 Tonight is on Ibogain. My name is Alan Kaye. I run the Hovereduction Commission in the United States. And I know from experience of when we put on Ibogain sessions at our conference, it's always been very packed. And we have a good crowd. And from experience also, there's a lot of interest from drug users as to the effect and the impact of Ibogain once they use it. Let's get on with this. I'm going to start off with Hamidatza. As much as I'm working, I guess it is. My presentation is on the history of the science and politics and advocacy of Ibogain. Science, like every other avenue of human endeavor, is certainly has a political nature. I'm going to give you a brief overview of what Ibogain is. Oh, no. Ibogain is found in the West African plant in the southern half of Ibogain. The alkaloids are presently found in the bark of the root. And the usable forms include a scraped or ground root bark, as is used in a greedy religious ceremonies in the West Africa. There are also total alkaloid extracts that are used and purified chemical grades of Ibogain. And hopefully, one day, an improved and unregulated form of the drug. There's a considerable amount of data available on Ibogain from the most simple chemical information, such as this found in Merck Index. And this gives you a sort of a background where the botanical source is used for hundreds of years in African medicine and religion. In 1901, Ibogain was isolated by Dibowsky and Landren. In 1958, its molecular structure was determined by Bartlett. In 1962, I discovered its anti-addictive effects. In 1991, the National Institute of Drug Abuse in the United States initiated the evaluation of Ibogain. In 1993, the Food and Drug Administration approved a clinical study of Ibogain. And in 1995, Maida Nationalist Drug Abuse held an important looking clinical resume. Ibogain has been driven by the patents because it allowed us to raise funds for development. And there were five patents in the area beginning in 1985 and proceeding through 1992. And these patents were for the treatment of narcotic dependence, cocaine and amphetamine dependence, alcohol dependence, nicotine and tobacco dependence, and polydrug dependence. This is a brief overview of the points in the regulatory and scientific development of Ibogain. In 1986, the first attempt at drug development of Ibogain was by the Dora Wiener Foundation in 1983. The foundation was not able to raise any significant funding. In 1986, a for-profit corporation, NDA International, was established and subsequently raised $4 billion towards the approval of Ibogain, initiating research impact development. In 1991, the National Institute on Drug Abuse approved their Ibogain research project. In 1993, we sought FDA approval for the University of Miami clinical studies under a contract to NDA International. This briefly, and I'll put it very briefly, it covers a wide period of development, of commercial involvement of Ibogain. The discovery in 62 and 63, in 81 through 96, there was patent development in 1987. We had the first extractions performed at the Center for National Research in France. The first publication was by Jolent at Erasmus University, showing that Ibogain diminished opioid withdrawal and then Stanley Glick between 1986, and in fact, right through the present time, has published possibly 3,000 papers on Ibogain and an Ibogain congener called 18-myslapsic coronary. Between 1988 and 1990, the International Coalition for Addicts Self-Help and the Dutch Admin of Self-Help Focus Groups, known as DASH, involved themselves in providing Ibogain to Dutch and American and European heroin users. Patricia Broderick at the City University of New York between 1990 and 1996, involved herself with the study of Ibogain's effects on cocaine, and between 1990 and 1993, FDA International, with cooperation of Professor Dr. Jan Bastian's conducted clinical studies in the Netherlands. Dr. Sanchez Ramos and Dr. Masch at the University of Miami between 1991 and 1996, were involved in the FDA study. The National Institute on Drug Abuse Ibogain study period was between 1991 and 1996. Between 1994 and 1996, clinical studies moved to hospitals under the Republic of Panama, Panama City. Between 1993 and 1996, Dr. Islani evaluated Ibogain's effects on alcohol dependence. And between 1993 and 1996, Dr. Popek at the National Institute of Health and at the Polish Ministry of Science provided a review of Ibogain and sub-studies concerned with cell stimulant nature. In 1996 and 1997, an Israeli company, U-MTEC, planned for clinical studies in Israel. NIDA, National Institute of Drug Abuse, initially rejected Ibogain research. NIDA was petitioned to perform Ibogain research between 84 and 90, first by the Dora Wiener Foundation and later by FDA International, a company established to make Ibogain available as an approved medication. In 91, NIDA formed its Medications Development Division and accepted a product profile review from FDA International that resulted in NIDA