Cocaethylene Levels in Patients Who Test Positive for Cocaine

doi:10.1016/S0196-0644(96)70266-4

Annals of Emergency Medicine

Volume 27, Issue 3, March 1996, Pages 316-320

Presented in part at the Society for Academic Emergency Medicine Annual Meeting, San Francisco, May 1993.

https://doi.org/10.1016/S0196-0644(96)70266-4 Get rights and content

Abstract

Study objective: To determine the presence of cocaethylene, an active metabolite of the combination of cocaine and ethanol, among trauma patients who test positive for cocaine. Methods: We assembled a case series of 416 consecutive urban trauma center patients with major trauma. Urine was tested for the presence of the cocaine metabolite benzoylecgonine. Plasma was quantitatively assayed for cocaine, ethanol, and cocaethylene. Results: Of the study subjects, 158 (38%) were positive for benzoylecgonine. Of the 114 of these subjects who had adequate plasma specimens, 68 (60%) tested positive for cocaethylene (mean, 41±27 ng/mL; range, 3 to 213 ng/mL), all tested positive for cocaine (mean, 92.9±52 ng/mL), and 56% were positive for ethanol (mean, 175±85 mg/dL). We found poor correlation between admission levels of cocaethylene and cocaine (R=.02), even when subjects were stratified by ethanol level. The correlation between cocaethylene and ethanol levels was weak (R=.24). Of the 68 patients who tested positive for cocaethylene, 29% tested negative for ethanol. Plasma was also assayed from 94 subjects who tested negative for benzoylecgonine; 9% had detectable levels of cocaine, and 2% had detectable levels of cocaethylene. Conclusion: Cocaethylene was present in more than half of the subjects who tested positive for cocaine. [Brookoff D, Rotondo MF, Shaw LM, Campbell EA, Fields L: Cocaethylene levels in patients who test positive for cocaine. Ann Emerg Med March 1996;27:316-320.]

Section snippets

INTRODUCTION

Most cocaine users report that they use cocaine concurrently with ethanol.¹ The simultaneous use of these two drugs has spawned an epidemic of dual addiction.² The production of cocaethylene, an active metabolite of the combination of cocaine and ethanol, may sustain this pattern of drug use.² Cocaethylene is a potent stimulant3, 4 that enhances and extends the effects of cocaine.³

The results of animal studies show that cocaethylene is more toxic than cocaine2, 5, and the findings of studies in

MATERIALS AND METHODS

We carried out this study at the Hospital of the University of Pennsylvania between July 1991 and April 1992. The treatment protocol for patients seen in the ED with major trauma (defined as Injury Severity Score greater than 16) included sampling of blood and urine for toxicology testing. The complete toxicology screen included analysis of serum for volatile alcohols by means of head-space gas chromatography and testing of urine by the use of enzyme-multiplied immunoassay techniques (EMIT

RESULTS

During the study period, 450 patients presented with major trauma; 416 underwent urine toxicology testing. Of the patients tested, 158 (38%) were positive for benzoylecgonine. One hundred fourteen of these patients (72%) had plasma samples adequate for quantitative analysis of cocaine, ethanol, and cocaethylene. The remaining patients had inadequate plasma samples and were excluded from analysis. The Table shows the characteristics of these groups.

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Of the 114

DISCUSSION

We found that more than half of the patients who tested positive for cocaine also tested positive for cocaethylene. Spot levels of cocaine and ethanol were not good predictors of the presence or level of cocaethyelene. Nearly a third of the subjects who tested positive for cocaethylene tested negative for ethanol. It has already been shown that cocaine and cocaethylene do not interfere with the measurement of ethanol in serum.⁶ We also found that urine screening for benzoylecgonine was a

Acknowledgements

The authors are grateful to Arthur L Kellermann, MD, MPH, and Stephen T Miller, MD, for reviewing the manuscript; and to Bela B Hackman, MD, for help with statistical analysis.

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Crack-cocaine addiction is an important public health problem worldwide. Although there is not a consensus, preliminary evidence has suggested that cognitive impairments in patients with crack-cocaine dependence persist during abstinence, affecting different neuropsychological domains. However, few studies have prospectively evaluated those deficits in different phases of abstinence.
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These water-soluble metabolites are excreted in the urine. The frequent concomitant use of cocaine and ethanol results in the hepatic formation of the active metabolite, cocaethylene, which has euphoric and sympathomimetic effects similar to cocaine but may also have greater toxicity.6,7 The longer half-life of cocaethylene (2.5 hours) may prolong the euphoric effects of cocaine.
Increased serum brain-derived neurotrophic factor is predictive of cocaine relapse outcomes: A prospective study
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Cocaine dependence is associated with high relapse rates, but few biological markers associated with relapse outcomes have been identified. Extending preclinical research showing a role for central brain-derived neurotrophic factor (BDNF) in cocaine seeking, we examined whether serum BDNF is altered in abstinent, early recovering, cocaine-dependent individuals and whether it is predictive of subsequent relapse risk.
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High correlations in serum BDNF across days indicated reliable and stable serum BDNF measurements. Significantly higher mean serum BDNF levels were observed for the cocaine-dependent patients compared with healthy control participants (p < .001). Higher serum BDNF levels predicted shorter subsequent time to cocaine relapse (hazard ratio: 1.09, p < .05), greater number of days (p < .05), and higher total amounts of cocaine used (p = .05).
High serum BDNF levels in recovering cocaine-dependent individuals are predictive of future cocaine relapse outcomes and may represent a clinically relevant marker of relapse risk. These data suggest that serum BDNF levels may provide an indication of relapse risk during early recovery from cocaine dependence.
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Cocaine and alcohol are frequently co-abused. The majority of cocaine users (up to 90%) report co-administering EtOH during cocaine binges (Brookoff et al., 1996; Magura and Rosenblum, 2000). The high prevalence of co-abuse of alcohol with cocaine in humans has been postulated to be predicated upon both a common genetic factor that predispose an organism to abuse multiple substances, including alcohol, and the interaction of the drugs within the organism (Uhl, 2004, 2006; Uhl et al., 2008).
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Stress was assessed in 36 inpatient treatment engaged CD individuals and 36 demographically matched healthy control (HC) participants using the Perceived Stress Scale (PSS) and repeated morning salivary cortisol levels over three consecutive days. The Rey Auditory Verbal Learning Test (RAVLT) was conducted to measure verbal learning, memory, and executive function. Prospective assessment of cocaine use outcomes during 90 days following discharge from inpatient treatment was also conducted.
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^☆: From the Departments of Medicine*, Surgery^‡, Clinical Pathology and Laboratory Medicine^§, and Nursing^∥, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania.

^☆☆: Address for reprints: Daniel Brookoff, MD, PhD, Department of Medical Education, Methodist Hospital, 1265 Union Avenue, Memphis, Tennessee 38104, 901-726-8255, Fax 901-726-8254

^★: Reprint no. 47/1/70881

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Cocaethylene Levels in Patients Who Test Positive for Cocaine☆,☆☆,★

Abstract

Section snippets

INTRODUCTION

MATERIALS AND METHODS

RESULTS

DISCUSSION

Acknowledgements

Drug Alcohol Depend

Life Sci

Pharm Biochem Behavior

Life Sci

Life Sci

Ann Emerg Med

Cocaethyelene: Unique cocaine metabolite displays high affinity for the dopamine transporter

J Neurochem

Comparative behavioral pharmacology and toxicology of cocaine and its ethanol derived metabolite, cocaine ethyl-ester

Life Sci

Drug Abuse Warning Network: Annual Emergency Room Data