 Ladies and gentlemen, and it's a pleasure to speak on this subject. In fact, I was invited, and I should actually say that the title of my talk is important. I'm talking about, principally talking about what I regard as the lack of evidence of I began for treatment of heroin dependence specifically. I was invited by the International Network of People Who Use Drugs to give this talk and I'm grateful to them for that invitation. And as a stalwart supporter of user organizations, of course, I accepted. The form of the invitation specified that they wanted me to provide a harm reductionist scientist critique on Ibogaine. And having accepted that invitation, that's exactly what I'll do. Now, obviously this is an area where there are a wide difference of views. I think it's important before we go through the discussion to emphasize the values that I think many of us in this room, many of us at this conference hold dear as central values for harm reduction. And that is a tolerance and respect for different views to base policy and practice on evidence and regarding the reduction of harm as the paramount aim of our activities. Before dealing with Ibogaine specifically, I think it's important to talk a little bit about the regulation of drugs. And I noticed that Howard said that the goal of his activities, what he'd like to see is that Ibogaine will become available as a regulated drug. And that's the notion of looking at medications in terms of them being regulated is certainly something that resonates with me. There was an era when medications were not regulated and that was not a happy era. Medications have been progressively regulated throughout the 20th century and it's been an important protection for all people, but particularly for vulnerable populations. And I would certainly include injecting drug users in that category. I'm going to talk about a little bit about how medications are regulated, whether Ibogaine is an effective treatment for heroin dependence, whether Ibogaine actually assists heroin detoxification, whether it's a safe drug, whether we should be doing, some people should be doing more Ibogaine research and discuss a little bit about Ibogaine advocacy before going on to conclusions. Now as I mentioned, the area of medical regulation of medications has been I think an important advance in medicine during the 20th century and the whole system got shaken up very considerably in the 1960s due to the catastrophe that occurred when Thalidomide was made available and caused large numbers of deformities in children where it was given to their pregnant mothers. So after Thalidomide, a new concept developed in medical regulation throughout the world and that is to regard all new drugs were considered to be ineffective and unsafe until proven otherwise and that's a central concept in medical regulation. And all developed countries have accepted this approach for all new drugs without exception. So drugs used for diabetes and breast cancer and heart disease and I think drugs used for the treatment of drug dependence should be no exception. And I think if we want to argue the case that Ibogaine should be exempt from that general rule I would like to see what kind of a case can be made for why drug users should be exposed to the risks of medications of unknown effectiveness and unknown safety. So let's turn to the question of whether Ibogaine is effective as a treatment for heroin dependence. I think many of us in this room would recognize that we badly need new treatments for heroin dependence. A lot of people around the world who start using heroin, not all, but a lot of them get into serious difficulties and cause great grief to themselves, loved ones and their communities. We've got some good treatments for heroin dependence. We don't have nearly enough treatments for heroin dependence. So I think there'd be widespread agreement with that. Opioid substitution treatments like methadone and buprenorphine are certainly effective and safe, but we have very few treatments to offer people these days. And I would also argue that finding new treatments for heroin dependence is an even greater priority, a much greater priority than finding new agents for use in heroin detoxification. What kind of evidence do we seek when we're looking for data that shows that any kind of treatment is effective? Well, we'd like to see numbers of studies, not just one or two, but numbers of them, preferably from a number of different countries. That's not essential and certainly desirable. We'd like to see studies preferably with different kinds of designs. And we'd like to see these studies being, having rigorous designs, including if possible randomized control trials, which is still the gold standard in this area, although there's controversy about that too. And a very important criterion is the publication of studies in reputable referee journals. These are all standard for treatments of all conditions that we can think of. But I think it's beyond argument that the evidence that I've gained is effective as a treatment for heroin dependence at the moment is minimal. There are relatively few studies. It's not clear to me how many of the studies in humans have been gone before human research in ethics committees, and I think that's an area that should be a concern. Many of the studies involve small numbers of subjects. Many involve self-reported data. Follow-up periods are generally short. The quality of design is not overwhelming. Most of these studies have not been published in referee journals. And when you look at the fine print, many of them contain a lot of uncertainty about the confidence of the conclusions. There's a lot of mites and maybes and could-haves and appears to and that sort of thing. Could I again be useful for heroin detoxification? And by detoxification, let me