 What I'd like to share with you today is a bit of the regulatory challenges that we face to make MDMA into a prescription medicine. But the most important message that I'd like to leave you with is that the FDA is our friend. The FDA is not pro-psychedelic or pro-medical marijuana, but the FDA is pro-science over politics. And there has been multiple efforts by various politicians to pressure the FDA to stop approving MDMA research or to be more difficult on marijuana research than they are. And the FDA has resisted those pressures. So since 1990, when they first gave permission to Rick Strossman to do a DMT study, and then in 1992, when they had their advisory committee meetings to talk about our MDMA for cancer patients with anxiety study, and they decided then to open the door to psychedelic research, we've basically had an open door at the FDA. But what they've said was that they will regulate psychedelics and marijuana the same way they regulate any other drug from any other for-profit pharmaceutical company. So we have to meet those standards. It's very difficult. But just to have unbiased, fair evaluation of the data is a tremendous benefit in the world of prohibition. So the FDA and the science approach has really been our ally. And I think it's justifiable that we are going to try to do a major, major effort to work through the FDA. Now, this started the regulatory engagement in 1984. So this is a picture of me here, let's see, spying on the DEA. So about 30 days before that, they decided that they wanted to criminalize MDMA. And they only knew about ecstasy. They didn't know about the underground therapeutic use. And so with the group of people, we decided we would sue the DEA. And so this was right before I walked into the door to surprise them with a lawsuit and the existence of this whole underground psychedelic therapy community that they didn't know anything about. Now, I was also saying, yes, it should be a medicine, but I don't think the whole idea of prohibition was a good idea. And so that got me kind of characterized as the Timothy Leary of the 80s, which was not a very successful strategy in view of what we've heard about the backlash for Timothy Leary. So it's kind of delicate and I've learned over time kind of how to navigate this. But we basically, we won the lawsuit. The administrative law judge said, yes, it should be a medicine. The DEA resisted that, rejected it. We sued him a couple of times in the appeals courts. We won, eventually the DEA figured out how to satisfy the judge. And MDMA was criminalized. And the only way out is through the FDA. So in 1986, I started MAPS as basically a non-profit psychedelic and medical marijuana pharmaceutical company. And what I recognized is that, how does a small non-profit without, with very little resources, make a drug into a medicine when the pharmaceutical company will tell you it costs over a billion dollars for every drug that they make into a medicine? And there are good answers to that. And it's mainly this Akito strategy. The idea is that you use the energy of your opponents and their momentum against them. And so what we have now is governments all over the world have been trying to show what's bad with MDMA. And what's bad with marijuana, what's bad with LSD. And so there are now over 5,000 papers in Medline under MDMA or Ecstasy. And we estimate somewhere around $300 million, at least have been spent on those studies. And they're in the public domain. The risks of MDMA are very well characterized. Now, a lot of it is about the risks of ecstasy. And a lot of times ecstasy, we don't know really what it is. But that's the worst case scenario in a sense. Impure drugs taken with other things in public settings. And so we know sort of the worst cases. And there's been some money put into mechanism of action research. And over 1,100 people have received MDMA now in clinical settings. And only about 160 have been in map studies. So there is a lot of information to suggest that in clinical settings, MDMA can be administered safely. So what I've tried to do though, starting actually in the middle 90s, was to recognize that when the regulators look at this idea of letting psychedelic research go forward, they're looking at what happens if it's approved. How are we going to control it that way? And so what the FDA has is a program called REMS, the Risk Evaluation and Mitigation Strategies. Many of you may have heard about thalidomide, which was a drug that was given for women for morning sickness that causes birth defects. And the FDA sort of made its name on blocking that from being marketed in the United States. But thalidomide is now medicine in the US for certain kinds of cancer. And the FDA developed a whole set of procedures, how to control the risks of thalidomide and then expanded and expanded into this REMS procedure. And so the things that we've told regulators that we're going to be doing as part of our REMS is the most important part is that it's not like any other drug that once it's approved, any doctor can prescribe it. The prescription of MDMA or psilocybin or LSD for therapeutic use will be limited because the drug is not the treatment. The treatment is drug-assisted psychotherapy. And so only those people that are trained in the psychotherapy will be able to administer the drug and will be able to prescribe it. Then it's only going to be in certain kind of clinics, certain kind of centers that are set up physically to promote psychedelic research or actually psychedelic