San Francisco Veterans Affairs: Treating PTSD with MDMA-Assisted Psychotherapy

so I get the honor today to introduce dr. Michael MIT Hofer he is triple board-certified in psychiatry internal medicine and emergency medicine he attended medical school at the Medical University of South Carolina College of Medicine where he also did psychiatry residents residency and is currently on the psychiatry faculty he also did a medical residency at the University of Virginia and he practices psychiatry in Charleston South Carolina where he splits his time between clinical research and outpatient clinical practice specializing in treating patients with PTSD and I feel like I could I could say a lot but I think I'll kind of summarize and and borrow a quote from a colleague James Henry who introduced him last night who said that this work really exemplifies one of the primary goals of psychiatry which is to develop and utilize the best treatments for people with with mental disorders so with that I will turn the mic over to dr. Matt Hooper thanks very much for February Shakespeare and UK arranging this it's really a pleasure to be here and until yesterday I'd never had a chance to speak at a VA before I spoke with the Palo Alto VA yesterday and now I'm here which feels very exciting to me because for the last year our main thrust of our research has been with veterans so you know you're working with veterans every day here and it's I really hope we can have a conversation about this after I've done my slides but it's been you know I work with my wife annie is co therapist for this therapy she's a psychiatric nurse and we've been really grateful to have the chance to get to know this group of really remarkable young people the veterans we've been working with and we've been very struck by you know how much they've been suffering but also how much determination they've had to do their own healing and also the really striking degree to which they're focused on wanting to heal help other veterans get the help they need so it's it's a very moving experience for us to begin working in this community I I was speaking to a veteran a young man who was a marine in Iraq who finished the study that except for the long term follow-up finished most of the study about six months ago and I was talking to him last week and he said you know as bad as it was to be in Iraq what was even worse for me was finding my bat my body back home but my mind still in Iraq and what I did in the study allowed me to bring the rest of me home and I'm so aware of all the veterans who bodies are here but they're not fully at home and I know that you experience this every day so I feel as if we have a common purpose what you're doing here and what we're trying to do to find the best possible array of treatments for people veterans and other people suffering from PTSD so I'm really really grateful to have a chance to talk to you I am on the I'm actually on the clinical faculty at the Medical University but I want to give a disclaimer that the research is not happening at the university it's we do it and my office and it's sponsored by maps which is a private nonprofit so I don't have references on most of my slides but this is a very good source this is was our original investigators brochure for the FDA and it's a review literature review of all the English language literature on MDMA that Ilsa Jerome who works for maps updates a couple times a year so it's a good source for references so I'd like to just touch briefly on the history of MDMA a little bit about its effects why we thought it was a good idea to study MDMA for PTSD and then tell you a little bit about our clinical trials and you know this is going to be kind of an overview so I'm not going to give a huge amount of detail on the trials but I'll try to give you kind of the nuts and bolts in that and in the end and talk a little more about our ongoing study with veterans MDMA is a molecule that looks a little bit like methamphetamine and a little bit like mescaline which kind of fits with its effects I'm not much of a chemist but that makes sense to me it's been off patent for since 1914 it was patented by Merck as a precursor drug precursor compound and never used by them it's actually first synthesized a hundred years ago and in 1912 so it's off patent drug companies aren't interested in it Maps as our sponsor is acting kind of like a non-profit drug company to see if we can bring it through the drug drug development stages of the FDA and it's sometimes kind of lumped with other psychedelics but it's it's quite different from the classical psychedelics like LSD or psilocybin in that it tends to Dave Nichols of chemists at Purdue has suggested the term intact again sort of referring to the fact that sort of helps people touch within their it be in touch with their own feelings and also more connection with other people a greater sense of closeness to others in empathy and you know in the literature it says it tends to cause it a kind of easily controlled state with little sense of loss of loss of control what we've seen with people with severe PTSD is that's not as true as you might think often people with with PTSD do experience a sense of losing control and fear about that and you know especially perhaps veterans who for whom you know being at war was so much about vigilance and trying to be under control on uncontrolled situations were potentially lethal so it's not you know that's something to take into account it requires proper support to help people work with that in some ways being able to let go of control is an important part of the the therapeutic process but it's not easy necessarily you know the pharmacological profile is quite complex a lot of it has to do with mono Amin release especially serotonin but also norepinephrine and dopamine and it also has affinity for some receptors 5ht – also norepinephrine ACTH and histamine and it increases levels of a number of hormones probably the most interesting in terms of the psychological effects are prolactin and oxytocin in that list it's been classified in schedule one since 1985 before that it was used by a number of psychiatrist and psychotherapist as an adjunct to therapy you know it wasn't it it wasn't a legal drug but it wasn't illegal either didn't have a status so it was used there were some case reports published but no controlled trials were done there was actually a three-month period when it was in schedule three during the legal proceedings when maps was suing the DEA for not following their own rules but it ended up in Schedule one nonetheless so you know MDMA has a certain amount of baggage as a compound to be doing research with because it already has a reputation not all of which is favorable in many people's eyes so that's made part of this an uphill a pill effort but it also has an upside in that