Chapter 15 Molliver's Travels
Behind the scenes, as is often the case, the postponement of the Day One
Ibogaine story was being dictated by other agendas and other schedules.
In April, unbeknownst to Lotsof or the treatment activists, the FDA and
NIDA huddled to sort out a plan t o deal with the unprecedented publicity
of the Day One special. They set a date of August 25th for a formal hearing
of the full FDA Advisory Panel on Substance Abuse as to Deborah Mash's Investigational
New Drug (IND) Application. Once that hearing was scheduled, there was a
temptation built-in for Day One Producers to keep the Ibogaine story in
the can, and peg the air-date to the news-interest around August 25th. Even
if NIDA, in the person of Frank Vocci, hadn't sincerely believed any delay
by the m edia was in the best interest of the project (the longer thereby
to put off potential anti-psychedelic backlash), it was highly unlikely
that Herb Kleber and CASA would not have found out independently and advised
ABC brass of the new timetable.
Treatment activists were among the last to find out-- not until the end
of June did Vocci and Lee Cummings tell Beal of the August hearing. After
the Hotel Pierre zap, which Beal and Johann Moore recounted in delightful
detail to the floor of ACT UP a s they announced their next action--a zap
of the FDA/NIDA on July 6--Amy Bauer objected that only floor-approved zaps
were supposed to get meeting-time. So at the next meeting, enough people
were fed up with two years of talk and still no addict access, and the July
6th zap passed, 38 to 27, with a third of the floor abstaining.
Far more important was Dana's decision, amidst the uncertainty surrounding
the failure of the treatment of the kid from Columbia, to quit ducking the
Molliver toxicity data and get to the press with it first--but as evidence
of a new, cerebellar mecha nism of addiction instead of an indication of
danger in humans. Another writer, Richard Alan Miller, had already gotten
the basic story into print, in the eco-journal GREEN EGG, obviously after
reviewing Goutarel's monograph (See Appendix, page 194). He wrote the following,
under "Possible Mechanisms":
"Some new theories have recently been proposed, based on EEG readings
of patients undergoing ibogaine treatment\ in clinical situations.
"Normally, the stages of wakefulness of the human brain are: normal
waking state, NREM (slow wave or deep) sleep, PGO (pontogeniculo-occipital
waves, and REM (rapid eye movement or paradoxical) sleep. REM sleep is the
period where most dreams occur. P GO waves are considered to be the principle
coding tool that acts at the cortical level in recording thegenetic/epigenetic
acquisition necessary for the individuation of the human brain. In other
words, it is the software-writer aspect of the Self. 170
"In Ibogaine therapy, while the patient is in the near-death dream
state, the PGO brain pattern has been found to overlap the standard low
alphoid brain state. This precipitates fundamental shifts in instinctual
learning patterns, possibly the underly ing cause of ibogaine's erasure
of addictive behavior patterns.
"In addition, through random activation mechanisms, PGO waves eliminate
from certain types of neuronal networks an informational overload linked
to pathological behavior, thus "cleaning out the neuronal circuitry."
REM sleep apparently includes a sort ing-out and disposal process of the
"residues" stirred up by the PGO wave sleep pattern. The actual
dream state could be considered the "reboot" of the personality
rewrite.
"In essence, ibogaine allows one to reconfigure the genetic and cultural
programming one receives at birth, much like changing the config-sys file
of a computer. The REM aspect then reboots the consciousness patterns with
a new autoexec.bat file for habits, needs, and the manner in which one approaches
desires.
"In humans, the oneiric effects which are produced by hallucinogens
do not enable us to approach the dream mechanisms directly. These two phenomena
(dreams and halluncinations) cannot be linked together as one item. The
principal difference between th em resides in the way in which the stages
of wakefulness are organized, with the suppression of REM sleep and the
intrusion of PGO waves into the arousal (waking) stage and in NREM (or slow)
sleep.
"The post ibogaine therapy organization of consciousness becomes: waking
(arousal) stage, stage of PGO waves, hallucination stage, and then the sleep
stage. It is possible that hallucinatory manifestations in combination with
the waking dream eliminat es residuals stirred up by the PGO wave pattern
in the absence of REM sleep.
"According to the Mitsogho tribe, the initiate will see the Bwiti only
twice in his life, on the day of his initiation and one the day of his death.
This means that the visions at the approach of death are the same as those
termed "normative visions," as when at the time of dying, some
individuals see their whole life pass before them. In those who are rescued
from death, a spectacular transformation is observed. They no longer fear
death; they feel stronger, more optimistic, calmer, and contemplate their
life more positively.
"This is precisely what was described by the heroin addict described
above after hisibogaine treatment. He felt that God had appeared before
him and shown him a series of visions on how he arrived at addiction to
heroin. Once he emerged from the dream stage, he no longer felt as if he
were the same person--because he was not the same person.
"A more detailed description is needed of the precise form of dream
therapy, an important aspect of the initiation of the Bwiti of the Fang.
The ibogaine offers a hallucinatory tool for assisting the effectiveness
and efficiency of current dream thera py protocols. The added structure
of a virtual-space type of platform for the therapist to act as a (shaman)
guide is described in a paper called "VR Therapy" by Iona Miller."
