.1016/j.bcp.2021.114751 34464621
    [Google Scholar]
  83. Sogos V. Caria P. Porcedda C. Mostallino R. Piras F. Miliano C. De Luca M.A. Castelli M.P. Human neuronal cell lines as an in vitro toxicological tool for the evaluation of novel psychoactive substances. Int. J. Mol. Sci. 2021 22 13 6785 10.3390/ijms22136785 34202634
    [Google Scholar]
  84. Martins D. Gil-Martins E. Cagide F. da Fonseca C. Benfeito S. Fernandes C. Chavarria D. Remião F. Silva R. Borges F. Unraveling the in vitro toxicity profile of psychedelic 2c phenethylamines and their N-Benzylphenethylamine (NBOMe) analogues. Pharmaceuticals 2023 16 8 1158 10.3390/ph16081158 37631071
    [Google Scholar]
  85. Zwartsen A. Hondebrink L. Westerink R.H.S. Changes in neuronal activity in rat primary cortical cultures induced by illicit drugs and new psychoactive substances (NPS) following prolonged exposure and washout to mimic human exposure scenarios. Neurotoxicology 2019 74 28 39 10.1016/j.neuro.2019.05.004 31078573
    [Google Scholar]
  86. Cocchi V. Gasperini S. Hrelia P. Tirri M. Marti M. Lenzi M. Novel psychoactive phenethylamines: Impact on genetic material. Int. J. Mol. Sci. 2020 21 24 9616 10.3390/ijms21249616 33348640
    [Google Scholar]
  87. Rigg N. Abu-Hijleh F.A. Patel V. Mishra R.K. Ketamine-induced neurotoxicity is mediated through endoplasmic reticulum stress in vitro in STHdhQ7/Q7 cells. Neurotoxicology 2022 91 321 328 10.1016/j.neuro.2022.06.004 35728656
    [Google Scholar]
  88. Jaehne E.J. Salem A. Irvine R.J. Pharmacological and behavioral determinants of cocaine, methamphetamine, 3,4-methylen-edioxymethamphetamine, and para-methoxyamphetamine-induced hyperthermia. Psychopharmacology 2007 194 1 41 52 10.1007/s00213‑007‑0825‑9 17530474
    [Google Scholar]
  89. Ponzoni L. Daniela B. Sala M. Abuse potential of methylenedioxymethamphetamine (MDMA) and its derivatives in zebrafish: Role of serotonin 5HT2-type receptors. Psychopharmacology 2016 233 15-16 3031 3039 10.1007/s00213‑016‑4352‑4 27318987
    [Google Scholar]
  90. Martín-López M. Muela A.T. Cavas M. Navarro J.F. Effects of para-methoxyamphetamine (PMA) on agonistic encounters between male mice. Pharmacol. Biochem. Behav. 2018 167 9 16 10.1016/j.pbb.2018.02.002 29453997
    [Google Scholar]
  91. Gough B. Imam S.Z. Blough B. Slikker W. Ali S.F. Comparative effects of substituted amphetamines (PMA, MDMA, and METH) on monoamines in rat caudate: A microdialysis study. Ann. N. Y. Acad. Sci. 2002 965 1 410 420 10.1111/j.1749‑6632.2002.tb04182.x 12105116
    [Google Scholar]
  92. Corrigall W.A. Robertson J.M. Coen K.M. Lodge B.A. The reinforcing and discriminative stimulus properties of para-ethoxy- and para-methoxyamphetamine. Pharmacol. Biochem. Behav. 1992 41 1 165 169 10.1016/0091‑3057(92)90077‑S 1539067
    [Google Scholar]
  93. Páleníček T. Balíková M. Rohanová M. Novák T. Horáček J. Fujáková M. Höschl C. Behavioral, hyperthermic and pharmacokinetic profile of para-methoxymethamphetamine (PMMA) in rats. Pharmacol. Biochem. Behav. 2011 98 1 130 139 10.1016/j.pbb.2010.12.011 21167195
    [Google Scholar]
  94. Steele T.D. Katz J.L. Ricaurte G.A. Evaluation of the neurotoxicity of N-methyl-1-(4-methoxyphenyl)-2-aminopropane (para-methoxymethamphetamine, PMMA). Brain Res. 1992 589 2 349 352 10.1016/0006‑8993(92)91298‑S 1382813