starting their Ibogain research program. The first scientific publication of Ibogain's anti-addictive effects was by Jolib, who published it in 88, on the effects of Ibogain diminishing withdrawal and deloxo precipitated morphine-dependent rats. NIDA, National Institute of Drug Abuse, which votes 85% of drug addiction research worldwide, responded with a paper from their intramural researchers entitled, Ibogain Fails to Reduce Naloxo-Precipitated with Dural and Morphine-Dependent Rats. That was answered, and this is where we begin to see the politics of science as they really dive again, but politics are evident in science as they are in any other human endeavor. Additional research was that supported that Jolib's findings were published by Stanley Glick from Albany Medical College, who evaluated Jolib's work, who evaluated Sharp and Jackie's work and provided his own work and determined that Ibogain did, in fact, diminish morphine withdrawal in morphine-dependent rats. Jolib then went and demonstrated Ibogain's effects on cocaine, and as you can see, there is a dose dependence decline in cocaine self-administration based on single and multiple administrations of Ibogain, whereas Vani evaluated Ibogain's effect in the rat on alcohol intake, and there again you can see a dose dependent response of the diminishment of alcohol intake caused by Ibogain. Albert and myself at Frank and Luciana Bastions did a review article evaluating the outcome in patients who were principally treated in the Netherlands and Panama for opiate withdrawal, and MASH in 2001 published a heroin study, and you can clearly see that there's diminishment of opiate withdrawal signs in her patients. Now, many of the subjects who take Ibogain describe the effects, one of the effects is returning them to a pre-adaptive state, and in terms of the science, what we have to look at is that Ibogain served to decrease induced levels of dopamine activity in drug-experienced animals or humans from elevated sensitized levels back to baseline levels, and that's the way scientists describe it in the rat. Human subjects describe it as being returned to a pre-adaptive state. Tissue distribution, this is a paper by Hau and Glick, and it was very important because there was a question as to what was the nature of Ibogain's long-lasting effects with MASH proposing that Ibogain's metabolite in your Ibogain was a long-acting drug, but Glick's theory, which I believe holds more relevancy, is that Ibogain is sequestered in the fat, released over time, and the reason that we were seeing nor Ibogain levels of Ibogain's metabolite longer out is that when nor Ibogain was metabolized, it throws a higher of the plasma levels up than Ibogain and is therefore observable for a greater time out than Ibogain. NIDA, at this point, contracted with neurotoxicology as Mark Molyver to investigate the neurotoxicity of Ibogain, and the Molyver in this paper indicated markers which demonstrated at a price of at least four times the therapeutic dose that there appeared to be markers for neurotoxicity. Now, that was responded to by Molinari and Glick's group and showed that at 40 milligrams a kilogram, which is a higher dose that would be used in humans, but a good dose in a rat that there was no neurotoxicity. Molyver then published again at Molyver, by the way, it's a brilliant researcher. Published again, showing that the exact area of neurotoxicity were in carpentry cells, but I think this matter gets resolved when in 2000, Zoo et al published on a dose response study of Ibogain, and what makes this a very interesting study is that it was accomplished in part out of the National Toxicological Research Lab which is an FDA laboratory, and it showed no neurotoxicity whatsoever in rats at 25 milligrams a kilogram. Other researchers indicated no evidence of neurotoxicity in a primate in a mouse, and a post-mortem neuropathological study of a woman who was treated with 30 milligrams of Ibogain showed no neuropathology. There were a number of review papers, all very excellent, this one by Glick, Mechanisms of Action of Anti-Addictive Effects of Ibogain. Albert and Catler and I recently published on a review of the use of Ibogain outside of the African-British religious context, and if you look at PubMed, which is a public access to the National Medical Database, you can see there are over 280 papers now published on Ibogain. Majority on Ibogain's effect on narcotic dependence. Ibogain has multiple mechanisms of action and receptor system effects where drugs of abuse also show activity, using glutopamine, opiates, serotonin, NMDA, nicotinic, GNDF, and signal transduction independent of receptor binding. The objective of the pharmaceutical industry is to return a profit to corporate shareholders, and this greatly affects the selection of compounds and indications for drug development and tends to discourage the development of innovative drugs to treat addiction. NIDA has focused on already existing drugs which are