In 1962, a 19-year-old heroin addict from the Bronx, Howard Lotsof, received a white powder sample of an obscure African plant from a chemist friend.
"He was going through a freezer he had, and the freezer was full of different types of drugs," Lotsof says in an interview for the 2004 documentary film, Ibogaine: Rite of Passage. "He pulled out a small vial and said, 'I think you'll be interested in this.' And I said, 'Well, what is it?' And he said, 'Well, it's an African hallucinogen and it lasts 36 hours.'"
Lotsof took the drug. About 33 hours later, he remembered thinking, "I'm going to sleep for a week and I'm never going to take this drug again."
But then he went outside, and realized he wasn't in withdrawal. He looked at a tree and the clouds in the sky.
"I realized for the first time in my life, I was not frightened," he said, "and perceived that my entire life had been full of fear."
Lotsof was the first person to note that ibogaine, a hallucinogen derived from the bark of the Tabernanthe iboga plant, appears to relieve the symptoms of heroin withdrawal. Until that point, the plant, primarily found in Gabon, on the Atlantic coast of Africa, had mostly been used by the Bwiti religion as part of puberty initiation rites.
Lotsof's 2010 obituary in The New York Times, following his death at 66 from liver cancer, notes that following his recovery he started a lifelong campaign to research ibogaine and make it available to other addicts.
As a result of his work, thousands of recovered addicts and some scientists believe the drug has the potential to end addictions to everything from heroin to cocaine. Other studies and clinical information also apparently show early potential for the drug in treatment of other drug addictions, nicotine addiction, alcohol addiction, some mood disorders, Parkinson's Disease and even Hepatitis C.
Lotsof, reportedly, went on to persuade a Belgian company to produce ibogaine in pill form for addicts in the mid-1980s, and started the Dora Weiner Foundation in an effort to develop and advocate for the drug. Around that time, he received a patent for ibogaine to be used to counter addiction. His work provided data to the National Institute on Drug Abuse that led to research and ultimately paved the way to getting the U.S. Food and Drug Administration to approve clinical trials of the drug in 1993.
But the trials never were completed. Apparently, the reasons included contractual disputes, safety concerns, and — the biggie — a gigantic price tag. It's thought that completing the trials with private funding would cost tens of millions of dollars.
Lotsof, however, continued to participate in research of the drug until his death. He was the founder of NDA International, a for-profit drug company, and the Global Ibogaine Therapy Alliance (GITA), a nonprofit dedicated to advocating for ibogaine and supporting research of the drug. GITA, based in Montreal, continues his mission.
Despite all this, ibogaine is illegal in the United States, where it's listed as a Schedule I substance. For one thing, the drug causes intense hallucinations, frequently described as a "waking dream" by addicts, many of whom say the trip is a form of spiritual and psychological healing. Also, the drug does carry significant health risks, including death.
Addicts still access the drug, mostly at clinics in countries where the drug is legal or unregulated (that includes Canada and Mexico). But those clinics generally charge drug addicts thousands of dollars for ibogaine and often a host of other treatments, from massage to sweat lodges (See "Psychedelic miracles," July 20).
Lotsof's dream hasn't died yet. Years after his death, he may be close to realizing his goals — at least in part.
Aside from GITA, ongoing research and a patchwork of clinics, one of the lasting impacts of Lotsof's quest was a connection he made with Dr. Stanley D. Glick, professor emeritus of neuroscience and experimental therapeutics at Albany Medical College.
Glick, now retired, says he remembers the initial call from the former heroin addict.
"My research for about 40 years was focused on the neurobiology of drug addiction," Glick says. "And somewhere about 1989, I got a call from a gentleman by the name of Howard Lotsof. He described himself as a previous heroin addict and multi-drug user in the 1970s, and somewhere along the line he and a few of his friends went to some party where they were given ibogaine. How it got into this country is not clear, but it got there. And supposedly, out of the seven people who took it — apparently, they were all drug addicts — supposedly five of them lost their craving for drugs."
Glick recalls that Lotsof had started a company to promote ibogaine and contacted a lot of researchers.
"He thought he would tell the world about it and be embraced as a savior that rid the world of this terrible scourge," Glick remembers. "And then he found out that there's such a thing as science, the FDA, clinical trials, rules, regulations, whatever. And he realized that in order to get anywhere, he was going to have to get scientists to study it.
"So he started calling just about every drug abuse scientist in the country, and, for better or for worse, I was the first one that was fool enough to get interested and curious about it."
