Ibogaine

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Ibogaine

• Alicia Summers

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Ibogaine

• An indole alkaloid found in the tabernathe iboga
  plant

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Chemical Composition

• 12-methoxyibogamine, C20H28N2O

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History of Use

• Found in Western Africa

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BWITI

• Used in Bwiti rituals
• Initiation ritual for both men and women to
  become part of the group
• 3 day process, spiritual journey to meet
  ancestors
• May meet the Bwiti primordial male/female

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History Continued

• Howard Lotsof, a heroin addict tried Ibogaine in
  early 70s and found it cured his addiction
• Began immediate campaign for use of ibogaine for
  addiction treatment
• US banned ibogaine in early 70s along with other
  hallucinogens, now a Schedule I drug
• FDA approved clinical trials for addiction in 1993

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Pharmacokinetics

• Ibogaine has a pKa of 8.1
• Both water and lipid soluble
• LD50 82mg/kg i.p. in guinea pigs, 327mg/kg
  intragastrically in rats
• Generally taken orally
• Grind root into powder and mix with water
• Most commonly in pill form - encapsulated
  hydrochloride (off-white powder synthesized or
  chemically extracted from root bark)
• If injected (in mice), diffused rapidly into
  brain-maximum concentrations in 10 seconds
• Half life approximately 1 hour in rodents
  (Dhahir, Zetler et al.)
• Subject to significant levels of first pass
  metabolism (Popik et. Al, 1998)
• Majority of ibogaine is metabolized in the liver
  by the cytochrome P4502D6 (CYP256) into the
  active metabolite 12-hydroxyibogamine
  (noribogaine)

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Pharmacodynamics

• Very complex mechanisms of action
• Agonist on 5-HT receptors
• Kappa opioid agonist
• Affinity for dopamine transporters
• Sigma receptor sites
• Antagonist of NMDA receptor
• High affinity for nicotine receptors blocks
  nicotine induced dopamine release in nucleus
  accumbens

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Noribogaine

• Effects similar to that of ibogaine, works on
  many of the same receptors but for an extended
  amount of time
• Has a tenfold higher affinity for 5-HT
  transporter than ibogaine (inhibits reuptake)
• m- and k-opioid receptor agonists, full m agonist

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Pharmacological Effects

• Animal Studies
• Decrease in detection of sensory information
  (Kesner et al. 1994)
• Low doses- increase in locomotor activity in mice
  Chen et al, 1958 as reported in Popik et al.,
  1998)
• Higher doses inactivity and state of suspension
  (Kesner et. al., 1994 Sershen et al., 1992)
• Very high doses produced ataxia and convulsions
  (Layer et al., 1996)
• Produced tremors in rats up 2 hours after
  administration (Popik et al., 1998)
• According to a meta-analysis (Popik et al.,
  1998), multiple studies have shown fear response
  in cats and dogs
• Does not appear to have rewarding or aversive
  effects

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Pharmacological Effects

• Human Studies
• University of Miami, Neurology Depart
• In high doses, Ibogaine produces tremors, loss of
  motor coordination and balance, and
  hallucinations
• Vestag, 2002
• In small doses, works as stimulant
• In larger doses, deeply emotional visions
• Popik et al., 1998
• Numerous actions
• CNS stimulant
• Nausea, vomiting, incoordination, dizziness
• Trance like state and hallucinations

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Uses in Treatment of Drug Dependence

• Animal Studies
• Ibogaine, injected I.P. dose dependently reduces
  alcohol intake in rats (Rezvani et al., 1995)
• Ibogaine dose-dependently reduced morphine and
  cocaine intake 1 hour after treatment in rats and
  24 hours after treatment (Glcik et al., 1994)
• Ibogaine hydrochloride reduced cocaine preference
  in mice for at least 5 days (Sershen et al.,
  1994)
• A single injection of ibogaine produced a
  significant decrease of cocaine intake for 48
  hours (Cappendijk, 1993)

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Clinical Trials of Ibogaine in Humans

