Sentetik Kannabinoid: Sokak Dilinde ˝Bonzai˝

Hint keneviri bitkisinden elde edilen ve kannabinoid reseptörlerine (CB1, CB2) etki eden kannabis (esrar) en eski psikoaktif maddelerdendir. Sentetik kannabinoidler ise yapısal olarak değişiklikler gösteren ve aynı reseptörler ile etkileşen yeni nesil psikoaktif maddelerdir. Sokak dilinde “Bonzai” olarak bilinen “(1-pentyl-1H-indol-3-yl)-1-naphthalenyl-methanone” diğer adıyla JWH-018 uyuşturucu piyasasında ilk tespit edilen sentetik kannabinoiddir. Sentetik kannabinoidler fonksiyonel olarak esrarın etken maddesi olan delta-9-tetrahidrokannabinol (Δ9-THC) benzemekte ve sigara gibi içildiğinde esrarın etkisini taklit etmektedir. Ancak bu ürünlerin çoğu THC’den daha güçlüdür ve daha büyük sağlık riski oluşturmaktadır. Avrupa’da bu maddeler 2004 yılı başlarında itibaren internet üzerinden ve özel marketlerde satışa sunulmuştur. Tüm dünyada olduğu gibi ülkemizde de yetişkinler ve gençler arasında sentetik kannabinoid kullanımında bir artış gözlenmektedir. Bu maddelerden bazıları ülkemizde 2010 yılından itibaren Erken Uyarı Sistemine göre yasaklanan maddeler arasına alınmıştır. Bu çalışmada kullanımı giderek artan sentetik kannabinoidlerin farmakolojik, toksikolojik ve genel özelliklerini sunma amaçlanmıştır.

Synthetic cannabinoid: in the street language ˝bonsai˝ (Full-text language: Turkish)

Cannabis (marijuana) which is obtained from cannabis sativa has an effect on cannabinoid receptors (CB1 and CB2) and known as one of the oldest psychoactive substances. From another point of view, synthetic cannabinoids are the new generation synthetic pschoactive substances interacting with the same receptors and showing differences in structure. In the street language bonzai, “(1-pentyl-1H-indol-3-yl)-1-naphthalenyl-methanone”, also known as JWH-018 group, is a drug belonging to the group of synthetic cannabinoids. Synthetic cannabinoids are operationally similar to delta-9-tetrahidrokannabinol (Δ9-THC) and imitates the effects of marijuana when smoked. However, many of them are stronger than THC and pose a greater health risk. At the beginning of 2004, it started to be sold on the internet and also private markets. An increase at the demand is observed in the use of synthetic cannabinoid use among the teenagers and adults not only in Turkey but all around the World.   Some of these compounds were put at the prohibited substances list in our country since 2010, according to the Early Warning System (EWS). In this study we aimed to present farmacological, toxicological ve general properties of the increasingly used synthetic cannabinoid.

