Ethanol/cocaine interaction: Cocaine and cocaethylene plasma concentrations and their relationship to subjective and cardiovascular effects

Perez‐Reyes, Mario; Jeffcoat, A

doi:10.1016/0024-3205(92)90224-d

Cited by 147 publications

(72 citation statements)

References 16 publications

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“…Postmortem studies link lethal overdose with cocaethylene (Jatlow et al, 1991), which has been estimated to increase the risk of sudden death by 18-25 fold when compared to cocaine alone (Andrews, 1997). Cocaethylene has pharmacological properties that are similar to those of cocaine (Jatlow et al, 1991;McCance-Katz et al, 1998;McCance-Katz et al, 1993), and controlled studies report that the combined use of cocaine and alcohol produces more euphoria than cocaine alone (Farre et al, 1993;McCance-Katz et al, 1998;Perez-Reyes & Jeffcoat, 1992). Aside from using alcohol to enhance cocaine euphoria, these patients also drink to counter irritability and insomnia produced by cocaine binges.…”

Section: Introductionmentioning

confidence: 99%

Gender differences with high-dose naltrexone in patients with co-occurring cocaine and alcohol dependence

Pettinati

Kampman

Lynch

et al. 2008

Journal of Substance Abuse Treatment

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This is a randomized, double blind, placebo-controlled clinical trial that evaluated the efficacy of a higher than typical daily dose of naltrexone (150mg/day), taken for 12 weeks, in 164 patients (n=116 men and n=48 women) with co-occurring cocaine and alcohol dependence. Patients were stratified by gender, and then randomly assigned to naltrexone or placebo, and to either cognitive behavioral therapy, or a type of medical management. The two primary outcomes were cocaine and alcohol use. Significant gender by medication interactions were found for cocaine use via urine drug screens [3-way with time] and self-reports [2-way], for drug severity [2-way], and for alcohol use [2-way]. Type of psychosocial treatment did not affect outcomes. Thus, 150mg/day of naltrexone added to a psychosocial treatment resulted in reductions in cocaine and alcohol use, and drug severity in men, compared to higher rates of cocaine and alcohol use and drug severity in women.

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Section: Introductionmentioning

confidence: 99%

Gender differences with high-dose naltrexone in patients with co-occurring cocaine and alcohol dependence

Pettinati

Kampman

Lynch

et al. 2008

Journal of Substance Abuse Treatment

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“…A number studies in the laboratory setting have assessed the interaction between alcohol and stimulants with inconclusive results, including the following combinations: ethanol and caffeine (Kerr et al, 1991), ethanol andcocaine (PerezReyes andJeffcoat, 1992;Farré et al, 1993Farré et al, , 1997Higgins et al, 1993;McCance-Katz et al, 1993), and ethanol and dextroamphetamine or metamphetamine Mendelson et al, 1995). Although in some studies, stimulants reduced the intoxication ratings, the drunkenness scores, or the deleterious effects of alcohol on psychomotor performance, significant pharmacological changes were not found in other investigations.…”

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confidence: 99%

3,4-Methylenedioxymethamphetamine (Ecstasy) and Alcohol Interactions in Humans: Psychomotor Performance, Subjective Effects, and Pharmacokinetics

Hernández-López

Farré²,

Roset³

et al. 2002

J Pharmacol Exp Ther

145

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3,4-Methylenedioxymethamphetamine (MDMA) is frequently consumed in association with alcohol. The effect of this combination in humans has not been previously investigated. Nine male healthy volunteers received single oral doses of 100 mg of MDMA plus 0.8 g/kg ethanol, 100 mg of MDMA, 0.8 g/kg of ethanol, and placebo in a double blind, double dummy, randomized crossover trial. Measurements included psychomotor performance, subjective effects, and pharmacokinetics. Plasma concentrations of MDMA showed a 13% increase after the use of alcohol, whereas plasma concentrations of alcohol showed a 9 to 15% decrease after MDMA administration. The MDMA-alcohol combination induced longer lasting euphoria and well being than MDMA or alcohol alone. MDMA reversed the subjective sedation induced by alcohol but did not reduce drunkenness feelings. MDMA did not reverse the actions of alcohol on psychomotor abilities. Combined use of MDMA and alcohol causes dissociation between subjective and objective sedation. Subjects may feel euphoric and less sedated and might have the feeling of doing better, but actual performance ability continues to be impaired by the effect of alcohol. Confirmation of these findings in further studies will be highly relevant in terms of road safety.

