Testimony to the Joint Assembly Taskforce on the Heroin Crisis:

IBOGAINE AND TREATMENT OF HEROIN DEPENDENCY

This month new articles about the use of Ibogaine in the treatment of addiction are appearing in DISCOVER, The New Scientist, the L.A. TIMES, the GUARDIAN of London, and DETAILS magazine. Yet even after dozens of articles in the press and scientific journals, most people are not aware that a treatment exists which can get people off drugs overnight--painlessly.

This rainforest alkaloid has been reported to act as an addiction interrupter across a wide spectrum of abused substances, legal and illegal, in more more than 200 peer-reviewed scientific papers. A unique effect is the simultaneous loss of multiple addictions--for example opiates, meth-amphetamine, crack, alcohol and cigarettes--after as little as a single treatment.

In the last few years, through the work of John Stuen of the National AIDS Brigade, it's become clear that most of the heroin in the Northeast United States has been re-processed with lidocaine and novocaine for a "speedball" effect in order to "punch through" methadone. In 12 samples turned into the NYPD, the stimulant content ranged from .05 to 20%. The immediate effect in addicts is that they need more injections, share more needles, spread more HIV and hepatitis C. And the Gold Standard of current treatment--methadone--is rendered worthless.

Ibogaine, on the other hand, is the first pharmacotherapy where, when the treatment wears off, addicts are free of both physical withdrawal and psychological craving. Methadone has a significant problem of deaths due to diversion. There is also a significant history of deaths with Ultra Rapid Opiate Detox, the procedure where naltrexone is injected after sedation with valium-like drugs. Dr Lance Gooberman of New Jersey was fined and lost his medical licence because he had 4 deaths out of 2350 procedures. And where opioid maintenance (methadone, buprenorphin) or blockers (naltrexone) fail to address the underlying dopaminergic disorder (craving), re-treatment with Ibogaine (should uncontrollable cravings re-cur, or in the event or relapse) is safe and easy.

With Ibogaine, the acute phase that requires bed-rest takes just two days. Even with a period to keep patients under observation in case you have to administer another, smaller dose after 4 to 6 days for residual cravings, folks can be back at work in just under two weeks. With 15 to 40% of treated subjects [depending on drug of abuse] remaining drug free for long periods of time after just one treatment, and more definitive resolution of the most refractory cases being acheived with two to four treatments over a two year period, it is difficult to understand why Ibogaine is not more accessible to the addicted population of New York state.

The problem is that Ibogaine was misclassified as a Schedule 1 drug at the end of the 1960's--a status which it has only in the United States, Belgium and Switzerland. It is legal everywhere else in the world. Efforts to change the status of Ibogaine by channeling it through the FDA approval process have foundered because no sponsor is willing step up the bat because of the stigma associated with a schedule 1 drug. The stumbling block, as always, is funding--plus lack of the support Ibogaine would have if more people realized it's not some far-off possibility in the distant future, but an option already available just over the border in Canada and Mexico.

Cures not Wars recommends that the State Legislature of New York seriously investigate re-scheduling Ibogaine down from Schedule 1 to Schedule 3, so that it can be given in most cases by nurse-practicianers. While it is a very powerful

medicine that ought to be administered only after screening for heart, liver and seizure disorders, 99 out of 100 cases do not require a hospital stay or supervision by a medical doctor. I am attaching a memorandum laying out the arguments for and problems surrounding re-scheduling at the state level and the probable effect of state action on Ibogaine's status under federal law.

Memo: Re-Scheduling Ibogaine Via the Legislature

Rescheduling Petition to move Ibogaine from Schedule I down to Schedule III.

1. Current Status

Rescheduling Ibogaine from Schedule I to Schedule III. Ibogaine currently is a Schedule I drug under the Controlled Substance Act ("CSA"). As Such, it has been stigmatized as purportedly having (a) a high potential for abuse; (b) no currently accepted medial use in treatment; and (C) lack of accepted safety for use under medical supervision.

Schedule I designation presents numerous difficulties for potential researchers and investigators. It serves to inhibit research, limit public funding, and discourage private investment capital needed for development of this promising anti-addictive medication.