treatment. And in our approach, we have people spend the night in the treatment center. So we feel that's really helpful to take people out of their daily patterns and give them time to reflect and integrate. And then we have a lot of non-drug psychotherapy the next day. So we're going to have regulated clinics like methadone clinics, kidney dialysis centers, then there's going to be a limit initially because of the concern about MDMA neurotoxicity, which is not completely resolved. We really don't believe that at the doses that we're giving, we don't see any evidence of functional consequences from neurotoxicity. But it is a very complicated issue. And so if we go to the FDA and we say, we're going to propose that people can only get MDMA 10 or 12 times in their whole life as part of therapy, that that's going to make the approval process a lot easier. And then later, we will work with them to expand the number of doses. But really for PTSD, we don't really believe people are going to need 10 to 12 exposures of MDMA. So the lifetime limit, then we have to standardize the therapy in this manualized therapy. We have to have very careful screening procedures. We will prohibit people from driving for a certain period of time. And then there'll be a national patient registry. So some people who are libertarians, this sort of drives them nuts. But everybody who's ever prescribed MDMA will be on a list. That's how we'll track how many times they've got MDMA. If doctors prescribe off-label, meaning for something else, we'll know what they prescribe for. And there'll be one pharmacy that ships it everywhere. So with these kind of strategies in place, the idea of medicalized MDMA-assisted psychotherapy is less threatening. As compared to medical marijuana, which from a regulatory point of view is a nightmare, because people take the marijuana, they do it at home, they can share it with whoever they want. You never track it. They need it every day. But MDMA-assisted psychotherapy is only administered in the presence of a male-female co-therapist team. Now we're also going to need medical grade MDMA, GMP MDMA. So in 1985, I had Dave Nichols made a kilogram of MDMA for us for $4,000. It's among the world's purest MDMA. It's the MDMA we still use today 31 years later. It's an extremely stable molecule, but it's not medical grade. So we have 960 grams of it left. We're offering it for free to researchers who want to do any kind of studies, animal studies, human studies. And we're having a kilogram of MDMA manufactured in this facility in Newcastle, in England. And if our research succeeds and the market grows, they can scale up. It's costing us $400,000 for one kilogram, which is an outrageous amount of money. But nevertheless, a lot of that is for the initial procedures. It'll get cheaper. We have standardized our psychotherapy as well in this manual. And we have it operationalized. We have adherence criteria. We have independent raters that we've trained that look and in order to give feedback to the therapist. And it's a non-directive approach. Basically, we're not the guide. The person's unconscious is the guide. And we follow and support where they're going. Now, we've heard a lot about this discussion about whether mystical experiences are correlated with therapeutic outcome. And that is the case with psilocybin with LSD. With MDMA, we've taken a look at that. And so this is the comparator doses. 0.6 on the questionnaire is considered a full mystical experience. So the mean is 0.46 for the active doses, which is pretty good in terms of mystical experiences from MDMA. And so people do have this sort of look out at the universe kind of experience. But the key difference between MDMA research and the classic psychedelic research is that there is no correlation between their cap score. That's the PTSD symptoms. And this is their mystical experience score. So you can see we have a lot of people that have had full mystical experiences. But basically, we do not believe that there is any correlation. If there were, we might want to direct the experience towards some sort of a mystical experience. But we really don't think that that's going to be the case. So we are going to be standardizing the therapy. We're going to be having our own training programs. We're going to have our own little certificate. We talked about this is actually for a TV show. They're having a psychedelic psychotherapy session. So they wanted some background on the wall. So they asked our graphic designers to make this for their TV show. And we will eventually set up psychedelic psychotherapy clinics. And these are just some examples. This is one of my favorites here. One day you'll be able to go to Google Maps and do a search on psychedelic clinics. And they'll be all over the place. The model here is the hospice center. The first hospice was in 1974. And 30 years later, there was 3,500 throughout America. So any community that has a hospice 20, 30 years from now is likely to have a psychedelic psychotherapy treatment center. And these are not going to be limited to MDMA. So that these treatment centers will be for whatever drugs have gotten approved. So we'll have people that are cross-trained and work with MDMA, work with LSD, work with psilocybin, eventually possibly work with ayahuasca or Ibogaine, things like that as well. Now one of the most important challenges is the double blind. How do you do a double blind with a drug that's pretty obvious if you've taken it? And so the most important thing