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  • 1. Yargıç, İ., Sentetik kannabinoidler. Yeni Nesil Psikoaktif Maddeler Sempozyumu Kitabı, 2013:9-11. http://www.atk.gov.tr/pdf/ psikoakifmaddeler.pdf (erişim tarihi: 05/03/2014). 2. Aşıcıoğlu, F., Yeni Nesil Psikoaktif Maddeler. Yeni Nesil Psikoaktif Maddeler Sempozyumu Kitabı, 2013:3-5. http://www.atk.gov.tr/Pdf/ psikoakifmaddeler.pdf (erişim tarihi: 05/03/2014). 3. Gaoni, Y., Mechoulam, R., Isolation, Structure and partial synthesis of an active constituent of hashish, J Am. Chem. Soc. 1964, 86, 1646-1647. 4. Howlett, A. C., Barth, F., Bonner, T. I., Cabral, G., Casellas, P., Devane, W. A., Felder, C. C., Herkenham, M., Mackie, K., Martin, B. R., Mechoulam, R., Pertwee, R. G., International Union of Pharmacology. XXVII. Classification of cannabinoid receptors, Pharmacol. Rev. 2002, 54, 161-202. 5. Ashton, C. H., Pharmacology and effects of cannabis: A brief review, Br. J. Psychiatry 2001, 178, 101-106. 6. Pacher, P., Bátkai, S., Kunos, G., The endocannabinoid system as an emerging target of pharmacotherapy, Pharmacol. Rev. 2006, 58, 389-462. 7. Ottani, A., Giuliani, D., HU 210: A potent tool for investigations of the cannabinoid system, CNS Drug Rev. 2001, 7, 131-45. 8. Adams, R., Chen, K. H., Loewe, S., Tetrahydrocannabinol homologs with a s-alkyl group in the 3-Position. XVI, J. Am. Chem. Soc.1945, 67, 1534–1537. 9. Weissman, A., Milne, G. M., Melvin, L. S., Cannabimimetic activity from CP-47,497, aderivative of 3-phenylcyclohexanol, J. Pharm. Exp. Therapy 1982, 223, 516-523. 10. Mechoulam, R., Lander, N., Breuer, A., Zahalka, J., Synthesis of the individual, pharmacologically distinct, enantiomers of a tetrahydrocannabinol derivative, Tetrahedron: Asym. 1990, 1, 315-318. 11. Huffman, J. W., Dai, D., Martin, B. R., Compton, D. R., Design, synthesis and pharmacology of cannabimimetic indoles, Bioorg. Med. Chem. Let. 1994, 4, 563-566. 12. Lan, R., Lu, Q., Fan, P., Gatley, J., Volkow, N. D., Fernando, S. R., Pertwee, R., Makriyannis, A., Design and synthesis of the CB1 selective cannabinoid antagonist AM-281: A potential human SPECT ligand, AAPS Pharm. Sci. 1999, 1, 2, 39–45. 13. UNODC. Synthetic cannabinoids in herbal products. United Nations Office on Drugs and Crime 2011. 14. Akgül, A., Aşıcıoğlu, F., Uyuşturucu maddelerde yeni trendler ve Erken Uyarı Sistemi; Demir, O. Ö., Sever, M., Eds., Örgütlü suçlar ve yeni trendler, Ankara, Polis Akademisi Yayınları, 2011, 29-56. 15. 2013 Türkiye Uyuşturucu Raporu. http://www.kom.gov.tr/Tr/Dosyalar/ 2013 Türkiye Uyuşturucu Raporu (erişim tarihi: 07/03/2014). 16. Gürdal, F., Aşirdizer, M., Aker, R. G., Korkut, S., Göçer, Y., Küçükibrahimoğlu, E. E., Review of detection frequency and type of synthetic cannabinoids in herbal compounds analyzed by Istanbul Narcotic Department of the Council of Forensic Medicine, Turkey, J. Forensic Leg. Med. 2013, 20, 667-672. 17. Karaalp A., Sentetik kannabinoidler (“Bonzai”), Türk Farmakoloji Derneği Bülteni 2015, 127, 5-9. 18. Eker, H., Sentetik Esrar İmalat Ticaret ve Arz Problemi. Yeni Nesil Psiko-Aktif Maddeler Sempozyumu Kitabı 2013, 5-6. http://www.atk.gov.tr/Pdf/psikoakifmaddeler.pdf, (erişim tarihi:05/03/ 2014). 19. Evren, C., Bozkurt, M., Sentetik kannabinoidler: son yılların krizi. Düşünen Adam Psikiyatri ve Nörolojik Bilimler Dergisi 2013, 26, 1-11. 