Brain Waves

How a UM doctor may soon unveil the ultimate cure for addictions,

and uncovered the mystery surrounding sudden cocaine deaths

(Reprinted from South Florida magazine)

By Nina L. Diamond. Photograph by Jane Mitchell

Cocaine overdoses had become more common in South Florida than frostbite in Alaska. At the peak of cocaine deaths, about seven years ago, Dr. Lee Hearn, laboratory director of the Metro-Dade Medical Examiner's Department, was at a loss to explain why so many people were dying of coke overdoses when the blood-levels of the drug were much lower than what was usually considered a lethal dose. The bodies came in, fluids and tissues were studied, and it was more of the same. Why were all these people dying?

Just a few minutes from Hearn's office near Jackson Memorial Hospital, west of downtown Miami, neuroscientist Dr. Deborah Mash, who'd known Hearn since their grad school days at the University of Miami, was busy running the UM School of Medicine's Brain Endowment Bank, teaching neurology and pharmacology, and keeping up with a full schedule of brain research. In her mid-30s then, Mash had already made a name for herself in Alzheimer's and Parkinson's disease research, and, as a specialist in pharmacology, she routinely played detective, studying the body's response not only to outside chemicals, but also to the ones the body itself created. By 1989, Hearn had noticed something quite unusual in the blood of fatal coke overdose cases. "As I reviewed cases, I saw that cocaethylene was often present in the blood. But nobody knew what it did."

Cocaethylene, discovered about 10 years ago, is manufactured by enzymes in the liver when cocaine and alcohol are mixed. It was thought to only be present in the urine, and to be of little consequence. So, when Hearn called scientists at Yale University and asked if they knew about any cocaethylene studies, he was told that this third drug, created by our own bodies, doesn't make its way into the blood stream. "Yes it does," Hearn replied. "We see it all the time." He sent samples. Yale verified them.

With proof in hand that he wasn't imagining things, Hearn went to his old pal Mash at UM. Backed by a National Institute on Drug Abuse (NIDA) grant, Mash and her colleagues had already embarked on a study of the cocaine overdose epidemic.

"Sometimes there's more cocaethylene in these people than cocaine," Hearn told Mash.

Convinced that cocaethylene was the culprit in the majority of these surprisingly deadly overdoses, Mash was determined to prove that it was not a harmless by-product, but a killer. She and Hearn joined forces, bringing their staffs at UM and the Metro-Dade Medical Examiner's office together in the name of science.

They worked on little else for the last part of 1990, and in record time-less than six months-Mash, Hearn and their team not only were the first to prove that cocaethylene is an active drug, they also had their breakthrough findings published in the January 1991 Journal of Neurochemistry.

"Miami is a unique place to do this research," says Mash, grabbing a precious 60 minutes out of her 12-hour work day to talk about their landmark findings and continued research, and the state of chemical addiction. At least twice a month, Mash is gone for days at a time, traveling the world to deliver research papers, conduct studies and touch base with the National Institutes of Health (NIH) in Bethesda, Maryland, where she is a consultant. For three months we spoke weekly, between her airport adventures. "Cocaine is one of the primary substances people here use and abuse. Not heroin, like elsewhere. And we have a high number of cocaine emergencies and overdoses."

Mash notes it's only fitting that, "as a transit point for cocaine entering the U.S.," Miami should also be home to the most promising research.

"We were trying to understand the toxicology. Many died from what should have been safe levels of cocaine in their bodies," she recalls. "We thought maybe there was a processing contaminant, a toxic by-product created when cocaine was made in labs. But that didn't explain it. We noticed that most people-five million Americans-combine cocaine with alcohol. It's the most frequent two-way drug combo. Could cocaethylene be the culprit? We measured it in specimens of blood, brain and liver tissues and found it higher in some instances than the levels of coke itself! Then we demonstrated that it's pharmacologically active. And we found that it packs the same 'reward punch' on the brain as cocaine and alcohol do separately, but cocaethylene gives a longer and stronger high and has a much longer half-life than cocaine."

