Canabinoides sintéticos: uma revisão sobre a interação biológica no organismo e as técnicas de detecção e quantificação utilizadas


Аннотация

Este trabalho apresenta uma revisão de literatura dos principais métodos utilizados na detecção de Canabinoides Sintéticos (CS) em matrizes biológicas e materiais apreendidos, levando em consideração o crescimento do comércio e utilização dessas substâncias por uma parte considerável da população, sua ligação ao Sistema Endocanabinoide e seus efeitos toxicodinâmicos. Foram abordadas técnicas instrumentais, como a Cromatografia Gasosa e Líquida acopladas à Espectrometria de Massas (GC-MS, LC-MS/MS), consideradas padrão-ouro na identificação e quantificação desses compostos. Discutem-se ainda métodos alternativos, como a Espectrometria de Massa em Tempo Real (DART-MS) ou a Fotoionização de Pressão Atmosférica de Dessorção (APPI-DS), bem como técnicas de triagem, a exemplo de ensaios colorimétricos e imunoensaios, apesar de suas limitações quanto à especificidade. O preparo das amostras biológicas - fluido oral, sangue, urina, cabelo e amostras autopsiadas - é destacado como etapa crucial no processo analítico, juntamente ao conhecimento dos metabólitos dos CS. Dentre as dificuldades enfrentadas, destacam-se as constantes alterações estruturais dessas substâncias, a necessidade de atualização de bancos de dados e a carência de padrões analíticos. Conclui-se que a combinação de métodos e o contínuo desenvolvimento de abordagens analíticas são fundamentais para a detecção eficaz dos CS no âmbito da toxicologia forense.