2. The Need to Reschedule

A petition or other action to reschedule Ibogaine will be necessary sooner or later. Given the current state of scientific knowledge regarding Ibogaine and its use in the treatment of opioid dependence, a downward rescheduling to Schedule III, a restrictive level for items with broad medical use with some paperwork and distribution requirements, would be an appropriate placement.

The question therefore is whether we should proceed sooner rather than later. Since the rescheduling process is lengthy,taking months and sometimes years to achieve, we should undertake an initiative to reschedule as soon as practical, perhaps in conjunction with an application for Orphan Drug Status.

3. Standing

The history of the litigation to re-schedule cannabis as a Schedule II drug makes it abundantly clear that the DEA's own re-scheduling process defers unduly to the original listing of certain drugs as Schedule I by Congress when the Controlled Substances Act was enacted in 1970. Judge Clarence Thomas's opinion in the U.S. vs the Oakland Buyer's Club made it clear that the Judicial Branch currently feels that it is up to Congress--not doctors or judges--to determine which substances have medical uses. Yet however much the U.S. Supreme Court may invoke the doctrine of Congressional Supremacy, the fact that 9 states have approved medical use of marijuana has had an undeniable political impact on all levels of the Federal Government

Ibogaine was grandfathered into the Controlled Substances Act because of the World Health Organization's 1968 classification of ibogaine with the hallucinogens as "a substance likely to cause dependency or endanger human health." By virtue of

being on that list, Ibogaine became schedule I when New York enacted its own version of the CSA. Therefore, the route of rescheduling Ibogaine through the state legislative process, while not perfect, may be the most practical way to proceed at this time--especially if pursued with a view to establishing a hearing record in tandem with the present effort in Congress.

4. Medical Use

Under Schedule I category, a drug is deemed to have no medically accepted use in treatment in the United States. UnderSchedule III the drug is deemed safe enough for general distribution, while maintaining record keeping and other regulations to prevent diversion. Schedule III is actually somewhat strict given that Ibogaine has no abuse potential, but we feel this level would offer the best compromise between full de-scheduling and the overly restrictive Schedule II (which includes cocaine and other dependence forming drugs). Ibogaine has no history as a "street drug" and its classification as a Hallucinogen is being questioned by scientific authorities.

When Ibogaine was first listed as a Schedule I substance, there was no known medical use. However, beginning in 1986, series of US patents were issued that disclosed new medical uses for Ibogaine for the first time. These included its use in the treatment of narcotic addiction (Lotsof, 1985); treatment for cocaine and amphetamine abuse (Lotsof, 1986), alcoholism (Lotsof, 1989), nicotine dependency (Lotsof, 1991); poly-drug dependency (Lotsof, 1992); reduction in excitotoxic brain damage (Olney, 1997); and for treatment of neuropathic pain (Olney, 1998). Other potential indications include treatment of Obsessive-Compulsive Disorder (OCD), as an additive to conventional drugs for drug-resistant tuberculosis, and in the resolution of cysts and the elimination of growths and cancers.

The rational for the medical use of Ibogaine in the treatment of addictive disorders is supported by scores of peer-review papers that indicate Ibogaine, among other things, ameliorates the withdrawal syndrome in opiate-dependent rats (Dzoljic, 1988; Glick, 1994), and alcohol (Rezvani, 1995) in the animal model.

In 1993, the FDA authorized the University of Miami researchers J. Sanchos Ramos and Deborah Mash to conduct a Phase 1 dose escalation study. But instead of completing that study, Dr. Mash moved the research to an off-shore location, where she and her colleagues conduct ongoing phase II studies on the island of St. Kitts, under the auspices of Healing Visions Institute for Addictions Recovery, Inc., a corporation doing business in the State of Florida.

According to a recent report in the Wall Street Journal by Naik (July 15, 2002), Dr. Mash supervised use of Ibogaine to treat about 300 drug-dependent patients. The patients, most of whom were American, paid an average of $10,000.00 for the treatment.