that you're trying to do is fool the experimenter and the raters. I mean, you want to fool the patient as well. But it's been pretty difficult to do. And this is one of the main criticisms of the early literature with psychedelics, with LSD in particular. So what I worked on in my dissertation was this idea that we would do dose response, that everybody gets MDMA. Some get low dose, some gets full dose. They all have the same expectancy. They don't know what dose they're going to get. All these different ranges of doses, from 25, 30, 40, 75, 100, 125, and 150, in our different studies. And what we've learned so far is that there is safety in clinical settings. We have a medium to large effect size. And the cause of the PTSD is irrelevant to the treatment. Our first study was women survivors of childhood sexual abuse. We've since Zoloft actually and Paxil, the only drugs approved by the FDA for PTSD, they tended to work only in women, not in men. And they even had big discussion, should they even approve it? So it didn't seem like it worked in men at all. But we then did studies with male combat veterans who had PTSD from war-related PTSD, and it worked then. So regardless of the cause of the PTSD, once you have that disorder, the treatment is the same. And this is really good from our point of view, because then we can enroll anybody, regardless of their cause, and it applies to a larger group of people. But the thing that we did not anticipate finding is that the low doses of MDMA here in the 25 to 40 milligram range actually had an anti-therapeutic property. Now what I mean by that is, we have shown in our first study with inactive placebo plus therapy compared to therapy plus MDMA, that the therapy alone has a therapeutic effect. When we add 25 to 30 or 40 milligrams, on average, people still benefit, but they benefit less than those people that had the inactive placebo. People get activated at these low doses, but they don't get the fear reduction. And so they're more uncomfortable, there's more dropouts at the low doses. It is more effective as a double blind, but it actually, in a way, gives us an unfair advantage if we're trying to compare what the therapy does by itself without a drug, and then what the therapy does when you add the MDMA. So from the FDA's point of view, using low dose MDMA with therapy isn't the best way for us to move forward. Now we're getting ready to submit this data to the FDA in what's called an end phase two meeting, and we have the good fortune of the former head of the FDA division of psychiatry products acting as our consultant right now. And so what he's suggested is that in psychiatric research, the double blind often fails in practice. It's not as solid as people claim that it is. There's side effect profiles, people can tell the difference. So this is the recommended protocol that we're gonna be proposing to the FDA, which is we're gonna compare, everybody gets screened, then we have three non-drug psychotherapy sessions. Basically it's a three and a half month process with weekly non-drug psychotherapy throughout the three and a half months punctuated once a month by an MDMA session. So one group will get 75 milligrams the first session. We also give half that initial amount as a supplemental dose after about two hours, and then we'll give the option of going up or staying the same in the second and third. And then there's more integrative sessions between here and then a two month follow up. And then the other group will get the therapy with placebo. So this actually will be compromised, you could say, from a double blind. It's amazing though, sometimes people have even guessed wrong when there was an inactive placebo. But what we've been told is that the most important things to eliminate bias from the FDA's perspective is random assignment, meaning everybody is similarly motivated and then you randomly assign them. And then what is your system of rating your outcomes? So you need a group of people that are not connected to the researchers, not connected to the therapists. And we've developed a process where we're gonna have about 10 or 15 people who are in a rate of reliability on the PTSD symptoms on the caps. And they will be randomly assigned to whatever person comes up next. And they won't necessarily know, is this the baseline? Is this their two month, is this their one year follow up? So they might even see this patient only one time. And it'll all done by telemedicine. And that's gonna be the system that we're gonna be proposing to the FDA. And for our first study, our first phase three, we're gonna have about 10 sites throughout the United States and Canada and Israel. And then the next study, which we hope will start around 2018 will be mostly here in Europe in different locations. Hopefully also here in the Netherlands. And we're gonna propose a different design for our second phase three study. You need two phase three studies. But what we're gonna propose here because there's government health insurance, because there's more interest in what the treatments cost. They're more interested in comparative efficacy. So again, because we're not really relying on the double blind in a classic way, we're gonna be proposing that we do our treatment session, our regular treatment here, and then this other group just gets standard of care SSRIs and people can supplement with therapy if they want or not. Now politically, it's been very important for us to engage groups of people that are highly respected by our