    [Google Scholar]
  95. Shin E.J. Dang D.K. Tran H.Q. Nam Y. Jeong J.H. Lee Y.H. Park K.T. Lee Y.S. Jang C.G. Hong J.S. Nabeshima T. Kim H.C. PKCδ knockout mice are protected from para-methoxymethamphetamine-induced mitochondrial stress and associated neurotoxicity in the striatum of mice. Neurochem. Int. 2016 100 146 158 10.1016/j.neuint.2016.09.008 27623093
    [Google Scholar]
  96. Piras G. Cadoni C. Caria F. Pintori N. Spano E. Vanejevs M. Ture A. Tocco G. Simola N. De Luca M.A. Characterization of the neurochemical and behavioral effects of the phenethylamine 2-cl-4,5-mdma in adolescent and adult male rats. Int. J. Neuropsychopharmacol. 2024 27 5 pyae016 10.1093/ijnp/pyae016 38546531
    [Google Scholar]
  97. Miliano C. Marti M. Pintori N. Castelli M.P. Tirri M. Arfè R. De Luca M.A. Neurochemical and behavioral profiling in male and female rats of the psychedelic agent 25I-NBOMe. Front. Pharmacol. 2019 10 1406 10.3389/fphar.2019.01406 31915427
    [Google Scholar]
  98. Ikonomidou C. Bosch F. Miksa M. Bittigau P. Vöckler J. Dikranian K. Tenkova T.I. Stefovska V. Turski L. Olney J.W. Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science 1999 283 5398 70 74 10.1126/science.283.5398.70 9872743
    [Google Scholar]
  99. Acevedo J. Siegel J.A. Neurobiological, behavioral, and cognitive effects of ketamine in adolescents: A review of human and pre-clinical research. Behav. Brain Res. 2022 435 114049 10.1016/j.bbr.2022.114049 35952776
    [Google Scholar]
  100. de Carvalho Cartágenes S. Fernandes L.M.P. Carvalheiro T.C.V.S. de Sousa T.M. Gomes A.R.Q. Monteiro M.C. de Oliveira Paraense R.S. Crespo-López M.E. Lima R.R. Fontes-Júnior E.A. Prediger R.D. Maia C.S.F. “Special K” Drug on adolescent rats: Oxidative damage and neurobehavioral impairments. Oxid. Med. Cell. Longev. 2019 2019 1 10 10.1155/2019/5452727 31001375
    [Google Scholar]
  101. Li Q. Wu H. Fan S. Liu D. Jiang H. Zhang Q. Pan F. The effects of sub-anesthetic ketamine plus ethanol on behaviors and apoptosis in the prefrontal cortex and hippocampus of adolescent rats. Pharmacol. Biochem. Behav. 2019 184 172742 10.1016/j.pbb.2019.172742 31348944
    [Google Scholar]
  102. Onaolapo A.Y. Ayeni O.J. Ogundeji M.O. Ajao A. Onaolapo O.J. Owolabi A.R. Subchronic ketamine alters behaviour, metabolic indices and brain morphology in adolescent rats: Involvement of oxidative stress, glutamate toxicity and caspase-3-mediated apoptosis. J. Chem. Neuroanat. 2019 96 22 33 10.1016/j.jchemneu.2018.12.002 30529750
    [Google Scholar]
  103. Wang J. Zhou M. Wang X. Yang X. Wang M. Zhang C. Zhou S. Tang N. Impact of ketamine on learning and memory function, neuronal apoptosis and its potential association with miR-214 and PTEN in adolescent rats. PLoS One 2014 9 6 99855 10.1371/journal.pone.0099855 24914689
    [Google Scholar]
  104. Zuo D. Liu Y. Liu Z. Cui J. Zhou X. Liu Y. Li Z. Wu Y. Alcohol aggravates ketamine-induced behavioral, morphological and neurochemical alterations in adolescent rats: The involvement of CREB-related pathways. Behav. Brain Res. 2018 349 80 90 10.1016/j.bbr.2018.05.003 29738804
    [Google Scholar]
  105. Luscher B. Feng M. Jefferson S.J. Antidepressant mechanisms of ketamine: Focus on GABAergic inhibition. Adv. Pharmacol. 2020 89 43 78 10.1016/bs.apha.2020.03.002 32616214