Библиографические ссылки

  1. A.Y. Simão; M. Antunes; E. Cabral; P. Oliveira; L. M. Rosendo; A. T. Brinca; E. Alves; H. Marques; T. Rosado; L. A. Passarinha; M. Andraus; M. Barroso; E. Gallardo. An Update on the Implications of New Psychoactive Substances in Public Health. International journal of environmental research and public 19(8): 4869 (2022).
  2. B. I. Tamba, et al. Challenges and opportunities in preclinical research of synthetic cannabinoids for pain therapy. Medicina (Kaunas) 56(1): 24 (2020).
  3. D. Silva; C. Moura. Farmacologia e toxicologia dos canabinoides sintéticos,“drogas emergentes”, e os seus impactos na saúde pública. Enciclopédia biosfera 19(40): n/a (2022).
  4. EMCDDA n/a. Perspectives on Drugs. Synthetic cannabinoids in Europe. European Union Drugs Agency n/a: 1-9 (2015, atualizado em 2017). Retirado em 01/04/2025, de
  5. http://www.emcdda.europa.eu/topics/pods/synthetic-canna binoids.
  6. J.N.A. Tettey; C. Crean; J. Rodrigues; T.W.A. Yap; et al. United Nations office on drugs and crime: recommended methods for the identification and analysis of synthetic cannabinoid receptor agonists in seized materials. Forensic Sci 3: 100129 (2021).
  7. World Drug Report n/a. Global Overview of Drug demand and Drug supply. United Nations Office on Drugs and Crime, UNODC Research E.21(XI.8): 1-108 (2021). Retirado em 01/04/2025, de https://www.unodc.org/res/wdr2021/field/WDR21_Bookl et_2.pdf.
  8. M. Spaderna; P. H. Addy; D. C. D. Souza. Apimentando as coisas: canabinoides sintéticos. Psicofarmacologia (Berl) 228: 525–540 (2013).
  9. P. Jankovics, et al. Detection and identification of the new potential synthetic cannabinoids 1-pentyl-3-(2-iodobenzoyl) indole and 1-pentyl-3-(1-adamantoyl) indole in seized bulk powders in Hungary. Forensic Sci. Int. 214: 27–32 (2012).
  10. S. D. Brandt, et al. Agonistas de receptores canabinoides sintéticos: perfis analíticos e desenvolvimento de QMPSB, QMMSB, QMPCB, 2F-QMPSB, QMiPSB e SGT-233. Drug Testing and Analysis 13: 175–196 (2021).
  11. E. D. Tsochatzis, et al. Identificação e caracterização analítica de uma nova substância sintética do tipo canabinoide em material herbáceo na Europa. Moléculas 26: 793 (2021).
  12. United Nations Office on Drugs and Crime (UNODC) n/a. World drug report 2015. Vienna: United Nations, UNODC Research E.15(XI.6): 1-118 (2015). Retirado em 01/04/2025, de https://www.unodc.org/wdr2015.
  13. J. C. Honorio, et al. Legal highs: um problema de saúde pública. Cadernos de Saúde Pública 30: 228-230 (2014).
  14. Brasil n/a. 5º Informe SAR - Canabinoides Sintéticos. Ministério da Justiça e Segurança Pública n/a: 1-9 (2023). Retirado em 16/05/25, de https://www.gov.br/mj/pt-br/assuntos/sua-protecao/politic as-sobre-drogas/subsistema-de-alerta-rapido-sobre-drogas -sar/5o-informe-sar-canabinoides-sinteticos-07-07-2023.p df.
  15. J. V. Pinto, et al. Cannabidiol as a treatment for mood disorders: a systematic review. The Canadian Journal of Psychiatry 65: 213-227 (2020).
  16. E. Navarro-Tapia, et al. Detection of the synthetic cannabinoids AB-CHMINACA, ADB-CHMINACA, MDMB-CHMICA, and 5F-MDMB-PINACA in biological matrices: a systematic review. Biology 11: 796 (2022).
  17. L.H. Parsons; Y.L. Hurd. Endocannabinoid signalling in reward and addiction. Nat Rev Neurosci 16: 579-594 (2015).
  18. G. Donvito; S.R. Nass; J.L. Wilkerson; et al. The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain. Neuropsychopharmacology 43: 52-79 (2018).
  19. A.C. Howlett; J.M. Qualy; L.L. Khachatrian. Envolvimento de Gi na inibição da adenilato ciclase por drogas canabimiméticas. Farmacologia Molecular 29: 307–313 (1986).
  20. K. Mackie. Distribution of cannabinoid receptors in the central and peripheral nervous system. Handb Exp Pharmacol 168: 299-325 (2005).
  21. S.H. Ramirez; J. Hasko; A. Skuba; et al. Activation of cannabinoid receptor 2 attenuates leukocyte-endothelial cell interactions and blood-brain barrier dysfunction under inflammatory conditions. J Neurosci 32: 4004-4016 (2012).
  22. L. Walter; A. Franklin; A. Witting; et al. Nonpsychotropic cannabinoid receptors regulate microglial cell migration. J Neurosci 23: 1398-1405 (2003).
  23. A.C. Howlett. International Union of Pharmacology. XXVII. Classification of Cannabinoid Receptors. Pharmacological Reviews, American Society for Pharmacology & Experimental Therapeutics (ASPET) 54: 161-202, (2002).
  24. W. Devane; L. Hanus; A. Breuer; R. Pertwee; L. Stevenson; G. Griffin; D. Gibson; A. Mandelbaum; A. Etinger; R. Mechoulam. Isolation and structure of a brain constituent that binds to the receptor cannabinoid. Science, American Association for the Advancement of Science (AAAS) 258: 1946-1949 (1992).
