Difficulties interpreting concentrations in fatal cases: example of 2,5-dimethoxy-4-chloroamphetamine

Springer Science and Business Media LLC - Tập 40 - Trang 383-392 - 2022
Benedicte Lelievre1, Vincent Dupont2,3, Celine Buchaillet2,4, Nathalie Jousset2, Marie Deguigne5, Vincent Cirimele6
1Laboratoire de Pharmacologie-Toxicologie, CHU Angers, Angers, France
2Service de Médecine Légale et Pénitentiaire, CHU Angers, Angers, France
3Service de Médecine Légale, CHU Rennes, Rennes, France
4Unité Médico Judiciaire, CHI Créteil, Créteil, France
5Centre Anti Poison, CHU Angers, Angers, France
6Laboratoire ChemTox, Illkirch, France

Tóm tắt

Death related to the use of drugs is evident when drugs are detected in biological matrices within toxic levels, but sometimes it can be less obvious. Intoxications after 2,5-dimethoxy-4-chloroamphetamine (DOC) use are occurring but up to date, only one fatality has been reported. Here we present the case of a young woman admitted to hospital as she presented vomiting, convulsions and cardiorespiratory arrest. Blood ethanol concentration was determined using gas chromatography with flame ionization detection and toxicological screenings (blood, gastric content and hair samples) were performed using liquid chromatography with diode array detection, gas chromatography or liquid chromatography with mass spectrometry detection. Her health state declined with cardiac troubles, organs failure and cerebral edema till death occurring 4 days later. The autopsy revealed the presence of hemorrhagic infiltration inside the left ventricle, pulmonary edema and hemorrhagic infiltration of the terminal ileum. The analysis of biological fluids confirmed the presence of DOC (< 10 ng/mL in cardiac blood sample), buprenorphine, cocaine and cannabis metabolites. The analysis of hair highlighted a history of drugs abuse. In the absence of evident identified cause, the hypothesis of a death due to acute drugs use within a history of chronic consumption of drugs has been put forward. The concentration of some substances such as new psychoactive substances can be low in biological matrices but the toxic effects can be additive and lead to death even within young people, hence the importance of the knowledge of consumption history.

Tài liệu tham khảo

Giorgetti A, Busardò FP, Tittarelli R, Auwärter V, Giorgetti R (2020) Post-mortem toxicology: a systematic review of death cases involving synthetic cannabinoid receptor agonists. Front Psychiat 11:464. https://doi.org/10.3389/fpsyt.2020.00464

Logan BK, Mohr ALA, Friscia M, Krotulski AJ, Papsun DM, Kacinko SL, Ropero-Miller JD, Huestis MA (2017) Reports of adverse events associated with use of novel psychoactive substances, 2013–2016: a review. J Anal Toxicol 41(7):573–610

UNODC (2020) Early warning advisory on new psychoactive substances, www.unodc.org/LSS/Page/NPS/pharmacology. Consulted 15 December 2020.

European Monitoring Centre for Drugs and Drug Addiction (2018) European drug report 2018: trends and developments. Publications Office of the European Union, Luxembourg

European Monitoring Centre for Drugs and Drug Addiction (2021) European drug report 2021: trends and developments. Publications Office of the European Union, Luxembourg

World Health Organization (2019) Critical review report: DOC (4-chloro-2,5-dimethoxyamfetamine). Expert committee on drug dependence. Forty-second meeting. Geneva, 21–25 October 2019. www.who.int/medicines/access/controlled-substances/Final_DOC.pdf?ua=1. Consulted 8 November 2020.

Calzada JN, Hernandez RR, Cebollada SD, Murillo EC, Guillen SM, Dufol AF (2015) Acute poisoning by DOC (2,5 dimethoxy-4-chloroamphetamine): report of 6 cases presenting together at the emergency department. Clin Tox 53:362

Shulgin A, Shulgin A (1991) PiHKAL: a chemical love story. Transform Press, Berkeley, CA

Burish MJ, Thoren KL, Madou M, Toossi S, Shah M (2015) Hallucinogens causing seizures? A case report of the synthetic amphetamine 2,5-dimethoxy-4-chloroamphetamine. Neurohospitalist 5:32–34. https://doi.org/10.1177/1941874414528939

Luethi D, Liechti ME (2020) Designer drugs: mechanism of action and adverse effects. Arch Toxicol 94(4):1085–1133. https://doi.org/10.1007/s00204-020-02693-7

