COCAETHYLENE AS A HAIR BIOMARKER TO PREDICT HEAVY ALCOHOL EXPOSURE AMONG COCAINE USERS
Main Article Content
Keywords
Cocaethylene, hair testing, high-risk population, biomarker, cocaine, benzoylegconine, FAEE
Abstract
Background
Cocaethylene (CE) is a cocaine metabolite formed during alcohol and cocaine co-consumption. There are no previous studies to assess the effectiveness of hair CE as a biomarker indicating chronic alcohol consumption among individuals who have consumed cocaine.
Objectives
To establish the ability of CE to predict chronic alcohol use among individuals testing positive for cocaine.
Methods
We studied all cases referred to our laboratory where both chronic cocaine and alcohol consumption were sought, and values of hair cocaine, benzoylegconine (BE), CE, and FAEEs (as marker of chronic alcohol consumption ) were available. Cocaine, BE and CE were screened by ELISA and confirmed using headspace-solid phase microextraction (HS-SPME) and GC-MS. FAEE were analyzed using HS-SPME and GC-MS/EI. Sensitivity, specificity, and predictive values of CE as a marker of alcohol consumption among cocaine users were calculated using different FAEE cutoffs.
Results
Cocaine (P<0.001) and BE (P<0.001) concentrations were associated with increased FAEE. The positive predictive value of CE to identify alcohol consumption was 0.66 for excessive drinking and 0.76 for chronic drinking among positive cocaine users. Negative CE ruled out almost completely excessive alcohol consumption.
Conclusion
Positive hair CE results had high specificity for chronic excessive alcohol consumption among cocaine users. With no established safe level of alcohol in pregnancy, identification of CE in hair of pregnant women who have used cocaine can serve as a biomarker for fetal alcohol spectrum disorder.
References
2. Trends in the Prevalence of Marijuana, Cocaine, and Other Illegal Drug Use National YRBS: 1991-2009 [U.S. Department of Health and Human Services at the Centre for Disease Control and Prevention website]. 2010. Available at:http://www.cdc.gov/healthyyouth/yrbs/pdf/us_drug_trend_yrbs.pdf. Accessed November 12,2011.
3. Youth Risk Behaviour Surveillance 2009 [U.S. Department of Health and Human Services at the Centre for Disease Control and Prevention website]. 2010. Available at: http://www.cdc.gov/mmwr/pdf/ss/ss5905.pdf. Accessed November 12, 2011.
4. InfoFacts from the National Institute on Drug Abuse. Nationwide Trends 2009 survey [National Institute of Health and U.S. Department of Health and Human Services at the Centre for Disease Control and Prevention website]. 2010. Available at: http://drugabuse.gov/pdf/infofacts/NationTrends .pdf. Accessed November 12, 2011.
5. Brookoff D, Raotondo MF, Shaw LM. Cocaethylene levels in patients who test positive for cocaine. Ann Emerg Med 1996;27:316-320.
6. McCance-Katz EF, Price LH, Dougle CJ, Kosten TR, Black JE, Jatlow PI. Concurrent cocaine–ethanol ingestion in humans: pharmacology, physiology, behavior, and the role of cocaethylene. Psychopharmacology (Berl) 1993;111:39–46.
7. Higgins ST, Rush CR, Bickel WK, Hughes JR, Lynn M, Capeless MA. Acute behavioral and cardiac effects of cocaine and alcohol combinations in humans. Psychopharmacology (Berl) 1993;111: 285–94.
8. McCance EF, Price LH, Kosten TR, Black JE, Jatlow PI. Cocaethylene: pharmacology, physiology and behavioral effects in humans. J Pharmacol Exp Ther 1995;274:215–23.
9. Hearn WL, Flynn DD, Hime GW, Rose S, Cofino JC, Mantero-Atienza E, Wetli CV, Mash DC. Cocaethylene: a unique cocaine metabolite displays high affinity for the dopamine Transporter. J Neurochem 1991;56(2):698-701.
10. Harris DS, Everhart ET, Mendelson J, Jones RT. The pharmacology of cocaethylene in humans following cocaine and ethanol administration. Drug Alcohol Depend 2003;72:169–182.
11. Hart C L, Jatlow P., Sevarino KA, McCance- Katz EF. Comparison of intravenous cocaethylene and cocaine in humans. Psychopharmacology (Berl). 2000;149:153–162.
12. Jeffcoat AR, Perez-Reyes M, Hill JM, Sadler BM, Cook CE. Cocaine disposition in humans after intravenous injection, nasal insufflations (snorting), or smoking. Drug Metab Dispos 1989;17: 153-159.
13. Bailey DN. Serial plasma concentrations of cocaethylene, cocaine, and ethanol in trauma victims. J Anal Toxicol 1993;17:79-83.