specify that I'm talking about achieving a safely comfortable withdrawal from the drug. And therefore I'm talking about something that's short-term. For me, detoxification is not a treatment, but it's really a preview to treatment. It's an important thing to provide. It should be part of the whole system, the whole package that's provided. But it's not as critical as the need to provide new treatments. We have a very good treatment in the form of buprenorphine for heroin detoxification. But in any case, there are many more studies of using ibogaine for detoxification than there are for treatment of heroin dependence. Still the literatures in a preliminary stage and a few of the studies, as I'm aware of them, compare ibogaine as an agent with other agents for detoxification. So overall, for me, this is still the evidence is unconvincing in terms of ibogaine being useful in humans with heroin dependence in terms of its effectiveness. The supporters of ibogaine make a number of claims. They argue that ibogaine reduces drug craving. This is a kind of secondary indicator. It's helpful if it's there, if it's not there, but it still provides other benefits. Those other benefits would be regarded as much more important, such as periods of abstinence following the exposure to the drug. They also claim that it reduces opioid withdrawal signs and symptoms, and some of that evidence has been presented tonight. And there's also argument that there are some papers that claim sustained complete resolution of opioid withdrawal syndromes, but I think some of those papers, most of those papers, leave something to be desired. Really, these studies are in what could only be described as phase one. There's no, it's not a criticism. Drugs go through phases. This is the first step in studying drugs is to go through so-called phase one studies, and that's where ibogaine is at the moment. Okay. Marsh, who's certainly a supporter of ibogaine, assessed ibogaine, the ibogaine literature as follows. There have been few reports of the effects of ibogaine in humans. Anecdotal accounts of the acute and long-term effects of ibogaine have included only a small series of case reports from opioid and cocaine addicts, with observations provided for only seven and four subjects respectively. That was published in 2001. Then, same article, the use of ibogaine for the treatment of drug dependence has been based on anecdotal reports from groups of self-treating addicts that the drug blocked opioid withdrawal and reduced craving for opioids and other illicit drugs for extended time periods. And also, she mentioned on, say, objective investigations of ibogaine's effects on drug craving and the science and symptoms of opioid withdrawal have not been done in either research or conventional treatment settings. So, what can we say about the safety of ibogaine in terms of its treatment for heroin dependence? Well, the kind of data we'd like to see is lots of laboratory studies of animals, and Howard has told us about some of those. We'd like to see studies in humans, initially short-term, later in the long term. As I said, we're still in phase one. There are no phase two or phase three studies here yet. Leaven deaths have been reported. On the other hand, some of these claims have been criticized. There's also claims of severe illness in after-expersion of ibogaine. Howard's already touched on the question about possible neurotoxicity in rat experiments. I think overall, we're still at a stage where the data for the safety of ibogaine is still at a minimal stage. And we should not make the mistake of assuming that it's going to be a safe drug simply because it's organic. Should we be doing more, or should somebody be doing more research on ibogaine? Howard's absolutely right that the pharmaceutical industry generally does very little research on drugs in this area for the reason that Howard mentioned. It seemed to be stigmatizing also for pharmaceutical companies. And researchers will be very selective about what drugs they will choose to do research on, whether they're researchers in the academic area or researchers in the commercial area. And they'll generally make decisions partly on theoretical grounds, but even more so on empirical grounds. How good is the data from the studies that have been done already? And they will also base their decisions on very hard-nosed assessments of what they regard as the likelihood of achieving success. Another problem in this area is that there are real concerns about pharmaceutical companies having intellectual property of a drug that is obtained from a plant like this. So should people just use ibogaine? Well, in my view, we've got so much experience from around the world of the high price that's been paid from cutting corners from bypassing the drug regulation, the medical regulation system. And philidomide is a case in point that went through the medical regulatory system at the time, wouldn't get through now. And we do have snakal drugs in the past and even in the present. And I think that's a drug which is actively promoted by some, yet the evidence of effectiveness is dismal and the evidence of lack of safety is quite impressive. And I hope we don't go into that. Ibogaine doesn't follow that sort of path. So I think we have to accept the assumption that ibogaine is ineffective and unsafe until evidence to the contrary emerges. Just wrapping up. So should we look at the question of advocacy for ibogaine? Well, Herbert Cleaver has said ultimately the usefulness of, or lack thereof, of ibogaine-related compounds in the treatment of addiction will rise or fall on the basis of research. He also said whether or not ibogaine is useful is a scientific question that can be answered by either by street demonstrations nor by avoiding careful control research. A scientist's