Barnett RY, Baker DD, Kelly NE, McGuire CE, Fassette TC, Gorniak JM (2014) A fatal intoxication of 2,5-dimethoxy-4-chloroamphetamine: a case report. J Anal Toxicol 38(8):589–591. https://doi.org/10.1093/jat/bku087

Turcant A, Prémel-Cabic A, Cailleux A, Allain P (1991) Toxicological screening of drugs by microbore high-performance liquid chromatography with photodiode-array detection and ultraviolet spectral library searches. Clin Chem 37(7):1210–1215

Matuszewski BK, Constanzer ML, Chavez-Eng CM (2003) Strategies for the assessment of matrix effect in quantitative bioanalyticalmethods based on HPLC-MS/MS. Anal Chem 75:3019–3030

Abbara C, Ferec S, Leroux G, Bretaudeau-Deguigne M, Lelievre B, Boels D, Turcant A (2017) 2,5-dimethoxy-4-chloroamphetamine, a LSD-like designer drug: clinical and analytical documentation of non-fatal exposure in five patients. Toxicol Anal Clin 28:S26. https://doi.org/10.1016/j.toxac.2017.01.002

Cirimele V, Sachs H, Kintz P, Mangin P (1996) Testing human hair for cannabis. III rapid screening procedure for simultaneous identification of THC, cannabinol, and cannabidiol. J Anal Toxicol 20:13–16

SOHT (Society of Hair Testing) (2019) Consensus for the use of alcohol markers in hair for supporting the assessment of abstinence and chronic alcohol consumption. www.soht.org/images/pdf/Revision_2019_Alcoholmarkers.pdf. Consulted 15 October 2021.

Ovaska H, Viljoen A, Puchnarewicz M, Button J, Ramsey J, Holt DW et al (2008) First case report of recreational use of 2,5-dimethoxy-4-chloroamphetamine confirmed by toxicological screening. Eur J Emerg Med 15:354–356. https://doi.org/10.1097/MEJ.0b013e3282fc765b

Aknouche F, Ameline A, Kernalleguen A, Arbouche N, Maruejouls C, Kintz P (2021) Toxicological investigations in a death involving 2,5-dimethoxy-4-chloamphetamine (DOC) performed on an exhumed body. J Anal Toxicol 45(5):e1–e7. https://doi.org/10.1093/jat/bkaa112

Pepin G, Gaillard Y (1997) Concordance between self-reported drug use and findings in hair about cocaine and heroin. Forensic Sci Int 84(1–3):37–41

Pergolizzi JV Jr, Magnusson P, LeQuang JAK, Breve F, Varrassi G (2021) Cocaine and cardiotoxicity: a literature review. Cureus 13(4):e14594. https://doi.org/10.7759/cureus.14594

Kim ST, Park T (2019) Acute and chronic effects of cocaine on cardiovascular health. Int J Mol Sci 20(3):584. https://doi.org/10.3390/ijms20030584

Tsatsakis A, Docea AO, Calina D, Tsarouhas K, Zamfira LM, Mitrut R, Sharifi-Rad J, Kovatsi L, Siokas V, Dardiotis E, Drakoulis N, Lazopoulos G, Tsitsimpikou C, Mitsias P, Neagu M (2019) A mechanistic and pathophysiological approach for stroke associated with drugs of abuse. J Clin Med 8(9):1295. https://doi.org/10.3390/jcm8091295

Vitcheva V (2012) Cocaine toxicity and hepatic oxidative stress. Curr Med Chem 19(33):5677–5682. https://doi.org/10.2174/092986712803988929

Glauser J, Queen JR (2007) An overview of non-cardiac cocaine toxicity. J Emerg Med 32(2):181–186. https://doi.org/10.1016/j.jemermed.2006.05.044

Musshoff F, Schwarz G, Sachs H, Skopp G, Franz T (2020) Concentration distribution of more than 100 drugs and metabolites in forensic hair samples. Int J Legal Med 134(3):989–995. https://doi.org/10.1007/s00414-020-02259-3

Feigin VL, Forouzanfar MH, Krishnamurthi R, Mensah GA, Connor M, Bennett DA et al (2013) Global burden of diseases, injuries, and risk factors study 2010 (GBD 2010) and the GBD Stroke Experts Group. Global and regional burden of stroke during 1990–2010: findings from the global burden of disease study 2010. Lancet 383:245–254

Wolff V, Jouanjus E (2017) Strokes are possible complications of cannabinoids use. Epilep Behav 70:355–363

