Topical Issues of Toxicology and Laboratory Identification of Synthetic Cannabinoids (Prepared According to the European Monitoring Centre for Drugs and Drug Addiction — EMCDDA)
The emergence of new smoking herbal products laced with synthetic cannabinoids can be considered as a new development in the field of designer drugs. In many countries, where spices and similar substances are available, they have become a significant problem. Government measures to control smoking blends for the last 10 years have been actively developed and implemented in Austria, Germany, France, Luxembourg, Poland, Lithuania, Sweden and are under consideration in other member states of the European Union. Nevertheless, a huge number of available and at the same time potentially dangerous psychotropic synthetic cannabinoids means that the activities carried out by states to control are ineffective.
Currently, little is known about the pharmacology, toxicology and safety of these compounds for humans. Types and amount of added synthetic cannabinoids in products may vary considerably, and some of the compounds may be active in very low doses that forms the possibility of accidental overdose with risk of severe psychiatric complications. In addition, the emergence of full cannabinoid receptor antagonists may lead to life-threatening conditions. Increase in the number of acute poisonings with synthetic cannabinoids and high hospital mortality require immediate search for effective methods of intensive care and laboratory diagnosis, bringing today the problem of synthetic cannabinoids in priority task of clinical toxicology and intensive care.
Cases of acute poisonings with smoking blends are observed in Kyiv over the past 5 years. In the group of poisonings with psychotropic drugs, herbal mixtures comprise about 1 %. Deaths during the period of 2012–2014 were not observed. Age of victims, predominantly males, was recorded in the range of 18 to 39 years. The clinical picture is characterized by lesions of the central nervous system, hallucinations, agitation, motor activity. Intensive therapy consists of a symptomatic treatment aimed at preventing complications from respiratory and cardiovascular systems; specific antidotes and pharmacological antagonists were not used. Test systems for detecting narcotic drugs and psychotropic substances in the urine didn’t give positive results, in a few cases there was a positive test for marijuana. According to the regional departments for the treatment of poisonings, there are registered very severe cases of poisonings with lethal outcome. In severe cases, the characteristic pattern is brain edema, respiratory and circulatory failure. In the described clinical manifestations of acute central nervous system damage, an analogy with severe and irreversible damages arising in cases of poisoning with inhaled drugs (glue BF) has been noted.
Free distribution of smoking mixtures is a significant toxicological problem. Complexity of toxic-chemical identification of products does not allow timely detection of toxic components and development of appropriate therapeutic measures. Variability of the chemical composition of smoking mixtures makes them potentially dangerous to the consumer. Such effects of mixtures as carcinogenicity, the ability to form a physical dependency remain unexplored. Mass poisonings among young people, high levels of deaths require to consider the problem of the distribution of dangerous products with the participation of all interested parties. Collaborative researches of toxicologists, forensics, clinicians, state control bodies will help to create an effective system to prevent undesirable consequences which may occur as a result of the use of designer drugs.
Full Text:PDF (Русский)
Ahmedzai S., Carlyle D., Calder I., Moran F. Anti-emetic efficacy and toxicity of nabilone, a synthetic cannabinoid, in lung cancer chemotherapy // British Journal of Cancer. — 1983. — 48. — 657-663.
Arntson A., Ofsa B., Lancaster D., Simon J.R., McMullin M., Logan B. Validation of a novel immunoassay for the detection of synthetic cannabinoids and metabolites in urine specimens // J. Anal. Toxicol. — 2013. — 37. — 284-287.
Aung M.M., Griffin G., Huffman J.W. et al. Influence of the N-1 alkyl chain length of cannabimimetic indoles upon CB (1) and CB (2) receptor binding // Drug Alcohol Depend. — 2000. — 60. — 133-40.
Auwärter V., Dresen S.,WeinmannW. et al. «Spice» and other herbal blends: harmless incense or cannabinoid designer drugs? // J. Mass Spectrom. — 2009. — 44. — 832-7.
Ashton J.C., Wright J.L., McPartland J.M., Tyndall J.D.A. Cannabinoid CB1 and CB2 receptor ligand specificity and the development of CB2-selective agonists // Curr. Med. Chem. — 2008. — 15. — 1428-43.
Atwood B.K., Mackie K. CB2: A cannabinoid receptor with an identity crisis // Brit. J. Pharmacol. — 2010. — 160. — 467.
