OBSCURE PLANT MAY BE KEY TO BREAKING ADDICTION'S HOLD

WASHINGTON -- The answer to America's drug problem may lie somewhere in the
roots of an obscure plant that grows wild in African rain forests. That is,
if only scientists could read and follow the directions the plant seems to
be giving them.

With a single capsule -- or perhaps several over a period of weeks --
heroin addicts, alcoholics, cocaine users, even smokers might erase or at
least interrupt their cravings. One researcher talks hopefully of a skin
patch from which addicts would slowly absorb a compound that blocks the
biochemical events that trigger the desire to smoke, shoot up or drink.

But after several million dollars' worth of federally funded research,
efforts to understand the plant and the properties of a compound squeezed
from its cells have foundered on a tangle of lawsuits and conflicting
scientific results.

That is unfortunate, said Dr. Stanley Glick, chairman of the department of
pharmacology and neuroscience at Albany Medical College in New York. "In my
view, it is something that certainly should be investigated," Glick said.
"When you hear the same stories from enough people enough times, you have
to believe that there's something at least worth investigating."

The stories Glick and others have been hearing for a decade involve the
results of "offshore" treatment of drug addicts at clinics in the Caribbean
and Panama with a substance called ibogaine. In dozens of cases, addicts
report that a day or two after taking ibogaine, a relatively mild
hallucinogen, they are strangely free of cravings.

The plant from which ibogaine is extracted is Tabernanthe iboga, and
hunters in the African nation of Gabon have known about it for centuries.
They say eating small quantities of iboga root enables them to remain
alert, yet motionless, for hours on end.

But until 1962, when Howard S. Lotsof, then a New York film student,
decided to try the drug, no one knew of its effect on addiction.

Lotsof said that he and several friends were experimenting with a variety
of psychoactive drugs, including LSD and heroin. He had no intention of
ending any kind of drug use when he heard about ibogaine and decided to
give it a try, he said.

"Thirty hours later, my desire to use heroin had vanished," he recalled. He
suggested that several other friends give it a try, and they had the same
experience.

For years, Lotsof did nothing about ibogaine. But in 1980, he decided the
discovery was too important to be ignored. He filed patents on the use of
the drug to treat addiction and formed a New York corporation, NDA
International Inc. The purpose of the company is to market a preparation he
named Endabuse, composed of capsules that contain an ibogaine compound, and
to pursue research. He sought Food and Drug Administration approval for
clinical trials of the drug.

By then, ibogaine had been designated a controlled substance by the U.S.
Drug Enforcement Administration, like cocaine and marijuana. With the
cooperation of physicians in the Netherlands, Lotsof opened a clinic to
treat heroin addicts there, where it was legal.

Several patients reported the treatments relieved their cravings. Others
were not helped. One young woman died.

Meanwhile, Lotsof met Dr. Deborah Mash, a brain researcher at the
University of Miami School of Medicine. In 1992, Lotsof's company and the
university signed a contract for Mash to conduct research on ibogaine and
seek FDA approval for human trials. Under the contract, Lotsof and NDA
retained the rights to ibogaine and any "discoveries, inventions or
improvements" growing out of Mash's research.

In 1993, FDA approved her proposal for a clinical trial in which a few
volunteers would take ibogaine to assess its side effects. About the same
time, animal studies into the drug's effect were beginning to show results.

In studies at Albany Medical College, funded by the National Institute on
Drug Abuse, Glick found that drug-addicted laboratory rats injected with
ibogaine appeared to lose their craving for heroin, cocaine and nicotine.
Other researchers found that ibogaine interfered with addiction to alcohol,
Glick said.

Although no one knows why this happens, Glick and others theorize that
something in ibogaine hinders the molecular processes by which drugs
stimulate the feeling of pleasure and craving in the brain. "I think there
is enough information to warrant doing reputable clinical investigations,"
Glick said. "There is a wealth of animal data. I think there is very good
evidence, and some of it we provided, that the drug may interfere with
addiction to opiates, stimulants, (alcohol) and nicotine."

But other animal experiments were not so encouraging. Scientists at Johns
Hopkins University reported that ibogaine destroyed brain cells in rats.
Another study showed it caused heart problems.

Then the lawsuits began.

In 1997, Mash sued NDA and Lotsof, accusing him of failing to keep up his
end of the contract by not obtaining adequate patent protection for a new
ibogaine-related compound she and her associates had discovered. She sought
$50,000 in damages and asked a federal court in Miami to let her and the
university out of the contract. Lotsof countersued, accusing the university
and Mash of defrauding him and stealing his patented uses of ibogaine. He
also said that by operating an ibogaine clinic on the Caribbean island of
St. Kitts, the university and Mash were illegally competing with a similar
clinic he had opened in Panama to obtain clinical data.

Mash said she owned no interest in the St. Kitts clinic, where she
acknowledges ibogaine is used to treat addicts, but said her husband, a
Miami lawyer, is legal adviser to "investors" behind the St. Kitts clinic.
She also said patients pay up to $10,000 for her treatments.

The FDA-approved trials are on hold because of lack of money to continue
and because of the lawsuits, she said. Meanwhile, after spending more than
$2 million on research grants, the National Institute on Drug Abuse is
losing interest in ibogaine. "The drug doesn't look terribly promising in
terms of the risks and benefits," said Frank Vocci, director of its
Medications Development Division.

Vocci said he believes Glick is the only researcher still receiving support
from the institute for ibogaine experiments. And Glick said he thinks it is
unlikely ibogaine will ever be approved as a drug to treat addiction, but
he still believes further research is worthwhile. "I also think there is a
good possibility that safer and more (effective) derivatives of ibogaine
could be successfully developed," he said. "Ibogaine is a benchmark against
which such derivatives will be compared and, for that reason alone, it is
important to know as much about ibogaine as possible."

Mash said she remains optimistic about ibogaine, despite the problems she
has had in obtaining money for research. She said ibogaine and its
derivatives offer hope of "a very gentle way for an addict to detox,"
perhaps someday through a skin patch.

Checked-by: Richard Lake