Copyright 1993 The New York Times Company
The New York Times
October 27, 1993, Wednesday, Late Edition – Final
SECTION: Section C; Page 11; Column 1; Science Desk; Health Page
LOAD-DATE-MDX: November 16, 1993
LENGTH: 1604 words
HEADLINE: A Bizarre Drug Tested in the Hope of Helping Drug Addicts
BYLINE: By SANDRA BLAKESLEE
BODY: DRIVEN by a deep sense of frustration that efforts to cure drug addiction are going nowhere, Federal researchers are testing a bizarre, mind- altering drug called ibogaine as a possible new treatment for cocaine and heroin addiction.
The drug, drawn from the roots of a West African shrub, has been tried on only 60 people. But several doctors and patients say that the compound works wonders, often banishing symptoms of withdrawal and craving for months if not years. Intrigued and at the same time skeptical, researchers have decided to see if the drug works as well as its supporters claim.
Their work with ibogaine has opened the door to a new theory of how the brain becomes addicted to substances like heroin, cocaine, nicotine and alcohol.
The theory, which runs counter to current models of drug dependency, suggests that addiction is rooted in the cerebellum, the area of the brain where the connections for motor coordination, memory and dreams meet, and that it involves the same kind of ingrained conditioning that informs learning to walk in early childhood.
Ibogaine advocates claim that a single dose of ibogaine taps into this critical brain circuit and banishes withdrawal symptoms and drug cravings, sometimes for extensive periods.
Evidence Is Anecdotal
But scientists who are familiar with the drug urge caution. “At this point, there is no credible scientific evidence that ibogaine cures addiction,” said Dr. Herbert Kleber, a psychiatrist and director of the division of substance abuse at Columbia University College of Physicians and Surgeons in New York. “All the evidence is anecdotal and not based on carefully controlled scientific studies.”
Nevertheless, since every effort to find a cure for cocaine addiction has so far failed, “it is appropriate to look at any promising agent to see if it works,” Dr. Kleber said. “It would be foolish to rule anything out.”
And, indeed, driven by this sense of frustration and a Congressional mandate to seek effective treatments for drug abuse, Federal researchers are taking a close look at ibogaine. In the last year the National Institute of Drug Abuse has sponsored 18 animal studies on the compound. And in August, the Food and Drug Administration decided to let researchers begin limited testing of the drug in humans. At least three clinical trials are planned.
“The F.D.A. recognizes drug-abuse disorders as being lethal disorders with no good current therapy,” said Dr. Curtis Wright, a medical officer at the agency. “Right now we don’t have any other candidate drug that looks as good as ibogaine. At least we have a group of patients and doctors who say this stuff works.”
Initiation Rites in Gabon
Used in pubertal initiation rites in Gabon, ibogaine induces a powerful altered state for at least 48 hours, during which young people are said to come into contact with a universal ancestor called Bwiti.
In 1962, when psychedelic drugs were newly popular in the United States, a group of 20 recreational drug users, including a young heroin addict named Howard Lotsof, heard about the drug and decided to try it. Of the seven who were heroin addicts, five, including Mr. Lotsof, claimed that taking the drug extinguished, at least temporarily, their desire for heroin. The other two, in spite of similar feelings, decided to go on using heroin anyway, Mr. Lotsof said in a recent interview, because they were Beat Generation poets and, they said, they liked being junkies.
“For ibogaine to work,” Mr. Lotsof said, “you have to not want to continue on drugs. Some people don’t want to kick their habit and ibogaine cannot help them.”
When the AIDS epidemic began claiming the lives of thousands of drug addicts, Mr. Lotsof’s continuing interest in ibogaine grew into a crusade. In the mid-1980’s, he persuaded a Belgian company to manufacture ibogaine in capsule form and begin offering it to addicts in the Netherlands, where drug policies are lenient. Like LSD, mescaline and many other drugs, ibogaine is illegal in the United States.
Of the 60 people who have been treated thus far, 50 were recruited by an addict self-help group in the Netherlands, Mr. Lotsof said. “These were people who had failed all other treatments and had completely hit bottom,” he said. Very little information exists about the long-term effect of the drug, but at least three remained free of drugs for several years.
“We anticipate that many of the 50 volunteers fell back into drug use,” Mr. Lotsof said, “but we have no way of tracking them.”
Treatment with ibogaine is ordinarily a three-stage process. After taking a capsule, a patient first lies quietly until, after a couple of hours, he or she falls into a waking dream state. “When you open your eyes the dream stops,” Mr. Lotsof said. “The drug does not produce euphoria. Instead, people find that repressed memories are released in the dreams, memories that may have markers saying ‘don’t go near this, it hurts.’ ” He stressed that this is a very different state from hallucination, over which a patient has no control.