• Anecdotal support (Rienzo et al., 1997)
• Mash et al., 2000
• 27 opioid and cocaine dependent men and women
  (mostly men)
• Assigned one of three fixed doses 500, 600 or 800
  mg
• Single-dose administration resulted in fewer
  self-reports of craving for cocaine and opiates
• Also found significantly reduced depression
  symptoms

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Limitations

• Not enough clinical trials
• Need research with control groups
• No funding for research in the US
• Reports of death from other countries cause of
  concern
• US is leery to use Ibogaine because a hallucinogen

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References

• Cappendijk, S.L. and Dzoljic, M.R. (1993)
  Inhibitory effects of ibogaine on cocaine
  self-administration in rats. European Journal of
  Pharmacology, 241, 261-265.
• Della Sera, E.A., and Jethmal, E.G. (1999/2000)
  Neurologic, electroencephalographic and general
  medical observations in subjects administered
  ibogaine MAPS. Bulletin of the Multidisciplinary
  Association for Psychedelic Studies, 9 (4),
  27-30.
• Glick, S.D., Kuehne, M.E., and Raucci, J. (1994)
  Effects of iboga alkaloids on morphine and
  cocaine self administration in rats relationship
  to tremorigenic effects on dopamine release in
  nucleus accumbens and striatum. Brain Research,
  657, 14-22.
• Kesner, R.P., Jackson-Smith, P., Henry, C., and
  Amann, K. (1994). Effects of ibogaine on
  sensory-motor function, activity, and spatial
  learning in rats. Pharmacology, Biochemistry and
  Behavior, 51 (1), 103-109.
• Layer, R.T., Skolnick, P, Bertha, C.M., Kuehne,
  M.E., and Popik, P. (1996). Structurally modified
  ibogaine analogs exhibit differing affinities for
  NMDA receptors. European Journal of Pharmacology,
  309 (2) 159-165.
• Mash, D.C., Kovera, C.A., Pablo, J., Tyndale,
  R.F., Ervin, F.D., Williamsn, I.C., Singleton,
  E.G., Mayor, M. (2000). Ibogaine Complex
  pharmacokinetics, concerns for safety and
  preliminary efficacy measures. Nueorbiological
  Mehcaninsms of Drugs of Abuse, 914,394-401
• Mash, D.C., Staley, J.K., Pablo, J., Raymon, L.,
  Levin, B., Doepel, F.M., Duoyon, R., Hearn, W.L.,
  and Sanchez-Ramos, J. Progress Report. University
  of Miami, Department of Neurology.
• Obach, R.S., Pablo, J., and Mash, D.C. Cytocrhome
  P4502D26 catalyzes the O-demethlyation of the
  psychoactive alkaloid ibogaine to
  12-hydroxibogamine. University of Miami,
  Department of Neurology.
• Pablo, J., Kovera, C.A., and Mash, D.C. Progress
  Report. University of Miami, Department of
  Nuerology.
• Popik, P., and Skolnick, P. (1998). The
  Alkaloids. Vol 52, p197-231. San Diego Academic
  Press.
• Rezvani, A.H., Overstreet, D.H., an Leef, Y.W.
  (1995) Attenuation of alochol intake by ibogaine
  in 3 strains of alcohol preferring rats.
  Pharmacology, Biochemistry and Behavior, 52,
  615-620.
• Rienzo, P., Beal, D., and Members. (1997)The
  Ibogaine Story Report on the Stanton Island
  Project. New York Autonomedia.
• Sershen, H., Harsing, L.G., Hashim, A., and
  Lajtha, A. (1992) Ibogaine reduces
  amphetamine-induced locomotor stimulation in
  C57BL/6By mice, but stimulates locomotor activity
  in rats. Life Sciences. 51(13) 1992, 1003-1011.
• Sershen, H., Hashim, A. and Lajtha, A. (1994)
  Ibogaine reduces preference for cocaine
  consumption in C57BL/6By mice. Pharmacology,
  Biochemistry, and Behavior, 47,13-19.
• Vestag, B. (2002). Addiction treatment strives
  for legitimacy. Journal of the American Medical
  Association. Retrieved from www.ibogaine-therapy.
  net.