ibogaine from forest to lab
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Iboga & Ibogaine:
From the forestto the laboratory
Howard S. LotsofDora Weiner FoundationStaten Island, NY
Les Journees Gabonaises aux USATacoma, MD
August 15, 2008
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Ibogaine Found in a West
African plant Tabernantheiboga. Used in Bwiti religion
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Gabons first President, Leon Mba
was Bwitist and defended T. iboga
use in French colonial courts.
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Scientific literature for fifty years described
the plant as 1m - 2m in height but, examples
exist in the forest 5m in height (Omboue)
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Iboga alkaloids are concentrated
in the bark of the root
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Usable forms include scrapedor ground root bark 2% - 4%
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Physical Characteristics of ibogaine base
Source Merck IndexChemical formula C20H26N2O
Mol. Wt. 310.42
Melting Point 152-153
Practically insoluble in water.
Soluble in ethanol, ether, chloroform
Molecular structure
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Blue = Nitrogen, Red = Oxygen,
Black = Carbon, White = Hydrogen
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Botanical source Tabernanthe iboga. Used for 100s of yearsin African medicine and religion, particularly in Gabon by
Bwiti
1901 ibogaine isolated by Dybowski and Landrin
1958 molecular structure determined Bartlett et al.
1962 Lotsof discovers Antiaddictive effects
1967 Claudio Naranjos and Leo Zeffs work with ibogainein psychotherapy
1991 National Institute on Drug Abuse (NIDA) initiatesevaluation of ibogaine
1993 Food and Drug Administration (FDA) approvesclinical study of ibogaine
Background: Ibogaine
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1994 Clinical studies in hospitals Republic of Panama.
1996 St. Kitts facility initiates treatment of 400 patients withibogaine.
2000 Iboga declared national treasure by government ofGabon.
2004 Israeli Ministry of Health approval of ibogaine clinicalstudies
Background: Ibogaine (cont.)
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Lotsof patents advanceddevelopment
1. Rapid method for interrupting the narcoticaddiction syndrome, US 4,499,096 (1985)
2. Rapid method for interrupting the cocaine andamphetamine abuse syndrome US 4,587,243(1986)
3. Rapid method for attenuating the alcoholdependency syndrome, US 4,957,523 (1989)
4. Rapid method for interrupting or attenuating thenicotine/tobacco dependency syndrome, US5,026,697 (1991)
5. Rapid method for interrupting or attenuating poly-drug dependency syndromes, US 5, 124,994(1992)
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Ibogaine:A Broad Spectrum Anti-Addictive
1. Opioids1. Heroin
2. Morphine
3. Opium
4. Methadone
2. Cocaine
3. Methamphetamine
4. Alcohol
5. Nicotine6. Polydrug dependence
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Ibogaine:Other uses
1. Antibacterial
2. Antifungal
3. Possible antiviral4. Psychotherapy
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Preclinical Studies
Rats, mice, dogs, primates
Oral or IP
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Self-Administrationstudies
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First scientific publication of
ibogaine antiaddictive effects
- Dzoljic et al. -
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Additional research supports Dr. Dzoljics findings. Dr.
Stanley D. Glick at Albany Medical College begins the
publication of what will become dozens of research
papers showing reduction in drug use and withdrawal.
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Ibogaine effects on cocaine
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Ibogaine effects on cocaineDose and regimen
(Cappendijk & Dzoljic)
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Ibogaine effects on alcohol
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Ibogaine effects on alcohol
Dose effect
(Rezvani et al. 1995)
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Tissue distribution and availability
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Return to preaddictive state?
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Neurotoxicity questions
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Xu et al. eventually produce research
showing no neurotoxicity at clinical
doses(2000)
Xu et al accomplished research in part at the National Center
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Xu et al. accomplished research in part at the National Center
for Toxicological Research an FDA laboratory. The research
demonstrated no neurotoxicity in rats at 25 mg/kg.
Other research indicated no evidence of neurotoxicity in theprimate and mouse, and postmortem neuropathological
examination in a woman treated with up to 30 mg/kg.
