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Nov 10, 1999, 3:00:00 AM11/10/99
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Rooting for a Miracle / Disputed derivative of African plant

studied as cure for drug addicts

BY: By Jamie Talan. STAFF WRITER

EDITION: ALL EDITIONS

SECTION: Discovery

DATE: 11-09-1999

C03

FOR AT LEAST 100 YEARS, ibogaine, a chemical derived for the

root of an African plant, has been thought to have transforming powers.

Now touted by some for its ability to stop drug craving, the substance

remains controversial.

This past weekend, dozens of scientists who have worked with

ibogaine in the laboratory, and some who have used it experimentally on

drug addicts, arrived at New York University School of Medicine for the

first scientific conference on the substance.

Some say ibogaine, which is taken in a single oral dose, could be a

"magic bullet." Many more say that the plant substance could, at the

very least, help scientists unravel the biological underpinnings of drug

abuse.

But the substance has long been entwined in complex legal, social,

medical and scientific issues that complicate efforts to develop it as a

treatment for drug addiction, among them its unusual history and its

hallucinatory effects.

In 1963, a young New York heroin addict discovered that a one-time

recreational use of ibogaine abolished his desire for heroin. This same

man, Howard Lostof of Staten Island, has spent years trying to convince

scientists and federal regulators of ibogaine's powers.

Now, Lostof says, his day has come. "To have scientists come

together to discuss ibogaine is a dream come true," says Lostof, now 56.

He remembers well that as a "neophyte" heroin addict he experienced

a "complete change in my philosophy of heroin after I took ibogaine." It

wasn't until the mid-1980s that Lostof decided to take patents out for

his discovery, and it was then that he began his hunt for a scientist

interested in studying the substance.

But even scientific data-more than 140 animal and lab studies have

been done to show that it does indeed have some power in reducing drug

craving-might not be enough to get the substance into the hands of

companies with enough money to develop it. The fact that a former addict

laid claim to the therapeutic benefits of ibogaine has been cited as one

of the reasons pharmaceutical companies and the federal government have

passed on developing it as a treatment for drug abuse.

But scientists at the meeting say there is a more rational

explanation: Ibogaine causes visual and auditory hallucinations, said

Dr. Stanley Glick, a professor of pharmacology and neuroscience at

Albany Medical Center and one of the presenters at the meeting.

"It's extremely unlikely that ibogaine will ever be approved for use

in this country," because of its hallucinogenic effects, Glick says.

It's hard to get pharmaceutical companies interested in developing

compounds to help drug addicts, many scientists at the conference agree.

Testing has been fraught with concerns, including difficulties with

involving what can be an unreliable and transient population in clinical

trials.

But Glick says he has found evidence in his work with animals

suggesting that a study of ibogaine is worth pursuing.

"When you see the data and you talk to patients who were treated

with the substance, you've got to believe," he says. He has extensively

interviewed 12 patients who received the compound in facilities outside

of the United States "and only one had a negative reaction," he says.

Normally, he and others agree, detoxifying addicts is very difficult,

and keeping them off drugs is virtually impossible. Even the very best

treatments claim only a 30 percent success rate.

The ibogaine supporters, including Lotsof, who used to run treatment

programs in the Netherlands and Panama, say their success rates are 70

percent. "If true," Glick says, "that is remarkable. I find it hard to

discount all of these stories." Dr. Kenneth Alper, an assistant

professor of psychiatry and neurology at New York University, said he

organized the conference "with hopes that people will become interested

in studying ibogaine as a potent therapy." His colleague, Dr. Daniel

Luciano, also has witnessed people who, after one treatment of ibogaine,

had no craving for heroin and did not experience any withdrawal

symptoms. In many of these addicts, the effects would last weeks,

months, even years in some cases, Luciano said.

It was the strength of the animal work and the anecdotal reports

that led federal drug researchers at the National Institute of Drug

Abuse to spend a few million dollars studying ibogaine from 1992 to

1995. In March of 1995, about 75 people met at the federal building in

Rockville, Md., to discuss the scientific findings and the fate of the

substance. Many of the consultants were from pharmaceutical companies.

The vote came in against testing ibogaine in humans.

It was too risky, the consultants said. There had been two deaths

overseas of women who had taken the substance, and while it couldn't be

proved that ibogaine was the trigger, the reasoning was: Why take the

chance? Ibogaine is what scientists call "a dirty drug." It has so many

unusual effects and probably taps so many brain systems that it is hard

to know precisely why the drug is effective at eliminating withdrawal

symptoms and reducing the physical and psychological craving for

narcotics.