14. Farre M, De La Torre R, Gonzales ML, Teran MT, Roset PN, Menoyo E, Cami J. Cocaine and alcohol interactions in humans: Neuroendocrine effects and cocaethylene metabolism. J Pharmacol Exp Ther 1997;283:164–176.
15. Swift R. Direct measurement of alcohol and its metabolites. Addiction 2003;98(Suppl 2):273- 280.
16. Kulaga V, Gareri J, Fulga N, Koren G. Agreement between the fatty acid ethyl ester hair test for alcohol and social workers' reports. Ther Drug Monit 2010;32(3): 294-299.
17. Pragst F, Rothe M, Moench B, Hastedt M, Herre S, Simmert D. Combined use of fatty acid ethyl esters and ethyl glucuronide in hair for diagnosis of alcohol abuse: interpretation and advantages. Forensic Sci Int 2010;196(1-3):101-110.
18. Süsse S, Selavka CM, Mieczkowski T, Pragst F. Fatty acid ethyl ester concentrations in hair and self-reported alcohol consumption in 644 cases from different origin. Forensic Sci Int 2010;196(1-3): 111-117.
19. Haller DL, Acosta MC, Lewis D, Miles DR, Schiano T, Shapiro PA, Gomez J, Sabag-Cohen S, Newville H. Hair analysis versus conventional methods of drug testing in substance abusers seeking organ transplantation. Am J Transplant 2010;5:1305-1311.
20. Laposata M. Fatty acid ethyl esters: ethanol metabolites which mediate ethanol-induced organ damage and serve as markers of ethanol intake. Prog Lipid Res 1998;37:307–316.
21. Yegles M, Labarthe A, Auwärter V, Hartwig S, Vater H, Wennig R, Pragst F. Comparison of ethyl glucuronide and fatty acid ethyl ester concentrations in hair of alcoholics, social drinkers, and teetotallers. Forensic Sci Int 2004;145(2-3):167-173.
22. Cooper GA. Hair testing is taking root. Ann Clin Biochem 2011;48(Pt 6):516-30.
23. Pragst F, Balikova MA. State of the art in hair analysis for detection of drug and alcohol abuse. Clin Chim Acta 2006;370(1-2):17-49.
24. Aleksa K, Walasek P, Fulga N, Kapur B, Gareri J, Koren G. Simultaneous detection of seventeen drugs of abuse and metabolites in hair using solid phase micro extraction (SPME) with GC/MS. Forensic Sci Int. 2011;[Epub Ahead of Print]
25. Kulaga V, Velazquez-Armenta Y, Aleksa K, Vergee Z, Koren G. The effect of hair pigment on the incorporation of fatty acid ethyl esters (FAEE). Alcohol Alcohol 2009;44(3):287-92.
26. Farré M, de la Torre R, Llorente M, Lamas X, Ugena B, Segura J, Camí J. Alcohol and cocaine interactions in humans. J Pharmacol Exp Ther 1993;266(3):1364-73.
27. Perez-Reyes M. The order of drug administration: its effects on the interaction between cocaine and ethanol. Life Sci 1994;55(7):541-50.
28. Henderson GL, Harkey MR, Zhou C. Incorporation of isotopically labeled cocaine into human hair: race as a factor. J Anal Toxicol 1998;22:156-165.
29. Laizure SC, Mandrell T, Gades NM, Parker RB. Cocaethylene metabolism and interaction with cocaine and ethanol: role of carboxylesterases. Drug Metab Dispos 2003;31(1):16-20.
30. McCance-Katz EF, Price LH, McDougle CJ, Kosten TR, Black JE, Jatlow PI. Concurrent cocaine-ethanol ingestion in humans: pharmacology, physiology, behavior, and the role of cocaethylene. Psychopharmacology (Berl) 1993;111(1):39-46.
31. Scheidweiler KB, Cone EJ, Moolchan ET, Huestis MA. Dose-related distribution of codeine, cocaine, and metabolites into human hair following controlled oral codeine and subcutaneous cocaine administration. J Pharmacol Exp Ther 2005;313(2):909-15.
32. Goldberger BA, Cone EJ, and Kadehjian L. Unsuspected ethanol ingestion through soft drinks and flavored beverages. J Anal Toxicol 1996;20:332–333.
33. Hubbard DL, Wilkins DG, Rollins DE. The incorporation of cocaine and metabolites into hair: effects of dose and hair pigmentation. Drug Metab Dispos 2000;28(12):1464-1469.
34. Gossop M, Manning V, Ridge G. Concurrent use and order of use of cocaine and alcohol: behavioural differences between users of crack cocaine and cocaine powder. Addiction 2006;101(9): 1292-1298.