title: Metabolic plasticity and the energy economizing effect of ibogaine, the principal alkaloid of Tabernanthe iboga.
abstract: BACKGROUND
  The root bark of iboga plant-Tabernanthe iboga has been used traditionally in Central Africa as a psychoactive substance in religious rituals, while in smaller doses it is appreciated due to its stimulant properties. The iboga root bark, iboga extract or pure ibogaine are being recognized in the West as an anti-addiction remedy and their use is increasing.
  
  
  OBJECTIVE
  Our previous studies have demonstrated a transient ATP pool reduction under ibogaine accompanied by the induction of energy metabolism related enzymes. The present study aimed to find the cause of this energy deprivation and to foresee its immediate and long-term impact on metabolism. The overall project is designed to disclose the common mechanism of action at these seemingly diverse indications for iboga use, to predict eventual adverse effects and to build the grounds for its safe and beneficial utilization.
  
  
  METHODS
  The rate of carbon dioxide (CO(2)) as a marker of energy metabolism in stationary yeast model under aerobic conditions in the presence of ibogaine at concentration of 1, 4 and 20mg/l was measured for 5h by gas chromatography. The overall oxidative load was determined fluorimetrically by 2',7'-dichlorofluorescein diacetate (H(2)DCFDA) and in vitro antioxidant properties of ibogaine were defined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) test.
  
  
  RESULTS
  The CO(2) production under ibogaine was temporarily increased in a dose dependent manner. The increased energy consumption as an early effect of ibogaine was proven by the fact that in spite of energy mobilization, the ATP pool has been simultaneously decreased. Although increased cellular respiration co-produces reactive oxygen species (ROS), the overall oxidative load was significantly lowered by ibogaine. Since ibogaine does not show any significant in vitro antioxidant properties, the results indicate its stimulating influence on physiological oxidative stress defence system.
  
  
  CONCLUSIONS
  Ibogaine triggers remodeling of the housekeeping metabolism. Under the initial energy cost it results in increased efficacy of physiological antioxidative systems, which reduce oxidative damage and lowers basal metabolic needs. Together with induced catabolic enzymes they set a new metabolic equilibrium that saves energy and makes it easily available in case of extra needs. While healthy organism profits from improved fitness and mental performance and can withstand higher stress without risking a disease, due to the same principle ibogaine provides beneficial support at the recovery after diseases including addiction syndrome.
authors: OMI Institute, Trnovska 8, Ljubljana, Slovenia. roman.paskulin@siol.net
authors: Roman
authors: R
authors: Paškulin
authors: Polona
authors: P
authors: Jamnik
authors: Tjaša
authors: T
authors: Danevčič
authors: Gordana
authors: G
authors: Koželj
authors: Rok
authors: R
authors: Krašovec
authors: Dijana
authors: D
authors: Krstić-Milošević
authors: Duško
authors: D
authors: Blagojević
authors: Borut
authors: B
authors: Strukelj
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D001713:Biphenyl Compounds / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects*; D007050:Ibogaine / Q000494:pharmacology*; D016488:Medicine, African Traditional; D018384:Oxidative Stress / Q000187:drug effects*; D008517:Phytotherapy; D010851:Picrates / Q000378:metabolism; D024301:Plant Bark; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots; D019966:Substance-Related Disorders / Q000188:drug therapy; D030014:Tabernaemontana / Q000737:chemistry*; D015003:Yeasts / Q000187:drug effects / Q000378:metabolism
chemical_list: D001713:Biphenyl Compounds; D010851:Picrates; D010936:Plant Extracts; D002245:Carbon Dioxide; D007050:Ibogaine; D000255:Adenosine Triphosphate; C004931:1,1-diphenyl-2-picrylhydrazyl