society and that are suffering and for whom MD make it help. And for us right now, because of our misguided war policies, we've got a lot of veterans who have suffering from PTSD. And so we've done a lot of outreach to the military and Brigadier General Laurie Sutton was in charge of PTSD treatment for the Department of Defense. And she saw our first study and she says, when it comes to the health and well-being of those who serve, we should leave our politics at the door and not be afraid to follow the data. There's now an evidence base for this MD may therapy and a plausible story about what may be going on in the brain to account for the effects. We've also had Dr. Richard Rockefeller who's on the left there who was chairman of the Board of Advisors of Doctors Without Borders. He was very helpful, very essential. And his cousin Senator Jay Rockefeller was on the Senate Veterans Affairs Committee. And so he ended up writing to the Department of Defense and the VA and encouraged them to do MD may research for PTSD. So now we're actually doing studies with VA trained therapists who have non-drug methods that they realize work for a lot of people but leave a lot of people treatment resistant. And so now they're open to blending MDMA with their existing therapies. So we're about to start one called MDMA assisted cognitive behavioral conjoined therapy in dyads. So it's couples therapy. One member has PTSD but it affects the relationship. It's with this woman Candace Monson who is in charge of women's health at the Boston VA. And the breakthrough for us here is that we have FDA permission to give both members of the couple MDMA, not just the person with PTSD. And because you can only work through the FDA to medicalize a disorder but one of the best uses of MDMA is couples in relationships but we can never make it into a medicine for couples therapy. It's not a disorder. So here we're sort of backing into couples therapy but it's about really treating PTSD. There's another approach called prolonged exposure. There's about 3000 VA therapists who know prolonged exposure. You sort of repeat the trauma over and over until it doesn't make you so reaction but it does retraumatize people. So there's a woman Dr. Barbara Rothbaum at Emory University and the Atlanta VA and we're gonna work with her on blending MDMA with prolonged exposure. These are not our treatment method. They won't count for phase three but they are outreach to the military and to the therapeutic research community for PTSD. And they've already done an animal study about showing fear extinction from MDMA, an animal model. Now again to try to prepare the society for MDMA for psychedelic psychotherapy, one of our projects has been called the Zendo project. We do psychedelic harm reduction at festivals all over the world. And if we, the drug war used to be what worries about the counterculture, about people who are tuning in, tuning on, dropping out, protesting the Vietnam War, that has faded over the last 50 years. Now it's mostly parents worried about their kids. That's the driver of public support for the drug war. So if we can show where young people are going to do these experiences that we can help them manage the difficult experiences that sometimes they end up having when they were just narrowly looking for fun and they get more serious. So we have the Zendo project and also we've done some work with marijuana for PTSD. So marijuana for PTSD is a palliative treatment but in the US there is a government monopoly on marijuana legal for FDA research. It's kind of silly to say government monopoly because marijuana is everywhere but there's only one place that has a federal license for marijuana. And so we've focused on trying to break the resistance to marijuana research and we just got a $2.1 million grant from the state of Colorado and we're about to start a study in 76 veterans and it was featured on CNN weed three by Sanjay Gupta. Now I just want to show you one last thing and then I'll be done which is that when I first started maps in 1986 up until just a few years ago my understanding was that MDMA is a generic drug that psilocybin and LSD are all in the public domain and once we make them into medicines then anybody could market them. But it turns out I did not realize that in 1984 under President Reagan they passed a law to facilitate research in drugs in the public domain. And so you can't get a patent but they give you data exclusivity which means that if you're the sponsor to make a drug into a medicine and you're the first to make it into a medicine nobody can use your data for five years to argue for a generic. Somebody could produce their own data if they wanted or they could make MDMA into a medicine for something else. But there's a chance that we would have the only opportunity to sell MDMA by prescription for a period of five years. And that's something that we've thought because I'm constantly asking people for money it gets kind of, it's great when people say yes but we have a chance now to become a sustaining nonprofit because we're one of the few nonprofits that's trying to make a product at the end. So if we end up selling MDMA we can sell it for a little bit more than it costs us and then we can use that money to fund further research but that's selling it at a profit is a taxable proposition. Can't stay inside the nonprofit. So we've started what's called the public benefit corporation. So people have heard, perhaps you've heard about some of the main arguments that are against