(GREEN EGG, p. 37, Summer '93)
Howard had wanted to downplay the implications of Molliver's discovery of
a cerebellar site of action because it involved findings of ibogaine toxicity,
and Howard had unpublished data from Miami showing no toxicity in primates.
However, inasmuch as s erious damage in Molliver's rats was only occurring
at sub-lethal doses, Beal couldn't see any reason not to point out that
early paraclinical171
observations of a REM-like mechanism of action with Ibogaine--as well as
the effect he was predicting in the gait centers--would be dramatically
confirmed if Ibogaine acted on the cerebellum, the seat of movement, coordination
and reflex. Just because Molliver had located the cerebellar site by deliberately
inducing cell damage with a sublethal dose was no reason to sit on the revolutionary
implications of his discovery.
So it was without any inkling as to the Aug. 25th FDA hearing date, or the
suspension of treatments in Holland due to a heroin O.D., that Dana sent
his new report to science writers who'd gotten the previous volume at NEWSWEEK
and the BALTIMORE SUN, along with the story line-- "Ibogaine Reveals
New Mechanism of Addiction." Both writers had previously indicated
interest, pleading that their plates were too full at the time. With an
article on Howard appearing in the June OMNI, however, the time was no w
ripe. Basic interviews were all done with both NEWSWEEK and the SUN before
either the August 25 hearings or heroin O.D. became known, and Dana, after
ascertaining Ibogaine was not the cause of the death, decided to honor the
exclusive of the NEW YORK T IMES MAGAZINE writer who'd been covering that
set of treatments. His discussion with Vocci, who refused to meet July 6th,
produced nothing either to justify calling off the July 6th zap or changing
the articles set to appear in NEWSWEEK and the SUN.
A day before the NIDA/FDA zap Dana, David Goldstein and Noah Potter met
with O'hearn and Molliver at Johns Hopkins. Mark Molliver, from experiments
with harmaline tremor 20 years earlier, suspected that Ibogaine must be
working in the inferior oli ve, a kind of knot on the brainstem that
branches directly up into the inside of the cerebellum. As Molliver explained
it, the olivo-cerebellum was in effect one formation. What he'd discovered
(See illustration,) was that excitation of the olive by Ibogaine
triggered the rhythmic firing, lasting many hours, of a layer of unusually
well-shielded super-switcher cells in the cerebellum, called Purkinje
cells. Purkinjes are completely interconnected with synaptically rich
olivo-cerebel lar climbing fibers which project from the inferior olive.
In rats treated with a sublethal dose of Ibogaine (100 mg-per-kg, or about
80% of the L.D.50), sustained rhythmic firing of these Purkinje cells caused
prolonged tremor and loss as many as 10-15% of Purkinjes. Earlier researchers
lacked the sophistica ted technique to detect the effect--because it appeared
in very narrow stripes running from front to back in the centralvermis between
the right and left hemispheres of the cerebellum. Molliver believes each
stripe is, in effect, an individual parallel processor module. The vermis
controls the vestibular sense--balance--which would explain the trunkal
ataxia (difficulty in standing, coupled with a strong urge to lie down)
human addicts experience during the initial phase of the treatment.
The positive news was that Purkinje cell loss in rats was not a direct toxic
effect of Ibogaine, but a secondary, excito-toxic effect. Ibogaine action
in the olive was triggering over-production of a natural neuro-transmitter
in the Purkinjes, whic h were apparently firing until they died-- a case
of death by overstimulation. But no direct toxicity was occurring in the
inferior olive, and it wasn't until after the Ibogaine wore off that Purkinjes
would start to degrade and leave vacuoles (pits). Thi s lag made Molliver
and O'hearn hopeful some blocker could be found that could limit the damage
without blocking Ibogaine's anti-addictive effect. If some cell death turned
out to be necessary to erase the template of addiction from the cerebellum,
as Mol liver at first suspected, he thought a second drug that stopped tremor
might block the worst of it.
One thing Molliver and O'hearn were pretty sure of was that a 5-methoxy
group projecting like a key from the upper lefthand side of the Ibogaine
molecule specifically "fits the lock"--the receptors in the inferior
olive, which activate the cerebellum . But the key difference of Ibogaine
from harmaline, when compared side-by-side (See below.) is the perpendicular
"porch" on the lower right of theIbogaine molecule; Dana proposed
that this must be the part of the molecule responsible for the property
of weakly binding to the kappa opiate receptor, which (according
to Glick) harmaline does not share. There was discussion of whether the
kappa receptor might be involved with the mechanism of the "opium
dream"--as distinct from opiate anal gesia produced by mu opiate
receptor agonists like methadone--and whether by occupying kappa
receptors, the well-known potentiation of opiates by Ibogaine would be accomplished
by "freeing up" opiate to occupy more mu receptors.
Dana, remembering descriptions of Ibogaine's characteristic "oscillating"
effect during onset, kept asking O'hearn and Molliver if some form of oscillating
brainwave activity might not be the mechanism of "cerebellar reset."
Molliver a-greed that if the anti-addictive property turned out not to be
due to the equivalentof pharmaco-chemical psycho-surgery, the REM-like mechanism
suggested by Gouta-rel and the French would be the next logical explanation.
