Recorded February 2, 2001, At the Golden Gate Club Presidio, San Francisco
and sponsored by the Lindesmith Center-Drug Policy Foundation


Rick Doblin, our final panelist, and following very logically along here, is founder and president of MAPS, the Multidisciplinary Association for Psychedelic Studies, a non-profit membership-based research and educational organization, sponsoring clinical studies designed to obtain FDA approval for use of MDMA as a prescription medicine. He recently earned a Ph.D. in public policy from the Kennedy School of Government at Harvard University. I spent a little bit of time back there. They used to call it the belly of the beast there. His dissertation focused on the regulation of the medical use of psychedelics and marijuana. In your packet he actually has something he has authored called "A Clinical Plan for Partnering with the FDA" for this effort. So...Dr. Doblin.


Thank you. It's a pleasure to be here today and to see all of you here. There's four major points that I'd like to make today. The first one is that MDMA works. I think you've heard that from some of the speakers. It's not been shown in clinical trials but I think that it's my operating assumption that MDMA is both a safe and effective adjunct to psychotherapy.

The second point is that we can develop it through the FDA into a prescription medicine. I think the kit has outlined how the FDA will look at this. I've developed what I believe is a reasonable accurate $4 million five-year plan to move MDMA through the FDA system.

The third point is that once it's approved by the FDA, I think that we can develop an effective regulatory regime that will control its medical use so that it will be limited to clearly identified medical purposes. And one of the concerns that we all know in terms of the medical use of marijuana is that medical use is the same as legalization. The concern of the various government agencies is that approval of medical use of marijuana will not be able to be limited. Part of my dissertation was to become, to let loose of the inner authoritarian in my nature and to design a highly controlled regulatory regime, and I felt that I was able to do that. And some of the proposals that I'll identify now may make some of the libertarians in the audience squirm a little bit, but I believe that we can develop a highly regulated systems, within the powers that the FDA does have.

And then, the fourth point is that the expansion of the medical model can, in a series of gradual expansions, pave the way for the legalization of, excuse me, of MDMA, can pave the way for the legalization of MDMA through an increasingly broader criteria of who can use it. So I think the medical model, while it's often, government's major point of attack, that medicalization of marijuana, and medicalization of these drugs is just a front to help with the legalization of these drugs in a broader context, I think it's necessary to acknowledge that that's not true, inherently*.* The contexts for medical use are completely different and the arguments are completely different for broader legalization but that the science base that's developed in the studies that work on the medical use and also the models of regulatory control that we develop in the medical use and, as we can imagine their expansion, it can play a role. So I would like to acknowledge that and say that I think that I'll outline a series of ways where I think that once we have this highly controlled medical model, that it can be relaxed in a gradual way.

I think that one of the sad points that future historians will come to the conclusion, is that when they look back when MDMA was made Schedule 1 drug in 1985, it's taken us now 15 years to have the first approved scientific study of the medical use of MDMA, the one that Jose Carlos has spoken about, and Marcela, and that the lost benefits to the American Public, to the patients of the world, over this period of time. It will take us at least five more years to move MDMA through the FDA system. That whatever benefits have come from the criminalization of MDMA and the reduction of problems associated with its abuse, I think that those benefits will be substantially dwarfed by the lost benefits of the therapeutic use that didn't happen during that period of time [clapping].

Now, one of the reasons that I think MDMA can be made into a prescription medicine has to do with the institutional mission of the FDA. The FDA really does respond to attempts to alleviate suffering and to promote healing in patients. Their primary mission is not to support the war on drugs, their primary is to work to develop medicines to treat patients. And they are comfortable and have established procedures and have experienced employees to, and can work with drugs of abuse. Cocaine is a prescription medicine, methadone is a prescription medicine, fentanyl, various synthetic prescription heroins are prescription medicines. So the FDA is not inherently opposed to making a drug a into a prescription medicine if it has a substantial abuse potential.

I think the institutional mission of the National Institute on Drug Abuse is different. It's primary mission is to develop and fund scientific research into the risks of drugs of abuse. I wouldn't say that NIDA is our enemy in this but I would say that NIDA is not interested and is not in a position to fund anything looking at the benefits of MDMA. So we shouldn't look to NIDA.

I think the area where NIDA is a little bit in opposition to the development of medicines has to do with marijuana, and that's where NIDA has a monopoly on the supply of marijuana for research. There's a farm at the University of Mississippi that grows marijuana under contract to the National Institute of Drug Abuse and if you want to get permission for the research of marijuana you have to get permission of NIDA and their institutional mission is not that sympathetic so that we've had situations where protocols for marijuana have been approved by the FDA but NIDA would not provide the marijuana.

