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MAPS: Great ibogaine article from JAMA
Here's a great article on ibogaine, from the Journal of the American Medical
Association. The only change I'd make in the article is that it lets NIDA off
way too easily for deciding, at a 1995 meeting, not to fund ibogaine
research. That was a cowardly political decision that hide behind exaggerated
estimates of the risks of ibogaine.
Addiction Treatment Strives for Legitimacy
by Brian Vastag
Journal of the American Medical Association
Vol. 288 No. 24, pp. 3096-3101, December 25, 2002
Addiction Treatment Strives for Legitimacy
New York -- Some drugs are made in laboratories. Others, like
penicillin, are discovered by accident. And then there's ibogaine, a
sacramental substance from West Africa that some say interrupts heroin,
cocaine, and other addictions. Over the past 40 years, the tale of
ibogaine's flirtation with legitimacy boasts more twists than the roots
of Tabernanthe iboga, the shrublike source of ibogaine.
After riding the backpacks of Westerners to the radical 1960s New York
City underground, ibogaine rose from a counterculture star to a serious
project funded by the National Institutes of Health (NIH). In 1995,
after spending several million dollars on laboratory and animal studies,
the NIH decided not to pursue ibogaine development. Since then, patent
disputes have divided the drug's champions; a growing network of
informal clinics has sprung up; and pharmacologists have discovered that
ibogaine works on the brain in a manner unlike that of any other known
drug (see sidebar 1).
After all this, ibogaine and two of its derivatives appear closer to
legitimacy now than ever before. In 1998, a University of Miami Medical
Center researcher opened an ibogaine clinic on the Caribbean island of
St Kitt's. Although the US Food and Drug Administration (FDA) had
approved human trials with ibogaine, Deborah Mash, PhD, associate
professor of neurology and pharmacology at Miami, could not secure
funding for a stateside study. Instead, she solicited private investment
and won favor from the government of St Kitt's, where a team of
physician counselors and addiction specialists now collect data that
Mash hopes will cement support for US trials of ibogaine or its
Tabernanthe iboga, the West African source of ibogaine, used by some to
Meanwhile, another pharmacologist, Stanley Glick, MD, PhD, director of
the Center for Neuropharmacology and Neuroscience at Albany Medical
Center, has painstakingly moved a derivative of ibogaine toward its own
clinical trial. After 12 years of basic research on scores of molecular
variations on the ibogaine theme, Glick recently forged an agreement
that represents his best chance for a clinical trial. Signed in November
2002, the contract obligates investors to raise $5 million within 2
years to fund the first human studies of 18-methoxycoronaridine (18-MC).
But even as ibogaine's supporters sniff success, they worry that the
drug's origins will continue to stunt its development. "It's been a
continuous battle for respect," said Glick. "Ibogaine has really become
notorious because it didn't originate in a lab, but in the
Mash is concerned that burgeoning unsanctioned use will compromise years
of laboratory and clinical work. "We've got this explosion of
underground clinics, and I'm scared that everything I work for is going
to go right down the toilet," Mash said in a recent telephone interview.
As an endowed, tenured professor, Mash has all the right credentials: a
29-page curriculum vitae listing 155 publications; a history of millions
of dollars in federal grants; a spot at the table of several National
Institute on Drug Abuse (NIDA) review committees; and a reputation as a
brilliant brain scientist.
And yet, Mash feels that ibogaine's tumultuous history (see sidebar 2)
has isolated her. "I'm the only one [doing clinical research]," she
said. "I figured, somebody ought to test the damn thing. You know,
either it works or it doesn't."
SCIENTISTS LOOK INTO USE
In 1999, Kenneth Alper, MD, PhD, assistant professor of psychiatry at
New York University School of Medicine, hosted the first serious
scientific conference devoted to ibogaine. He and Glick compiled the
proceedings into a thick volume (Alkaloids Chem Biol. 2001;56:1-330). In
the preface, Geoffrey Cordell, PhD, a pharmacology researcher at the
University of Illinois at Chicago, writes that while ibogaine probably
"won't save the world from addiction," it deserves a "prominent position
in the list of anti-addictive strategies" under study.
Animal data support Cordell's conclusion. Dozens of articles referenced
in the conference proceedings report reductions in self-administration
of morphine, heroin, cocaine, alcohol, and nicotine in rodents given
ibogaine. The effects last from 1 to 5 days, depending on dosage and
other variables. Noribogaine and 18-MC produced similar results.
That means the central hurdle for ibogaine's supporters is amassing
compelling human data. While unknowable scores of addicts continue
ingesting ibogaine hydrochloridea purified powder -- or ibogaa
whole-plant extract containing a dozen or more active alkaloids -- few
trained researchers witness the events.
"There's basically one big uncontrolled experiment going on out there,"
said Frank Vocci, PhD, head of antiaddiction drug development at NIDA.