Glick says Lotsof never followed through on promises of research funding. Still, Glick continued to look into the drug.
There were setbacks to Glick's work. In the early 1990s, researchers at Johns Hopkins University discovered that ibogaine had some neurotoxicity problems. It was later also found to have some cardiovascular toxicity, which in some cases can even lead to death if not treated.
And then, of course, there was the fact that ibogaine caused hallucinations — not a plus if you're trying to bring a drug to market.
In 1995, Glick says, the National Institute on Drug Abuse convened a consensus conference on ibogaine, and anyone who had researched it was invited to give a presentation, including Glick. Consultants, he says, were brought in to decide if the drug was worth pursuing, but decided against it. There had been several deaths attributed to ibogaine at the time, leading to concerns.
"After that, the National Institute on Drug Abuse used their consultants' opinions to abandon it altogether," he says. "And unfortunately, there's never been a controlled clinical trial of ibogaine conducted, which I think is really a tragedy."
Glick says one problem is that people don't seem to accept that drug addiction is a disease. Many physicians are loath to treat drug users, he says, adding that it's been estimated that only 15 percent of drug users who need treatment nationwide are receiving it.
(It actually might be less than that. According to the National Institute on Drug Abuse website, "In 2011, 21.6 million persons aged 12 or older needed treatment for an illicit drug or alcohol use problem, but only 2.3 million received treatment at a specialty substance abuse facility.")"Imagine," he says, "if we had statistics like that for heart disease or cancer or diabetes or anything."
Glick, now 71, never abandoned ship. He spent much of the remainder of his career exploring ibogaine, mostly in partnership with Dr. Martin E. Kuehne, emeritus professor of chemistry at the University of Vermont. Ibogaine, Glick thought, had a lot of promise if he could somehow fix its side effects.
Kuehne, he says, began "sending me one derivative of ibogaine after another — we eventually tested about 60 of them — but it was about the 15th compound that we found what we were looking for. Meaning that we found a drug that seemed to produce all the positive putative effects of ibogaine — it worked in all of the addiction models in the laboratory similar to how ibogaine had worked — but it lacked all the toxicity.
"It's called 18-Methoxycoronaridine, or 18-MC for short."
Glick and Kuehne discovered 18-MC — which Glick does not believe will cause hallucinations — around 1995. Glick had a number of false starts finding a company to develop the drug, but eventually hooked up with Savant HWP Inc. of San Carlos, California, just south of San Francisco.
Glick says he hopes to see 18-MC approved in his lifetime. Even now, he says, he regularly takes calls from desperate heroin addicts or their parents hoping to get the drug.
"It's always depressing," he says, "because I can't give them any help right now."
Stephen Hurst, president and CEO of Savant HWP, explains 18-MC this way.
"Organic molecules have what's known as a backbone structure, a skeletal structure, and it can be a carbon chain, a circle of carbon atoms ... so ibogaine and 18-MC share the same chemical backbone," he says.
Glick and Kuehne, he says, changed the "side chains" — the molecules that hang off of the backbone. Then 18-MC, he says, proved to be the side chain change that had the desired effect — anti-addictive qualities, minus the psychedelic effects and toxicity.
Hurst calls 18-MC an extremely exciting drug because it does something that no other addiction drug has ever done.
"Addictions can come from different areas," he explains. "You know, cocaine works in a different way than heroin works. Nicotine works in a different way than heroin and cocaine. Methamphetamine works differently. Alcohol works differently. But they all have the same result, which is they all result in a — if you will — a storm of dopamine in the reward centers of the brain, which has neurons that project into the frontal cortex.
"So, you actually have the precept of pleasure as a result of these compounds. And I mean, we all know, pleasurable experiences are very compelling. They're sure a lot more compelling than unpleasurable ones.
"... The brain learns to seek out these compounds, these substances, or engage in these behaviors that cause this dopamine storm, if you will. And that becomes associated with environmental cues. What the brain will do is if you give it an environmental cue, it will already start to up-regulate the dopamine, but then if you don't get the substance, the brain kind of shuts everything down and withdraws dopamine back into the neurons in the pleasure centers of the brain. And that causes extreme distress.
"That's what craving is caused by. That's what causes recidivism and alcoholism and smoking and opiate — any form of addiction. As I describe it, it's why I can go into a Starbucks with the best of intentions of coming out with a tea and a banana, and end up walking out of the door with three bites out of a scone."