As to the role of PGO waves, he explained they were apparently evidence
of neural perception of light.
But Dana was also remembering something else--something Bob Sisko had said
about the hot and cold flashes and sweats Nico perceived as withdrawal symptoms--diminished
but still present--as his first Ibogaine treatment was wearing off. "Sweats,
hot a nd cold flashes-- are also side-effects of the Ibogaine," said
Sisko. "He was just feeling the Ibogaine." If the physical symptoms
were the same, must not the brainwave activity be very similar? In wave
mechanics there is a phenomena where two closely-mat ched wave fronts heterodyne,
cancelling each other out. Otherwise-- "Where do the withdrawal symptoms
go?"
Dana's working hypothesis was that human brain architecture differs enoughfrom
rats so that instead of tremor and cell damage, Ibogaine excitation is shunted
into the REM circuits, the natural mechanism of nightly tremor and cerebellar
"forgetting." S o instead of a model of selective cell-destruction,
Dana's basic premise was that a REM-like random activation mechanism triggers
or promotes the same kind of healing that takes place when a stroke victim
learns to use remaining brain capacity to replac e missing function--an
effect not to be interfered with, although it would still be helpful to
find something that would block any cell-breakdown after Ibogaine wore off.
The big question was whether a level of excitation might be found that would
revers e addiction without causing over-stimulation.
Molliver and O'hearn agreed the focus should be finding a "window"
between the lowest effective dose and the dose level where Purkinjes start
breaking down, but were not too optimistic. Individual cells were still
being lost (less than 1%, but still detectably) at 25 mg.-per-kg. Wasn't
oral Ibogaine less toxic than i.v.? No, as a matter of fact the effect of
25 mg-per-kg oral Ibogaine slightly more damaging than i.v., because it
hung around longer in the body, and the tremor lasted longer. Molliver felt
the degree of cerebellar damage in rats seemed to coincide with length of
tremor. His most interesting aside, in reaction to the news that Kaposi's
patients were getting some speedlike effect with their vinblastine, was
his thought that the Ibogaine -like half of the vincristine or vinblastine
might be having psychoactive effects distinct from the lower, toxic moiety.
(See page below)
The leaflet zap and picket the next day, July 6, was 3 times the size of
the original action in 1991. It had significant support from Philly ACT
UP for the first time. And virtually every worker in the building got an
open letter to Dr. Curtis Wright of FDA Pilot Drug asking why, if it was
permissible to give vinblastine--an Ibogaine cogener but 40 times more toxic--to
treat Kaposi's Sarcoma, it wasn't kosher to use Ibogaine to keep addicts
from contracting or transmitting AIDS to begin with.Jonatha n Bor from the
BALTIMORE SUN came and left before everybody gottogether at 11 AM for a
real ACT UP moving picket. But he interviewed Paul Morcone, owner--"and
also a client"--of three methadone clinics, who wanted to give all
his clients the Ibogaine opt ion. Before it was over, Terry Toigo of FDA
AIDS Coordination came down and asked for a meeting between ACT UP and Curtis
Wright.
The ACT UP side was all for a meeting, but later rather
than sooner, so they could ask questions after they were better briefed
on the run-up to the hearings Aug. 25. During the
delay, in one of those typical twists of Ibogaine coincidence, the NEW YORK
TIMES published a story (see preceding pages, 175-76 by Sandra Blakeslee,
"Mystery of Sleep Yields as Studies Reveal Immune Tie,"
which threw some unexpected light on the oft-observed rapid healing effect
of Ibogaine. What she dis cussed were new findings--that in auto-immune
disorders, the normal synchronicity is disrupted, of the deep sleep wave
with a rhythmic contraction of the intestine and the rise and fall of certain
sleep-inducing cytokines such as tumor necrosis factor (T NF). And since--as
Molliver had explained at the very first meeting--all such rhythmic brainwave
activity is generated by the cerebellum, what this all suggested was that
something that resets the cerebellum might have a role in fighting AIDS.
Especial ly since the inferior olive, site of Ibogaine action, functions
as the cerebellum's "clock." Then on August 9th, the BALTIMORE
SUN published the first story to explain--not just effects of Ibogaine on
the dopamine receptors of Glick's rats--but the new , cerebellar mechanism
of addiction suggested by Molliver and O'hearn's work at Johns Hopkins.
(See story, pages 179-80) [Authenticating the information-burst as
it were (in terms of VALIS... or Bwiti), a quote from Adam Nodelmann on
his Ibogain e visions of the assassinations of the Kennedys, King and Malcolm
X coincidentally (synchronistically) makes it into print.]
With things heating up nicely, Dana requested the presence--as ARC medical
affairs officer and the only person with comparative information on the
efficacy of other addiction medications and Ibogaine--of Carlo Contoreggi.
He ended up instead with Vocc i and Grudzinskas for NIDA, and having to
ask them to bring Carlo. But he got a meeting for activists with FDA/NIDA
on standards of approval for Ibogaine almost 2 hours long--and just a week
before August 25th.
Best of all, the day before the meeting, the second story on Ibogaine and
the new mechanism of addiction appeared in NEWSWEEK. (See page 162).