Consequently, supporters have had to rely on anecdotal accounts. At a
pivotal 1995 NIDA meeting, Howard Lotsof, credited with discovering
ibogaine's purported antiaddictive potential, presented a collection of
case reports. He reported that 10 (19%) of 52 treatments led to
cessation of heroin or cocaine use for a year or longer; 15 (29%)
treatments led to 2 months or less of sobriety. The remaining treatments
were followed by sober periods between 2 months and 1 year. Despite
Lotsof's report, the NIDA peer review panel voted nine to four to reject
a clinical grant application from Mash.
She regrouped and eventually opened the Healing Visions clinic in St
Kitt's. In 2000, Mash and colleagues published the data from 27 cocaine-
or heroin-addicted patients treated at the center (Ann N Y Acad Sci.
2000:914;394-401). The researchers conclude that "self-reported
depressive symptoms and craving were significantly decreased" at 1 month
after stopping treatment with ibogaine. They also note that ibogaine
treatment "decreased participants' desire and intention to use heroin."
Mash is now analyzing safety and efficacy data for 257 patients.
At Healing Visions, patients receive what Mash calls "state-of-the-art
care," with round-the-clock monitoring and access to the latest
emergency equipment. But individuals who seek out ibogaine in other
settings receive no such supervision. "It's caveat emptor," said NIDA's
Vocci also said that safety was "not the main concern" at the pivotal
1995 NIDA meeting, which he chaired. However, that review panel did cite
safety issues. One reviewer wrote that the drug's toxicology profile was
"less than ideal," with bradycardia leading the list of worrisome
In fact, between 1989 and 2000, three reports of patients dying after
taking ibogaine surfaced, sparking a swirl of questions about the drug's
safety. The first death, of a 40-year-old woman in France, apparently
stemmed from preexisting heart disease. A lack of medical information
hindered investigations into the other two deaths and led to conflicting
conclusions about whether ibogaine was to blame.
In a 1996 radio interview with WBAI in New York City, Mash said that, in
the French case, the patient "was very sick, she had a very sick heart
and she shouldn't have been given ibogaine under any circumstances. . .
." And in the second death, "we don't completely know the mechanism of
lethality, but it did appear to be respiratory collapse in this case.
The bottom line is that you need to be under medical supervision. . . .
Ibogaine is an important drug but it is not to be used outside the
medical establishment, not ever, ever, ever."
Despite Mash's warnings, unsanctioned ibogaine use appears to be
soaring. A sophisticated "underground railroad" of sorts has sprung up
in New York, spearheaded by Dana Beal, a long-time marijuana
legalization advocate. When heroin- or cocaine-addicted individuals
develop an interest in ibogaine, they often call Beal, who acts as
During an interview in his home, the one-time headquarters of the
radical 1960s Yipster Times newspaper, Beal said that if he thinks
someone is a good candidate for ibogaine, he helps arrange a visit to an
The best known operation, according to Beal, is in the Netherlands at
the Amsterdam home of Sara Glatt, who practices various types of
alternative medicine. Glatt has treated some 85 people during the last 3
years. When an addicted individual arrives, Glatt asks for a history of
heart problems or bad experiences with psychedelic drugs. Judging from
that information and the individual's weight, Glatt provides between 2 g
and 6 g of powdered iboga, the whole-plant extract that contains at
least a dozen active ingredients in addition to ibogaine.
Whereas Glatt charges upward of $1000 for her services, the newest
clinic, in Vancouver, British Columbia, offers free ibogaine. The
clinic's founder, Marc Emery, won 2000 of 140 000 votes in the 2002
Vancouver mayoral election running on a platform of open access to
ibogaine. He recently solicited an ibogaine e-mail list for feedback on
a proposed treatment regimen.
Lotsof, on the other hand, has already published a rigorous protocol
(Lotsof H, Wachtel B. Manual for Ibogaine Therapy: Screening, Safety,
Monitoring, and Aftercare, First Revision. Published online. Available
at http://www.ibogaine.org/manual.html. Accessed November 26, 2002). In
the preface to the first revision, Lotsof and coauthor Boaz Wachtel
write that the manual is "intended for lay-healers who have little or no
medical experience, but who are nevertheless concerned with patient
safety and the outcome of ibogaine treatments." The manual suggests
inclusion and exclusion criteria, ibogaine regimens and doses, and
considerations for posttreatment care. A naive physician would likely
accept it as a standard medical protocol.
Back in the realm of sanctioned drug development, Glick and Mash are now
focused on bringing their respective ibogaine derivatives into clinical
trials. "That's certainly the way to go now," said Vocci. Alper voiced a
similar opinion, saying that he views ibogaine as proof of concept that
the best hope for a therapeutic drug lies with ibogaine derivatives.
Glick, too, is certain that the FDA will never approve ibogaine. In
addition to safety concerns and the drug's social history, the
hallucinogenic effects of ibogaine (see sidebar 1) could be problematic.
