The Synthetic Cannabinoids

Abstract

Synthetic cannabinoids are defined as psychoactive substances that trigger the endocannabinoid system. They are largely used as narcotics, although some of their effects are used for therapeutic purposes. In the last decade, recreational use in Europe and the United States has increased more than other psychoactive substances. In Turkey it is called "Bonzai" or "Jamaica". In addition, a stronger effect than cannabis, affordability, easy accessibility and freedom from standard drug testing contribute to the increasing use of synthetic cannabinoids. In this article, we will examine the structure and toxicology of synthetic cannabinoids and review the diagnosis and treatment of synthetic cannabinoids in the light of current literature.

Keywords

• poisoning
• emergency medicine
• synthetic cannabinoids
• Δ9-THC; tetrahydrocannabinol

References

1. Aşıcıoğlu FJYNP-AMSK. Yeni nesil psiko-aktif maddeler. 2013:3-5.
2. Drugs EMCf, Addiction D. Perspectives on drugs: synthetic cannabinoids in Europe. Publications Office of the European Union Luxembourg; 2017.
3. Gaoni Y, Mechoulam RJJotAcs. Isolation, structure, and partial synthesis of an active constituent of hashish. 1964;86(8):1646- 7.
4. Mills B, Yepes A, Nugent KJTAjotms. Synthetic cannabinoids. 2015;350(1):59-62.
5. Lafaye G, Karila L, Blecha L, Benyamina AJDicn. Cannabis, cannabinoids, and health. 2017;19(3):309-16.
6. Solimini R, Busardo FP, Rotolo M, Ricci S, Mastrobattista L, Mortali C, et al. Hepatotoxicity associated to synthetic cannabinoids use. 2017;21.
7. Tettey JN, Crean C, Rodrigues J, Yap TWA, Lim JLW, Lee HZS, et al. United Nations Office on Drugs and Crime: recommended methods for the identification and analysis of synthetic cannabinoid receptor agonists in seized materials. 2021;3:100129.
8. Liu CM, Jia W, Meng X, Hua ZDJJoFS. Identification and quantification of 10 indole/indazole carboxamide synthetic cannabinoids in 36 herbal blends by gas chromatography‐mass spectrometry and nuclear magnetic resonance spectroscopy. 2021;66(6):2156-66.