Dana handed out color xeroxes to Vocci, Grudzinskas, Contoreggi, and for
FDA, Curtis Wright, Dan Spiker, Belinda Hayes, Corinne Moody and Nancy Stanisec.
Present for ACT UP besides Dana were Vic Hernandez, Dr. Iris Long, David
Goldstein, Jeff Eberhardt and Kiyoshi Kuromiya.
The ACT UP side pushed for an immediate parallel track process for NIDA
MDD's own Phase II trials, on the assumption Aug 25th Hearings would allow
research in some form to go forward. Besides reiterating ACT UP's position
that Ibogaine toxicity be c ompared with vincristine and vinblastine, Dana
said this problem should be looked at anew to see if there was a common
neuro-mechanism of action -- by including a small number of HIV-positive
addicts with KS in NIDA Ibogaine trials. He proposed that a sm all interagency
task force under a clinician (he nominated Carlo) be set up with all necessary
authority, to meet night and day, working on nothing but Ibogaine.
The big counter-argument from the government was their own spectacular disaster
with FAIU, a chemotherapy that at first seemed to show promise in clearing
hepatitis virus from the body completely. It was safe in dogs, but fatally
toxic in humans, who lacked a protective enzyme dogs have. Half the subjects
in the first human trial required emergency liver transplants, and several
died. Of course it could be equally true that Ibogaine was safe in primates,
and toxic only in rats. But NIDA MDD felt there were still too many uncertainties
about Ibogaine in humans. Nonsense, said Vic--get ethnobotanists in with
data on human use in Africa. Jeff said most of NIDA's problems could be
surmounted by doing a large, simple Ibogaine trial.
The showdown came one week later, in the ballroom of a Holiday Inn in Silver
Spring. Preliminary research in animals had produced tantalizing evidence
of genuine addiction interruption, but toxicity findings had held up clinical
trials for a year- -and might well doom further testing in humans. The FDA
hearings in Aug. 25th were covered by dozens of media including ABC Day
One, Los Angeles Times, UPI, AP, The New York Times Magazine, CBS National
Newsradio, CNN and the NBC Nightly News, along with other Washington, D.C.
print and electronic media. The Press Table outside listed more than two
dozen names.
The entire FDA Advisory board was present, as well as representatives of
various divisions of NIDA and ARC. The NIDA/FDA medical bureaucracy had
its own roped off area in the audience of about three hundred seats. Harm
reduction groups including th e D.C. and Philly needle exchanges, ICASH,
and ACT UP activists from four cities were there---along with NDA International,
their lawyers, consultants, as well as a "who's who" of independent
Ibogaine researchers--everyone who counted was there to decide the future
of Ibogaine.
As the principles began to sit around the U-shaped table and the audience
filled in, the room took on an electric intensity. The activists were up
first, with a series of appeals that Curtis Wright later was to admit made
the difference in a very clos e decision. Dana Beal, the first to speak,
succeeded in framing the issue with a cogent appeal to apply the same safety
standard as vincristine or vinblastine --and let Ibogaine research go forward.
Vic Hernandez questioned the basis of putting the origi nal IND on hold
at all. Iris Long presented data on the devastating spread of AIDS among
women via addiction. Jon Paul Hammond of Philadelphia made anemotional appeal
on behalf of needle exchangers: use Ibogaine to make treatment on demand
a reality. Jeff Eberhardt handed out a Medication Development Scorecard
(see chart, page 182), showing the failure of NIDA's other potential treatments
to pan out in testing. Bob Sisko delivered a plea on behalf of ICASH to
reconcile harm reduction and demand reductio n with Ibogaine. Howard Lotsof
made an impassioned statement for NDA on human rights.
Then came Belinda Hayes of the FDA, who presented the basic FDA version
of the data on Ibogaine. As the hearing unfolded, Glick, Sershon and the
independent researchers presented well-designed studies showing efficacy,
while MDD animal researchers l ike Steve Dworkin demonstrated the inability
of the standard agonist/antagonist model even to measure the interruption
effect as distinct from the ataxia.
But the major controversy was the findings of Molliver and O'hearn in rats,
versus Deborah Mash and Sanchez-Ramos in primates. The high point of the
morning came with the presentation by Mark Molliver of his findings on cerebellar
toxicity. His larg e, color slides showed that Ibogaine toxicity in the
cerebellum of rats, which was significant at 100 mgs.-per-kg, appeared to
fall off logarithmically, so that Purkinje-loss at 25 mgs.-per-kg. was not
even 1% ("You can count the individual cells lost, " said Molliver
later.) Yet the level of damage at the higher dose seemed impressive, and
ACT UP conceded that 16-18 mg.s.-per-kg. was actually more like the standard
dose for addicts--an estimate that stuck with the press.
The turning point that morning was when Curtis Wright asked Frank Vocci
if they were not in fact in possession of as much pre-clinical data as is
usual when an IND is approved. Vocci answered unhesitatingly, "Yes."
