Transcript Abuse Liability & Drug Scheduling: Role of FDA

Introduction to Presentation by HS Lotsof
1. Ibogaine (brief review)
2. Ibogaine Development
2006 NYC Ibogaine Conference
Columbia University
Saturday, February 25
Ibogaine Found in a West
African plant Tabernanthe
iboga
T. Iboga is Valued
for its roots
Iboga alkaloids are concentrated
in the bark of the root
Usable forms include scraped or
ground root bark
Total Alkaloid extract
Courtesy Sara Glatt
Purified Chemical
Proposed as an approved regulated drug
Physical Characteristics of ibogaine base
Source Merck Index
Chemical formula
C20H26N2O
Mol. Wt.
310.42
Melting Point
152-153°
Practically insoluble in water.
Soluble in ethanol, ether, chloroform
Molecular structure
Ibogaine Development
or Lack Thereof:
Politics
Policy
Prejudice
Profit
Science
Howard S. Lotsof
Dora Weiner Foundation
http://www.doraweiner.org
Politics
The activities within a government or agency or other
human endeavor that may include debate and conflict.
Prohibition
Legalization or Regulation
War on Drugs
War on Some Drugs
War on Drug Users
Drug Politics may be top down from
government agencies such as the
ONDCP
DEA
FDA
Drug Politics are also bottom up from
grassroots organizations such as the
SSDP
Harm Reduction Coalition
Cures Not Wars
Precedents for Ibogaine
Activist Organizations
•
International Coalition for Addict Self-Help
(ICASH)
•
Dutch Addict Self-Help (DASH)
•
Cures-Not Wars (ibogaine and other issues)
•
Ibogaine Underground
ICASH logo
Used to attract attention of government officials
and media
Nico Adriaans was one of the founders of both the Rotterdam
Junkies Union and Dutch Addict Self-Help (DASH). DASH was
an ibogaine self-help organization that petitioned the Dutch
government and organized drug users to demand ibogaine
availability. DASH provided ibogaine at no cost to heroin
users.
ICASH Organizing in the US
Cures-Not-Wars placed pressure on
NIDA to support Ibogaine research
through protests
Mindvox Ibogaine List
(user advocacy continues)
“We all got to help each other best we can. No one
else gives a shit ‘bout us hippy freak junkies? ”
anon.
To join send an email to
[email protected]
Ibogaine underground appears 2004
“FM- I'm not really privy to what's happening in that
regard here in the US. Suffice to say, nothing has
worked which is why we're here. We feel that
continuing the focus offshore, outside the US, has not
served a majority of people inside the US. Like many
other grassroots movement, which facilitated change,
treatments, sessions, need to be done where they
belong, in all major US cities, as cost effectively as
possible. “
http://www.drugwar.com/ibonyc.shtm
Policy
A course or principle of action adopted or proposed by
a government, party, business, or individual
Harm Reduction
Demand Reduction
How Ibogaine is Viewed
Ibogaine represents both harm
reduction and demand reduction
DEA desk officer in the Netherlands asks how the
Dutch are allowing a demand reduction drug like
ibogaine to be researched in the Netherlands?
Ibogaine proponents view the drug as significant harm
reduction tool and basis for political action.
Prejudice
A generally negative preconceived opinion that is not
based on reason or actual experience
Prejudice incorporates
Discrimination
The unjust or prejudicial treatment of different
categories of people or things.
Stigma
A mark of disgrace associated with a particular
circumstance, quality, or person : the stigma of
chemical dependence.
Discrimination
Focuses attention on those who
produce rejection and exclusion
Stigma
Focuses attention on the
victim
Prejudice, stigma and discrimination, in
part, determine what drugs will be
regulated, what drugs will not be
regulated and what medications will be or
not be made available to treat chemical
dependence
Ibogaine Effects on Stigma
Ibogaine is reported to have the ability
to remove the stigmatized condition,
transforming the patient to a state
often described as a preaddictive.
Additional Ibogaine Effects on Stigma
The transformation of a stigmatized person
into one who is not stigmatized will have
significant effects on the person and the
society within which the individual lives as it
allows for personal growth and the
possibility of a greater contribution to
society. This dynamic is expressed within
the activities of the ibogaine advocacy
movement in the services they offer to
chemically dependent persons and the
political actions taken to promote ibogaine
availability.
Profit
A financial gain, The difference between the amount
earned and the amount spent in buying, operating, or
producing something : | their eyes brightened at the
prospect of profit.
Politics
Policy
Prejudice
Science
Profit is a core issue in the
pharmaceutical industry whose
primary purpose is to return profit to
corporate shareholders.
This effects what drugs will be developed and
the areas of medicine for which drugs will be
available.
Science
The intellectual and practical activity encompassing the
systematic study of the structure and behavior of the
physical and natural world through observation and
experiment
Politics
Policy
Prejudice
Profit
Intellectual Conformity
National Institute on Drug Abuse
(NIDA) funds 85% of drug addiction
research worldwide
NIDA Initially Rejects Ibogaine
Research.
NIDA was petitioned to perform ibogaine research 1984 1990, first by the Dora Weiner Foundation and from 1986 on
by NDA International, Inc., a company established to make
ibogaine available as an approved medication. In 1991, NIDA
formed its Medications Development Division (MDD) and
accepted a Product Profile Review (PPR) from NDA
International that resulted in NIDA starting their ibogaine
research program.
The following are examples demonstrating the
scientific contention between NIDA and proibogaine researchers that played out between
1988 and 2000.
First scientific publication of
ibogaine antiaddictive effects
NIDA Response: It doesn’t work
Ibogaine Scientists Answer
NIDA contracts neurotoxicologist Mark
Molliver to determine ibogaine
neurotoxicity
Ibogaine researcher Helen
Molinari responded
Further research by O’Hearn
and Molliver
Xu et al. eventually produce research
showing no neurotoxicity at clinical
doses (2000)
Xu et al. accomplished research in part at the
National Center for Toxicological Research an
FDA laboratory. The research demonstrated no
neurotoxicity at 25 mg/kg.
Ibogaine science continues to grow providing
100s of peer reviewed papers
A few key papers relating to ibogaine research
and second generation ibogaine-like drugs to
treat chemical dependence follow. These include
ibogaine effects on opioid narcotics.
Ibogaine effects on cocaine
Ibogaine effects on alcohol
Tissue distribution and availability
Review papers
Opioid withdrawal in human subjects
Second generation ibogaine-like
drug, metabolite noribogaine is
identified
Another second generation ibogaine-like
drug, 18-methoxycoronaridine, diminished
morphine withdrawal
18-methoxycoronaridine effects on
alcohol
18-methoxycoronaridine effects on
methamphetamine and nicotine
18-methoxycoronaridine and noribogaine have not
been administered to human subjects. Ibogaine
remains the only iboga alkaloid that has been shown to
be effective in humans, supporting claims made in the
original ibogaine patents awarded between 1985 and
1992.
Ibogaine Patents
1. Rapid method for interrupting the narcotic addiction syndrome, US
4,499,096 (1985)
2. Rapid method for interrupting the cocaine and amphetamine abuse
syndrome US 4,587,243 (1986)
3. Rapid method for attenuating the alcohol dependency syndrome,
US 4,957,523 (1989)
4. Rapid method for interrupting or attenuating the nicotine/tobacco
dependency syndrome, US 5,026,697 (1991)
5. Rapid method for interrupting or attenuating poly-drug dependency
syndromes, US 5, 124,994 (1992)
Why ibogaine is not available
1.
Industry deems ibogaine not to be profitable. (not a maintenance
drug)
2.
The molecule is found in nature and cannot be owned.
3.
Stigmatized patient population with liability higher than general
population.
4.
Government, industry and academia chose to place their interest
to treat narcotic dependence in the development of opiate drugs
with which they are familiar.
5.
Ibogaine represents a new scientific paradigm to the
understanding of addiction.
6.
Lack of prioritization of pharmacotherapies.
7.
Intellectual conformity.

