By Michael E. Miller
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By David Villano
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Mash's work on coca-ethylene also led her to an advisory role with NIDA and participation on peer-review committees evaluating grant proposals -- high-level contacts that would help her in developing her FDA application for human ibogaine trials.
But obtaining the FDA's permission to perform safety trials on ibogaine veterans ended up creating research obstacles that Mash hadn't anticipated. Because many experienced ibogaine users were middle-aged, they were at risk of developing other medical conditions -- heart or liver disease, for example -- that would make it difficult for the team to isolate the effects of ibogaine. Others were too ill, their immune and vascular systems ravaged by prolonged drug use.
Mash finally tracked down nine research subjects in acceptable physical condition, all of them current or former patients of Lotsof. But flying them to South Florida -- from their homes around the globe or from Panama, where Lotsof's treatment program was under way -- added greatly to the cost of testing.
Then in May 1994, one of the university's ibogaine research subjects, a 36-year-old woman with a twenty-year history of drug abuse, died in Fort Lauderdale, where she had come to participate in medical tests as part of the university's study. The patient, "N.H.," had been undergoing ibogaine treatment in Panama and had agreed that when she died she would donate her brain to assist Mash's research. "If she died because of ibogaine," says Mash, "I needed to tell the FDA."
Mash assisted in the postmortem. The cause of death proved to be loss of blood to the bowel, caused by an obstruction. The following day Mash examined the woman's brain in her lab at the University of Miami. "She had taken [ibogaine] four times at the high end of the FDA doses," Mash says. "The high end, the high-end FDA doses, and no brain damage!" That fact would help to show that the drug could be safe for human trials.
During the same year Mash's team discovered a metabolite -- a chemical created by the body's processing of ibogaine -- that she believed could be even more effective than ibogaine in combating addiction. She says she shared her discovery with Lotsof, explaining what "noribogaine" was and how the researchers had come upon it. Lotsof agreed to give the university a share of any profits from noribogaine, and in December 1994 NDA International and the university amended their original contract so that it guaranteed the university a twelve-percent share of any possible future sales of noribogaine and its derivatives.
Mash and her colleagues later formulated a theory that noribogaine combined with chemicals found in the brain called betacarbolines could possibly work more effectively than either ibogaine or noribogaine alone. At the time, she was still studying Lotsof's ibogaine treatments in Panama, and she says she kept him fully informed about her discovery. (Lotsof contends he already knew about noribogaine and its potentially enhanced effects in combination with betacarbolines.) But any further research into these new chemical relatives depended on Mash first testing ibogaine's safety in humans, and the high costs had made those trials increasingly difficult to complete.
Mash was trying to obtain more money from NIDA for her research, and she believed that the new information she had developed, both from studying the brain of N.H. and from noribogaine, could only help her. Armed with this new data, she returned to the FDA in 1995 and asked for permission to expand her trials so she could administer the drug to cocaine addicts and others who had never tried ibogaine. The FDA agreed. Finally, Mash would be allowed to study the effects of ibogaine on subjects with no previous exposure to it.
To complete the study, Mash and her team estimated they needed to raise at least $7000 per patient per dose of ibogaine in order to pay the costs of medical tests done before and after the treatment, and she says she could not responsibly launch such a study if she didn't have a guaranteed source of funding.
During 1993 and 1994 Mash's team submitted four grant requests to NIDA to finance parts of the investigation, but the agency rejected all the proposals.
"NIDA has totally backed away from [ibogaine]," says Dr. Stanley Glick, chief of the pharmacology department at Albany College of Medicine in New York; he has performed extensive research on ibogaine and its effects in rats. In 1989 Glick had also worked with Lotsof, who paid the Albany research team for its work. "There's no question that there's a political barrier. Why it's there I really don't understand, but I received advice from people I know at NIDA, who were acting in my best interest, advising me to work on something else."
Mash's last, and largest, funding request was for a $1.5 million NIDA grant to underwrite a team of 22 researchers. The plan was to slowly increase the dosage and determine at what levels it could safely be administered. Mash also designed the study so that it could answer some preliminary questions about the drug's efficacy, in case the FDA eventually approved further testing. NIDA held several public hearings about the drug, and Lotsof, who continued his ibogaine treatments in Panama, attended every one. But Mash was careful not to ask him to testify in favor of her application, even though she had been running tests on his patients.