Effects of ibogaine per os application on redox homeostasis in rat liver and erythrocytes

Teodora Vidonja Uzelac, Nikola Tatalović, Milica Mijović, Gordana Koželj, Aleksandra Nikolić Kokić, Zorana Oreščanin Dušić, Mara Bresjanac, Duško Blagojević


Paper description:

  • Ibogaine, administered as a single oral dose (1-25 mg/kg body weight) is used as an addiction-interrupting agent.
  • We examined the in vivo effect of a single per os dose of ibogaine (1 or 20 mg/kg) on hepatic and erythrocyte antioxidant defenses after 6 and 24 h.
  • Ibogaine increased overall energy consumption, estimated by the level of liver glycogen. Ibogaine had no effect on antioxidant defense but increased TBARS concentration, pointing to mild hepatic oxidative stress.

Abstract: Ibogaine, administered as a single oral dose (1-25 mg/kg body weight), has been used as an addiction-interrupting agent. Its effects persist for up to 72 h. Ex vivo results showed that ibogaine induced cellular energy consumption and restitution, followed by increased reactive oxygen species production and antioxidant activity. Therefore, the aim of this work was to explore the effect of a single oral dose of ibogaine (1 or 20 mg/kg body weight) on antioxidative defenses in rat liver and erythrocytes. Six and 24 h after ibogaine administration, histological examination showed glycogenolytic activity in hepatocytes, which was highest after 24 h in animals that received 20 mg/kg ibogaine. There were no changes in the activities of superoxide dismutases, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase in the liver and erythrocytes after ibogaine treatment, regardless of the dose. Hepatic xanthine oxidase activity was elevated in rats that received 20 mg/kg compared to the controls (p<0.01), suggesting faster adenosine turnover. TBARS concentration was elevated in the group treated with 1 mg/kg after 24 h compared to the controls (p<0.01), suggesting mild oxidative stress. Our results show that ibogaine treatment influenced hepatic redox homeostasis, but not sufficiently to remodel antioxidant enzyme activities at 6 and 24 h post-ibogaine application.


Received: September 18, 2018; Revised: November 28, 2018; Accepted: 2018; Published online: December 6; 2018

How to cite this article: Vidonja-Uzelac T, Tatalović N, Mijović M, Koželj G, Nikolić-Kokić A, Oreščanin-Dušić Z, Bresjanac M, Blagojević D. Effects of ibogaine per os application on redox homeostasis in rat liver and erythrocytes. Arch Biol Sci. 2019;71(1):133-44.


ibogaine; glycogen; antioxidant enzymes; lipid peroxidation; xanthine oxidase

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Alper K. Ibogaine: A Review. Alkaloids Chem Biol. 2001;56:1-38.

Popik P, Layer R, Skolnick P. 100 years of ibogaine: neurochemical and pharmacological actions of a putative anti-addictive drug. Pharmacol Rev. 1995;47(2):235-53.

Alper K, Lotsof H, Kaplan C. The ibogaine medical subculture. J Ethnopharmacol. 2008;115(1):9-24.

Sheppard S. A preliminary investigation of ibogaine: case reports and recommendations for further study. J Subst Abuse Treat. 1994;11(4):379-85.

Global ibogaine therapy alliance [Internet]. Montreal: The Global Ibogaine Therapy Alliance; 2016. Clinical Guidelines for Ibogaine-Assisted Detoxification; 2016 Sep 11 [cited 2018 Nov15]. Available from: http://www.ibogainealliance.org/guidelines/.

Alper K, Lotsof H, Frenken G, Luciano D, Bastiaans J. Treatment of acute opioid withdrawal with ibogaine. Am J Addict. 1999;8(3):234-42.

Mash D, Kovera C, Buck B, Norenberg M, Shapshak P, Hearn W, Sanchez-Ramos J. Medication development of ibogaine as a pharmacotherapy for drug dependence. Ann N Y Acad Sci. 1998;844:274-92.

Schep L, Slaughter R, Galea S, Newcombe D. Ibogaine for treating drug dependence. What is a safe dose? Drug Alcohol Depend 2016;166:1-5.