This extra kick was often the last kick. "It's more potent than cocaine in causing deaths," says Mash. "It's more lethal than cocaine."

Her work, she says, is "like reading chapters of a very good detective story." The much-published 41-year-old scientist shies away from the term "workaholic." Instead, she likes to say that "science is away of life. You don't walk away from this."

Despite the fact that she's married to prominent Dade Democratic party leader and attorney Joe Geller (" Joe who?" she quips. "I hardly ever see him."), and has been a commissioner for the City of North Bay Village since 1988, Mash's life is otherwise consumed by her scientific crusade. "Intellectually, I never grow weary of it. I love the discovery. Every day I'm faced with something new. I learn every day."

Mash grew up in Hollywood, where her teachers fast-tracked her in math and science when she showed both interest and tremendous talent. A competitive kid, she won science fairs with her biochemistry projects, and, as a senior in high school, she "discovered brain science while studying psychology." She knew then, she says, that it would be her life's work.

"I briefly toyed with being a medical doctor," she recalls. "But I wanted to devote 100 percent of my life to research."

Mash has never fit the stereotype of the stuffy scientist who's quiet, prim and unaware of life outside the lab. Far from it. In college at FSU, she looked like Cher, with waist-length black curls, an exotic aura, and eye-catching, funky leather outfits. Ever the crusader, Mash spoke out against the Vietnam War and whatever other social causes stirred her passions. At his law school graduation, her husband, Joe, blurted out an impromptu plea to stop the death penalty while on stage receiving his diploma. They were-and still are-quite the couple.

Now, her crusade is to understand, prevent and treat drug and alcohol addiction, both scientifically and sociologically. "I pore over research at home, I design experiments in the car on the way to the lab. To combat abuse, we have to understand brain changes and dependency. Then we can design specific therapeutic intervention. When we understand craving, we can know how to block it," she says enthusiastically. "We want to stop the progression, to keep people off drugs and alcohol. We all pay, and it's a hefty price tag. Just look at the crack babies."

Mash and her colleagues approach the problem from all angles. "We now have the Comprehensive Drug Research , Center at UM to study and bridge the relationship between scientists and treatment people," she says. "Classic treatment approaches have largely failed. It's an illness, and we have to design new treatments based on what we're learning about how these chemicals change the brain. We're also studying the long-term effects of drug and alcohol abuse."

She's now researching how cocaine and alcohol accelerate cardiovascular disease. "Cocaine and alcohol do major damage to the heart and brain. We're looking at heart disease and cognitive and behavioral problems in people. Cocaine may cause depletion of dopamine in the brain, which may lead to Parkinson's disease. We already know this is true of amphetamines. People taking them over time were stricken with movement disease not unlike Parkinson's."

Combining cocaine and alcohol takes an even higher toll on the body. "The dual addiction is a harder addiction to break. We're looking into that. And it causes thickening of the arteries. We think the deterioration is happening quickly, too. Hearts that are 30 look like they're 70. We may see a young generation die off from heart disease."

Cocaethylene also plays a role in AIDS. "It may give the HIV virus a boost," Mash reveals. "And our discovery that cocaethylene is active in the body has helped spawn this new angle in HIV research."

But the most exciting, most mind-boggling development in the history of drug and alcohol treatment is the new drug ibogaine. And guess who may get to introduce this bona fide cure for addiction? That's right-Mash and her colleagues at both UM and the Metro-Dade Medical Examiner's department. As we go to press, she's awaiting approval from the Food and Drug Administration (FDA) to conduct safety trials. This is the first step-testing ibogaine on people in a controlled scientific setting-in the official process that makes a drug legal for use in the United States.

"The FDA has been very responsive on this one," Mash says, feeling 99 percent certain that they will grant her request. "We have a congressional mandate to help people get off drugs. And we know that drugs are co-factors for HIV."

Mash is just the latest link in the ibogaine story, but the one that will bridge the gap between anecdotal evidence and the scientific proof needed for FDA approval. Ibogaine is derived from the roots of Tabernathe iboga, a shrub native to equatorial Africa, where tribes have long used it in small doses to remain alert while hunting, and in larger doses during sacred rituals.