  25. L. Hanus; R. Mechoulam. Cannabinoid chemistry: an overview. Cannabinoids as Therapeutics. Basiléia: Birkhäuser Verlag 2: 23-46 (2005).
  26. V. M. Saito; C. T. Wotjak; F. A. Moreira. Exploração farmacológica do sistema endocanabinoide: novas perspectivas para o tratamento de transtornos de ansiedade e depressão? Revista Brasileira de Psiquiatria 32: 57-514 (2010).
  27. J.B. Zawilska; D. Andrzejczak. Next generation of novel psychoactive substances on the horizon - A complex problem to face. Drug and Alcohol Dependence 157: 1-17 (2015).
  28. P. Pacher; N. M. Kogan; R. Mechoulam. Beyond THC and Endocannabinoids. Annual Review Of Pharmacology And Toxicology 60: 1-23, (2020).
  29. X. Hu; B.A. Primack; T.E. Barnett; R.L. Cook. Estudantes universitários e uso de K2: uma droga emergente de abuso em jovens. Tratamento, prevenção e política de abuso de substâncias 6: 16 (2011).
  30. M.J. Richter, et al. In vitro metabolic fate of the synthetic cannabinoid receptor agonists 2F-QMPSB and SGT-233 including isozyme mapping and carboxylesterases activity testing. Journal of Analytical Toxicology 46: 198-206 (2022).
  31. L.C.L. Paixão; S.G. Pereira; H.C.S. Melo. Técnicas de preparo de amostras biológicas para a identificação de drogas facilitadoras de crime. Altus Ciênc. 17: 143–165 (2023).
  32. H. Durmus; E. Unal; E. Sener; H. Yildiz; Y. Onur. Colorimetric determination of (aminoalkyl) indole-containing synthetic cannabimimetics. Anal. Sci. 34: 1419–1425 (2018).
  33. R.C.A. Isaacs. A structure–reactivity relationship driven approach to the identification of a color test protocol for the presumptive indication of synthetic cannabimimetic drugs of abuse. Forensic Sci. Int. 242: 135–141 (2014).
  34. J. Lee; H. Jiang. Analysis of indole and indazole amides synthetic cannabinoids by differential Raman spectroscopy based on ANN. J Forensic Sci. 67(6): 2242-2252 (2022).
  35. A. Arntson; B. Ofsa; D. Lancaster; J.R. Simon; M. McMullin; B. Logan. Validation of a novel immunoassay for the detection of synthetic cannabinoids and metabolites in urine specimens, J. Anal. Toxicol. 37: 284–290 (2013).
  36. K. Kuwayama, et al. Rapid chemical examinations of canabis and its related herbal products. Japanese Journal of Science and Technology 18: 143–153 (2013).
  37. J. Schürenkamp, et al. Difficulties arising from new blood collecting tubes for ethanol determination. Toxichem Krimtech 82: 268–272 (2015).
  38. S. W. Toennes; G. F. Kauert. Importance of vacutainer selection in forensic toxicological analysis of drugs of abuse. Journal of Analytical Toxicology 25: 339–343 (2001).
  39. N.Y. Ashri; M. Abdel-Rehim. Sample treatment based on extraction techniques in biological matrices. Bioanalysis 3: 2003–2018 (2011).
  40. N. Simpson; E. M. Thurman; M. S. Mills. Solid-phase extraction: principles and practice. New York: Wiley 16: n/a (1998).
  41. J. Znaleziona, et al. Determination and identification of synthetic cannabinoids and their metabolites in different matrices by modern analytical techniques – a review. Analytica Chimica Acta 874: 11-25 (2015).
  42. D.C.M. Bordin; F.F.S.S. Monedeiro; E.D. Campos; M. Alves; L. Bueno; B. Martinis. Técnicas de preparo de amostras biológicas com interesse forense. Sci Chromatogr 7(2): 125- 43 (2015).
  43. T.J. Kauppila; M. Flink; T. Haapala; T. Aalto; M. Aalberg; I. Ketola; T. Kotiaho; R. Kostiainen. Desorption atmospheric pressure photoionization-mass spectrometry in routine analysis of confiscated drugs. Forensic Sci. Int. 210: 206–212 (2011).
  44. M. Grabenauer; W. Moore; B. E. Levine; M. F. Dobrowolski; M. R. Casale. Analysis of synthetic cannabinoids using high-resolution mass spectrometry and mass defect filtering: implications for non targeted screening of designer drugs. Anal. Chem. 84: 5574–5581 (2012).
  45. United Nations Office on Drugs and Crime n/a. Synthetic cannabinoids in herbal products. n/a n/a: 1-24 (2011). Retirado em 01/04/25, de https://www.unodc.org/documents/scientific/Synthetic_Ca nnabinoids.pdf.
  46. L. Mercolini; M. Protti. Biosampling strategies for emerging drugs of abuse: towards the future of toxicological and forensic analysis. Journal of Pharmaceutical and Biomedical Analysis 130: 202–219 (2016).
  47. J. Thorspecken; G. Skopp; L. Pötsch. In vitro contamination of hair by marijuana smoke. Clinical Chemistry 50: 596–602 (2004).
  48. I. Shah, et al. A review of bioanalytical techniques for evaluation of cannabis (marijuana, weed, hashish) in human hair. BMC Chemistry 13: 1–20 (2019).
  49. F. Franz, et al. Synthetic cannabinoids in hair—Pragmatic approach for method updates, compound prevalences and concentration ranges in authentic hair samples. Analytica Chimica Acta 1006: 61–73 (2018).