The fact is that a team of renown US doctors, pharmacologists, and addiction professionals have found the use of Ibogaine in the treatment drug dependency medically acceptable, but are compelled to administer it to US citizens in an offshore setting. This clearly demonstrates the pressing need to reschedule Ibogaine from a Schedule I to a Schedule III substance. Based upon the state of scientific knowledge at the present time, rescheduling is wholly appropriate.

In keeping with the language of Schedule III, which stipulates reporting and distribution restrictions regarding its prescription and medical uses, Ibogaine is intended to be administered in the treatment of opioid/stimulant detoxification under supervision of a registered nurse or equivalent treatment professional, with access to specific vital signs monitoring and certain emergency response equipment

and procedures.

5. Potential for Abuse:

Schedule I, II and II stipulate that the drug has potential for abuse.

While we do not need to refute this notion in order to qualify for the downward reduction to schedule III status, it should be noted that the perception that Ibogaine has "a high potential for abuse" has not been born out by either science or statistics.

None of the consultants to NIDA in the 1995 Ibogaine Review Meeting identified the possible abuse of Ibogaine as a potential safety concern (Alper 2001). Ibogaine is reportedly neither rewarding nor aversive in the conditioned place preference paradigm (Parker, 1995).

Despite being a Schedule I substance for over 30 years, there has been no reports of Ibogaine abuse among drug users. There has never been a seizure of any consequence of Ibogaine reported by either the Drug Enforcement Administration (DEA) or local law enforcement anywhere in the United States, nor have there been any reports of street arrests forpossession or use of Ibogaine.

The only reported illicit use of Ibogaine consisted of anecdotal reports by or about addict self-help organizations and individuals who utilize the drug for purposes of detoxification. It should further be noted that those who have taken the drug report that it's effects were not pleasant or enjoyable and that most show no desire to repeat the experience --chiefly because of the length: 1 to 3 days (conveniently congruent to the most acute phase of heroin withdrawal).

The available evidence does not appear to suggest that Ibogaine has significant potential for abuse. Nevertheless, Ibogaine is still controlled and scheduled as if it "has a high potential for abuse, and has no medical use or value", both of which are totally untrue. Because of its current Scheduling we anticipate that the questions relating to possible diversion to the illicit market will be raised. Since Ibogaine is intended to be administered only in a controlled medical setting, the chance of diversion is minimal. Furthermore, there has been no reported street use of Ibogaine as a drug of abuse.

6. Safety Considerations

A Schedule I designation carries the supposition that there is a lack of accepted safety for the use of the drug.

Since being designated a Schedule I substance, multiple laboratories have evaluated Ibogaine for signs of neurotoxicity. While O'Hearn (1993) reported neurotoxic effects at a dose range of 100 mg/kg, Molinari (1996) found no neurotoxicity present at 40 mg/kg.

Xu (2000) reported that 25 mg/kg corresponds to a no-observable-adverse effect level (NOAEL). The dose range utilized in treatment of opioids withdrawal (15-25 mg/kg) falls within the NOAEL range. The LD50 of p.o. Ibogaine is reportedly 145 mg/kg i.p. in the rat and 175 mg/kg in mice.

Glick et al (1999) found no change in the resting heart rate or blood pressure at a dose of Ibogaine of 40 mg/kg i.p. Mash (1999) reported intensive cardiac

monitoring in 39 human subjects dependent on cocaine and/or heroin who received fixed doses of Ibogaine (500, 600, 800 or 1,000 mg. ) No significant adverse effects were seen under study conditions.

Luciano (1998; 2000) reported results of EEGs administered before and after Ibogaine treatment where addicted patients received 20-25 mg/kg. No General medical or EEG abnormalities were seen. At 24 hours after treatment, all neurological examinations were normal, and patients did not have subjective or objective signs of withdrawal.

Mash (2001) reported she has evaluated the safety of Ibogaine in more than 150 patients receiving a dose within the reported therapeutic range (8, 10, 12 mg/kg) under open label conditions, and that a single dose of Ibogaine was well tolerated in drug dependent subjects. No significant adverse effects were seen under study conditions.