There are many people, hundreds of people in the United States that have schedule I licenses to produce synthetic drugs and so what we've been able to do with the able assistance of Dr. Dave Nichols at Purdue University is have a supply of MDMA manufactured that meets FDA standards. This was in 1985. The supply is, unfortunately, almost still entirely there. We haven't had permission to do that much in the way of research. But we have an independent, non-governmental source of MDMA for research. So what that means is that our work is focused on obtaining institutional review board approvals at institution and obtaining approval from the FDA, but we do not need to deal with the National Institute on Drug Abuse.

Now, the safety profile of MDMA I think, is sufficient to move it through the FDA system. As Kit outlined, before you can do phase I studies you need to do fourteen day toxicity studies in two species. Early on, MAPS was founding in 1986 with the recognition that we would need to move thorough the FDA system, and the first thing that MAPS did is open up what's called a drug master file at the FDA with 28 day toxicity studies in the dog and the rat. And I happened to be there when the dogs were sacrificed and if you can imagine, there was four or five autopsy tables with teams all around, taking apart these dogs and I was sitting in the middle, standing in the middle, telling them stories about the therapeutic potential of MDMA, why we were killing these dogs. And there was something really holy, I would say, about the feeble attempts of science to understand what goes on. So that these, uh, its general considered inhumane to do animal studies. Most people are against it, particularly most people that would be supportive of MDMA research. But I think that animal studies have crucial important role to play and that there is something sacred about the scientific process.

Now, the results of these studies were reassuring. We did not find that MDMA hurt any organ systems of the body and we did not find that MDMA killed brain cells. We did not look at specific reductions in serotonin but I believe that we can say that from the existing data there are no non-neurotoxic safety issues related to the physical effects of MDMA on the body. There are effects of MDMA on the heartbeat, there are other issues, but I think that the safety profile of MDMA will be sufficiently characterized, is sufficiently characterized, and is sufficiently mild so that we can work it through the FDA system. Plus we only need to administer a few doses in therapy.

In terms of neurotoxicity, my view is that the risk is an acceptable level, and I would go further, not to dismiss the importance of the neurotoxicity, but I would say that the neurotoxicity of MDMA is irrelevant to virtually all of the therapeutic uses that we are thinking of developing. Particularly therapeutic uses that are not biologically based, so that when we talk about post-traumatic stress, that has to do with incidents that happen, when we talk to people dealing with terminal illness, those are situations where its not necessarily the case that the people have already preexisting serotonin deficits, so I think that the neurotoxicity issue is something that we can easily address. George Ricaurte mentioned the research of Dr. Franz Vollenweider in Switzerland. He's conducted research. It's not been published. It's only been in a few patients. We need to do more. But he's taken people who have never done MDMA and he has given them PET scans to look for serotonin uptake sites, he's given them up to 1.7 milligrams per kilogram of MDMA and then tested them about a month later, and there's no evidence of serotonin changes.

Now, it may be that there were serotonin changes but that they were below threshold, but what that means is that they are minimal and within acceptable levels. We have information from Dr. George Ricaurte's research, he published it in Lancet, where people who have...14 MDMA users...have an average of 224 exposures to MDMA, an average of 386 milligrams of MDMA each time. Just think about that. An average dose is about 100 milligrams so these people are taking almost four pills of 100 milligram doses, and they've done this 224 times. And in order for George to be confident that whatever results he'd get were not due to pre-existing serotonin deficits, he screened out people that had depression, that had various indications that would be related to serotonin deficits. So, we have a group of people there who have taken MDMA massive number of times, massive amounts and did not show classic signs of serotonin functional consequences of serotonin neurotoxicity. So, I think that we can, in pretty good consciences, suggest that the neurotoxicity is not likely to be a problem.

The other evidence I'd like to point out to you is a study with Karin Bolla who did look at the effect of MDMA on memory. The neurotoxicity of MDMA has most closely been identified in scientific studies with deficits in memory. Karin Bolla worked with some of the same patients that George worked with and was able to determine in that group, if people took 440 milligrams per month or less, now these are people who have done this for a period of, a sustained period of at least two years, at least 50 doses, that they showed no memory deficits whatsoever, and were scored the same as the controls. So, I think that it's... I feel confident that the neurotoxicity issue can be addressed.