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Antibacterial studies
tuberculosis
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Antifungal studies
Candida albicans
Ib i M lti l
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Ibogaine: Multiple
mechanisms of action& receptor system effects wheredrugs of abuse also show activity
Dopamine
OpiateSerotonin
NMDA (N-methyl-D-aspartic acid)
Nicotinic
GDNF (Glial cell derivedneurotrophic factor)
Signal transduction
independent of
receptor binding
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These systems define thepharmacology of human behavior,affecting pain, pleasure, anxiety anddepression as well as, neuron growthwith an inherent impact on memoryand learning.
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Clinical StudiesSafety and Efficacy
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In 2004, in support of clinical studies NIDA makesavailable a Drug Master File (DMF) provided toFDA comprising 16 volumes of data ofapproximately 4,000 pages.
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Partial list of broad-ranging studies in FDA Drug Master File(DMF) included in the 16 volumes of data submitted by USNational Institute on Drug Abuse (NIDA) for ibogaine.
Acute Oral Toxicity Study of Ibogaine HCl in Rats.
32 Day Range-Finding Study of Ibogaine in Rats.
Dose Response Neurotoxicity Study of Ibogaine in Rats.
Dose Response Effect of Ibogaine on Analgesia and
Mortality in Morphine-Dependent Rats.Pharmacokinetic Studies of Treatment Drugs Ibogaine.
14 Day Dose Range-Finding Toxicity Study of Ibogaine
HCl in Dogs.
Acute Neurotoxicity Study of Ibogaine HCl in Dogs.
Salmonella/Mammalian-Microsome Plate IncorporationMutagenicity Assay (AMES Test).
L5178Y/TK +/- Moue Lymphoma Mutagenesis Assay
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Comparative safety perspectivesDrug-related fatalities (d-rf)
Ibogaine/iboga (1989-2006) 11 d-rf
Methadone (2004) (USA) 3965 d-rf
FDA approved drugs in US hospitals
(1999) 112,000 d-rf
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1. Ibogaine significantly reduces withdrawal2. Interrupts drug craving
3. Interrupts drug self-administration
4. Returning patients to a preaddictive state
5. Eliminates stigma
6. Returns free choice
7. Antibacterial
Ib i
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Ibogaine:Stages of effect
1. Visualization or wakingdream-like experience
3 - 6 hours
2. Cognitive evaluation8 - 20 hours
3. Residual stimulation
12 - 72 hours
Ib i
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Ibogaine:Side-effects
1. Nausea or vomiting
2. Ataxia
O i id ithd l i
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Opioid withdrawal in
human subjects
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Objective Opioid Withdrawal Signs
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Clinical Toxicology, 2(2):209-224, 1969
Copyright 1973
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1. The waking dreamstate
2. Retrieval of early memories
3. Motion related nausea
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Stigma
A mark of disgrace associated with aparticular circumstance, quality or
person: for instance the stigma ofchemical dependence.
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Ibogaine Effects on Stigma
Ibogaine has the ability to remove thestigmatized condition, transforming thepatient to a state often described as apreaddictive. The transformation of astigmatized person into one who is notstigmatized will affect the individual,allowing a greater contribution to self and
society, improving quality of life issues.
Growth in number of ibogaine treated
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Growth in number of ibogaine treated
patients
Countries included in paper
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Countries included in paper
1. USA2. Chile
3. Switzerland
4. Panama
5. Brazil6. St. Kitts
7. Mexico
8. Czech Republic9. UK
10.Canada
11.Netherlands
12.Slovenia13. Gabon*
14.France
*Initiation of foreign nationals including drug treatment - limited
Typology of ibogaine providers
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Typology of ibogaine providers
and #s of patients treated (ca.2006) TOTAL = 3414
1. Medical model (824)
2. Lay provider/treatment guide (1213)3. Activist/self-help (200)
4. Religious/spiritual (1177)
Reasons for treatment
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Reasons for treatment
1. Total = 3414 (ca. 2006)
2. Substance-related disorders = 68%
3. Opioid withdrawal = 53%
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Taking the hidden population
estimates (20% - 30%) into accountallow an estimated range of
approximately 4300-4900
individuals who took ibogaine oriboga alkaloids outside of Africa asof February 2006.
Ibogaine science continues to grow providing
100 f i d i tifi
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100s of peer reviewed scientific papers
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