Metabolic passage –              its costs and benefitsGITA                         Roman Paškulin, M.D., Ph.D.Vancouver, ...
Iboga - Tabernanthe iboga
Traditional use:Tonic and stimulantReconvalescence after diseasesRitual substance – initiation into adulthoodReligious use
Addiction interrupter:Reduction of symptoms and signs of abstinence syndromeAcceleration of detoxificationTolerance revers...
Influence on diverse receptors, transporters and enzymesEffects last longer than the presence of ibogaine in the bodyLong ...
Structural proteins-   cytoskeleton
Functional proteins-enzymes, receptors, transporters
2-D electrophoresis
Quantification of changes
Peptide mapping by mass spectrometry
Ibogaine 20 mg/kg i.p. 24 and 72hEnzyme              Accession     Fold      Fold      Theoretical   Score   Matched      ...
Metabolism of glucose – ATP production
Ibogaine 1 mg/l in media 5hSpot Enzyme          Swiss-Prot     Fold        Theor.       Matched    Mascot                 ...
ATP pool under ibogaine                             0regarding the control (%)Difference in ATP pool                      ...
Carbon dioxide production                                               1,6                                               ...
Protein synthesis                  Treated            Control         Ratio               Ratio                  Σ Normali...
ATP pool after ibogaine                            100                            80regarding the control (%)Difference in...
Stabile metabolic shift in the epigenetic landscape
Ibogaine pharmacodynamics
Influence on the total oxidative load                 1,8                 1,6                 1,4                 1,2Relat...
Influence on the total oxidative loadCalculated      Ibogaine        Oxidative load    Ascorbic acid   Oxidative loadiboga...
Why do you need narcotics Mr. Lee?I need junk to get out of the bed in the morning, to shaveand eat breakfast. I need it t...
It is not that a warrior learns shamanism as time goes by;rather, what he learns as time goes by is to save energy.This en...
Increased energy availability•   accelerates metabolic turnover,    facilitates metabolic adaptations -    detoxification ...
Study showed that ibogaine’s influence onmetabolism is neither species nor tissue specificEffect is not mediated by bindin...
Pharmacodynamics of Entheogen Drugs –                Influence on Gene ExpressionOMI, Institute for Anthropological Medici...
October 3 - Roman Paskulin
October 3 - Roman Paskulin
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October 3 - Roman Paskulin