After NIDA rejected ibogaine clinical trials, both Mash and Glick struck
out with the pharmaceutical industry, which has been traditionally cool
to antiaddiction drugs. The Pharmaceutical Research and Manufacturers of
America (PhRMA) reports that in 1999, for example, its roster of drug
giants had 10 antiaddiction agents in clinical trials. The same
companies had more than 400 cancer drugs in clinical development. When
asked to explain the disparity, Jeff Trewhitt, spokesman for PhRMA,
said, "We certainly don't know a reason, unfortunately."
But ibogaine researchers and others, including a spokeswoman for the
Substance Abuse and Mental Health Services Administration (SAMHSA), say
that addiction stigma and low profit potential are keeping companies
Whatever the case, the dearth of pharmaceutical and other treatments
means that the societal costs of addiction will continue to climb.
SAMHSA reports that in 2000, illicit drug addiction cost the United
States $160 billion in medical care, lost productivity, and crime and
incarceration, up from $117 billion in 1997. Illicit drug addiction is
here to stay.
So too, it appears, is ibogaine.
An Odd Drug
Other hallucinations passed before my eyesburning skulls and faces, the
figures of women in black dresses stretching out long white arms toward
me from the edges of my visionbut when I tried to speak of them, they
disappeared. Meanwhile, the iboga was making me sick. I fought back
waves of nausea. I wanted to reach the deeper visionary state, but I was
also afraid of the drug.
Journalist Daniel Pinchbeck, in Breaking Open the Head: A Psychedelic
Journey Into the Heart of Contemporary Shamanism. New York, NY: Broadway
At low doses, ibogaine is a mild stimulant. At high doses, users report
deeply emotional visions, sometimes pleasant, sometimes harrowing.
Patrick Kroupa, who credits ibogaine with 3 years of sobriety after 15
years of addiction, said, "It was like dying and going to hell 1000
Whatever the subjective experience, pharmacologists have spent decades
puzzling out the brain effects of ibogaine. Their conclusion: it's
unlike any other known drug. Kenneth Alper, PhD, assistant professor of
psychiatry at New York University School of Medicine, said that the drug
appears to work on "every neurotransmitter system we know about." It
binds to N-methyl-D-aspartate receptors and µ- and -opioid receptors;
all three play prominent roles in current theories of addiction.
Ibogaine also acts as an antidepressant by binding to serotonin
transporters, thereby increasing serotonin levels in the nucleus
accumbens. Evidence of impact on the dopamine and acetylcholine systems
is less compelling, but deserves consideration, said Alper (Alkaloids
Chem Biol. 2001;56:2-33).
Most recently, Stanley Glick, MD, PhD, published support for his theory
that ibogaine reduces drug-seeking behavior in rodents by blocking a3b4
nicotinic receptors (Eur J Pharmacol. 2002;438:99-105).
Meanwhile, Deborah Mash, PhD, a neuroscientist at University of Miami
Medical Center, is convinced that ibogaine is nothing but a short-acting
prodrug. It quickly metabolizes into noribogaine, she said, which boasts
a half-life so long that she has been unable to measure it. This
property, she believes, explains ibogaine's purported ability to block
drug cravings for weeks or months (Alkaloids Chem Biol.
(Return to text.)
A Brief History of Ibogaine
1885: First published description of religious use of Tabernanthe iboga
in Gabon appears in France; it reports that initiates of the Bwiti
religion eat rootbark to induce visions and "meet their ancestors."
1939: Sold in France as a stimulant until 1970.
1962: Howard Lotsof, a 19-year-old from Staten Island, receives ibogaine
from an LSD chemist and gives it to 19 other people. He later reports
that five of seven heroin and cocaine addicts in this group, including
himself, stop illicit drug use for up to 18 months and experience little
or no acute withdrawal.
1970: The US Food and Drug Administration (FDA) classifies ibogaine as a
Schedule I drug, making it illegal. Belgium also outlaws ibogaine, but
today it remains legal in the rest of the world.
1985: Lotsof receives a US patent for use of ibogaine in opioid
withdrawal. Additional patents describing ibogaine treatment for cocaine
and other addictions follow.
1989: Ibogaine addiction treatment begins in informal clinics in the
Netherlands. By 2002, informal clinics have opened in the United
Kingdom, Canada, Slovenia, and Mexico.
1991: After intense pressure from activists, the National Institute on
Drug Abuse (NIDA) begins funding preclinical toxicology and other
laboratory research on ibogaine.
1993: The FDA approves a US clinical trial of ibogaine sponsored by
University of Miami neuroscientist Deborah Mash, PhD.
1995: NIDA review committee rejects funding for Mash's clinical trial.
1999: Mash opens ibogaine clinic on Caribbean island of St Kitt's. By
late 2002, she has collected safety and efficacy data on 257 addicted
2002: Long-running legal dispute between Lotsof and Mash ends with the
University of Miami winning patents for noribogaine, a metabolite of
ibogaine. Stanley Glick, MD, PhD, director of the Center for
Neuropharmacology and Neuroscience at Albany Medical Center, signs
contract to bring ibogaine derivative 18-MC into clinical trials.B.V.
(Return to text.)
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