The Effect of Methamphetamine on Biotransformation of Ethanol: Pilot Study

O. Zendulka 1 , 2 , M. Sabová 1 , 3 , J. Juřica 1 , 3 , M. Machalíček 4 , P. Švéda 4 , M. Farková 4 , und A. Šulcová 1
  • 1 Masaryk University in Brno, Central European Institute of Technology, Experimental and Applied Neuropsychopharmacology research group
  • 2 Masaryk University in Brno, Faculty of Medicine, Department of Pharmacology, Czech Republic
  • 3 Masaryk University in Brno, Faculty of Medicine, Department of Pharmacology
  • 4 Masaryk University in Brno, Faculty of Science, Department of Chemistry


Methamphetamine is one of the most popular recreational drugs in Central Europe and is often combined with ethanol. Various interactions between these two substances have been described including the influence of administered ethanol on biotransformation of methamphetamine. The aim of the present study was to describe the opposite effect - the influence of methamphetamine on biotransformation of ethanol in rats. Methamphetamine was administered for 10 days (10 mg/kg/day) i.p. and ethanol was delivered as an intragastric bolus (2 g/kg) on the10th day of experiment to both methamphetamine administered rats and control animals. The pharmacokinetic experiment on the whole animal was performed and plasma samples were drawn at the 40th, 120th, 210th and 300th minute after ethanol administration. Ethanol plasmatic levels reached significantly lower values in the 40th and 120th interval when compared to controls. Differences were insignificant in the last two intervals. Our results suggest that chronic methamphetamine administration induces ethanol biotransformation. We suppose that this effect is caused by induction of alcohol dehydrogenase metabolic activity or by allosteric interaction of methamphetamine and this enzyme. More studies have to be conducted to confirm or disprove our hypothesis.

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  • Boleda MD, Julia P, Moreno A, Pares X. Role of Extrahepatic Alcohol-Dehydrogenase in Rat Ethanol-Metabolism. Arch Biochem Biophys. 1989;274:74-81.

  • Caldwell J, Dring LG, Williams RT. Metabolism of [C-14]Methamphetamine in Man, Guinea-Pig and Rat. Biochem J. 1972;129:11-22.

  • Dostalek M, Hadasova E, Hanesova M, et al. Feet of methamphetamine on the pharmacokinetics of dextromethorphan and midazolam in rats. Eur J Drug Metab Pharmacokinet. 2005;30:195-201.

  • Dostalek M, Jurica J, Pistovcakova J, et al. Effect of methamphetamine on cytochrome P450 activity. Xenobiotica. 2007;37:1355-1366.

  • EMCDDA - European Monitoring Centre for Drugs and Drug Addiction. Problem amphetamine and methamphetamine use in Europe. 978-92-9168-450-2. ( Acessed August 28, 2012

  • Gutierrez-Lopez MD, Llopis N, Feng S, Barrett DA, O'Shea E, Colado MI. Involvement of 2-arachidonoyl glycerol in the increased consumption of and preference for ethanol of mice treated with neurotoxic doses of methamphetamine. Br J Pharmacol. 2010;160:772-783.

  • Holt S. Observations on the Relation between Alcohol Absorption and the Rate of Gastric-Emptying. CMAJ. 1981;124:267-277.

  • Chuang JY, Chang WT, Cherng CFG, Kao GS, Yu L. Repeated co-administrations of alcohol- and methamphetamine-produced anxiogenic effect could be associated with the neurotoxicity in the dentate gyrus. Journal Neural Transm. 2011;118:1559-1569.

  • Liang M, Liu Y, Zheng N, Ananda S, Liu L. Distribution of methamphetamine and its metabolite amphetamine in acute and subacute ethanol-methamphetamine combination abuse model rats. J Anal Toxicol. 2012;36:30-35.

  • Lieber CS. Ethanol metabolism, cirrhosis and alcoholism. Clinica Chimica Acta. 1997;257:59-84.

  • Lin LY, Kumagai Y, Hiratsuka A, et al. Cytochrome P4502D Isozymes Catalyze the 4- Hydroxylation of Methamphetamine Enantiomers. Drug Metab Dispos. 1995;23:610-614.

  • McGehee RE, Ronis MJJ, Cowherd RM, Ingelman-Sundberg M, Badger TM. Characterization of Cytochrome-P450 2E1 Induction in a Rat Hepatoma Fgc-4 Cell Model by Ethanol. Biochem Pharmacol. 1994;48:1823-1833.

  • Mendelson J, Jones RT, Upton R, Jacob P 3rd. Methamphetamine and ethanol interactions in humans. Clin Pharmacol Ther. 1995;57:559-568.

  • Minarikova V, Hadasova E, Möritz K, Scheuch E, Siegmund E. Comparison of the influence of methamphetamine and phenobarbital on the activity of hepatic microsomal monooxygenases in the rat. Homeostasis in Health and Disease. 2006;44:135-137.

  • Nishiguchi M, Kinoshita H, Taniguchi T, et al. Effects of chronic alcohol administration on changes of extracellular dopamine and serotonin concentration induced by methamphetamine-comparison of two different alcohol preference rat lines. Nihon Arukoru Yakubutsu Igakkai Zasshi. 2002;37:555-576.

  • Ronis MJJ, Huang JA, Crouch J, et al. Cytochrome-P450 Cyp-2E1 Induction during Chronic Alcohol Exposure Occurs by a 2-Step Mechanism Associated with Blood- Alcohol Concentrations in Rats. J Pharmacol Exp Ther. 1993;264:944-950.

  • SAMHSA - Substance Abuse and Mental Health Services Administration, Office of Applied Studies. Drug Abuse Warning Network, 2006: National Estimates of Drug- Related Emergency Department Visits. DAWN Series D-30, DHHS Publication No. (SMA) 08-4339, Rockville, MD, 2008.

  • Shimosato K. Urinary excretion of p-hydroxylated methamphetamine metabolites in man. II. Effect of alcohol intake on methamphetamine metabolism. Pharmacol Biochem Behav. 1988;29:733-740.

  • Shimosato K, Oda H, Ohmae M, Tomita M, Doi Y. Biphasic effects of alcohol drinking on methamphetamine metabolism in man. Alcohol. 1988;23:351-357.

  • Yamada T, Hayashida M, Nihira M. Influence of ethanol on metabolism of methamphetamine in rats including hair analysis. Nihon Arukoru Yakubutsu Igakkai Zasshi. 2001;36:182-200.

  • Yamamura T, Hishida S, Hatake K, Taniguchi T, Ouchi H. Effects of methamphetamine and ethanol on learning and brain neurotransmitters in rats. Pharmacol Biochem Behav. 1992;42:389-400.

  • Yamauchi J, Marukawa S, Hishida S. Simultaneous administration of ethanol emphasizes the effect of methamphetamine on central nervous system in rat with high alcohol preference. Nihon Arukoru Yakubutsu Igakkai Zasshi. 2000;35:28-47.

  • Zendulka O, Jurica J, Sabova M, Sulcova M. Methamphetamine does not influence the metabolic activity of CYP 1A2, 2C6 and 2D2 isoenzymes in the animal study. Activitas Nervosa Superior Rediviva. 2010;52:269-271.


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