20. TUBİM (2013) Emniyet Genel Müdürlüğü Kaçakçılık ve Organize Suçlarla Mücadele Daire Başkanlığı EMCDDA 2013 Ulusal Raporu (2012 Yılı Verileri): Reitox Ulusal Temas Noktası Türkiye: Yeni Gelişmeler, Trendler, Seçilmiş Konular. Ankara, Türkiye Uyuşturucu ve Uyuşturucu Bağımlılığı İzleme Merkezi. 21. TUBİM Emniyet Genel Müdürlüğü Kaçakçılık ve Organize Suçlarla Mücadele Daire Başkanlığı EMCDDA 2014 Ulusal Raporu (2013 Yılı Verileri): Reitox Ulusal Temas Noktası Türkiye: Yeni Gelişmeler, Trendler, Seçilmiş Konular. Ankara, Türkiye Uyuşturucu ve Uyuşturucu Bağımlılığı İzleme Merkezi, 2014. 22. Auwarter, V., Dresen, S., Weinmann, W., Mueller, M., Puetz, M., Ferreiros, N., ‘Spice’ and other herbal blends: Harmless incense or cannabinoid designer drugs, J. Mass Spect. 2009, 44, 832-837. 23. Pertwee, R. G., Pharmacology of cannabinoid receptor ligands, Curr. Med. Chem. 1999, 6, 635-64. 24. Eminler, A. T., Yıldırım, M., Uslan, M. İ., Köksal, A. Ş., Parlak E., Sentetik kannabinoidler (Bonzai) ve gastrointestinal sistem üzerine etkileri: “Kannabinoid Hiperemezis Sendromu”, Güncel Gastroenteroloji 2014, 18, 459-463. 25. Pacher, P., Mechoulam, R., Is lipid signaling through cannabinoid 2 receptors part of a protective system? Prog. Lipid Res. 2011, 50, 193-211. 26. Seely, K. A., Prather, P. L., James, L. P., Moran, J. H., Marijuana-based drugs: Innovative therapeutics or designer drugs of abuse? Mol. Interv. 2011, 11, 36-51. 27. Gluodenis, T. J., Identification of synthetic cannabinoids in herbal incense blends, Forensic Magazine 2011, 4, 31–35. 28. Penn, H. J., Langman, L. J., Unold, D., Shields, J., Nichols, J. H., Detection of synthetic cannabinoids in herbal incense products, Clin. Biochem. 2011, 44, 1163-1165. 29. Vandrey, R., Dunn, K. E., Fry, J. A., Girling, E. R., A survey study to characterize use of spice products (synthetic cannabinoids), Drug. Alcohol. Depend. 2012, 120, 238-241. 30. Beal, J. E., Olson, R., Laubenstein, L., Morales, J. O., Bellman, P., Yangco, B., Lefkowitz, L., Plasse, T.F., Shepard, K. V., Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS, J. Pain Symptom. Manage. 1995, 10, 89-97. 31. Pertwee, R. G., Pharmacology of cannabinoid CB1 and CB2 receptors, Pharmacol. Ther. 1997, 74, 129-180. 32. Wood, D. M., Dargan, P. I., Novel psychoactive substances: How to understand the acute toxicity associated with the use of these substances, Ther. Drug Monit. 2012, 34, 363-367. 33. Schneir, A. B., Cullen, J., Ly, B. T., “Spice” girls: Synthetic cannabinoid intoxication, J. Emerg. Med. 2011, 40, 296-299. 34. Hoyte, C. O., Jacob, J., Monte, A. A., Al-Jumaan, M., Bronstein, A. C., Heard, K. J., A Characterization of synthetic cannabinoid exposures reported to the national poison data system in 2010, Ann. Emerg. Med. 2012, 60, 435-438. 35. Artuç, S., Doğan, K. H., Demirci, Ş., New trend in narcotic drugs: Synthetic cannabinoid, Adli Tıp Bülteni 2014, 19, 198-203. 36. Seely, K. A., Lapoint, J., Moran, J. H., Fattore, L., Spice drugs are more than harmless herbal blends: A review of the pharmacology and toxicology of synthetic cannabinoids, Progress Neuropsychopharmacol. Biol. Psychiatry 2012, 39, 234-243. 