a lot of governments around the world have spent a great deal of money studying him the AMA because of its recreational use so there lots of there was lots of preclinical data maps did actually contribute to a little bit of that but there was also a lot of data that that wasn't necessary to pay for in order to be in a position to move forward then there were at the time we started our Phase two trial there had been a number of phase 1 trials the first one was at UCLA by Charlie Grove which was Maps was sponsoring but there were others around the u.s. and in Europe and there have been quite a few since then as well so we were in a position to start out doing Phase two obviously the question of toxicity is important to touch on it's a long and complicated subject but just suffice it to say it can be there it can be very serious acute toxicity and people do die from it it's quite rare considering the large number of doses that are taken but it's still something to be taken seriously it can be dangerous in the wrong setting and in animal studies there there's evidence of changes in serotonin neurons with high doses there's argument about how well that applies to humans and the doses they're used in humans and in my opinion the answer is it really doesn't apply much the there's a lot of there have been a lot of studies of recreational users with kind of mixed results and mixed interpretations of those you know these studies are hard to interpret because they're retrospective there has been one prospective trial and other ones but almost all of them are retrospective you don't know what the pre MDMA functioning was and you don't know if they took MMA or what else they took so it's difficult but in the best studies with the cleanest samples that the data is actually reassuring they didn't find much what's most important to us is the data in phase one and Phase two trials and now there have been more than 500 people in phase one and Phase two trials there have been no drug-related serious adverse events no evidence of neurotoxicity and we have some data from our first study about that that I'll show you so you know it appears from this that the like any drug it's not without risk but the risk benefit ratio in the number of doses we're using a pure MDMA and well screen people in controlled settings the risk benefit ratio seems to be very favorable I think you know I asked yesterday does anybody here think we don't need more and better treatments for PTSD didn't think so you know there are some good treatments that we certainly have some things we can offer people prolonged exposure and CPT probably being the best researched and also you know the recognized therapies by the American Psychiatric Association also include psychodynamic therapy and EMDR and there are lots of pharmacotherapies only two drugs with FDA indication sertraline in paroxetine but many as you know well many other drugs are used but overall if you look at even in the best hands and clinical trials of specific therapies if you account for dropouts I say conservatively 25 to 50% of people are not adequately served by these therapies and I think the real world clinical situation is worse than that and so that's it you know several million people in the US alone every year and as you're very well aware the incidents of PTSD and veterans returning from Iraq and Afghanistan is is really alarmingly high it's hard to pin the number down but it's probably around at least 18% and in a study from here by dr. seal at all they found I'm sure you know this in the people that screened positive for PTSD here the San Francisco VA fewer than 10% received what they consider to be optimal treatment so and that's certainly from not from lack of trying you know I I know that so it but it's just a very very challenging problem and we need we need to add to this list of possible therapies with more and more effective ones so why MDMA for PTSD well you know I think we'd probably also all agree that psychopharmacology does not cure PTSD the drugs may help with some of the symptoms but it seems pretty clear that psychotherapy is extremely important for PTSD so you know why doesn't why does it work sometimes and not other times well that's very complex but I think common reasons are either fear anxiety that people either get so overwhelmed by revisiting the trauma and therapy that they won't do it or they're flooded but edna foa with prolonged exposure would call over engaged so the therapy doesn't work or conversely they have so much emotional numbing that they may be able to report the trauma talk about it but they don't engage emotionally so the therapy doesn't work I'm sure you all see that every day and so those are two big reasons for psychotherapy not being effective and the other factor is people with PTSD can have a lot of problem with trust and that interferes with the therapeutic alliance so if there's a compound that can decrease fear and defensiveness and increase trust and empathy it makes sense that that might help to overcome some of these obstacles to effective therapy that was our thinking and an additional effect is you know so overcoming those kind of would allow people to reprocess the trauma in therapy an additional effect we think is that at least part of the time people with MDMA people usually have some affirming sort of positive experiences which can help them correct kind of negatively skewed perception of the world in their situation so that can also is a potential way it could help this is taken from Pat Agins audience book trauma in the body it kind of illustrates what I'm talking about so you know this isn't a new idea that fear or defensive this unit interfere with therapy this is like the level of arousal with hyper arousal up here increased emotional reactivity intrusive imagery disorganized cognitive processing and hypo arousal down here absence of sensation and numbing of emotions disabled cognitive processing and as you know people with PTSD are prone to being at both of these one or the other of these ends of the arousal spectrum so this Zone in the middle the window of tolerance or optimal arousal zone is where a therapeutic processing can happen and that you know this is described with other kinds of therapy but our thinking is that MDMA seems to give people several hours in which it brings them into this optimal arousal zone or window of tolerance so they can process the trauma in ways that they might not have been able to before in therapy and of course there are lots of ways to look at this you know our studies are not designed to figure out why it works the FDA doesn't really care luckily we wouldn't have many psychiatric medicines if we had to show how they work but they care whether they work or not so we're focused on finding out whether we can show that they work but we're of course very interested in