Banerji S., Deutsch C.M., Bronstein A.C. Spice ain’t so nice // Clin. Toxicol. Phila. — 2010. — 48. — 632.
Bebarta V., Ramirez S., Varney S. Spice: A new «legal» herbal mixture abused by young active duty military personnel // Subst. Abuse. 2012. — 33. — 191.
Castellanos D., Singh S., Thornton G., Avila M., Moreno A. Synthetic cannabinoid use: A case series of adolescents // J. Adolescent Health. — 2011. — 49. — 347.
Cohen J., Morrison S., Greenberg J., Saidinejad M. Clinical presentation of intoxication due to synthetic cannabinoids // Pediatrics. — 2012. — 129. — e1064.
Compton D.R., Rice K.C., De Costa B.R., Razdan R.K., Melvin L.S., Johnson M.R., Martin B.R. Cannabinoid structure-activity relationships: Correlation of receptor binding and in vivo activities // J. Pharmacol. Exp. Ther. — 1993. — 265. — 218.
European Monitoring Centre for Drugs and Drug Addiction (EMCDDA). Forensic identification, pharmacology and toxicology of synthetic cannabinoids // Thematic papers. Understanding the 'Spice' phenomenon. — Lisbon: European Monitoring Centre for Drugs and Drug Addiction, 2009. — Available at: http://www.emcdda.europa.eu/publications/thematic-papers/spice.
Every-Palmer S. Synthetic cannabinoid JWH-018 and psychosis: An explorative study // Drug Alcohol Depen. — 2011. — 117. — 152.
Faircloth J., Khandheria B., Shum S. Case report: Adverse reaction to synthetic marijuana // Am. J. Addict. — 2012. — 21. — 289.
Felder C.C., Joyce K.E., Briley E.M., Mansouri J., Mackie K., Blond O., Lai Y., Ma A.L., Mitchell R.L. Comparison of the pharmacology and signal transduction of the human cannabinoid CB1 and CB2 receptors // Mol. Pharmacol. — 1995. — 48. — 443.
Forrester M., Kleinschmidt K., Schwarz E., Young A. Synthetic cannabinoid and marijuana exposures reported to poison centers // Hum. Exp. Toxicol. — 2012. — 31. — 1006.
Forrester M., Kleinschmidt K., Schwarz E., Young A. Synthetic cannabinoid exposures reported to Texas poison centers // J. Addict. Dis. — 30. — 351. — 2011.
Frank B., Serpell M.G., Hughes J., Matthews J.N.S., Kapur D. Comparison of analgesic effects and patient tolerability of nabilone and dihydrocodeine for chronic neuropathic pain: randomised, crossover, double blind study // Brit. Med. J. — 2008. — 336. — 199.
Gunderson E., Haughey H., Alt-Daoud N., Joshi A., Hart C. «Spice» and «K2» herbal highs: A case series and systematic review of the clinical effects and biopsychosocial implications of synthetic cannabinoid use in humans // Am. J. Addict. — 2012. — 21. — 320.
Heath T., Burroughs Z., Thompson J., Tecklenburg F. Acute intoxication caused by a synthetic cannabinoid in two adolescents // J. Pediatr. Pharmacol. Ther. — 2012. — 17. — 177.
Henquet C., Krabbendam L., Spauwen J., Kaplan C., Lieb R., Wittchen H.U., Van Os J. Prospective cohort study of cannabis use, predisposition for psychosis, and psychotic symptoms in young people // BMJ. — 2005. — 330. — 11.
Hermanns-Clausen M., Kneisel S., Hutter M., Szabo B., Auwärter V. Acute intoxication by synthetic cannabinoids — Four case reports // Drug Test. Anal. — 2013. — 5. — 790.
Hopkins C.Y., Gilchrist B.L. A case of cannabinoid hyperemesis syndrome caused by synthetic cannabinoids // J. Emerg. Med. — 2013. — 45. — 544.
Howlett A.C., Breivogel C.S., Childers S.R., Deadwyler S.A., Hampson R.E., Porrino L.J. Cannabinoid physiology and pharmacology: 30 years of progress // Neuropharmacology. — 2004. — 47. — 345.
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.
