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

Abstract

This study presents a literature review of the main methods used for the detection of Synthetic Cannabinoids (SCs) in biological matrices and seized materials, taking into account the growing trade and use of these substances by a significant portion of the population, their interaction with the Endocannabinoid System, and their toxicodynamic effects. Instrumental techniques such as Gas and Liquid Chromatography coupled with Mass Spectrometry (GC-MS, LC-MS/MS), considered the gold standard for the identification and quantification of these compounds, are addressed. Alternative methods, such as Direct Analysis in Real Time Mass Spectrometry (DART-MS) and Atmospheric Pressure Photoionization Desorption (APPI-DS), as well as screening techniques such as colorimetric assays and immunoassays, are also discussed, despite their limitations in specificity. The preparation of biological samples - oral fluid, blood, urine, hair, and autopsy specimens - is highlighted as a crucial step in the analytical process, along with knowledge of SC metabolites. Among the challenges encountered are the constant structural modifications of these substances, the need for updated databases, and the lack of analytical standards. It is concluded that the combination of methods and the continuous development of analytical approaches are essential for the effective detection of SCs in the field of forensic toxicology.

Keywords

synthetic cannabinoids
Forensic Toxicology
Immunochromatographic tests
Biological evidence
canabinoides sintéticos
Toxicologia
Cromatografia
Amostras Biologicas
Espectrometria

References

  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).
Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Copyright (c) 2026 Brazilian Journal of Criminalistics

Share

Download

pdf (Português (Brasil))

Author(s)