Phil Skolnick, a neuroscientist at Eli Lilly and Co., worked on

ibogaine when he directed a laboratory at the National Institutes of

Health. One of his post-doctoral fellows, Piotr Popik, had read about

ibogaine in 1993 and thought that it was having its effects on an

important brain receptor called the NMDA-glutamate channel. And, in his

hands, Popik found that the substance did indeed block this channel. A

few years earlier, other scientists had reported that substances that

block these NMDA receptors stopped tolerance to heroin, morphine and

nicotine.

Ibogaine, the federal scientists demonstrated, had a weak affinity

for these receptors. The team also found that it targeted more than 15

different receptors in the brain.

But if the substance is having its beneficial anti-drug effects

through the NMDA receptor, Skolnick told colleagues at the ibogaine

conference, perhaps new molecules could be developed to target this

brain system. Pharmaceutical companies are competing to develop

so-called NMDA antagonists, and several have been dropped on reaching

the human stage of development after it was observed that the substances

triggered transient schizophrenia-like symptoms in users.

Doctors who have been with addicts during ibogaine treatment say it

does not cause the psychedelic hallucinations that had led drugs like

LSD to be classified as illegal substances. Indeed, it has powerful

effects on the brain, and one of the most striking, Alper says, is the

experience of an intense dream-like waking state.

"Patients say that it's like watching a rapid slide show of their

lives-a life review. They come away with great insights." He believes

that this process, which takes place in the first 24 hours after

swallowing a single capsule, has some effect on learning and memory and

could in part explain the drug's positive effects.

But others say it is the drug's effects on the biology of the brain

that impact behavior. Dr. Deborah Mash has been studying ibogaine since

the early 1990s, and it was her group at the University of Miami School

of Medicine that originally teamed up with Howard Lostof to submit a

proposal to the FDA to use ibogaine in humans. After a falling out with

Lostof-the two are now in federal court over patent issues-Mash turned

her attention to an ibogaine metabolite or byproduct called noribogaine,

which she said works on serotonin receptors and on receptor sites that

morphine targets.

Other scientists think ibogaine may work on a pathway in the brain

region called the nucleus accumbens, which has been linked to reward and

motivation.

This pathway is regulated in large part by a brain chemical called

dopamine.

Whatever the exact system may be, Mash believes that ibogaine works.

Because of the pending litigation, she has had to take her research

to the island of St. Kitts, where addicts come to receive ibogaine.

Unlike conventional experimental drug trials, they pay for the

treatment. Mash said that 80 Americans have been through her program and

that "we've demonstrated that ibogaine is effective at blocking

withdrawal." If addicts can make it through the difficult withdrawal

phase without symptoms, it is much easier to begin psychotherapy or

other types of support interventions. But it also seems that ibogaine

has longer-lasting effects, even though the substance is cleared from

the brain after the first day.

She said many patients have continued to remain free of heroin for a

few years.

"We care about the science and whether it can help people," said

Mash. "If there is something fundamental about ibogaine, maybe we can

learn from it. This may be the lead molecule that points us in the right

direction." Luciano, who also presented his findings at the meeting,

said that "there is definitely something there-to see heroin and cocaine

addicts have no signs of withdrawal and then a week later say they have

no desire for the drug was very dramatic.'' Mash said patients still

will need psychotherapy and counseling to beat their addiction, and even

to make sense of the ibogaine experience-patients have talked about the

life review, and then the deep introspection that follows. She said the

treatment looks promising for heroin, morphine and alcohol, but it

doesn't seem to work against crack cocaine.

No one can doubt that ibogaine has traveled a great distance from

its use as a visionary sacrament in the villages of Central and West

Africa. There, natives undergoing rituals of enlightenment eat the roots

of the Tabernanthe iboga plant. Ironically, the ritual is referred to as

"cracking the skull," and the amounts ingested are 60 times the amount

used in the clinics to treat drug abuse.

ILLUSTRATION/PHOTO: 1) Photo by Richard Slattery - Dr. Kenneth Alper

organized a

conference to encourage the study of ibogaine as a therapy. 2) Photo

by Moises Saman - Howard Lostof.

KEYWORDS: PLANT. RESEARCH. TREATMENT. DRUG. ABUSE. IBOGAINE. AFRICA. QUOTE.


For in depth ibogaine information: http://www.ibogaine.desk.nl

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