then developed for addiction as a new indication, and not the development of fundamentally new pharmacological studies such as Ibogain. And this was the first page of an agreement between NIDA and Ricket Bankeser to develop Lupin-Orphan and sign in 1994 and 1995 at the Ibogain Review Meeting based principally on the statements of industry representatives, NIDA decided not to fund clinical studies of Ibogain. However, in 2004, based on the possibility of foreign clinical studies, NIDA made available under the Freedom of Information Act a drug master file that had been provided to the FDA consisting of 16 volumes of data of approximately 4,000 pages. And this gives you an idea of some of the studies. There were acute oral toxicity studies, 32 days dose-ranging studies, dose-response neurotoxicity studies, dose-response effects of Ibogain on analgesia and mortality of morphine-dependent rats, pharmacognetic studies, dose-ranging toxicity studies in the dog, acute neurotoxicity studies in the dog. There were what they called an Ames test which is a mutagenicity test and a lymphoma mutagenesis and genesis assay which indicated that Ibogain was not a mutagenetic. Now, among the 16 volumes of data, mutagenesis studies showing Ibogain not to be a glutamide drug, and this is the final report from the Ames test indicating that the results of the study indicated that it did not cause positive response with any of the testers' trains in the presence or absence of Orocholera-induced rat liver enzyme. And this is, okay, thank you. So, I'm going to, what we have here is a period of safety study of Ibogain indicating that between 89 and 2006, there were 11 drug-related fatalities with Ibogain. In 2004, there were 3965 drug-related fatalities with methadone, and in 1999, there were 112,000 drug-related fatalities from FDA-approved drugs in U.S. hospitals. Ibogain, an activist advocacy organization that played an important role in Ibogain development, the International Coalition for Attic Self-Help in 1989, initiated studies in addicts. Dutch addicts self-help picked that work up in 1990. Sheila's not wore support of that work beginning in 1994. And in 2004, an underground movement began in the United States called Freedom Room, which is probably treated approximately 300 heroin and methadone-dependent patients. This was a logo used by ICASH to attract attention. It was very effective. Nico Adrienz was one of the founders of both the Rotterdam Junkies Union, Dutch addict self-help DASH, and also then the first established per-needle exchange in 1981. DASH was an Ibogain self-help organization that petitioned the Dutch government and organized drug users to demand Ibogain availability. DASH provided Ibogain at no cost to heroin users. This was a photograph taken during a parade at the avenue of Ibogain organizing in the United States by Ibogain advocates. And Chua's not wore, petitioned, was very important in petitioning the National Institute on Drug Abuse to initially evaluate Ibogain in their studies between 1991 and 1995. Thousands of these leaflets of Storm Niter were given out in Washington and Bethesda, Maryland. There's a mind box internet list which consists of thousands of users who can discuss their experience with Ibogain and they're also providers and medical doctors on the list. This is one of the statements of one of the users. We feel that continuing the focus offshore outside the U.S. has not served the majority of people inside the U.S. like many other grassroots movements. So we want to see this in all major U.S. cities. And Ibogain represents both harm reduction and demand reduction. And I'll go into that at a later point after showing you at the time. What is important is Ibogain's effect on stigma. Stigma is a mark of disgrace associated with a particular circumstance, quality or person. For instance, the stigma of chemical dependence. Ibogain's effect on stigma, Ibogain has the ability to remove the stigmatized condition, transforming the patient to a state often described as pre-individed. The transformation of a stigmatized person to one who is not stigmatized will affect the individual allowing greater contribution to self and society, improving the quality of life issues. Why Ibogain is not available, less important than past to Ibogain availability. Former suitable companies or government agencies are needed to finance regulatory development. Supplies of former suitable great Ibogain, this has now been facilitated. A grassroots constituency demanding availability now being facilitated. Political advocacy slowly coming online. The scientific community supporting Ibogain has been there. We hope that we will see further and significant research in the future. I'll go to that show. Okay, why it should be available, it should be available because it significantly reduces withdrawal, it interrupts drug craving, it returns patients to a pre-addictive state and eliminates stigma, returns free choice, and is in your hands. Back here.