The next big issue is cost. And many of you may have heard Dr. Lester Grinspoon who's talked about how it cost several hundred million dollars to make drugs into medicines and therefore marijuana can never be made into a medicine. We have to do something else. The latest figures by Dr. Joe Dimassi at Tufts Center for the Study of Drug Development which collects information from pharmaceutical industry, is 1998 dollars, it was $313 million on average to make a drug into a medicine. That's a lot of money. So how are we as a community to raise that amount of money. The first to say is that was looked at from a perspective of a profit-making pharmaceutical company. And so, this process of making a drug into a medicine that takes seven to 15 years...there's what's called opportunity costs. You invest the money in the first year and in the animal studies it takes you fifteen years to get the drug approved but through all that time you could just as easily have put the mo ney into the bank and earned interest. So that of this $313 million, roughly half of that is just foregone income.

So, when we're trying to develop MDMA in the context of a non-profit organization people give the money, they get a tax deduction, they're not expecting a return, so that we don't have to worry about opportunity cost. And then Kit outlined the number of failures that are the result of this process in terms of the pharmaceutical company getting drugs through the system. This number that's been developed is the amortization of all the attempts to make drugs into a medicine, and then the cost of the failures are factored in. So that if you just take one drug, and we're starting with MDMA, we know it works, believe it works, the costs are substantially less. You don't have all these 5,000 chemical syntheses, you don't have 250 drugs going into animal testing, you don't have 20 drugs going into the Phase I trials, and when you're through with it, one or two getting out the end.

So that the cost is reasonable, and furthermore what we have now is an advantage, a major advantage. Because MDMA is such a widespread drug of abuse, governments around the world have invested substantial sums of money to try to understand its risks. There are now over 950 papers in the scientific literature about the effects of MDMA. Many of these..most of these are in animals, some of them are in human studies, all of this in the human... is in the public domain. So that we can appropriate all of this data and submit it to FDA as part of our package and we don't have to replicate a lot of it. We don't have to spend the money on that.

Now, tomorrow we're having a meeting to talk about protocol development and we have...MAPS had a team for the last year and a half, actually, reviewing all these studies, summarizing all these findings from all these studies. And it's a tremendous advantage. So that from $313 million I think that it's possible to move MDMA through the system for in the range of $4 million. I've looked at Zoloft for post-traumatic stress and I've filed a freedom of information action request with the FDA. I've got all the documents. Zoloft was approved on the basis of 385 patients. I've looked at other drugs...looked through the literature for the studies into other anti-depressants, for treating depression, anti-anxiety agents, and so its a reasonable assumption that for somewhere in the neighborhood of 500 patients that we can generate sufficient information from two well-controlled...adequate and well controlled clinical trials to move it through the FDA.

To talk about controversial drugs, Marinol which we know as the all THC pill, was developed on the basis....for cancer chemotherapy, on the basis of 454 patients. So let's say I'm wrong, let's say its not $4 million, let's say its $8 million. Well, roughly seven to eight million dollars has been spent on the state medical marijuana initiatives. I think that as a community we can come up with these resources.

Now, let's assume that it's approved. I think it can be effectively regulated. One problem is that the FDA can't regulate off-label prescription. They can't can't control that. Roughly 40 to 50 percent of the drugs that are approved are prescribed for indications that the FDA did not specifically approve them for. Either its a different dosing schedule, different doses. But there are other ways.

I think MDMA should be prescribed only by psychiatrists, and only by psychiatrists who've had special training. I that while it's true that therapists will be more effective if they have taken MDMA, I do not think that we should require that of the therapists who get this licensing. I think that there should be two-part license system, one should be for therapists who've gone through the training and had their own experiences. The other should be for psychiatrists who've gone through the training and decided not to. The reasons is I don't think we want to create this sort should I say it...just..we want to bring the skeptics into the system. We don't want to say you've gotta do this drug. If people don't want to do this drug they should be able to go through the training process and patients should be able to tell which group people were in. But we just wanna have special training.

We should only permit it in special facilities, and methadone maintenance clinics are one model. They're a little bit more highly regulated but I think that you can more adequately monitor it...more adequately control it. I think that we have a situation, sadly, that we know that in the past some psychiatrists who've worked with MDMA have sexually abused their patients. And I think we need to acknowledge that and we need to create centers where that's less likely to happen. I think it's more likely to happen in private practice. And I think we should have a national patient data base so that every off-label prescription is monitored and registered. We should have one mail order pharmacy so that only doctors who have submitted data about their uses and only have been registered can get it.....

(tape changes to another speaker)