Cocaine and Alcohol Interactions in Humans: Neuroendocrine Effects and Cocaethylene Metabolism1
- Magí Farré,
- Rafael De La Torre,
- María L. González,
- María T. Terán,
- Pere N. Roset,
- Esther Menoyo and
- Jordi Camí
- Department of Pharmacology and Toxicology, Institut Municipal d’Investigació Mèdica (IMIM), Autonomous University of Barcelona, Barcelona, Spain
Abstract
The effects of 100 mg of intranasal cocaine in acute alcohol intoxication (0.8 g/kg) were evaluated in eight experienced and nondependent healthy volunteers in a double-blind double-dummy, controlled, randomized, crossover clinical study. The combination of alcohol and cocaine produced greater increases in HR, rate-pressure product and pleasurable-related subjective effects (euphoria, well-being) compared with the effects of cocaine. The drug combination reduced the alcohol-induced sedation, but feelings of drunkenness were not significantly counteracted. Cardiovascular changes induced by the combination condition caused an increase in myocardial oxygen consumption that may be related to an increased risk of cardiovascular toxicity. The augmented subjective euphoria may explain why the drug combination is more likely to be abused than is cocaine or alcohol alone. Plasma cortisol concentrations were significantly higher after concomitant alcohol and cocaine use than with cocaine alone. The administration of cocaine did not alter alcohol-induced hyperprolactinemia. Although cocaine produced a slight decrease in plasma concentrations of prolactin when administered alone, it did not antagonize the effects of alcohol on prolactin secretion when alcohol and cocaine were given simultaneously. The combination increased cocaine and norcocaine plasma concentrations, and induced the synthesis of cocaethylene and norcocaethylene. The enhancement of cocaine effects in the drug combination may be due to initially increased cocaine plasma levels followed by the additive effect of cocaethylene, although a pharmacodynamic interaction could not be excluded.
Footnotes
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Send reprint requests to: Dr. Jordi Camí, Institut Municipal d’InvestigacióMèdica (IMIM), Autonomous University of Barcelona, Doctor Aiguader 80, E-08003 Barcelona, Spain.
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↵1 This work was supported by grants from ’Fondo de Investigación Sanitaria’ (92/0152), CIRIT (GRQ93-9303) and CITRAN Foundation. Preliminary findings were presented in part at the 56th Annual Scientific Meeting of the Committee on Problems of Drug Dependence, June 1994, Palm Beach, Florida, and at the 57th Annual Scientific Meeting of the Committee on Problems of Drug Dependence, June 1995, Scottsdale, Arizona.
- Abbreviations:
- A
- amphetamine group
- ACTH
- adrenocorticotropic hormone
- ANOVA
- analysis of variance
- ARCI
- Addiction Research Center Inventory
- AUC
- area under the curve
- BG
- benzedrine group
- CRF
- corticotropin-releasing factor
- FPIA
- fluorescence polarization immunoassay
- HR
- heart rate
- LSD
- lysergic acid dyethylamine group
- MBG
- morphine-benzedrine group
- MEIA
- microparticle enzyme immunoassay
- PCAG
- pentobarbital-chlorpromazine-alcohol group
- TRH
- thyrotropin-releasing hormone
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- Received October 14, 1996.
- Accepted June 23, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