    [Google Scholar]
  106. Chen W.H. Chui C. Yin H.L. The antemortem neurobehavior in fatal paramethoxymethamphetamine usage. Subst. Abus. 2012 33 4 366 372 10.1080/08897077.2011.638736 22989280
    [Google Scholar]
  107. Spoelder A.S. Louwerens J.K.G. Krens S.D. Jager N. LeCouffe N.E. de Ruijter W. Brunt T.M. Unexpected serotonin syndrome, epileptic seizures, and cerebral edema following 2,5‐dimethoxy‐4‐bromophenethylamine ingestion. J. Forensic Sci. 2019 64 6 1950 1952 10.1111/1556‑4029.14214 31643086
    [Google Scholar]
  108. Vines L. Sotelo D. Johnson A. Dennis E. Manza P. Volkow N.D. Wang G.J. Ketamine use disorder: Preclinical, clinical, and neuroimaging evidence to support proposed mechanisms of actions. Intell. Med. 2022 2 2 61 68 10.1016/j.imed.2022.03.001 35783539
    [Google Scholar]
  109. Liang H. Tang W.K. Chu W.C.W. Ernst T. Chen R. Chang L. Striatal and white matter volumes in chronic ketamine users with or without recent regular stimulant use. Drug Alcohol Depend. 2020 213 108063 10.1016/j.drugalcdep.2020.108063 32498030
    [Google Scholar]
  110. Höflich A. Hahn A. Küblböck M. Kranz G.S. Vanicek T. Windischberger C. Saria A. Kasper S. Winkler D. Lanzenberger R. Ketamine-induced modulation of the thalamo-cortical network in healthy volunteers as a model for schizophrenia. Int. J. Neuropsychopharmacol. 2015 18 9 pyv040 10.1093/ijnp/pyv040 25896256
    [Google Scholar]
  111. Liao Y. Tang J. Liu J. Xie A. Yang M. Johnson M. Wang X. Deng Q. Chen H. Xiang X. Liu T. Chen X. Song M. Hao W. Decreased thalamocortical connectivity in chronic ketamine users. PLoS One 2016 11 12 e0167381 10.1371/journal.pone.0167381 27977717
    [Google Scholar]
  112. Huang M.C. Chen C.H. Liu T.H. Chung A.N. Liu Y.L. Quednow B.B. Bavato F. Comorbidity of ketamine dependence with major depressive disorder increases the vulnerability to neuroaxonal pathology. J. Psychiatr. Res. 2023 158 360 364 10.1016/j.jpsychires.2023.01.009 36640660
    [Google Scholar]
  113. Chung A.N. Huang M.C. Liu T.H. Chang H.M. Chen P.Y. Liu Y.L. Bavato F. Ketamine-dependent patients with persistent psychosis have higher neurofilament light chain levels than patients with schizophrenia. Asian J. Psychiatr. 2024 100 104167 10.1016/j.ajp.2024.104167 39111088
    [Google Scholar]
  114. Hung C.C. Liu Y.H. Huang C.C. Chou C.Y. Chen C.M. Duann J.R. Li C.S.R. Lee T.S.H. Lin C.P. Effects of early ketamine exposure on cerebral gray matter volume and functional connectivity. Sci. Rep. 2020 10 1 15488 10.1038/s41598‑020‑72320‑z 32968108
    [Google Scholar]
  115. Hunger A. Kebrle J. Rossi A. Hoffmann K. Benzimidazol‐derivate und verwandte heterocyclen. II. Synthese von] 1‐aminoalkyl‐2‐benzyl‐benzimidazolen. Helv. Chim. Acta 1960 43 3 800 809 10.1002/hlca.19600430323
    [Google Scholar]
  116. Ujváry I. Christie R. Evans-Brown M. Gallegos A. Jorge R. de Morais J. Sedefov R. DARK classics in chemical neuroscience: Etonitazene and related benzimidazoles. ACS Chem. Neurosci. 2021 12 7 1072 1092 10.1021/acschemneuro.1c00037 33760580
    [Google Scholar]
  117. Dahan A. Franko T.S. Carroll J.W. Craig D.S. Crow C. Galinkin J.L. Garrity J.C. Peterson J. Rausch D.B. Fact vs. fiction: Naloxone in the treatment of opioid-induced respiratory depression in the current era of synthetic opioids. Front. Public Health 2024 12 1346109 10.3389/fpubh.2024.1346109 38481848