obligation is to keep looking for safe and effective methods to prevent and treat this great international scourge. Finally, he said whether the actions against NIDA were ultimately helpful, harmful or insignificant in getting the desired results is not totally clear. Then he went on to say, my own view is that there may have been a short-term gain or a long-term loss because of perceived marginalisation of the drug. I won't go through these conclusions in the interest of time, but I think the main point I'd like to make is that we really, in 2008, it may be different in 2009 and beyond, we really do not have evidence that ibogaine is an effective and safe treatment for heroin dependence and nor do we have evidence that it's an effective and safe agent for use in heroin detoxification. And like I said, ART is one of the government's main reference group meetings, so we will take some questions as opposed to statements at this time for Alex, and then people will want to challenge some of the assumptions in Alex's presentation from the audience after, and we can do that. Hi, I'm Dr. Alberto Sola. I run an ibogaine clinic in Cancun, Mexico. And how can you say that there's no good evidence of effectiveness in the craving and the use of drugs when there is several hundred papers with rats and dogs with self-administered ibogaine and cocaine that do decrease those self-administered drugs when injected with ibogaine? Well, it's not just my assessment. It's also the assessment of Marsh, as I just showed you, who regards herself as an advocate for ibogaine. And it's because it's not just the existence of multiple publications. The publications have to conform to a certain type and standard, and the publications don't conform to those types of standards. There are preliminary studies, there are small numbers, self-reported... I'm not talking about the humans. I'm talking about the animal models that have proved that it does reduce the consumption of heroin and cocaine. Those of you who didn't hear down the back the question is what about the laboratory studies. Laboratory studies are interesting, but they form the basis for how scientists will decide whether or not to investigate a drug in human subjects. But on their own, they are not regarded as proof of efficacy or of safety. They are interesting, and they help to decide whether or not to proceed with studies in humans. But on their own, they're not evidence of efficacy or safety. Just to update the data for efficacy that you presented from Deborah Mash, the evidence for efficacy and acute withdrawal are two case series with about 65 patients showing the resolution of withdrawal symptoms. There is also the series in regards to drug dependence, which was made in the heroin remanence, that was presented to NIDA that was the basis for their decision to go forward with their NIDA Ibogaine project. That was about 52 patients who were followed for a period of up to a couple of years. About a third of them had abstinence beyond the six-month period of follow-up. That's a treatment effect that's roughly equivalent to about six months in a therapeutic community. And then there's also the existence of the Ibogaine cell culture itself, the rate uncontrolled experiment as Frank Vachi has referred to, in which over 50% of people who take Ibogaine have done so for the treatment of opioid detoxification, for which there's not much of a placebo effect. And this is expanded on the base of word of mouth by about 30% over a five-year period, annual 30% growth rate, so it's quadrupled since 2001 to 2006. Nonetheless, I would agree that this is not the stuff of which drug approval is made. And I think there's two perspectives from which to look at this. The perspective from which I look at it is an interesting pharmacological paradigm, which I've referred to, and those are quoting my exact words that I've published. But I think the perspective you're looking at is someone who's responsible for implementing drug policy on a national level, or making drugs available on a national level. And we need to differentiate whether you're talking about the progression through preclinical phase one, phase two, and phase three is what you require. Presently, I think the preclinical proof of concept model is very strong. The toxicological evidence was sufficient for the FDA to approve going forward with phase one study. Phase one study reached the dose of four milligrams per kilogram, which is not the dose that's commonly used for detoxification. And the trail ends there. So I think from your perspective, you're looking at a drug that is somewhere into phase one with phase two and phase three not completed, and you're saying that the drug approval process has not been satisfied. And I think that's objectively an unarguable point of view. But I think also in terms of whether this is a scientific paradigm, it's interesting that all of the evidence, including the accounts of those treated and the existence of the subculture and the confluence of the animal model with the human model in conditions where there's no placebo effect to speak of, the Cochrane reviews, which are the apotheosis of evidence-based medicine, there are 56 studies that they felt using conventional methods, clonidine, our alpha-2 agonist, methadone, bubrenorphine. There are 56 studies that they felt in their reviews were sufficient evidence of quality to include. Only three could have a placebo condition, and all three of those, any treatment effect. In fact, any treatment was quite robust. So the idea that in an uncontrolled study you can observe a treatment effect of opioid withdrawal I think has some credibility. But again, I think the major difference that we're talking about here is whether you're looking at this at a national level, as you are, in terms of implementing drug