9. Tettey JNA, Crean C, Rodrigues J, Angeline Yap TW, Lee Wendy Lim J, Shirley Lee HZ, 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 Science International: Synergy. 2021;3:100129.
10. Alves VL, Gonçalves JL, Aguiar J, Teixeira HM, Câmara JSJCRiT. The synthetic cannabinoids phenomenon: from structure to toxicological properties. A review. 2020;50(5):359- 82.
11. Patel M, Manning JJ, Finlay DB, Javitch JA, Banister SD, Grimsey NL, et al. Signalling profiles of a structurally diverse panel of synthetic cannabinoid receptor agonists. 2020;175:113871.
12. Ruparel NB, Patwardhan AM, Akopian AN, Hargreaves KMJMp. Desensitization of transient receptor potential ankyrin 1 (TRPA1) by the TRP vanilloid 1-selective cannabinoid arachidonoyl-2 chloroethanolamine. 2011;80(1):117-23.
13. Oleson EB, Cheer JFJCSHpim. A brain on cannabinoids: the role of dopamine release in reward seeking. 2012;2(8):a012229.
14. Brown TM, Brotchie JM, Fitzjohn SMJJoN. Cannabinoids decrease corticostriatal synaptic transmission via an effect on glutamate uptake. 2003;23(35):11073-7.
15. Irie T, Kikura-Hanajiri R, Usami M, Uchiyama N, Goda Y, Sekino YJN. MAM-2201, a synthetic cannabinoid drug of abuse, suppresses the synaptic input to cerebellar Purkinje cells via activation of presynaptic CB1 receptors. 2015;95:479-91.
16. Yano H, Adhikari P, Naing S, Hoffman AF, Baumann MH, Lupica CR, et al. Positive allosteric modulation of the 5-HT1A receptor by indole-based synthetic cannabinoids abused by humans. 2020;11(10):1400-5.
17. Lobato-Freitas C, Brito-da-Costa AM, Dinis-Oliveira RJ, Carmo H, Carvalho F, Silva JP, et al. Overview of synthetic cannabinoids ADB-FUBINACA and AMB-FUBINACA: clinical, analytical, and forensic implications. 2021;14(3):186.
18. Canazza I, Ossato A, Vincenzi F, Gregori A, Di Rosa F, Nigro F, et al. Pharmaco-toxicological effects of the novel thirdgeneration fluorinate synthetic cannabinoids, 5F-ADBINACA, AB-FUBINACA, and STS-135 in mice. In vitro and in vivo studies. 2017;32(3):e2601.
19. Gurney S, Scott K, Kacinko S, Presley B, Logan BJFSR. Pharmacology, toxicology, and adverse effects of synthetic cannabinoid drugs. 2014;26(1):53-78.
20. Tatusov M, Mazer-Amirshahi M, Abbasi A, Goyal MJTAJoEM. Clinical effects of reported synthetic cannabinoid exposure in patients admitted to the intensive care unit. 2019;37(6):1060-4.
21. Martinotti G, Santacroce R, Papanti D, Elgharably Y, Prilutskaya M, Corazza OJC, et al. Synthetic cannabinoids: psychopharmacology, clinical aspects, psychotic onset. 2017;16(5):567-75.
22. Cooper ZD. Adverse Effects of Synthetic Cannabinoids: Management of Acute Toxicity and Withdrawal. Current psychiatry reports. 2016;18(5):52.
23. Mills B, Yepes A, Nugent K. Synthetic Cannabinoids. The American journal of the medical sciences. 2015;350(1):59-62.
24. Riederer AM, Campleman SL, Carlson RG, Boyer EW, Manini AF, Wax PM, et al. Acute Poisonings from Synthetic Cannabinoids - 50 U.S. Toxicology Investigators Consortium Registry Sites, 2010-2015. MMWR Morbidity and mortality weekly report. 2016;65(27):692-5.
25. Armenian P, Darracq M, Gevorkyan J, Clark S, Kaye B, Brandehoff NP. Intoxication from the novel synthetic cannabinoids AB-PINACA and ADB-PINACA: A case series and review of the literature. Neuropharmacology. 2018;134(Pt A):82-91.
26. Müller HH, Kornhuber J, Sperling W. The behavioral profile of spice and synthetic cannabinoids in humans. Brain Research Bulletin. 2016;126:3-7.
27. Tsatsakis A, Docea AO, Calina D, Tsarouhas K, Zamfira LM, Mitrut R, et al. A Mechanistic and Pathophysiological Approach for Stroke Associated with Drugs of Abuse. Journal of clinical medicine. 2019;8(9).
28. Aksel G, Güneysel Ö, Taşyürek T, Kozan E, Çevik Ş E. Intravenous Lipid Emulsion Therapy for Acute Synthetic Cannabinoid Intoxication: Clinical Experience in Four Cases. Case reports in emergency medicine. 2015;2015:180921.
29. Armenian P, Darracq M, Gevorkyan J, Clark S, Kaye B, Brandehoff NP. Intoxication from the novel synthetic cannabinoids AB-PINACA and ADB-PINACA: A case series and review of the literature. Neuropharmacology. 2018;134:82- 91.