Huffman J., Zengin G., Wu M., Lu J., Hynd G., Bushell K., Thompson A., Bushell S., Tartal C., Hurst D. et al. Structureactivity relationships for 1-alkyl-3-(1-naphthoyl)indoles at the cannabinoid CB1 and CB2 receptors: Steric and electronic effects of naphthoyl substituents. New highly selective CB2 receptor agonists // Bioorg. Med. Chem. — 2005. — 13. — 89.
Huffman J.W., Dai D., Martin B.R., Compton D.R. Design, synthesis and pharmacology of cannabimimetic indoles // Bioorg. Med. Chem. Lett. — 1994. — 4. — 563.
Huffman J.W., Szklennik P.V., Almond A., Bushell K., Selley D.E., He H., Cassidy M.P., Wiley J.L., Martin B.R. 1-Pentyl-3-phenylacetylindoles, a new class of cannabimimetic indoles // Bioorg. Med. Chem. Lett. — 2005. — 15. — 4110.
Hoffman A.F., Lupica C.R. Mechanisms of cannabinoid inhibition of GABAA synaptic transmission in the hippocampus // J. Neurosci. — 2000. — 20. — 2470-9.
Huffman J.W., Marriott K.C. Recent advances in the development of selective ligands for the cannabinoid CB(2) receptor // Curr. Top. Med. Chem. — 2008. — 8. — 187-204.
Hurst D., Loeffler G., McLay R. Psychosis associated with synthetic cannabinoid agonists: A case series // Am. J. Psychiatry. — 168. — 1119. — 46.
Jankovics P., Váradi A., Tölgyesi L., Lohner S., Németh-Palotás J., Balla J. 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. — 2012. — 214. — 27. 33. Jiang W., Zhang Y., Xiao L., Van Cleemput J., Ji S., Bai G., Zhang X. Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepressant-like effects // J. Clin. Invest. — 2005. — 115. — 3104.
Jinwala F.N., Gupta M. Synthetic cannabis and respiratory depression // J. Child Adol. Psychop. — 2012. — 22. — 459.
Johnston L.D., O’Malley P.M., Bachman J.G., Schulenberg J.E. The Rise in Teen Marijuana Use Stalls, Synthetic Marijuana Use Levels, and Use of «Bath Salts» Is Very Low (a Monitoring the Future report) // http://www.monitoringthefuture.org/data/12data.html(accessed November 15, 2013)
Kikura-Hanajiri R., Uchiyama N., Kawamura M., Ogata J., Goda Y. Prevalence of new designer drugs and their legal status in Japan // Yakugaku Zasshi. — 2013. — 133. — 31.
King J., Singleton N., Howard R. Analogue Controls: An Imperfect Law; UK Drug Policy Commission // http://www.ukdpc.org.uk/publication/analogue-controls-an-imperfectlaw/ (accessed November 15, 2013)
Kuster J.E., Stevenson J.I., Ward S.J., D’Ambra T.E., Haycock D.A. Aminoalkylindole binding in rat cerebellum: selective displacement by natural and synthetic cannabinoids // J. Pharmacol. Exp. Ther. — 1993. — 264. — 1352.
Lapoint J., James L., Moran C., Nelson L., Hoffman R., Moran J. Severe toxicity following synthetic cannabinoid ingestion // Clin. Toxicol. — 2011. — 49. — 760.
Laaris N., Good C.H., Lupica C.R. D9-tetrahydrocannabinol is a full agonist at CB1 receptors on GABA neuron axon terminals in the hippocampus // Neuropharmacology. — 2010. — 59. — 121-7.
Little P.J., Compton D.R., Johnson M.R., Melvin L.S., Martin B.R. Pharmacology and stereoselectivity of structurally novel cannabinoids in mice // J. Pharmacol. Exp. Ther. — 1988. — 247. — 1046.
Logan B.K. Marijuana and driving impairment / ElSohly M.A. (Ed.) Marijuana and the Cannabinoids, Chap 12; Humana Press: Totowa, N.J., 2007.
Logan B.K., Reinhold L.E., Xu A., Diamond F.X. Identification of synthetic cannabinoids in herbal incense blends in the United States // J. Forensic. Sci. — 2012. — 57. — 1168.
Maccarrone M., Valensise H., Bari M., Lazzarin N., Romanini C., Finazzi-Agrò A. Relation between decreased anandamide hydrolase concentrations in human lymphocytes and miscarriage // Lancet. — 2000. — 355. — 1326.