Leal M, Michelin K, Souza D, Elisabetsky E. Ibogaine attenuation of morphine withdrawal in mice: role of glutamate N-methyl-D-aspartate receptors. Prog Neuropsychopharmacol Biol Psychiatry. 2003;27(5):781-5.

Glick S, Maisonneuve I, Kitchen B, Fleck M. Antagonism of alpha 3 beta 4 nicotinic receptors as a strategy to reduce opioid and stimulant self-administration. Eur J Pharmacol. 2002;438(1-2):99-105.

Paškulin R, Jamnik P, Obermajer N, Slavić M, Štrukelj B. Induction of energy metabolism related enzymes in yeast Saccharomyces cerevisiae exposed to ibogaine is adaptation to acute decrease in ATP energy pool. Eur J Pharmacol. 2010;627(1-3):131-5.

Paškulin R, Jamnik P, Danevčič T, Koželj G, Krašovec R, Krstić-Milošević D, Blagojević D, Štrukelj B. Metabolic plasticity and the energy economizing effect of ibogaine, the principal alkaloid of Tabernanthe iboga. J Ethnopharmacol. 2012;143(1):319-24.

Nikolić-Kokić A, Oreščanin-Dušić Z, Spasojević I, Slavić M, Mijušković A, Paškulin R, Miljević Č, Spasić M, Blagojević D. Ex vivo effects of ibogaine on the activity of antioxidative enzymes in human erythrocytes. J Ethnopharmacol. 2015;164:64-70.

Paškulin R, Jamnik P, Živin M, Raspor P, Štrukelj B. Ibogaine affects brain energy metabolism. Eur J Pharmacol. 2006;552(1-3):11-4.

Oreščanin-Dušić Z, Tatalović N, Vidonja-Uzelac T, Nestorov J, Nikolić-Kokić A, Mijušković A, Spasić M, Paškulin R, Bresjanac M, Blagojević D.The effects of ibogaine on uterine smooth muscle contractions: relation to the activity of antioxidant enzymes. Oxid Med Cell Longev. 2018;2018:5969486.

Mash D, Kovera C, Pablo J, Tyndale R, Ervin FR, Kamlet J, Hearn W. Ibogaine in the treatment of heroin withdrawal. Alkaloids Chem Biol 2001;56:155-71.

Kontrimaviciūte V, Mathieu O, Mathieu-Daudé J, Vainauskas P, Casper T, Baccino E, Bressolle F. Distribution of ibogaine and noribogaine in a man following a poisoning involving root bark of the Tabernanthe iboga shrub. J Anal Toxicol 2006;30(7):434-40.

Mash D, Kovera C, Pablo J, Tyndale R, Ervin F, Williams I, Singleton E, Mayor M. Ibogaine: complex pharmacokinetics, concerns for safety, and preliminary efficacy measures. Ann N Y Acad Sci. 2000; 914:394-401.

Jeffcoat R, Cook C, Hill J, Coleman D, Pollack G. Disposition of [3H] ibogaine in the rat [abstract]. In: Harris L, editor. 55th Annual Scientific Meeting of the College on Problems of Drug Dependence; 1993 Jun; Toronto, Canada. Rockville: National institute on drug abuse; 1994. p. 309.

Baumann M, Rothman R, Pablo J, Mash D. In vivo neurobiological effects of ibogaine and its O-desmethyl metabolite, 12-hydroxyibogamine (noribogaine), in rats. J Pharmacol Exp Ther. 2001;297(2):531-9.

Koželj G. Development of an analytical method for the determination of alkaloids in biological samples. [dissertation]. [Ljubljana]: Faculty of Chemistry and Chemical Technology, University of Ljubljana. 2015.

Luna LG. Manual of histologic staining methods of the armed forces institute of pathology. 3rd ed. New York: McGraw-Hill; 1968.

Rehncrona S, Smith D, Akesson B, Westerberg E, Siesjo B. Peroxidative changes in brain cortical fatty acids and phospholipids, as characterized during Fe2+- and ascorbic acid-stimulated lipid peroxidation in vitro. J Neurochem. 1980;34(6):1630-8.

Ellman G. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959;82(1):70-7.

Misra H, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem. 1972;247(10):3170-5.