30. El Marroun H, Brown QL, Lund IO, Coleman-Cowger VH, Loree AM, Chawla D, et al. An epidemiological, developmental and clinical overview of cannabis use during pregnancy. Preventive Medicine. 2018;116:1-5.
31. Cristino L, Bisogno T, Di Marzo V. Cannabinoids and the expanded endocannabinoid system in neurological disorders. Nature reviews Neurology. 2020;16(1):9-29.
32. Dong C, Chen J, Harrington A, Vinod KY, Hegde ML, Hegde VL. Cannabinoid exposure during pregnancy and its impact on immune function. Cellular and molecular life sciences : CMLS. 2019;76(4):729-43.
33. Mereu G, Fà M, Ferraro L, Cagiano R, Antonelli T, Tattoli M, et al. Prenatal exposure to a cannabinoid agonist produces memory deficits linked to dysfunction in hippocampal longterm potentiation and glutamate release. Proceedings of the National Academy of Sciences of the United States of America. 2003;100(8):4915-20.
34. Pinky PD, Majrashi M, Fujihashi A, Bloemer J, Govindarajulu M, Ramesh S, et al. Effects of prenatal synthetic cannabinoid exposure on the cerebellum of adolescent rat offspring. Heliyon. 2021;7(4):e06730.
35. Alexandre J, Carmo H, Carvalho F, Silva JP. Synthetic cannabinoids and their impact on neurodevelopmental processes. Addiction biology. 2020;25(2):e12824.
36. Oudin MJ, Gajendra S, Williams G, Hobbs C, Lalli G, Doherty P. Endocannabinoids regulate the migration of subventricular zone-derived neuroblasts in the postnatal brain. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2011;31(11):4000-11.
37. Kim D, Thayer SA. Cannabinoids inhibit the formation of new synapses between hippocampal neurons in culture. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2001;21(10):Rc146.
38. Jiang W, Zhang Y, Xiao L, Van Cleemput J, Ji SP, Bai G, et al. Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressantlike effects. The Journal of clinical investigation. 2005;115(11):3104-16.
39. Miranda CC, Barata T, Vaz SH, Ferreira C, Quintas A, Bekman EP. hiPSC-Based Model of Prenatal Exposure to Cannabinoids: Effect on Neuronal Differentiation. Frontiers in molecular neuroscience. 2020;13:119.
40. Scheyer AF, Melis M, Trezza V, Manzoni OJJ. Consequences of Perinatal Cannabis Exposure. Trends in neurosciences. 2019;42(12):871-84.
41. Wu CS, Jew CP, Lu HC. Lasting impacts of prenatal cannabis exposure and the role of endogenous cannabinoids in the developing brain. Future neurology. 2011;6(4):459-80.
42. Szutorisz H, Hurd YLJN, Reviews B. High times for cannabis: Epigenetic imprint and its legacy on brain and behavior. 2018;85:93-101.
43. Gomes TM, da Silva DD, Carmo H, Carvalho F, Silva JPJPR. Epigenetics and the endocannabinoid system signaling: An intricate interplay modulating neurodevelopment. 2020;162:105237.
44. Andaloussi ZIL, Taghzouti K, Abboussi OJIJoDN. Behavioural and epigenetic effects of paternal exposure to cannabinoids during adolescence on offspring vulnerability to stress. 2019;72:48-54.
45. Tomas-Roig J, Benito E, Agis-Balboa R, Piscitelli F, Hoyer- Fender S, Di Marzo V, et al. Chronic exposure to cannabinoids during adolescence causes long-lasting behavioral deficits in adult mice. 2017;22(6):1778-89.
46. Hollins S, Zavitsanou K, Walker F, Cairns MJTp. Alteration of imprinted Dlk1-Dio3 miRNA cluster expression in the entorhinal cortex induced by maternal immune activation and adolescent cannabinoid exposure. 2014;4(9):e452-e.
47. Whiting PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, Hernandez AV, et al. Cannabinoids for medical use: a systematic review and meta-analysis. 2015;313(24):2456-73.
48. de Vries M, van Rijckevorsel DC, Wilder-Smith OH, van Goor HJEoop. Dronabinol and chronic pain: importance of mechanistic considerations. 2014;15(11):1525-34.
49. Cristino L, Bisogno T, Di Marzo VJNRN. Cannabinoids and the expanded endocannabinoid system in neurological disorders. 2020;16(1):9-29.
50. Sheng WS, Hu S, Min X, Cabral GA, Lokensgard JR, Peterson PKJG. Synthetic cannabinoid WIN55, 212-2 inhibits generation of inflammatory mediators by IL-1β-stimulated human astrocytes. 2005;49(2):211-9.