Ibogaine has been linked to several fatalities in Europe, and one in the United States. None of the reported deaths occurred under clinical conditions. Autopsy reports failed to establish that Ibogaine itself was the cause of death in any fatality, though several reports indicated Ibogaine could have been a contributing factor. The surreptitious use of heroin or other drugs has created a source of uncertainty regarding several reported fatalities. In the U.S., a death occurred in Florida within 30 days of an Ibogaine treatment administered abroad. Autopsy reports concluded that the death was due to natural causes and not related to Ibogaine.

7. Defining the Nature of Ibogaine

Ibogaine has been classified as a hallucinogen and as such, has been compared at times to LSD, also a schedule I drug. It should be noted that notwithstanding the comparison, Ibogaine has never shared the popularity of LSD, probably because it's effects are reported as being not pleasurable and interrupting drug use.

The concept that Ibogaine is a hallucinogenic drug is no longer unanimous in scientific circles. According to French chemist Robert Goutarel, former director of the Natural Substances Division of the CNRS (French National Center for Scientific Research), the best classification is of the effects is as "oneiropherenic" rather than hallucinogenic. Others prefer the term "REMogenic" to define the psychological effects of Ibogaine.

Oneirorphrenia has been defined as "states produced by drugs that differ from hallucinogenic states by the absence of any psychotic symptoms while sharing with the hallucinogenic experience the pre-eminence of a primary thought process." Mash (2001) reported that following the administration of Ibogaine, no episodes of psychosis or major affective disorder were detected. Luciano (1998) reported that in patients he observed receiving between 20 and 25 mg/kg, reality-testing remained normal in all cases, and there were no signs or symptoms of anxiety or thought disorder. These observations are consistent with the above definition of oneirophrenia.

Some, but not all, patients treated with Ibogaine experience visualizations during the dream-like state experienced at the initial onset of the drug. Luciano (1998) reported that only one of three patients receiving 20-25 mg/kg experienced visual Hallucinosis, and then, only when their eyes were cosec. Some have theorized that these are not hallucinations per se, but are visualizations of repressed memories revealed in a waking dream-like state. These visualizations appear to assist the patient in understanding his underlying psychopathology and bringing about cathartic change that supports the interruption of drug use.

Proponents of this theory sometimes refer to Ibogaine not as "hallucinogenic", but as "REM-ogenic", since it places the patient into a waking state or REM in which they experience the release of repressed memories visually, as if in a dream, albeit a "waking dream-like state". Anecdotal reports mention having observed REM-like eye movements in awake patients during treatments. This is wholly consistent with ibogaine-specific activation of the inferior olive (a nucleusin the brainstem) which projects to cerebellar vermis, an area of the brain found to have enhanced blood flow in PET imaging studies of normal REM sleep in humans and to coordinate rapid eye movements during dreaming.

Gouteral (1993) describes the psychological effects of Ibogaine as a state that involves a "dream phenomenon without loss of consciousness or change in the perception of the environment or any illusions or formal deterioration of thought and without depersonalization." He states that Ibogaine has been "unjustly condemned as a hallucinogen", and suggested that a REM-like state induced by Ibogaine corresponds to a window of heightened neural plasticity, with reprocessing of previously learned information and the formation of new associations. This process acts to modify the pathology of learned addiction, weakening thel links between drug-taking cues and responses.

8. Product Formulation and the Analogs Act

Iboga-based medications now include Ibogaine HCl, Des-methylated (or "nor") ibogaine, the experimental drug 18-methoxycoronaridine, and various whole plant alkaloid extracts. Among researchers and treatment professionals, each has its adherents.

Ibogaine HCl (or sulphate) is the principle alkaloid of Iboga Tabernanthe purified in a salt form. It is the most studied--and the only one ever approved by FDA to go into humans. The full-blown experience consists of a) the visualization, or waking dream phase, followed by b) the "clear" deep concentration phase, followed by the c) insomnia phase. Since ibogaine is de-methylated in its first pass thru the liver into "nor-ibogaine," the second phase (b) may be thought of as the nor-ibogaine phase, characterized by heightened serotonin level and very week opioid activity at the mu and delta opiate receptors.