Beutler E. Red cell metabolism: a manuel of biochemical methods. 3rd ed. NewYork: Grune and Stratton; 1982. 102 p.

Paglia D, Valentine W. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med. 1967;70(1):74-7.

Glatzle D, Vuilleumier J, Weber F, Decker K. Glutathione reductase test with whole blood, a convenient procedure for the assessment of the riboflavin status in humans. Experientia. 1974;30(6):665-8.

Habig N, Pabst M, Jakoby N. GST: 1st enzymatic step in mercapturic acid formation. J Biol Chem. 1974;249:7130-9.

Terada L, Leff J, Repine J. Measurement of xanthine oxidase in biological tissues. Methods Enzymol. 1990;186:651-6.

Drabkin D, Austin J. Spectrophotometric studies: II. Preparations from washed blood cells: nitric oxide hemoglobin and sulfhemoglobin. J Biol Chem. 1935;112:51-5.

Lowry O, Rosebrough N, Farr A, Randall R. Protein measurement with folin phenol reagent. J Biol Chem. 1951;193(1):265-75.

Hinkle E, Wiersma W, Jurs G. Applied statistics for behavioral sciences. 5th ed. Boston: Houghton Mifflin Company; 2002.

Levant B, Pazdernik T. Differential effects of ibogaine on local cerebral glucose utilization in drug-naive and morphine-dependent rats. Brain Res. 2004;1003(1-2):159-67.

de Groot H, Littauer A. Hypoxia, reactive oxygen, and cell injury. Free Radic Biol Med. 1989;6(5):541-51.

Rosell M, Regnsrtom J, Kallner A, Hellenius M. Serum urate determines antioxidant capacity in middle-aged men- a controlled, randomized diet and exercise intervention study. J Intern Med. 1999;246(2):219-26.

Nikolić A, Mijalković D, Nikolić-Kokić A, Kastratović D, Blagojević D, Davidović B, Spasić M. Elevated serum uric acid reduce heart damage in patients undergoing open-heart surgery. Acta Chir Iugosl. 2006;53(3):29-33.

Hough L, Pearl S, Glick S. Tissue distribution of ibogaine after intraperitoneal and subcutaneous administration. Life Sci. 1996;58(7):PL119-22.

Dhahir H. A Comparative study of the toxicity of ibogaine and serotonin. [dissertation]. [Indiana]: School of medicine, University of Indiana. 1971.

Maciulaitis R, Kontrimaviciute V, Bressolle F, Briedis V. Ibogaine, an anti-addictive drug: pharmacology and time to go further in development. A narrative review. Hum Exp Toxicol. 2008;27(3):181-94.

Obach S, Pablo J, Mash D. Cytochrome P4502D6 catalyzes the O-demethylation of the psychoactive alkaloid ibogaine to 12-hydroxyibogamine. Drug Metab Dispos. 1998;26(8):764-8.

Glue P, Winter H, Garbe K, Jakobi H, Lyudin A, Lenagh-Glue Z, Hung C. Influence of CYP2D6 activity on the pharmacokinetics and pharmacodynamics of a single 20 mg dose of ibogaine in healthy volunteers. J Clin Pharmacol. 2015;55(6):680-7.

Rezvani A, Overstreet D, Lee Y. Attenuation of alcohol intake by ibogaine in three strains of alcohol-preferring rats. Pharmacol Biochem Behav. 1995;52(3):615-20.

Blagojević D, Buzadžić B, Korać B, Saičić Z, Radojičić R, Spasić M, Petrović V. Seasonal changes in the antioxidative defense in ground squirrels (Citelluscitellus): Possible role of GSH-Px. J Environ Pathol Toxicol Oncol. 1998;17(3-4):241-50.

Petrović V, Saičić Z, Spasić M, Radojičić R, Buzadžić B. Hormones and antioxidant defence. In: Nygaard OF, Lipton AC, editors. Anticarcinogenesis and Radiation Protection 2. New York: Plenum Press; 1991. p. 405-16.

Chua H, Puchulu-Campanellaa E, Galan J, Tao W, Low P, Hoffman J. Identification of cytoskeletal elements enclosing the ATP pools that fuel human red blood cell membrane cation pumps. Proc Natl Acad Sci USA. 2012;109(31):12794-9.


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