ROOTING FOR A MIRACLE
Disputed Derivative Of African Plant Studied As Cure For Drug Addicts

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.