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October 3 - Roman Paskulin

  1. 1. Metabolic passage – its costs and benefitsGITA Roman Paškulin, M.D., Ph.D.Vancouver, 2012 OMI Institute, Slovenia
  2. 2. Iboga - Tabernanthe iboga
  3. 3. Traditional use:Tonic and stimulantReconvalescence after diseasesRitual substance – initiation into adulthoodReligious use
  4. 4. Addiction interrupter:Reduction of symptoms and signs of abstinence syndromeAcceleration of detoxificationTolerance reversionElimination of cravings
  5. 5. Influence on diverse receptors, transporters and enzymesEffects last longer than the presence of ibogaine in the bodyLong half-life of metaboliteNeurotrophin (GDNF) synthesis and releaseFunctional and structural remodeling - gene expression and proteome changes
  6. 6. Structural proteins- cytoskeleton
  7. 7. Functional proteins-enzymes, receptors, transporters
  8. 8. 2-D electrophoresis
  9. 9. Quantification of changes
  10. 10. Peptide mapping by mass spectrometry
  11. 11. Ibogaine 20 mg/kg i.p. 24 and 72hEnzyme Accession Fold Fold Theoretical Score Matched number over over Mr(Da)/ pI peptides control control 24 h 72 hGlyceraldehyde-3- Q9QWU4 1.13 3.21 36090/8.14 62 9phosphatedehydrogenaseMalate 42476181 1.42 3.64 36117/8.79 54 9dehydrogenaseAldolase A 6978487 1.23 2.45 39783/8.05 60 9Pyruvate kinase 206205 1.38 2.94 58314/7.19 70 10
  12. 12. Metabolism of glucose – ATP production
  13. 13. Ibogaine 1 mg/l in media 5hSpot Enzyme Swiss-Prot Fold Theor. Matched Mascot Accession Ibogaine/ Mr(Da)/pI peptides score number ControlGlyceraldehyde-3- P00359 6.3 35747/6.46 16 381phosphatedehydrogenase 3Phosphoglycerate P00540 4.6 44738/7.11 19 492kinaseEnolase 2 P00925 3.8 46914/5.67 22 933(2-phosphopyruvatedehydratase 2)Alcohol P00330 3.2 36823/6.26 29 694dehydeogenase 1Superoxide P00445 2.2 15855/5.62 7 125dismutase (Cu-Zn)
  14. 14. ATP pool under ibogaine 0regarding the control (%)Difference in ATP pool -10 -20 -30 1 g/L -40 4 g/L 20 g/L -50 0 1 2 3 4 5 Time of exposure (h)
  15. 15. Carbon dioxide production 1,6 1 mg/l 1,4Production of CO2 relative to control (fold) 4 mg/l 1,2 20 mg/l 1,0 0,8 0,6 0,4 0,2 0,0 -0,2 -0,4 0 1 2 3 4 5 Time (h)
  16. 16. Protein synthesis Treated Control Ratio Ratio Σ Normalized Σ Normalized (Treated/Control) (Corrected) Volumes (%) Volumes (%)High AbundanceProteins 36.398 50.103 0.726 1(NormalizedVolume ≥ 0.5 %)Low AbundanceProteins 63.602 49.897 1.275 1.756(NormalizedVolume < 0.5 %)
  17. 17. ATP pool after ibogaine 100 80regarding the control (%)Difference in ATP pool 60 40 20 0 -20 -40 -10 0 10 20 30 40 50 60 70 Time after washing (min)
  18. 18. Stabile metabolic shift in the epigenetic landscape
  19. 19. Ibogaine pharmacodynamics
  20. 20. Influence on the total oxidative load 1,8 1,6 1,4 1,2Relative value 1,0 0,8 0,6 0,4 0,2 0,0 K 0,2 mg/l 1 mg/l 4 mg/l 20 mg/l 100 mg/l Concentration of Ibogaine
  21. 21. Influence on the total oxidative loadCalculated Ibogaine Oxidative load Ascorbic acid Oxidative loadibogaine concentration ratio concentration reduction byconcentration in cytosol treated/control [µM] ascorbic acid[mg/l] [mg/l] [%]1 0,83 ± 0,03 76,26 ± 1,69 1 non-significant4 3,89 ± 0,06 76,67 ± 1,56 2 non-significant20 18,14 ± 0,34 43,45 ± 1,30 4 non-significant
  22. 22. Why do you need narcotics Mr. Lee?I need junk to get out of the bed in the morning, to shaveand eat breakfast. I need it to stay alive. William S. Burroughs, Junkie
  23. 23. It is not that a warrior learns shamanism as time goes by;rather, what he learns as time goes by is to save energy.This energy will enable him to handle some of the energyfields which are ordinarily inaccessible to him.Shamanism is a state of awareness; the ability to use energyfields that are not employed in perceiving the everyday-lifeworld that we know. Carlos Castaneda
  24. 24. Increased energy availability• accelerates metabolic turnover, facilitates metabolic adaptations - detoxification and reversal of tolerance• enhances mental agility, elevates mood and life will• facilitates introspection and insight into one’s own pathology, helps to locate and solve the problem• eliminates cravings and protects against recidive
  25. 25. Study showed that ibogaine’s influence onmetabolism is neither species nor tissue specificEffect is not mediated by binding of ibogaine toreceptors previously described in the literatureIbogaine shows remedial effect in differentpathological conditions, while in health it helps toresist stress in the adaptogene manner
  26. 26. Pharmacodynamics of Entheogen Drugs – Influence on Gene ExpressionOMI, Institute for Anthropological Medicine (www.omi.si)University of Ljubljana, SloveniaUniversite Montpellier 1, FranceUniversity of Belgrade, Serbia

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