World Health Organization. Cannabis. www.who.int/teams/mental-health-and-substance-use/alcohol-drugs-and-addictive-behaviours/drugs-psychoactive/cannabis. Consulted 8 November 2020

Matey JM, Moreno de Simon MD, García-Ruiz C, Montalvo G (2019) A validated GC–MS method for ketamine and norketamine in hair and its use in authentic cases. Forensic Sci Int 301:447–454. https://doi.org/10.1016/j.forsciint.2019.04.039

Kintz P (2010) Consensus of the Society of Hair Testing on hair testing for chronic excessive alcohol consumption. Forensic Sci Int 196(1–3):2. https://doi.org/10.1016/j.forsciint.2009.12.031

Cirimele V, Kintz P, Lohner S, Ludes B (2000) Buprenorphine to norbuprenorphine ratio in human hair. J Anal Toxicol 24(6):448–449. https://doi.org/10.1093/jat/24.6.448

Pirro V, Fusari I, Di Corcia D, Gerace E, De Vivo E, Salomone A, Vincenti M (2014) Hair analysis for long-term monitoring of buprenorphine intake in opiate withdrawal. Ther Drug Monit 36(6):796–807. https://doi.org/10.1097/FTD.0000000000000078

Tracqui A, Kintz P, Ludes B (1998) Buprenorphine-related deaths among drug addicts in France: a report on 20 fatalities. J Anal Toxicol 22(6):430–434. https://doi.org/10.1093/jat/22.6.430

Cirimele V, Kintz P, Ludes B (1997) Screening for forensically relevant benzodiazepines in human hair by gas chromatography-negative ion chemical ionization-mass spectrometry. J Chromatogr B Biomed Sci Appl 700(1–2):119–129. https://doi.org/10.1016/s0378-4347(97)00337-x

Kronstrand R, Forsman M, Roman M (2018) Quantitative analysis of drugs in hair by UHPLC high resolution mass spectrometry. Forensic Sci Int 283:9–15. https://doi.org/10.1016/j.forsciint.2017.12.001

Johansen SS, Dang LTVL, Nielsen MKK, Haage P, Kugelberg FC, Kronstrand R (2020) Temporal patterns of tramadol in hair after a single dose. Forensic Sci Int 316:110546. https://doi.org/10.1016/j.forsciint.2020.110546

Verri P, Rustichelli C, Palazzoli F, Vandelli D, Marchesi F, Ferrari A, Licata M (2015) Tramadol chronic abuse: an evidence from hair analysis by LC tandem MS. J Pharm Biomed Anal 102:450–458. https://doi.org/10.1016/j.jpba.2014.10.002

Cheze M, Gaulier JM (2014) Drugs involved in drug-facilitated crimes (DFC) analytical aspects. 2–hair. In: Kintz P (ed) Toxicological aspects of drug-facilitated crimes. Elsevier, Paris, pp 181–218

Ezaki J, Ayako R, Hasegawa MTM, Kibayashi K (2016) Fatal overdose from synthetic cannabinoids and cathinones in Japan: demographics and autopsy findings. Am J Drug Alcohol Abuse 42(5):520–529. https://doi.org/10.3109/00952990.2016.1172594

Yamaori S, Okamoto Y, Yamamoto I, Watanabe K (2011) Cannabidiol, a major phytocannabinoid, as a potent atypical inhibitor for CYP2D6. Drug Metab Dispos 39(11):2049–2056. https://doi.org/10.1124/dmd.111.041384

Maurer HH, Sauer C, Theobald DS (2006) Toxicokinetics of drugs of abuse: current knowledge of the isoenzymes involved in the human metabolism of tetrahydrocannabinol, cocaine, heroin, morphine, and codeine. Ther Drug Monit 28(3):447–453. https://doi.org/10.1097/01.ftd.0000211812.27558.6e

Gallelli L, Gratteri S, Siniscalchi A, Cione E, Sirico S, Seminara P, Caroleo MC, De Sarro G (2017) Drug-drug interactions in cocaine-users and their clinical implications. Curr Drug Abuse Rev 10(1):25–30. https://doi.org/10.2174/1874473710666170920143344

Müller CP, Homberg JR (2015) The role of serotonin in drug use and addiction. Behav Brain Res 277:146–192. https://doi.org/10.1016/j.bbr.2014.04.007

Thông tin
Thông tin xuất bản

Springer Science and Business Media LLC

Tập 40

383-392

Thông tin tác giả