After lunch there was a break for Patricia Broderick and Mikhael Dzoljic
to present their data--Dzoljic acheived 80% reductions in cocaine intake
in rats by determining that the correct regimen of Ibogaine administration
was weekly, not daily. During a break just afterwards, Dzoljic confessed
puzzlement over the exaggerated concern for a few cerebellar cells--"We
lose that many to wear and tear every day."
The day-long event peaked in intensity late in the afternoon when Deborah
Mash presented the Miami primate findings, which directly controverted the
findings of Molliver and O'hearn in rats. Deborah Mash's primates showed
nocerebellar damage. Urine and blood samples showed none of the telltales
of cell damage. But her test group was small--three animals--her slides
were not as big and convincing, and you had to ask if she'd looked in precisely
the right place: along the back-to-front "stripes" wh ere cerebellum
joins together between its right and left hemispheres--along thevermis .
Also the monkeys had been sedated with ketamine before Ibogaine administration.
Still, in the Miami primates Ibogaine tremor--reallyverging on ataxia--was
much short er and less pronounced than in the rat (she observed rats may
be "exquisitely sensitive" to Ibogaine). These findings actually
swayed Molliver and O'hearn, making them somewhat more inclined to think
Ibogaine might be safe in primates, but then she asked if he would estimate
Purkinje loss at 100 mg-per-kg. in his rats at 10-15%. Somehow that was
the figure that stuck in people's minds.
Then it was Sanchez-Ramos's turn to present neurological observations on
the two addicts whose treatments he'd witnessed in January in Lyden. Both
had a neurologic deficit before treatment. Again, it was Wright who asked
Sanchez-Ramos to repeat wh ether one of the two treatments he witnessed
in Holland hadn't indeed resulted in apparent interruption of a 40 mg. daily
methadone habit. "Without apparent withdrawal," he repeated. But
ACT UP wasn't allowed to ask Sanchez-Ramos to amplify another off- handed
observation-- about the disappearance of a facial tic during the other Ibogaine
treament. He seemed to imply animal and human research with Ibogaine would
uncover novel neuro-behavioral aspects of habit formation in addiction and
other inappropr iate cerebellar reflexes--and that this understanding might
even lead to treatments of movement disorders like Tourette Syndrome and
Parkinson's Disease.
At the climax of the afternoon, one of the panelists asked if any addicts
present who'd been treated could have a chance to comment. Bob Sisko from
ICASH rose and gave his most impassioned argument yet for the accelerated
introduction of Ibogaine. Yet , when the Advisory Panel began with their
own statements, an intense argument broke out on the significance and ramifications
of the toxicity results of Molliver and O'Hearn--whether FDA should permit
Phase I human experiments. A collective decision was necessary. Cicero,
a psychiatrist, adamantly opposed human research. So did the neuroscientist,
Ricaurte, arguably the leading expert on Serotoninergic degeneration. Both
Cicero and Larry Brown of the ARTC in Brooklyn got the 10-15% damage-level
mixed up with the therapeutic dose--expressing nervousness at addicts having
to take it as frequently as every 4 months. On the other hand, the consumer
advocate present said the people she was representing would all be dead
before Ibogaine became available. Now the advocates of going forward began
to speak out. But questions arose for Deborah Mash and the Miami team which
they could only answer by presenting still-unpublished data. The open portion
of hearing was now ended, and the Advisory Committee went in to executive
session, to make its final decision in secret. New York ACT UP repaired
in disgust to eat at a nearby Silver Spring diner.
When they got back to the Holiday Inn, they connected with Lotsof and Mash
on the way up to the NDA suite to watch themselves on Tom Brokaw. It was
apparent some approval had been given, but not enough. Only later did ACT
up learn that projected doses of 5, 10 and 25 mg.-per-kg. had been cut down
to 1, 2 and 5 mg.-per-kg. Or that the population of the Miami experiment
was limited to thosewho had already previously done Ibogaine safely. In
addition a novice reporter covering the hearings picked up and r epeated
the panel's errors about a 10-15% loss of Purkinje cells with Ibogaine in
the LOS ANGELES TIMES wireservice story. This prompted Mark Molliver to
fire off a letter requesting a correction which characterized the loss at
the therapeutic level as "v ery slight." The only break was that
the following Monday, August 30, ABC finally aired the Day One Special.
It had LSD footage from the '60's--but AIDS had been edited out.
Toward the end of the next week Dana got an excited call and a fax from
Mark Molliver (see reproduction). As predicted, vincristine turned out to
cause Purkin loss in the vermis of the cerebellum. Up to 80% during a typical
course of chemo, in fact. And now Sandra Blakeslee's editors in the Science
Section of the NEW YORK TIMES suddenly decided they wanted an Ibogaine article.
Just xeroxing up a copy of this report on the ACT UP xerox machine caused
a scene with office manager Walt Wilder, who cha rged it was all "social
and political background"--not "scientific," (even though
Sandra Blakeslee said that as background, it was "the best laid out
in advance of any article she'd ever written.") In reality the report
was the most effective weapon in t he harm reduction repertoire, but the
only way Dana could insure continued access to the xerox was to go back
to the floor for support.