37. Vardakou, I., Pistos, C., Spiliopoulou, C., Spice drugs as a new trend: Mode of action, identification and legislation, Toxicol. Lett. 2010, 197, 157-162. 38. Wood, D. M., Dargan, P. I., Novel psychoactive substances: How to understand the acute toxicity associated with the use of these substances, Ther. Drug Monit. 2012, 34, 363-367. 39. Zuba, D., Byrska, B., Maciow, M., Comparison of “herbal highs” composition, Anal. Bioanal. Chem. 2011, 400, 119-126. 40. Uchiyama, N., Kikura-Hanajiri, R., Ogata, J., Goda, Y., Chemical analysis of synthetic cannabinoids as designer drugs in herbal product, Forensic Sci. Int. 2010, 198, 31-38. 41. Dresen, S., Ferreirós, N., Pütz, M., Westphal, F., Zimmermann, R., Auwärte, V., Monitoring of herbal mixtures potentially containing synthetic cannabinoids as psychoactive compounds, J. Mass Spectrom. 2010, 45, 1186-1194. 42. Simmons, J., Cookman, L., Kang, C., Skinner, C., Three cases of “spice” exposure, Clin. Toxicol. 2011, 49, 431-433. 43. Simmons, J. R., Skinner, C. G., Williams, J., Kang C. S., Schwartz, M. D., Wills, B. K., Intoxication from smoking “spice”, Ann. Emerg. Med. 2011, 57, 187-188. 44. Hudson, S., Ramsey, J., King, L., Timbers, S., Maynard, S., Dargan, P. I., Wood, D. M., Use of high resolution accurate mass spectrometry to detect reported and previously unreported cannabinomimetics in “herbal high” products, J. Anal. Toxicol. 2010, 34, 252-260. 45. Winstock, A. R., Barratt, M. J., Synthetic Cannabis: A comparison of patterns of use and effect profile with natural cannabis in a large global sample, Drug Alcohol Depend. 2013, 131, 106-111. 46. Küçük E, Küçük İ, Kirazaldı Y. Y., A new threat in the emergency department: Synthetic cannabinoids (Bonzai, Jameika), Genel Tıp Dergisi 2015, 25, 18-22. 47. TUBİM Türkiye Uyuşturucu Raporu. Ankara, Türkiye Uyuşturucu ve Uyuşturucu Bağımlılığı İzleme Merkezi 2011. 48. Behonick, G., Shanks, K. G., Firchau, D. J., Mathur, G., Lynch, C. F., Nashelsky, M., Jaskierny, D. J., Meroueh C., Four postmortem case reports with quantitative detection of the synthetic cannabinoid, 5F-PB-22, J. Anal. Toxicol. 2014, 38, 559–562. 49. Sasaki, C., Saito, T., Shinozuka, T., Irie, W., Murakami, C., Maeda, K., Nakamura, N., Oishi, M., Nakamura, S., Kurihara, K., A case of death caused by abuse of a synthetic cannabinoid N-1-naphthalenyl-1-pentyl-1H-indole-3-carboxamide, Forensic Toxicol. 2015, 33,165–169. 50. Castaneto, M. S., Gorelick, D., Desrosiers, N., Hartman R. L., Pirard, S., Huestis, M. A., Synthetic cannabinoids: Epidemiology, pharmacodynamics, and clinical implications, Drug Alcohol Depend. 2014,144, 12-41. 51. Moran, C. L., Le, V. H., Chimalakonda, K. C., Smed¬ley, A. L., Lackey, F. D., Owen, S. N., Kennedy, P. D., Endres, G. W., Ciske, F. L., Kramer, J. B., Korni¬lov, A. M., Bratton, L. D., Dobrowolski, P. J., Wessin¬ger, W. D., Fantegrossi, W. E., Prather, P. L., James, L. P., Radominska-Pandya, A., Moran, J. H., Quantitative measurement of JWH-18 and JWH- 073 metabolites excreted in human urine, Anal. Chem. 2011, 83, 4228-4236. 52. Merola, G., Aturki, Z., D’Orazio, G., Gottardo, R., Macchiaa, T., Tagliaro, F., Fanali, S., Analysis of synthetic cannabinoids in herbal blends by means of nano-liquid chromatography, J. Pharm. Biomed. Anal. 2012, 71, 45- 53. 53. Coulter, C., Garnier, M., Moore, C., Synthetic cannabinoids in oral fluid, J. Anal. Toxicol. 