  50. G. Verstraete. Detection times of drugs of abuse in blood, urine, and oral fluid. Therapeutic Drug Monitoring 26: 200–205 (2004).
  51. S. Kneisel; V. Auwärter. Analysis of 30 synthetic cannabinoids in serum by liquid chromatography-electrospray ionization tandem mass spectrometry after liquid-liquid extraction. Journal of Mass Spectrometry 47: 825–835 (2012).
  52. K. E. Moeller; K. C. Lee; J. C. Kissack. Urine drug screening: practical guide for clinicians. Mayo Clinic Proceedings 83: 66–76 (2008).
  53. K. F. da Cunha, et al. Screening of 104 new psychoactive substances (NPS) and other drugs of abuse in oral fluid by LC–MS-MS. Journal of Analytical Toxicology 44: 697–707 (2020).
  54. D.J.Crouch ; M.A. Huestis; D. Holden; R. de la Torre; S.J. Salamone. Evaluation of saliva/oral fluid as an alternate drug testing specimen. Washington, DC: Office of Justice Programs, National Criminal Justice Reference Service n/a: 1-70 (2004). Retirado em 01/04/25, de https://www.ojp.gov/ncjrs/virtual-library/abstracts/evaluat ion-salivaoral-fluid-alternate-drug-testing-specimen.
  55. C. Hess, et al. Death due to diabetic ketoacidosis: induction by the consumption of synthetic cannabinoids? Forensic Science International 257: e6-e11 (2015).
  56. K. Hasegawa; A. Wurita; K. Minakata; K. Gonmori; I. Yamagishi; H. Nozawa; et al. Identification and quantification of 5-fluoro-ADB, one of the most dangerous synthetic cannabinoids, in the stomach contents and solid tissues of a human cadaver and in some herbal products. Forensic Toxicology 33: 112-121 (2015).
  57. SWGDRUG Recommendations Version 8.2. Scientific Working Group for the Analysis of Seized Drugs (2024). Retirado em 26/11/2025, de https://www.swgdrug.org/Documents/SWGDRUG%20Re commendations%20Version%208.2%20Final%20for%20 posting.pdf.
  58. H.S. Bombana. Substâncias psicoativas no sangue: métodos de análises toxicológicas e prevalência do uso em pacientes com lesões traumáticas. Tese de Doutorado, Departamento de Medicina Legal, Ética Médica e Medicina Social e do Trabalho, Universidade de São Paulo (2021).
  59. S. A. Borden, et al. Mass spectrometry analysis of drugs of abuse: challenges and emerging strategies. Mass Spectrometry Reviews 39: 703–744 (2020).
  60. J.N. Andres; H. Siddiqui; M. Fong. The chemists’ gold: an analysis of gas chromatography-mass spectrometry and future directions. Voices of forensic science 1(1): 231-249 (2021).
  61. B.N. Dias; C.R. Oliveira; B.M. Rodrigues. Raman spectroscopy and its peculiarities. Journal of Experimental Techniques and Instrumentation 4: 15-25 (2020)
  62. H. B. Napolitano; A. J. Camargo; Y. P. Mascarenhas; I. Vencato; C. Lariucci. Análise da difração dos Raios X. Revista Processos Químicos 1(1): 35-45 (2007).
  63. J.C. Ponce; A. C. Martins; R. L. Oliveira; M. J. Silva. Detecção de canabinoide sintético na ausência de padrão utilizando técnicas espectroscópicas e espectrométricas: um relato de caso. Rev. Sist. Único Segur. Pública 1: 39–50 (2021).
  64. S. Dresen; F. Ferreiros; M. Pütz; H. Westphal; H. A. Zimmermann; V. Auwärter. Development and validation of a LC–MS/MS method for the determination of synthetic cannabinoids in human serum. J. Mass Spectrom. 46: 163–171 (2011).
  65. R.A. Musah; J. D. Domin; S. L. Fenner; L. A. V. Kinyua; C. E. Sisco. Rapid identification of synthetic cannabinoids in herbal samples via direct analysis in real time mass spectrometry. Rapid Commun. Mass Spectrom. 26: 1109–1114 (2012).
  66. J. Teske, et al. Quantificação sensível e rápida do agonista do receptor canabinoide naftalen-1-il-(1-pentilindol-3-il) metanona (JWH-018) em soro humano por cromatografia líquida-espectrometria de massa em tandem. Journal of Chromatography B 878: 2659–2663 (2010).
  67. T. Sobolevsky; I. Prasolov; G. Rodchenkov. Detecção de metabólitos de JWH-018 na urina pós-administração de mistura para fumar. Forensic Science International 200: 141–147 (2010).
  68. A. Wohlfarth, et al. Metabolism of synthetic cannabinoids PB-22 and its 5-fluoro analog, 5F-PB-22, by human hepatocyte incubation and high-resolution mass spectrometry. Analytical and Bioanalytical Chemistry 406: 1763–1780 (2014).
  69. M. Hutter, et al. Characteristics of the designer drug and synthetic cannabinoid receptor agonist AM-2201 regarding its chemistry and metabolism. Journal of Mass Spectrometry 48: 885–894 (2013).

Лицензия Creative Commons

Это произведение доступно по лицензии Creative Commons «Attribution-NonCommercial-ShareAlike» («Атрибуция — Некоммерческое использование — На тех же условиях») 4.0 Всемирная.

Copyright (c) 2026 Revista Brasileira de Criminalística

Делиться

Авторы)