At this point Howard called up with incredible news. New studies were in
which seemed to show more cerebellar loss with either cold turkey withdrawal
ordelerium tremens from alcohol than with Ibogaine treatment--in fact, more
with continued use of alcohol or coke than with Ibogaine. Sandra Blakeslee
made a point of mentioning that in her article. But then every week, it
was delayed. Just coincidence, but some other breaking science development
kept bumping it.
Dana phoned Molliver again, asking about the tremor of withdrawal. Withdrawal
tremor is another excitotoxic feedback loop, perturbing the dopamine circuits,
which control movement. Cold Turkey withdrawal zaps Purkinjes. Continued
abuse zaps Purkinjes . The least loss is with Ibogaine, which is not paradoxical,
given that it apparently eliminates withdrawal. Could Ibogaine be generating
a "travelling wave" between the cerebellum and the pleasure pathway
that matched the rotating feedback loop of wi thdrawal/craving closely enough
to cancel it out? In that case, might the "very slight" Purkinje
loss stem instead from the greatly reduced withdrawal syndrome still present
during Ibogaine's waning phase?
Molliver now felt that if Ibogaine activity was indeed REM-like, there might
be no Purkinje cell loss in primates at all. To this Wright also added,
in further phone conversation with Dana re the cerebellar hypothesis, that
the FDA was aware of 1962 r eports in the SCIENTIFIC AMERICAN of abnormalities
or lesions in the midline vermis of Harlow's monkey infants--those raised
with nonmoving terrycloth "mothers"--who displayed the same characteristic
"shy-aggressive" behavior that researchers of the Chica go Project
later observed in preschoolers at risk for addiction.
Shortly after the medical marijuana protest outside the HHS on Sept 7th,
Dana announced to ACT UP that Harm Reduction was planning further protests
at FDA/NIDA in November. Philly ACT UP agreed on a date of Nov. 14th for
a weekend rally; work started on a leaflet for the great Midwest Harvest
Festival. But before a final decision to go ahead, Harm Reduction decided
to take up the NIDA and FDA offer of a further meeting, to see if enough
concessions could be obtained to make the zap unnecessary. This produced
not one but two additional meetings. The first was at Parklawn again, to
get Vocci and Wright together with Dhoruba bin Wahad, to update prospects
for a community-based Phase III Ibogaine trial in Harlem. But this quickly
lead to an invitation to the Oct 28th design session for MDD's own Phase
II trial at the Sheraton in Rockville.
The meeting Oct 4 started late and Dhoruba was delayed, which gave Dana
Beal and David Goldstein an opportunity to ask about the implications of
the August 25th Advisory Committee decision. David Goldstein asked Curtis
Wright to explain the exclusion criteria for Phase 1 human trials, especially
the exclusion of women of child bearing age. Curtis briefly explained that
these are only the initial parameters for the first group of human studies--
but that these had been decided by the FDA Advisory Boar d and they were
firm.
Dana Beal once again objected to the classification of Ibogaine as hallucinogenic,
and suggested that a more accurate term might be stimulant-oeneirogen. Curtis
explained that all psychoactive drugs legally could fall in only four categories:
1) sti mulant, 2) depressant, 3) narcotic, or 4) hallucinogenic. David Goldstein
asked about the use of Nitrous oxide for narcotic withdrawal (7,000 people
over 10 years) but Wright and Belinda Hayes indicated its status as a drug
of abuse was a mark against it . Ibogaine, on the other hand, they now considered
to have a low potential for abuse. Some discussion of community-based trials
did go on even before Dhoruba got there. But all MDD funding for clinical
trials for was tied up for at least a year finishing LAAM. The reason no
independent Ibogaine project was necessary was because only the only other
drugs they have under development are LAAM and buprenorphine.
Wright did let drop one important reason Ibogaine is getting consideration:
the danger of TB spreading via daily contact on the waiting lines for methadone.
Then he launched into a discussion about the "Alkaline Lake Experiment."
Alkaline Lake is an In dian Reservation in Canada with an 80% alcholism
rate.Nothing was working, until two natives came along who benefited from
the conventional 12-step therapy that was having no effect on the other
reservation inhabitants. What these two designed was a new p rogram incorporating
the history, myths, and spiritual traditions of their people. They started
a movement that cut alcoholism at Alkaline Lake drastically. If Dhoruba
could do something like that for Ibogaine, Wright thought it would improve
the impact .
In fact, Wright and Vocci were a lot happier discussing things years in
the future than in having Carlo at the Addiction Research Center provide
compassionate access for a few addicts right away . They were rife with
suggestions of independent research ers who might be interested in filing
INDs. Jean-Paul of Philadelphia ACT UP sat patiently for 40 minutes and
finally exploded at Wright and Vocci-- that HIV transmission intervention
can't wait, that the exclusion of PWA's was another stall. He was hea tedly
impatient at the slow pace. The general discussion on these topics was tabled
as Dhoruba arrived, a person Vocci and Wright were eager to meet.
Dhoruba was interested in getting word out in the Black community about
the FDA estimate on the probable lack of abuse liability of Ibogaine, which
Frank Vocci conceded was relevant. Dhoruba felt Ibogaine would probably
be acceptable to the community , but his initial concerns were that its
use be community based, and cognizant of the social-revolutionary aspects,
and that the sensitivity to medico-political ramifications was there to
support the accelerated introduction of this new addiction treatm ent.