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“…16,27 One proposed mechanism for increased cardiac toxicity of CϩE is that cocaine metabolism is decreased in the presence of ethanol, creating higher serum concentrations of cocaine. 3,4,14 This may be due to increased bioavailability of cocaine in the presence of ethanol, and the route and order of administration may play a role. 13,14,28,29 We did not observe a statistically significant increase in serum cocaine levels in the dogs receiving concomitant ethanol and do not believe that increased serum cocaine levels explain the hemodynamic or electrocardiographic changes we observed.…”

Section: Discussionmentioning

confidence: 99%

“…ACADEMIC EMERGENCY MEDICINE 2001; 8:211-222 C OCAINE and ethanol are the two most commonly abused drugs in the United States. 1,2 Twelve million Americans have used both cocaine and ethanol on a regular basis, 3,4 and when cocaine is abused, ethanol is also ingested 60-90% of the time. 1 Cocaine and ethanol in combination have been suggested to be more toxic than either drug alone.…”

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confidence: 99%

Untitled

2001

Academic Emergency Medicine

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Abstract. Objectives: Simultaneous abuse of cocaine and ethanol affects 12 million Americans annually. In combination, these substances are substantially more toxic than either drug alone. Their combined cardiac toxicity may be due to independent effects of each drug; however, they may also be due to cocaethylene (CE), a cocaine metabolite formed only in the presence of ethanol. The purpose of this study was to delineate the role of CE in the combined cardiotoxicity of cocaine and ethanol in a model simulating their abuse. Methods: Twenty-three dogs were randomized to receive either 1) three intravenous (IV) boluses of cocaine 7.5 mg/kg with ethanol (1 g/kg) as an IV infusion (CϩE, n = 8), 2) three cocaine boluses only (C, n = 6), 3) ethanol infusion only (E, n = 5), or 4) placebo boluses and infusion (n = 4). Hemodynamic measurements, electrocardiograms, and serum drug concentrations were obtained at baseline, and then at fixed time intervals after each drug was administered. Results: Two of eight dogs in the CϩE group experienced cardiovascular collapse.The most dramatic hemodynamic changes occurred after each cocaine bolus in the CϩE and C only groups; however, persistent hemodynamic changes occurred in the CϩE group. Peak CE levels were associated with a 45% (SD Ϯ 22%, 95% CI = 22% to 69%) decrease in cardiac output (p < 0.05), a 56% (SD Ϯ 23%, 95% CI = 32% to 80%) decrease in dP/dt max (p < .006), and a 23% (SD Ϯ 15%, 95% CI = 7% to 49%) decrease in SVO 2 (p < 0.025). Ventricular arrhythmias were primarily observed in the CϩE group, in which four of eight dogs experienced ventricular tachycardia. Conclusions: Cocaine and ethanol in combination were more toxic than either substance alone. Co-administration resulted in prolonged cardiac toxicity and was dysrhythmogenic. Peak serum cocaethylene concentrations were associated with prolonged myocardial depression.

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Ethanol/cocaine interaction: Cocaine and cocaethylene plasma concentrations and their relationship to subjective and cardiovascular effects

Cited by 147 publications

References 16 publications

Gender differences with high-dose naltrexone in patients with co-occurring cocaine and alcohol dependence

Gender differences with high-dose naltrexone in patients with co-occurring cocaine and alcohol dependence

3,4-Methylenedioxymethamphetamine (Ecstasy) and Alcohol Interactions in Humans: Psychomotor Performance, Subjective Effects, and Pharmacokinetics

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