The medical community

The pharmaceutical industry

Government
Failed to adequately respond
to make ibogaine available
Brief comparison of discovery and
development of ibogaine, methadone
and buprenorphine. All are effective in
treating opioid dependence.
Ibogaine
NYC
1962
Drug users
administer to
drug users
Multi-receptor
activity
Methadone
NYC
1964
Doctors administer to
drugs users
Opioid agonist
activity
Buprenorphine
Lexington, KY
1975
Government and
industry
Co-Development
Mixed opioid
agonist antagonist
activity
Background: Ibogaine
• Botanical source Tabernanthe iboga. Used for 100s of years in
African medicine and religion
• 1901 ibogaine isolated by Dybowski and Landrin
• 1958 molecular structure determined Bartlett et al.
• 1962 Lotsof discovers Antiaddictive effects
• 1991 NIDA initiates evaluation of ibogaine
• 1995 NIDA Ibogaine Clinical Review Meeting. Decision: No
clinical studies of ibogaine
Background: Methadone
• 1937 synthesized by Max Bockmühl and Gustav Ehrhart,
I.G. Farbenindustries. Patent issued 1941
• 1950 use in treatment of opioid abstinence syndrome
established in US
• 1964 use in opioid maintenance therapy
• 1964 - 1973 Golden age of Dole and Nyswander
• 1973 Federal regulation of Methadone
• 2002 Revised Federal regulation of Methadone
Background: Buprenorphine
• 1965 synthesized by KW Bentley at Reckitt & sons, UK.
• 1975 - 1978 DR Jazinski et al. Indicate utility in treating opiate addiction
• 1977 - 2003 John Lewis champions analgesic and antiaddictive
development
• 1994 NIDA signs CRADA with Reckitt & Colman Pharmaceuticals, Inc.
• 2000 Drug Addiction Treatment Act authorizes use in opioid
maintenance therapy
• 2002 FDA approves use to Reckitt Benckiser to treat narcotic addiction
Is NIDA responsible for blocking ibogaine?
1994 collaborative research and
development agreement for buprenorphine
NIDA director signs agreement to
develop buprenorphine 1994
NIDA says “NO” to clinical
development of ibogaine 1995
Paths to ibogaine availability
1. Pharmaceutical company or government agency
prepared to finance regulatory development.
2. Supplies of pharmaceutical grade ibogaine.
3. Grassroots constituency demanding availability of
ibogaine.
4. Political advocacy movement to pressure government
and industry into action.
5. A scientific community supporting ibogaine research.
Why ibogaine should be available
Based on drug user reports ibogaine is a
medication that significantly reduces withdrawal
signs and interrupts drug craving thus returning
patients to what they describe as a preaddictive
state. This is a state that most drug users thought
they would never experience again after years
of being dependent. It is a state in which free
choice is returned to the user and that is
important to understand.
Its in your hands now!