After four to five hours, a second stage, which Mr. Lotsof calls a cognitive-evaluation stage, begins, lasting 8 to 20 hours. “Many clients describe it as 2 to 10 years of psychoanalysis in 20 hours,” Mr. Lotsof said. “You have the complete underlying psychopathology of your life revealed to you, which helps you understand why you’ve been using drugs.”
The third stage is a period of intense wakefulness, which may last for a day or two.
The 18 animal studies sponsored by the drug institute in the last year have examined the pharmacological and toxicological effects of ibogaine, including experiments to see whether the drug relieves symptoms of withdrawal from heroin or cocaine addiction. In one such study, ibogaine had no effect. In another it offered some relief. And in yet another, animals experienced substantial relief from withdrawal symptoms, said Dr. Frank Vocci, head of the ibogaine research program at the drug institute.
Different investigators used different strains of mice and rats, which may explain the contradictions, Dr. Vocci said. Moreover, rodents, like humans, show a wide variation in their response to addictive drugs and to ibogaine. More work is needed in this area, he said.
Charting Brain Pathways
For another study, the drug institute asked Dr. Mark Molliver and Dr. Elizabeth O’Hearn, experts at the Johns Hopkins Medical School on how drugs damage brain cells, to examine ibogaine.
The researchers gave rats huge doses of ibogaine, reasoning that areas showing damage would reflect where the drug was active in the brain. Rats thus treated developed tremors and a lack of muscle coordination called ataxia, Dr. Molliver said. A close examination showed that some cells in the cerebellum were being destroyed by the drug.
The cerebellum is the part of the brain where smooth muscle motor control, balance and coordination are carried out, Dr. Molliver said. It helps the body get its bearings.
But recent research indicates that it also receives inputs from just about every other part of the brain, including the spinal cord and a central area of the brain stem where dreams are initiated. The cerebellum appears to play an important role in learning and remembering, particularly stereotypic behaviors, skills and conditioned responses, Dr. Molliver said.
Dr. Molliver said that he thinks ibogaine does not act directly on cells in the cerebellum. Rather, it seems to target an area of the brain stem called the inferior olive, a pacemaker that sends timing information to the cerebellum. Ibogaine activates olive cells for hours, causing them to release excitatory transmitters that flood cells in cerebellum, eventually killing some of them.
Most addiction research has focused on brain circuits that use the neurotransmitter dopamine as a reward, Dr. Molliver said. But if ibogaine eliminates drug withdrawal and craving — and Dr. Molliver stressed this has yet to be proved — it means addiction might be routed through the cerebellum and that different, perhaps undiscovered, neurotransmitters are involved.
“Addiction is learned,” Mr. Lotsof said. “It takes time to become dependent on any drug. Then people become sensitive to cues in the environment. If Dr. Molliver is right, we might be seeing with ibogaine an unlearning of the addiction process.” In other words, he said, the waking dreams elicited by the drug may literally unstructure the neural circuitry laid down when the addiction was acquired.
At the University of Florida Medical School in Miami, Dr. Deborah Mash is eager to begin human trials with ibogaine. Dade county has a serious AIDS and crack-cocaine epidemic, “and I don’t think we have any time to waste,” she said. “We need to find out if this drug works.”
Dr. Molliver’s findings have made the F.D.A. very worried that ibogaine might kill too many cells in the cerebellum, Dr. Mash said. But experiments in her laboratory show that ibogaine given in therapeutic doses does not cause similar brain damage in monkeys. And other studies show that there is more brain damage associated with cold-turkey withdrawal from opiates and cocaine than from ibogaine.
For now, Dr. Mash has permission from the F.D.A. to test extremely low doses of ibogaine in nine people who have already taken the drug to see how their bodies use the compound. Once that is done, she said, it should be possible, as early as next year, to test therapeutic doses in people who have never taken ibogaine.
GRAPHIC: Diagram: “Ibogaine Vs. Addiction: A Theory”
Some researchers think Ibogaine, a drug from the root of a West African shrub, taps a critical brain circuit involved in habitual behavior. The theory is that the drug acts on cells in the inferior olive, in the brain stem, a pacemaker for the cerebellum.
Cells extending from the inferior olive excite the many-branched Purkinje cells of the cerebellum, flooding them with neurotransmitters. The theory is that enough of the cells are destroyed to affect learning and remembering, particularly stereotypic behaviors, skills and conditioned responses.
(Source: “The Human Central Nervous System: A Synopisis and Analysis,” Nieuwenhuys, Voogd and Van Huiijzens)