availability, or whether you're looking at this from a scientific context in terms of evidence for an interesting effect. Another question that comes up, given the question, given the fact that there is really no clear prospect for I being to become available anytime soon, or I go to opioids to become available anytime soon, what is to be done by the individual who has failed other treatments and turned side again? I don't think there's an easy answer for this one, but I was wondering what your view is on that. Well, just to respond to what you said before I answer the question, there seem to be two parts to what you're saying, and the first part is addressing the question of evidence of effectiveness and safety, and I think we seem to have very similar view on that, that if we put that in terms of the level of evidence that's required for regulatory purposes to live against way short of that at the moment, then the second part of that is whether research should be done, and whether we like it or not, that decision is not going to be made by people in this room, it's going to be made by senior people in NIDA or in pharmaceutical companies or in academia, not necessarily in the United States. Let's not make that assumption. Just in terms of... I'm flattered by your assumption that I have some degree of power in my own country that we disabuse you of that straightaway, that my views are not... I regret to say not true with respect in which I think they deserve to be treated. In regard to your question about what would I say to people who might consider using Ibogaine, call me conservative if you like, but my doctor perspective, which I was asked to provide, is that people should use medications which are approved by regulatory authorities and in terms of medications, should not use medications other than that. And I don't feel at all conflicted or ambivalent about that. How about as a harm reductionist? Well, in terms of harm reduction, I think that we have plenty of evidence of other drugs that have been used outside the medical regulatory system, which have caused deaths, severe illness, and which haven't worked and which are sold as highly effective drugs. The medical literature is full of... not so long ago, people were claiming that extracts from an apricot kernel was a clear cure for cancer and that that was found to be not only ineffective, but also very damaging. Can you ask a question? I'm the 32nd Athena. Do you support clinical trials of Ibogaine? I don't have an opinion on it. I'm not really in a position to do that kind of research myself, so I wouldn't really make a decision about doing that work or not doing that work. It's not the sort of thing I do. Should we support clinical trials? It's up to you. Is there any money in desires? Hi, my name is John Lomburg and I work with a drug users group in Ireland, Ishka, it's called, and we advocate for the rights of people who are using drugs and who unfortunately maybe end up addicted to drugs and have to suffer the consequences and come with that. So within that and looking at treatment attempts to engage in treatment programs which aren't that readily available, as I'm sure everybody here is aware, it's quite difficult to get into treatment when one has made a decision to move in that direction. And there aren't enough, up to my mind, there aren't enough choices out there. You're given a corporate in the Irish perspective corporate gives us or allows us to decide to go on a methadone program if and when someone decides that they want to face or deal with the addiction. We don't have any other choices. There's no other drugs that are spoken about. So what I'd be asking is like that all treatment modalities would be considered. Now I understand this thing about trials and about having an efficacy around whether the drug is useful or not but from my perspective, drug users would use any drug if they hear about it. When I hear these comments or say 100% increase over 3 or 4 years, I mean rumor will dictate the amount of drugs used or the type of drug use or trends as they go. So I've heard about this again maybe 10 or 15 years ago or something like that. Can you ask the question now? Can I talk to the speakers? I used to be interested in it. I've never seen it. I've never experienced it. But from what I heard about it it's an interesting kind of drug. So I'm just saying about choice is around giving people the option to make choices. We're all grown, you know, we should be considered all kind of mature human beings hopefully, but you know being so just around that is our choice, thanks. Well, we agree on a lot. We agree seems to me you and me agree that this is a troubling condition for a lot of people that the treatment system leaves a lot to be desired and this is unfortunately in almost every country in the world people have difficulty getting into treatment and as you quite rightly point out when they get into treatment the options are very few. And I am ashamed to say I agree with that as someone who provides treatment I wish we could provide better treatment and more options. We have to play the cards that we're dealt with. In terms of recommending that people should use a drug of unknown effectiveness and unknown safety, as a doctor I don't advocate that as an individual I don't think it's a safe thing to do. I think that, I'm repeating myself but I think we have so many instances so many examples where panaceas have been recommended sold at high price found to be worthless and not only worthless but also dangerous and I don't think we know yet in 2008 that Ibogaine falls into that category but it might fall into that category and because of the thalidomide disaster that befell us 40 years ago I won't recommend and I won't use and I won't prescribe a drug unless I know that it is effective and that's safe.