2011, 35, 424-430. 54. Jager, A. D., Warner, J. V., Henman, M., Ferguson, W., LC-MS/MS method for the quantitation of metabolites of eight commonly-used synthetic cannabinoids in human urine an Australian perspective, J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci. 2012, 897, 22-31. 55. Teske, J., Weller, J. P., Fieguth, A., Rothamel, T., Schulz, Y., Tröger, H. D., Sensitive and rapid quantification of the cannabinoid receptor agonist naphthalen-1-yl-(1-pentylindol-3-yl) methanone (JWH-018) in human serum by Liquid Chromatog¬raphy–Tandem Mass Spectrometry, J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2010, 878, 2659-2663. 56. Dresen, S., Kneisel, S., Weinmann, W., Zimmermann, R., Auwärter, V., Development and validation of a Liquid Chromatography-Tandem Mass Spectrometry Method for the quantitation of synthetic cannabinoids of the aminoalkylindole type and methanandamide in serum and its application to fo¬rensic samples, J. Mass Spectrom. 2011, 46, 163-171. 57. Gregori, A., Damiano, F., Bonavia, M., Mileo, V., Varani, F., Monfreda, M., Identification of two cannabimimetic compounds WIN48098 and AM679 in illegal products, Sci. Jus.2013, 53, 286–292. 58. Özkanlı, F., Synthetic cannabinoids, FABAD J. Pharm. Sci. 2017, 42, 67-80. 59. Özşeker Efeoğlu, P., Dip, A., Dağlıoğlu, N., Gülmen, M. K., Synthetic Cannabinoids: A new generation marihuana, Türk Aile Hek. Derg. 2017, 21, 1, 34-40 60. Hu, X., Primack, B. A., Barnett, T. E., Cook, R. L., College students and the use of K2: An emerging drug of abuse in young persons, Subst. Abuse Treat. Prev. Policy 2011, 6, 1, 16-17. 61. Hoyte, C. O., Jacob, J., Monte, A. A., Al-Jumaan, M., Bronstein, A. C., Heard, K. J., A characterization of synthetic cannabinoid exposures reported to the national poison data system in 2010, Ann. Emerg. Med. 2012, 60, 4, 435-438. 62. Barratt, M. J., Cakic, V., Lenton, S, Patterns of synthetic cannabinoid use in Australia, Drug Alcohol Rev. 2013, 32, 141-46. 63. Bozkurt, M., Umut, G., Evren, C., Karabulut, V., Clinical characteristics and laboratory test results of patients admitted to outpatient clinic for synthetic cannabinoid usage, J. Psychiatry Neurol. Sci. 2014, 27, 328-334. 64. Mutlu, E., Alnıak, İ., Aksoy, U. M., Erkıran, M., The use of synthetic cannabinoids among probation population, J. For. Med. 2015, 29, 3, 169-178. 65. Karadeniz, H., Bayrak Elvan, H., Turna Ö., Şahin C., Çakıroğlu F., Arslan A. E., The evaluation of cases using synthetic cannabinoid in Trabzon and the surrounding provinces, J. For. Med. 2017 (doi: 10.5505/adlitıp.2017.45822) 66. UNODC, Recommended methods for the identification and analysis of synthetic cannabinoid receptor agonistsin seized materials, http://www.unodc.org/ documents/ scientific/STNAR 48_Synthetic_ Cannabinoids_ENG.pdf, (Erişim tarihi:12/03/2014). 67. Bertan, A., [Early Warning System] Türkiye Uyuşturucu ve Uyuşturucu Bağımlılığı İzleme Merkezi, 2010, 188-190. 68. 2013 Türkiye Uyuşturucu Raporu. Türkiye Uyuşturucu ve Uyuşturucu Bağımlılığı İzleme Merkezi, 2013. 69. Resmî Gazete. Bakanlar Kurulu Kararı, 29259 Sayı; 6 Şubat 2015. 70. Castellanos, D., Thornton, G., Synthetic cannabinoid use: recognition and management, J. Psychiatr. Pract. 2012, 18, 86-93.