the legalization of marijuana in the US and it's like oh big tobacco, big alcohol, they're gonna get marijuana, they're gonna market to kids, they're gonna do whatever they can. But that's what profit maximizing companies do all over the place and they forget about externalities. But a modification of capitalism has taken place called the benefit corporation. There's about 6,000 of these benefit corporations and they are chartered to maximize public benefit not profit. So I've said that should be the model, the regulatory model for how we sell MDMA by prescription. We're not trying to make the most money, we're trying to do the most social good. So the public benefit corporation is 100% owned by maps, no investors but that's how we're planning to work on this long term. Now you have to have your own, you have to evaluate the public benefit but there are no public benefit pharmaceutical companies right now and there are no off the shelf systems to evaluate your public benefit. So in Delaware where we're incorporated we're gonna be doing that ourselves and they permit that but we're working with ethicists at UPenn to develop how we think an ethical pharmaceutical company marketing psychedelics and marijuana should work and we're gonna have this over the next year and we'll be able to quantify our performance and a lot of that is just sharing the data, sharing the protocols, sharing all of our work, helping other people try to develop psychedelics because it's really about the social change, it's not about us being first although that would be nice but it's really about how we facilitate helping our cultures become more mature, more grounded, more spiritual to face the crises of the 21st century. Thank you. So as you're aware now in the US there's a situation where these people who are established in the medical marijuana industry are opposing legalization of marijuana even though that is most likely the outcome that's most beneficial to society. And so how are you gonna prevent similar kind of conflicts of interest arising between your framework and people who advocate even more deregulation? Well in Massachusetts where I live. Oh, oops, sorry. Oops. So in Massachusetts where I live it's gonna be marijuana legalization is on the ballot in November and what was likely a funding source was gonna be the dispensaries but the people that regulate the dispensaries, the State Department of Health made a deal with different dispensary owners to say we'll give you a license but you have to be against medical marijuana legalization. I mean against marijuana legalization. So that's where the conflict of interest comes in from the regulators providing licenses only people to oppose the broader reform. I don't think there's similar kind of pressures like that on the FDA for making psychedelics. I think the pressures are the other way actually because I talked to you about the data exclusivity. So you could say oh maps we should be against the legalization of psychedelics because then people can get it without going to a doctor without getting it from us without. So actually we're in favor of drug policy reform and human rights legal access to it. So I actually don't feel that there's any kind of financial pressure that's gonna be coming on the FDA or on us by people that have financial incentives to block what we're doing. I will say one different thing than George was saying is that at least for I was approached by somebody just a couple days ago and said that they could provide all the money we needed for phase three if it was in the form of an investment and I said no we don't want investors, we want donors because I think something that is so crucial to, you know as Roland was talking about survival of human species you know I don't, I wanna make it everything likely that it'll proceed and I think when you approach it from either a nonprofit or a benefit corporation rather than investors you're more likely to be responsible and act in a way that the regulators are more comfortable with. So we are just going to at least try to only use donated funds and then try to not be caught in this profit maximization way. And I would just add that we're not looking at profit maximization, we're still in a nonprofit mode but there are new types of debt financing that are being used for public health initiatives. So again this is a new place of innovative financing models for public health. Yeah and there's what's called social impact bonds. Yes exactly right. So but that I think is not gonna come at least for ours that's gonna like for example the veterans administration's got like 600,000 vets are on disability payments over $6 billion a year that the veterans administration pays every year to veterans but their therapists only see people once an hour every couple weeks. We have an eight hour to therapist session. They just can't do that. So once we can make MDMA into a medicine then we can negotiate with the Department of Defense and say we will provide these services and if they save you a certain amount of money from all these disability payments then you reimburse the service provider. And that's what's happening now for criminal recidivism. There's the cruelty of the drug war has eliminated all sorts of rehabilitation programs, education programs for people in jail. So now when they come out there's a very high 70, 80% of them go back to jail. So there are now programs being provided to people once they get out of jail by private actors who negotiate with the government if