Copyright © 1995-1996, Paul De Rienzo, Dana Beal
and Members of the Project
All Rights Reserved
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!