Back in 1962, Howard Lotsof, then "part of the New York film scene at NYU's film school, and a heroin addict, was looking for a new high, when he discovered ibogaine," says Mash. "After his 36-hour 'trip' on ibogaine, he found he had completely lost his desire for heroin, and had no withdrawal symptoms."

Lotsof gave the substance to other addicts, and they, too, were instantly un-hooked from the drugs that previously had controlled their lives. "The International Coalition for Addict Self-Help ran underground trial testing on ibogaine," Mash says, "and it was found to cure addictions to heroin, cocaine, amphetamines, alcohol and nicotine." This so-called anecdotal evidence has shown that ibogaine cures addiction almost 100 percent of the time. In 1986, Lotsof formed NDA International and secured a use patent on ibogaine for treating drug and alcohol addiction. Scientific study began in the Netherlands three years ago, with more than three dozen addicts as test cases. Mash was among the U.S. scientists and doctors invited to Leiden, Holland to witness ibogaine in action.

"It puts you into a 36-hour waking dream state. It's a psychoactive drug, but not a hallucinogen like LSD. During this altered state of consciousness, you relive your childhood experiences," she says. "You get to the roots of your addictions."

One trip on ibogaine is like 30 years on a therapist's couch.

"Ibogaine was used as a rite of passage from childhood to adulthood in Africa," says Hearn. "And now it can be used to reprogram the addict's life. He's detached from childhood recollection while on Ibogaine, but is reexamining it, coming to grips with it, perhaps understanding it for the first time. All neuroses are solvable this way, not just the ones that lead to addiction."

Using ibogaine, then, helps address the cause of the addiction. "Drug addiction is an illness of the spirit," says Hearn. "If you're going to cure it, you have to cure it at that level."

Scientists and treatment professionals have long known that trauma, insecurities, fears and the like are the very foundations of psychological distress, which includes addiction. "With addiction, people feel good because it fills a gap in their lives," notes Hearn. "The drug or alcohol substitutes for something lacking, and it's used to cope, too."

So, when you literally "trip down memory lane" with ibogaine, you come to grips with all those experiences you swept under your emotional carpet so long ago. This miracle drug also "cures the anxiety of detachment from a long-term habit," says Hearn, whose Metro-Dade Medical Examiner's lab will be involved in Mash's FDA safety trials by analyzing the long-term blood concentration of ibogaine.

So far, no one has ever had a "bad trip" on ibogaine, and the only side effect reported is slight nausea at the beginning of the 36-hour treatment. Mash has used ibogaine on monkeys and found that "it's not toxic to the brain," she says. "And there were no adverse effects in the people who took it in Holland. Toxicity only showed up in a study at Johns Hopkins University, and it was only toxic in ridiculously high doses."

While it's evident how ibogaine works psychologically, physiologically "it's still a mystery," Mash admits. "It doesn't bind to any known receptor in the brain." It has been shown to have an effect on dopamine, causing the brain to release less of this chemical, which in turn lessens the effects of cocaine.

Mash and her colleagues will test ibogaine on cocaine addicts during the FDA safety trials. Her team includes two medical doctors-one is a neurologist and the other a psychiatrist specializing in addiction-and a social worker who is an expert on inner-child work.

"Unfortunately, a negative bias has evolved surrounding the use of psychoactive drugs," Hearn laments, "because of the recreational use of drugs like LSD. But it's a mistake to label them as bad just because they're mind-active. We need to distinguish among them. Different drugs are different in their activities. This is not LSD. There are no bad trips, flashbacks or people wanting to jump off buildings to see if they can fly. Maybe ibogaine will change some of the misperceptions and open the door to research with psychoactive drugs."

Mash agrees, adding, "Treating drug dependence with a drug is still considered by people to be ironic."

But, summing up both ibogaine and her non-stop work delving into the brain, she sighs: "God works in strange and mysterious ways."