When all was said and done, the only choice the government side seemed to
leave the activists was to have them lobby Congress for more money for MDD.
What was clear was that there was still no Ibogaine for addicts. The negotiators
minus Dhoruba retu rned to the Monday night ACT UP meeting, where they asked
the floor to follow the lead of Philly ACT UP and field one more demonstration
Novermber 14th to protest further delays. It passed 15-to-one, with 4 abstentions
and the proviso that a better flyer be brought back to the floor for approval.
On Friday, Oct. 8th, Frank Vocci called Dana Beal and invited ACT UP to
an open design session for phase one/phase two Ibogaine trials Oct 28th.
The meeting was to be a more sedate affair, no press, a calm hot el lunch
buffet where the participants had time to talk privately and exchange information
and discuss issues. NIDA was following up the FDA's lead and opening up
its process, but with the objective of coopting further protest.
The day before, though, a highly irregular publication occured in the Wednesday
N.Y. TIMES Health Section. Sandra Blakelee's article (bumped once again
from that Tuesday's Science section by breaking developments with HIV receptors)
materialized as a practical demonstration of how the Ibogaine coincidence
factor tends to intervene in things-- as exactly the information to re-define
the outcome. Finally... the first complete explanation of Molliver's findings
and the cerebellar mechanism of addiction was present ungarbled (although
Blakeslee repeated the mistaken analogy to psychosurgery instead of Hobson's
theory of REM as cerebellar forgetting).
To this meeting were invited treatment specialists with years of experience,in
one case with 25,000 addicts, NIDA's in-house experts on hallucinogens,
and the consultants who were still finishing work on LAAM and buprenorphine.
The participants were presented with the draft protocol for a NIDA Phase
I/II Trial, prepared by MDD scientists, for discussion and comments. The
target date for start of the trials was May of 1994. Frank Vocci proposed
the initial trials will be four treatment groups of 6 to 8 people.
Mark Molliver did a mini-seminar on Ibogaine neuromorphology and function,
answering all questions, and presenting new findings of faint traces of
toxicity, showing secondary effect of the cerebellar excitation, in the
thalamus and locus coeruleus. If Ibogaine was not in fact erasing addiction
by very selectively targeting guilty Purkinjes--if the explanation, as Molliver
put it, was an "other excitatory mechanism"--cerebellar excitation
of the thalamus and locus coeruleus would be consistent with REM -like activity.
And increasingly that began to look like the only explanation, as panelist
after panelist rejected the selective chemical lesioning hypothesis as failing
to account for the cerebellar damage already known to be caused by alcohol,
for ins tance. Why wouldn't drinking "erase" the addiction of
alcohol, if that were the process involved?
Right after lunch Curtis Wright gave a presentation on the introduction
of breakthrough science and the obstacles to and possibilities inherent
in change. Through the late morning and into the afternoon, however, the
discussion centered on whether the safety and effectiveness issues should
be separated, The fellow leading the afternoon session was especially set
on doing Phase I Trials with nonaddicts, despite the fact that the interaction
of Ibogaine and the body chemistry of target group has to be studied if
it's ever to go into addicts. Even after Mash and Sanchez-Ramos explained
that the dose level run-up being discussed was the logical extendion of
their Miami trial, there were objections to followup ("Just peeing
in a bottle to follow up effect ," was the way Vocci put it). There
was a perverse feeling that unless it was being given to non-addicts, any
administration to addicts had to be double-blinded. (Several panelist kept
bringing up LSD.)
This split finally manifested itself around the issue of whether dose escalation
should be cut off with the onset of ataxia. Howard Lotsof stated bluntly
that addiction interruption had never occured without ataxia. This was the
point when all the pre paration, the education embodied in the serendipitous
publication the day before of Sandra Blakeslee's article (See article, next
two pages.) , explaining the Ibogaine visualizations and the ataxia as "REM-like
effects," paid off. The panel more or less agreed dose escalation in
the first NIDA-sponsored trial in humans should not break off when ataxia
started to appear.
But Dana's plea to remember the larger context of AIDS otherwise failed
to resonate. For the second time, he suggested NIDA run a comparative trial
of Ibogaine and another apocynacaeus rain forest plant alkaloid which has
been in contemporrary use by doctors in New Zealand to interrupt the narcotic
withdrawal syndrome. Mitragynine from Mitragyna speciosa or kratom has a
long history in Malaysia both as a plant of abuse and to detox addicts.
A 4-methoxy substituted tryptamine, Mitragynine is a psyche delic, similar
in action to Psilocin. But no one seemed interested in putting mitragynine
on the list of medications to be evaluated for treatment of drug dependency.
The consensus on that panel had heard the plea to respond to AIDS, but refused
to cut an y corners.
There was another problem. Neither Wright or Vocci possessed the power to
negotiate ACT UP's broader harm reduction agenda. They could not discuss
clean needles or a waiver to allow AIDS Buyer's clubs to supply medical
marijuana. A meeting was needed with the higher-ups, and one way to get
that was to go ahead with the Nov. 14th protest.