    [Google Scholar]
  118. Drug trafficking & cultivation. 2020 Available from: https://dataunodc.un.org/dp-drug-seizures
  119. Vandeputte M.M. Van Uytfanghe K. Layle N.K. St Germaine D.M. Iula D.M. Stove C.P. Synthesis, chemical characterization, and μ-Opioid receptor activity assessment of the emerging group of “Nitazene” 2-benzylbenzimidazole synthetic opioids. ACS Chem. Neurosci. 2021 12 7 1241 1251 10.1021/acschemneuro.1c00064 33759494
    [Google Scholar]
  120. Vandeputte M.M. Krotulski A.J. Walther D. Glatfelter G.C. Papsun D. Walton S.E. Logan B.K. Baumann M.H. Stove C.P. Pharmacological evaluation and forensic case series of] N-pyrrolidino etonitazene (etonitazepyne), a newly emerging] 2-benzylbenzimidazole ‘nitazene’ synthetic opioid. Arch. Toxicol. 2022 96 6 1845 1863 10.1007/s00204‑022‑03276‑4 35477798
    [Google Scholar]
  121. Vandeputte M.M. Tsai M.H.M. Chen L. Glatfelter G.C. Walther D. Stove C.P. Shi L. Baumann M.H. Comparative neuropharmacology of structurally distinct non-fentanyl opioids that are appearing on recreational drug markets worldwide. Drug Alcohol Depend. 2023 249 109939 10.1016/j.drugalcdep.2023.109939 37276825
    [Google Scholar]
  122. Malcolm N.J. Palkovic B. Sprague D.J. Calkins M.M. Lanham J.K. Halberstadt A.L. Stucke A.G. McCorvy J.D. Mu-opioid receptor selective superagonists produce prolonged respiratory depression. iScience 2023 26 7 107121 10.1016/j.isci.2023.107121 37416459
    [Google Scholar]
  123. Blanckaert P. Cannaert A. Van Uytfanghe K. Hulpia F. Deconinck E. Van Calenbergh S. Stove C. Report on a novel emerging class of highly potent benzimidazole NPS opioids: Chemical and in vitro functional characterization of isotonitazene. Drug Test. Anal. 2020 12 4 422 430 10.1002/dta.2738 31743619
    [Google Scholar]
  124. De Luca M.A. Tocco G. Mostallino R. Laus A. Caria F. Musa A. Pintori N. Ucha M. Poza C. Ambrosio E. Di Chiara G. Castelli M.P. Pharmacological characterization of novel synthetic opioids: Isotonitazene, metonitazene, and piperidylthiambutene as potent μ-opioid receptor agonists. Neuropharmacology 2022 221 109263 10.1016/j.neuropharm.2022.109263 36154843
    [Google Scholar]
  125. Skolnick P. Treatment of overdose in the synthetic opioid era. Pharmacol. Ther. 2022 233 108019 10.1016/j.pharmthera.2021.108019 34637841
    [Google Scholar]
  126. Pergolizzi J. Raffa R. LeQuang J.A.K. Breve F. Varrassi G. Old drugs and new challenges: A narrative review of nitazenes. Cureus 2023 15 6 40736 10.7759/cureus.40736 37485167
    [Google Scholar]
/content/journals/cn/10.2174/011570159X410522251117060555
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Psychoactive Synthetic Adulterants in Tablets Sold as MDMA after the COVID-19 Pandemic: Implications for Central Effects
Bentham Science Publishers ; https://doi.org/10.2174/011570159X410522251117060555
/content/journals/cn/10.2174/011570159X410522251117060555
/content/journals/cn/10.2174/011570159X410522251117060555
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  • Article Type:     Review Article
Keywords: Amphetamines ; nitazenes ; phenethylamines ; COVID-19 ; ecstasy ; synthetic cathinones

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