Within the last few years, various "free-base extracts" (Indra, Ethnogarden) have become available that contain all the alkaloids of the plant in a non-salt form. Besides being better-tolerated by knowledgeable addicts who reported that whole plant iboga extract is "less boring," the non-salt formulation seems to come on and drop off more gradually, lessening the risk of bradycardia during initial onset.

In the case of nor-ibogaine and 18-MC, patent-holders developed their compound explicitly to satisfy various safety concerns of the FDA and NIDA. They believe that their compounds, unlike Ibogaine HCl or the whole plant extracts, are sufficiently different that they do not fall under the CSA. However, since the molecular structure of all iboga congeners is virtually identical, and the mechanism of action is substantially the same, it is difficult to see how they would not fall under the purview the 1986 federal Analog Act if the classifying agency (DEA or Justice Dept.) chose to schedule them.

The only way that would happen is if they had a substantially different, and non-psychedelic, subjective effect. Therefore, it is in the interest of research into safer congeners of Ibogaine to re-schedule the parent plant and principal molecule in a less restrictive category.

9. Comments from interested parties

In response to any action to reschedule Ibogaine, there will no doubt be many comments by interested parties addressed to the Drug Enforcement Administration (DEA) regarding this matter. Some will favor rescheduling, others might be against it. We can anticipate comments will be submitted from such parties as: National Institute of Drug Abuse (NIDA) and their Medications Development Division (MDD); Department of Health and Human Services (DHHS); Food and Drug Administration (FDA); College of Problems of Drug Dependence (CPDD); American Association for the Treatment of Opoid Dependence (AATOD); American Psychiatric Association (APA); American Society of Addiction Medicine (ASAM); the National Alliance of Methadone Advocates (NAMA); and others.

We can probably anticipate public hearings, as the development of Ibogaine as a medical treatment for addiction has become a matter of great public interest. NIDA and FDA meetings relating to Ibogaine have always attracted public participation and generated interest from the media.

10. Effect of Rescheduling

The practical effect of rescheduling Ibogaine from Schedule I down to Schedule III will be to permit easier access to researchers and investigators to pursue Ibogaine research. If the reports up to the present of Ibogaine's reportedly high success rate with heroin and other addictions, we can expect Ibogaine to become the premiere treatment/ detox method allowing users to avoid most if not all withdrawal symptoms, while facilitating rapid psychological self assessment, reflection and ultimately a life experience free of both physical and emotional drug cravings. The cost savings provided by this method, as opposed to methadone maintenance, long term rehab, and prison, will be in the many billions of dollars annually. And this will happen with out posing any risk of illicit diversion or abuse.

References:

Aceto, M.D., Bowman, E., Harris, L.S., "Dependence Studies of New Compounds in the Rhesus Monkey, Rat, and Mouse," NIDA Research Monograph Series Problems of Drug Dependence 1989, 96:607 (1990)

Aceto, M.D., Bowman, E., Harris, L.S., "Dependence Studies of New Compounds in the Rhesus Monkey, Rat, and Mouse," NIDA Research Monograph Series Problems of Drug Dependence 1991, 119: 519 (1992)"Alper, K. "Ibogaine: A Review' The Alkaloids 56: 1-38 (2001)

Braun, A.R. et al. "Dissociated Pattern of Activity in Visual Cortices and Their Projections During Human Rapid Eye Movement Sleep," Science 279, 91-95 (1998)

Cappendijk, S,L,T, Dzolijic, M.R. "Inhibitory Effects of Ibogaine on Cocaine Self-Administration in Rats" Eur. J of Pharmacology 241:261-265 (1993)

Dzoljic, E.D., Kaplan, C.D., Dzoljic, M.R."Effects of Ibogaine on nalozone-percipitated withdrawal syndrome on chronic morphine-dependant rats", Archives of Intl. Pharmacodynamics 294, 64-70 (1988)

Goutarel, R., Golnhoffer, N., Sillans, R. "Pharmacodynamics...

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