Cocaethylene (ethylbenzoylecgonine) is the ethylester of benzoylecgonine. It is structurally similar to cocaine, which is the methyl ester of benzoylecgonine. Cocaethylene is formed by the liver in small amounts when cocaine and ethanol coexist in the blood.[1] In 1885, cocaethylene was first synthesized (according to edition 13 of the Merck Index),[2] and in 1979, cocaethylene's side effects were discovered.[3]
Metabolic production from cocaine
Cocaethylene is the byproduct of concurrent consumption of alcohol and cocaine as metabolized by the liver. Normally, metabolism of cocaine produces two primarily biologically inactivemetabolites—benzoylecgonine and ecgonine methyl ester. The hepatic enzyme carboxylesterase is an important part of cocaine's metabolism because it acts as a catalyst for the hydrolysis of cocaine in the liver, which produces these inactive metabolites. If ethanol is present during the metabolism of cocaine, a portion of the cocaine undergoes transesterification with ethanol, rather than undergoing hydrolysis with water, which results in the production of cocaethylene.[1]
Although it cannot be bought, cocaethylene is largely considered recreational in and of itself, with stimulant, euphoriant, anorectic, sympathomimetic, and local anesthetic properties with a longer duration of action than cocaine.[9][10] A 2000 study by Hart et al. on the effects of intravenous cocaethylene in humans found that "cocaethylene has pharmacological properties in common with cocaine, but is less potent," consistent with prior research.[9]
Risks
While cocaethylene is more dangerous when administered alone, research suggests that the increase in risk from combining cocaine and ethanol is "thought to be due to alcohol decreasing the metabolism of cocaine and, therefore, increasing [...] cocaine concentrations with only a minimal (if any) contribution to an increased risk from the formation of cocaethylene".[11]
Use in research about combined use of cocaine and alcohol
Some studies[12][13] suggest that consuming alcohol in combination with cocaine may be more cardiotoxic than cocaine and "it also carries an 18 to 25 fold increase over cocaine alone in risk of immediate death".[10]
Cocaethylene has been used as a biomarker for simultaneous alcohol and cocaine consumption. A 2021 study used this technique to show that people who consume alcohol and cocaine together have a higher risk of liver fibrosis.[14]
^ abLaizure SC, Mandrell T, Gades NM, Parker RB (January 2003). "Cocaethylene metabolism and interaction with cocaine and ethanol: role of carboxylesterases". Drug Metabolism and Disposition. 31 (1): 16–20. doi:10.1124/dmd.31.1.16. PMID12485948.
^Jatlow P, McCance EF, Bradberry CW, Elsworth JD, Taylor JR, Roth RH (August 1996). "Alcohol plus cocaine: the whole is more than the sum of its parts". Therapeutic Drug Monitoring. 18 (4): 460–464. doi:10.1097/00007691-199608000-00026. PMID8857569.
^Perez-Reyes M, Jeffcoat AR, Myers M, Sihler K, Cook CE (December 1994). "Comparison in humans of the potency and pharmacokinetics of intravenously injected cocaethylene and cocaine". Psychopharmacology. 116 (4): 428–432. doi:10.1007/bf02247473. PMID7701044. S2CID6558411.
^Wilson LD, Jeromin J, Garvey L, Dorbandt A (March 2001). "Cocaine, ethanol, and cocaethylene cardiotoxity in an animal model of cocaine and ethanol abuse". Academic Emergency Medicine. 8 (3): 211–222. doi:10.1111/j.1553-2712.2001.tb01296.x. PMID11229942.
^Farré M, de la Torre R, Llorente M, Lamas X, Ugena B, Segura J, Camí J (September 1993). "Alcohol and cocaine interactions in humans". The Journal of Pharmacology and Experimental Therapeutics. 266 (3): 1364–1373. doi:10.1016/S0022-3565(25)39392-4. PMID8371143.
^Tamargo, J. A., Sherman, K. E., Sékaly, R. P., Bordi, R., Schlatzer, D., Lai, S., Khalsa, J. H., Mandler, R. N., Ehman, R. L., & Baum, M. K. (2022). Cocaethylene, simultaneous alcohol and cocaine use, and liver fibrosis in people living with and without HIV. Drug and alcohol dependence, 232, 109273. https://doi.org/10.1016/j.drugalcdep.2022.109273
Landry MJ (1992). "An overview of cocaethylene, an alcohol-derived, psychoactive, cocaine metabolite". Journal of Psychoactive Drugs. 24 (3): 273–276. doi:10.1080/02791072.1992.10471648. PMID1432406.
Hearn WL, Rose S, Wagner J, Ciarleglio A, Mash DC (June 1991). "Cocaethylene is more potent than cocaine in mediating lethality". Pharmacology, Biochemistry, and Behavior. 39 (2): 531–533. doi:10.1016/0091-3057(91)90222-N. PMID1946594. S2CID36163843.
Hearn WL, Flynn DD, Hime GW, Rose S, Cofino JC, Mantero-Atienza E, et al. (February 1991). "Cocaethylene: a unique cocaine metabolite displays high affinity for the dopamine transporter". Journal of Neurochemistry. 56 (2): 698–701. doi:10.1111/j.1471-4159.1991.tb08205.x. PMID1988563. S2CID35719923.