So here's what makes 18-MC different, Hurst says:
"This is the first drug that there is conclusive research data that show that it's effective regardless of what the substance is," he says. "Which means that the drug is working at the central mechanism of the disease, which is dopamine disregulation in the reward centers in the mid-brain. ... This is the same part of the brain that our fight or flight mechanism comes from — it's very primitive. It's common in all mammals and all substances, and certain compulsive behaviors as well, basically they all — they may start off at different ends of town, but they all end up in the town square, which is dopamine disregulation.
"And this is the first drug that seems to reverse that dopamine disregulation in the reward centers of the brain."
Hurst says that so far, it appears that 18-MC is what it promised to be. The first round of testing in rats showed no cardiovascular or psychedelic effects, but it appears comparable to ibogaine in fighting addiction.
Additionally, he says, "We've done the initial human testing, which for this drug was a very important risk reduction point, because if we gave it to people and they started hallucinating, it would have been a nonstarter. We didn't see any signs of that kind of behavior in nonhuman primate studies that we did, but there's always a chance that a human being is going to deal with a drug very differently than a nonhuman primate or a rat or a dog. So, we had to make sure we did not have that problem."‘This is the first drug that seems to reverse that dopamine disregulation in the reward centers of the brain.’
The company is planning two years of testing on healthy humans, and then addicts, for starters. Those initial tests will likely look at issues like how the drug affects people with food in their stomach, if the effect is different depending on gender, which dosage level is optimal and whether tobacco interacts with the drug.
It's still early in the process for 18-MC, which is in the first phase of Food and Drug Administration testing. Generally, three phases are required, though sometimes drugs are allowed to go onto the market after two — other times it takes four. When the drug is considered to be safe enough to go to market, it's examined by an expert committee, which makes a recommendation to the FDA commissioner, who ultimately decides its fate.
Hurst says his company generally takes drugs through the first two phases of development independently, at a cost of perhaps $25 million to $50 million for a drug like 18-MC. When the drug reaches Phase 3, the company tries to partner with a multinational pharmaceutical company to help foot the bill for the most expensive tests.
All of this means that getting 18-MC to the market could take anywhere from two to five years, if everything goes well.
"We're very optimistic about this drug," he says, "but we're still very early in the human testing."
Interestingly, 18-MC also appears to work against a parasitic disease called Leishmaniasis, common in many countries including Brazil and Afghanistan. Millions of patients are affected by the disease, which comes in three forms that can cause everything from black, disfiguring lesions, to death, to the inability to eat. While it's treatable, 18-MC has the potential to treat the disease in a simpler fashion than is now available — with a pill.
Hurst says he's not positive what addictions 18-MC might be developed to treat. Since testing is so expensive, it will likely be targeted toward only some of the things it has the potential to treat, at least initially. That could be heroin, cocaine or nicotine addiction, for instance, or Leishmaniasis. Some of the considerations include what's easiest to get through the FDA, like heroin and nicotine treatment. But it also matters what the company can get funding to test.
For some, the development of 18-MC may be a disappointment. Addicts who have used ibogaine often say the hallucinations are a huge part of the healing experience, that they lead them through a reexamination of their lives and endow them with wisdom. But 18-MC wouldn't do that.
Still, with its ability to halt withdrawals, 18-MC has the potential someday to be the best treatment for serious drug addiction on the American market. Yet it may be hard to predict just how effective it would be.
First, there isn't exactly an official tracking system to measure ibogaine's effectiveness. Second, even with traditional methods, addiction recovery rates aren't straightforward.
That fact was noted by the Huffington Post in a Pulitzer Prize-nominated, eight-part series on a maintenance drug for opioid addicts called Suboxone, similar to the more commonly known Methadone. The January 2015 series, called "Dying to be free," outlines the struggle of addicts and their families to get access to Suboxone, which for many is more effective than 12-step programs. It also delves into problems with recovery statistics for opiate addicts.
And when it comes to ibogaine — or, someday, 18-MC — those statistics become trickier, because it's hard to define what ibogaine actually is.Doug Greene, GITA's patient advocacy coordinator at the nonprofit's Montreal headquarters, says in an interview with the Independent that it's important to remember ibogaine doesn't cure heroin addiction. It simply gives users a better chance, because it halts withdrawals and — through hallucinations — provides insights into one's life.
But once it's administered, patients should seek other treatments, including therapy. In some cases, Greene says, patients may even benefit from going on a maintenance drug like Suboxone or Methadone after ibogaine treatment.
"[Ibogaine is] a tool," he says. "It's an amazing, incredibly valuable tool to help people get into recovery."
(Last of a two-part series. Click here to see Part 1 of "Psychedelic miracles.")
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