Matsuda L.A., Lolait S.J., Brownstein M.J., Young A.C., Bonner T.I. Structure of a cannabinoid receptor and functional expression of the cloned cDNA // Nature. — 1990. — 346. — 561.
McLaughlin P., Lu D., Winston K., Thakur G., Swezey L., Makriyannis A., Salamone J. Behavioral effects of the novel cannabinoid full agonist AM 411 // Pharmacol. Biochem. Behav. — 2005. — 81. — 78.
McQuade D., Huds Gay M., Vardakou I., Pistos C., Spiliopoulou C. Spice drugs as a new trend: mode of action, identification and legislation // Toxicol. Lett. — 2010. — 197. — 157-62.
Mc Carberg B.H., Barkin R.L. The future of cannabinoids as analgesic agents: a pharmacologic, pharmacokinetic, and pharmacodynamic overview // Am. J. Ther. — 2007. — 14. — 475-83.
Pertwee R.G. Pharmacology of cannabinoid receptor ligands // Curr. Med. Chem. — 1999. — 6. — 635-64.
Pertwee R.G. Cannabinoid pharmacology: the first 66 years // Br. J. Pharmacol. — 2006. — 147(Suppl 1). — Р. 163-71.
Pertwee R.G. The pharmacology of cannabinoid receptors and their ligands: an overview // Int. J. Obes. (Lond). — 2006. — 30(Suppl 1). — Р. 13-8.
Thornton S.L., Wood C., Friesen M.W., Gerona R.R. Synthetic cannabinoid use associated with acute kidney injury // Clin. Toxicol. — 2013. — 51. — 189.
Tofighi B., Lee J.D. Internet highs — Seizures after consumption of synthetic cannabinoids purchased online // J. Addict. Med. — 2012. — 6. — 240.
Tung C.K., Chiang T.P., Lam M. Acute mental disturbance caused by synthetic cannabinoid: A potential emerging substance of abuse in Hong Kong // East Asian Arch. Psychiatry. — 2012. — 22. — 31.
Van Sickle M.D., Duncan M., Kingsley P.J. et al. Identification and functional characterization of brainstem cannabinoid CB2 receptors // Science. — 2005. — 310. — 329-32.
Vardakou I., Pistos C., Spiliopoulou C. Spice drugs as a new trend: mode of action, identification and legislation // Toxicol. Lett. — 2010. — 197. — 157-62.
Van der Veer N., Friday J. Persistent psychosis following the use of Spice // Schizophr. Res. — 2011. — 130. — 285.
Vandrey R., Dunn K.E., Fry J.A., Girling E.R. A survey study to characterize use of Spice products (synthetic cannabinoids) // Drug Alcohol Depen. — 2012. — 120. — 238.
Wiley J.L., Marusich J.A., Lefever T.W., Grabenauer M., Moore K.N., Thomas B.F. Cannabinoids in disguise: Δ(9)-Tetrahydrocannabinol-like effects of tetramethylcyclopropyl ketone indoles // Neuropharmacology. — 2013. — 75C. — 145.
Wiley J.L., Marusich J.A., Martin B.R., Huffman J.W. 1-Pentyl-3-phenylacetylindoles and JWH-018 share in vivo cannabinoid profiles in mice // Drug Alcohol. Depen. — 2012. — 123. — 148.
Wintermeyer A., Müller I., Thevis M. et al. In vitro phase I metabolism of the synthetic cannabimimetic JWH-018 // Anal. Bioanal. Chem. — 2010. — 398. — 2141-53.
Yeakel J.K., Logan B.K. Blood synthetic cannabinoid concentrations in cases of suspected impaired driving // J. Anal. Toxicol. — 2013.
Young A.C., Schwarz E., Medina G., Obafemi A., Feng S.Y., Kane C., Kleinschmidt K. Cardiotoxicity associated with the synthetic cannabinoid, K9, with laboratory confirmation // Am. J. Emerg. Med. — 2012. — 30. — e5.
Zimmermann U.S., Winkelmann P.R., Pilhatsch M., Nees J.A., Spanagel R., Schulz K. Withdrawal phenomena and dependence syndrome after the consumption of «Spice Gold» // Deut Ärzteblatt Int. — 106. — 464. — 20.
- There are currently no refbacks.
Copyright (c) 2016 EMERGENCY MEDICINE
This work is licensed under a Creative Commons Attribution 4.0 International License.
© Publishing House Zaslavsky, 1997-2018