Poster Number-75 - Cocaethylene: When Cocaine Meets Alcohol

Polysubstance drug use may be more the norm than taking individual recreational substances and a common pairing is cocaine with alcohol. Even among users, it is not widely appreciated that cocaine and alcohol interact together in important and potentially dangerous ways. When cocaine and ethanol are taken together, a psychoactive metabolite known as cocaethylene is produced which as similar pharmacological and psychoactive properties as cocaine, but it is more toxic to the cardiovascular and hepatic systems and has a longer plasma elimination half-life. For those consuming alcohol plus cocaine, it is often not possible to predict the serum concentration of cocaethylene in the body because the timing of ingestion of alcohol and cocaine as well as relative quantities play a role.


While cocaethylene is frequently encountered by first responders and emergency medical professionals, it has not been thoroughly studied and many clinicians are not aware of it, its role in overdose toxicity, cocaine-induced heart disease, and driving under the influence.  The purpose of our poster is to describe cocaethylene and its role in complicating overdose care.


Methods: This is a narrative review of the literature intended to raise awareness about cocaethylene and its possible effects on clinical outcomes of cocaine-using patients. Using cocaethylene as the keyword, the PubMed database was searched (473 results) and further articles were obtained using the “similar features” option in PubMed. When results were narrowed to the past five years, there were 63 total results. We searched Embase (542 results), Web of Science (2 results), and Cochrane Library (17 meta-analyses). We reviewed all of these materials in order to present a comprehensive overview of what cocaethylene is, how it occurs, and why clinicians need to consider it when treating patients who may have overdosed on cocaine.

Results:

Taking ethanol alters the metabolic pathway of cocaine; instead of hydrolysis with water, the cocaine undergoes transesterification with ethanol and produced cocaethylene. This is the only known situation in which a novel psychoactive substance is created entirely within the body. The overall effects of cocaethylene are like those of cocaine and the two molecules are structurally and chemically similar.

Consuming cocaine and ethanol together reduces clearance of both substances by about 20%.¹ Cocaethylene, like the parent drug, blocks dopamine reuptake and reinforces the stimulating effects of dopamine, contributing to the feelings of energy and focus. While cocaethylene and cocaine are equipotent in terms of producing the feelings of excitement and focus, cocaethylene has a much longer half-life ands its effects persist longer. While cocaine appears to block serotonin reuptake, cocaethylene is more selective for dopamine reuptake inhibition.

Cocaethylene increases blood pressure and heart rate to a greater extent than cocaine and is considered ten times as cardiotoxic.²  Cocaethylene worsens outcomes for trauma patients because of its deleterious hemodynamic and systemic effects.^3,4

The popularity of alcohol plus cocaine may be due to the fact that alcohol seems to prolong cocaine’s psychoactive effects. The phenomenon of polysubstance abuse is not well studied.


The clinical implications are concerning. When clinicians treat patients with cocaine intoxication, they should ask about alcohol use and consider that there may be a potent and potentially cardiotoxic metabolite. A patient who is still experiencing psychoactive effects long after consumption of cocaine may be experiencing the effects of cocaethylene, with a half-life about double that of the parent drug. Greater education is needed for substance users, even recreational drug users, as well as families, friends, and clinicians.


Conclusion: Cocaethylene is the only psychoactive substance produced entirely in the human body and it occurs when ethanol and cocaine are taken together. Considered far more cardiotoxic than cocaine and with a much longer half-life, cocaethylene is an important clinical consideration when treating patients with cocaine intoxication. While the psychoactive effects of cocaine and cocaethylene are similar (focus, energy, enthusiasm), cocaethylene is a more selective dopamine reuptake inhibitor. Greater awareness is needed among recreational drug users and clinicians. Clinicians may sometimes treat patients who appear to be under the influence of cocaine long after they have consumed it; such patients may be experiencing the prolonged and potentially dangerous effects of cocaethylene.

References: 1. 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.
2. Wilson LD, Jeromin J, Garvey L, Dorbandt A. Cocaine, ethanol, and cocaethylene cardiotoxity in an animal model of cocaine and ethanol abuse. Acad Emerg Med. 2001;8(3):211-222.
3. Brotto V, Lee G. Substance use and its implications for the critical care nurses: a literature review. Intensive Crit Care Nurs. 2007;23(2):64-70.
4. Oliveira KD, Fraga GP, Baracat ECE, et al. Prevalence of cocaine and derivatives in blood and urine samples of trauma patients and correlation with injury severity: a prospective observational study. Eur J Trauma Emerg Surg. 2019;45(1):159-165.