they reduce recidivism then their investors get paid back. So that's where I think we'll endorse and look for social impact bonds but I don't think we can make the case yet until we have FDA approval for the treatment and we've demonstrated. And in Europe the difference is the new innovative pathways to patients including the medicines adaptive pathways to patients for EMA or for the early access to medicine scheme in the UK actually provide conditional market access for well-defined patient populations so that you can actually move faster in that world here. Yeah, and I'll say one other thing about that which is that once we start phase three we're anticipating around 450 people is all we need in phase three to show efficacy and the FDA has said that looks likely but they want to see more people for safety and there's a program called expanded access which means on a compassionate basis once you have phase three running and you're showing that you've got waiting lists and it's a serious or life-threatening illness people have tried other things then people can get into this program and they can pay for their own therapy and then we can train hundreds more therapists to provide it on a compassionate basis and we gather safety data but not efficacy data because it's not double-blind. So I think there are ways that the FDA has developed these procedures to expand it at a more rapid rate even before they've approved the drug as a medicine just when it's in phase three and you've got a waiting list. Rick, you talked about how using MDMA for couples like couples therapy is a really obvious use of MDMA. Yeah, and I was sort of wondering one, are there any steps forward being taken sort of looking at that? And two, if there aren't, what kind of ways can you see going forward if that may be happening? Do you not think it will happen? Yeah, well, again because we have limited resources we're trying to focus on making it into a medicine and there is no way to somehow call a difficult relationship a disease feels that way but there's no way to really get that in the DSM so the diagnostic statistical manual of the psychiatry. So I don't think there's any way possible to make MDMA through the FDA for couples therapy. And so what we're hoping is that sort of other kind of scientists will see the results that we get from this couples therapy study where we have a lot of measures of the relationship but really we're looking at the PTSD from the one person but if we can show at least preliminary evidence that the relationship communication styles, things like that have improved then maybe social scientists, other people will find different kind of grant money to explore it more but really the answer is legalization because how do we get it out from, for people that want personal growth? We all have trauma to some degree, we all have different kind of unresolved issues but if it doesn't rise to the level of a clinical diagnosis we're not gonna be able to go through the medical pathway so I think really from a public health perspective we need to move beyond access to just patients and that's drug policy reform and human rights. I should say though that people can still be treated at the clinics so these clinics idea can actually be expanded for all sorts of people can have these experiences not just patients so that's what I think where the clinic model starts moving towards models for legalization. Rick, when you just said about not wanting to go down the investment route there were two things you said firstly that you didn't wanna go outside of public benefit corporation and secondly that you thought that would be easier to work with the regulators so it was my understanding that public benefit corporations do can turn a profit as you were talking about turning a profit but they just don't maximize profit at the expense of whatever the social goals of the company are so is it not the case that you could take investment but still keep, there would be a return on profit for the investors but still have your social goals first and then secondly surely the pharmaceutical industry is very much more used to working with totally for profit corporations so I don't see why you said that that would be the regulatory benefits of being a public benefit corporation. Okay so I think it's more of the social resistance to psychedelics, the kind of fears about psychedelics and the fears about marijuana legalization that make me feel like, I mean we're getting a lot of people who are helping us from Big Pharma who are saying because you're doing this in a non-profit context so maps the non-profit actually is the IND holder with the FDA and we just happened to 100% own a benefit corporation mainly because we're gonna need to pay taxes on the income if we get it. So we could technically take investors in the benefit corporation because it is a for-profit taxable but I don't wanna do that, I don't think that's politically a smart way to go but technically it's possible and it's true that the pharmaceutical companies are for-profit, FDA is used to that but I just think that the society, it's so important that we make it and society is so resistant that that's the approach I'd prefer to take. And I would just add that what's really important in this is that we look at the fact that there are gonna be eras of development just as in life and that there may be models that work today and might be more efficacious today and that those models can change over time. Yeah. Thank you. You're welcome. Yeah.