Along about Wednesday in the week before the Harm Reduction rally, Nancy
Stanisec called up and asked why there was a protest when they'd been so
willing to meet. "What do you mean?" asked Dana. "We offered
you the cure for crack, and you won't even l et us have a little marijuana
for our friends with wasting syn-drome." He demanded to meet with Kessler,
Gebbe, Lee Brown and the new head of NIDA, when one was appointed, on a
broad harm reduction agenda.
The demonstration on Sunday, Nov. 14 at the Parklawn building of NIDA/FDA,
was largely a media success because of the coincidental appearance that
morning of a medical marijuana article in the NEW YORK TIMES, placed onceagain
weeks before by ACT UP Harm Reduction, with no inkling publication would
be so synchronistic. The angle was a Hasidic Rabbi who defies civil authority
to bring medical marijuana to the very sick in his community--a contact
made as a kind of consolation prize for the Ibogaine c linic that never
happened in Prague. Within days he would be on network talks shows. It made
it hard to ignore that day's protest. 65 activists from medical marijuana,
clean needle, and Ibogaine groups from five cities demonstrated, with coverage
by 4 l ocal TV stations and one radio network. All assembled were also energized
and entertained by the massive presence of the mobile Thomas K. Forcade
Assault rock 'n roll soundstage, the legendary Rock Against Racism battlewagon,
equipped with megawatt spe akers, and full recording capabilities, a serious
symbol of activist organization. But although there were twice as many people
as there'd been in July, the organizers were worried--there should have
been hundreds.
Sure enough, when Dana called Nancy Stanisec on Nov. 16th she said the Office
of AIDS Coordination could not facilitate such a harm reduction meeting,
and said we must contact Lee Brown, Gebe and so-on independently. The next
day he put in one more c all, to Curtis Wright. He asked flat-out for a
waiver equivalent to the needle exchange for medical marijuana. The FDA
couldn't be trusted regulating herbs, Dana said, if they didn't clean up
their act with cannabis. Wright said the problem was NIDA, that Marvin Schneider,
their policy man on marijuana, was unwilling to sign on to anything that
might "signal kids pot is okay." Wright said they were very concerned
about the uptick of pot use among 8th graders. Dana replied the absence
of a corresponding ri se in coke use showed harm reduction education was
working; we need more explicit separation of soft from hard drugs--not less.
The Dutch had a 40% reduction in their core addiction rate by separating
out marjuana; if we could get 40% with Ibogaine it wou ld be a miracle drug.
The fact that pot was competitive again with crack is an additional benefit
.
Wright seemed unconvinced. But then
an interesting thing happened. ThatThursday, during the first day of the
Drug Policy Foundation Conference at the L'Enfant Plaza Hotel, Ric Doblin
was suddenly called away to a surprise two hour FDA meeting at the Parklawn
Building, with Wright and Dan Spiker. It was such a surprise that Ric didn't
even turn up for his own long-scheduled afternoon MAPs organizing workshop.
A few people looking for the MAPS session instead found Dana and David Goldstein
holding for th on ancient Gnosticism and Ibogaine. One of them turned out
to be a sleep researcher and addictionologist from Milwaukee,Ed Friedrichs.
When Dana got to the part about REM and healing, Friedrichs became very
excited.
"What you're saying exactly dovetails with my findings about REM and
addiction. Most addicts have major sleep disorders, you know--many since
childhood. They can't complete REM without waking up--so they never get
the deep, post-REM slow wave sleep. I 've been giving them just enough desipramine
and melaril to keep them from waking up--and some of them REM for days,
but they get a good sleep for the first time and their withdrawal and craving
abate.
"The thing is, the body can't heal itself without the deep sleep that
comes immediately after REM. I had a gal in the hospital, an ex-alcoholic
with a history of d.t.'s. She was an AA councilor; all that coffee had given
her an ulcer, and the y had her in to take out her stomach. Well, she couldn't
sleep at all, and after 4 days spontaneously lapsed into delerium tremens.
Once you've had d.t.'s, simple sleep deprivation can trigger a recurrence.
On the fifth day her stitches popped out and he r wound came completely
open. It never had a chance to heal."
"So instead of REMing," said Dana, "she lapsed into an excito-toxic
loop! Which blocked deep sleep, slow wave sleep, completely! After Ibogaine,
people don't need REM at first. They awake completely refreshed each time
after just a few hours of deep sleep. They have a REM surplus. And they
appear to glow."
"It's simple, really," continued Friedrichs. "The relationship
between REM and healing is that deep sleep can't happen without successfully
completion of REM. Healing doesn't happen without deep sleep."
When Ric Doblin returned from his FDA meeting, he said that Curtis Wright
had mentioned the ACT UP rally. They offered him two important concessions.
First they agreed to approve marijuana as an herb, in line with their new
standards for herbs, inste ad of a compound, requiring decades of study
of 60 active ingredients and their interactions. Second, they agreed to
consider an application for orphan drug status for marijuana, to provide
$400,000 to pay for Doblin's comparative trial of marijuana versu s marinol
at San Franscisco General.
Why in a hundred years, we could have approval of practically every herb
currently in use!
©1995 ~ Cures Not Wars
Last updated February 4, 1995
Table of Contents.
Table
of Contents.