Ibogaine From Forest to Lab

7/31/2019 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

Ibogaine From Forest to Lab

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