how they might be working so this neurocircuitry model of PTSD in which you know it's viewed as a deficit and extinction of fear conditioning kind of fits with what I'm talking about – and we know that in people with PTSD it's been found that they have you know the fear and the extinction of fear conditioning is mediated by hippocampus amygdala and prefrontal cortex interactions and we know that people with PTSD have increased activity in the amygdala reduced hippocampal volume and activity and decrease activation of the medial prefrontal cortex that's PTSD in a separate population of normal volunteers it was found that MDMA causes some changes sort of opposite of that increases in cerebral blood flow and the ventral medial prefrontal cortex and elsewhere and decreases of activity in the left amygdala no one has studied people with PTSD before and after MDMA with imaging we would love to do that we've been trying to do it I think like a good VA hospital would be a good place to do such a thing so but this sort of would fit with the idea that MDMA could put people in a position to process things more effectively and extinguish fear conditioning so this was our first study phase two clinical trials safety and efficacy of mdma-assisted psychotherapy and people with treatment resistant PTSD we got original FDA approval for this in 2001 and then it took us until that was the fall of 2001 it took us until February 2004 to get IRB and DEA approvals and that's kind of a story in itself but suffice it to say the DEA was not overeager to expedite the approval of this but they really didn't have a choice once the fda approved it and we've actually had very I'm sorry is it okay anyway the fact is we were able to get approval and we have a good working relationship with FDA and DEA so a month later we enrolled our first subject and then we finished in September 2008 and published results in Journal of psychopharmacology in 2010 so our hypothesis was that we could safely administer MDMA to people with chronic PTSD and that it would produce improvement in PTSD symptoms four days after each of two or three actually each of two experimental sessions with mdma-assisted therapy and a two month follow-up so we screened 134 people on the phone 27 people in person in order to enroll in randomized 23 we had to drop out so 21 people completed it and 13 were randomized to MDMA eight randomized to placebo that was what we call stage one of the protocol and then at stage two the people who got the SIBO could have left to go through it again with open label it was an open label crossover arm they could go back through the whole process of the therapy and MDMA it was double bond besito controlled we actually had 20 treatment resistance subject which was our original number we added a 21st subject of veteran at the end who had not had treatment because when he was an active duty as a Marine officer he went to the medical officer and was sent to an outside contract theorist and told he had depression to take Zoloft and he said that doesn't make any sense to me and he actually had classic PTSD so we were got permission to include him just so we get more experience with veterans but he's not included in the data I'm going to show you because he he hadn't been shown to be treatment resistant the Department of Defense was treatment yesterday I guess you could say and we defined that as having had at least three months the treatment of it with an SSRI or SNRI and at least six months of psychotherapy in fact most people had had years of therapy and many medications because the the duration of PTSD in this cohort was more than 19 years before they ended the study originally it was all crime related PTSD and that's what most of the subjects were childhood sexual abuse or rape because we just added veterans at the very end so there's only one veteran in the twenty but in our current study it's all veterans which I'll show you in a minute so the protocol was in stage one sixty percent would receive it MDMA on two or three occasions and forty percent we received placebo on two or three occasions on two occasions the reason it's two or three with the MDMA is that we amended the protocol halfway through because it was a pilot study and we added a third session but the data I'm going to show you is based on two sessions we did have some further improvement with the third session but we stuck with our original design of twenty you know to placebo versus two MDMA sessions so all the data I'm going to show you is based on that then stage two as I said was an open-label crossover arm and when people went through the whole thing again with open label MDMA there was no take home MDMA this is a treatment in which people receive there's always a kind of disappointment in the Kratt and they say that this was MDMA was given only under direct supervision with male and female therapists present the whole time for at least eight hours in this case myself and my wife is male and female therapy team and then there's an overnight stay in the in the clinic with a nurse under present the initial dose was 125 milligrams followed by half of that an optional supplemental dose two hours later and an important point is there were a lot of non drug therapy sessions we thought it was extremely important to prepare people well for the experience we'd meet with them twice for 90 minutes before their first session and then to follow them closely with integration sessions to help them integrate the experience because this is not like a magic bullet where you just you're better it's a process and and it's it can people can have waves of increased difficult emotions during the therapeutic process it continues to unfold after the session so we would meet within the next morning before they went home call them every day on the phone for a week and meet with them every week approximately for a month until the next session so the MDMA or placebo sessions were all day sessions a month apart and the integration sessions occurred in between and we measured the blood pressure impulse every 15 minutes in the temperature every hour during the MDMA or placebo sessions we were not but we are now we now in our current vet study got permission from FDA to cover up the blood pressure and pulse monitor but for the first study we had to had to watch it so there was a problem with the blind being transparent I'll talk more about that but we were able to guess what people got the independent Rader was effectively blinded remained effectively blinded but we were actually you know we tracked this we didn't kind of want to we didn't have a don't-ask-don't-tell policy about the blind the way some drug studies do we had to record whether we thought they what they thought they got and we'd asked them what they got and we recorded and it did turn out that we always guessed correctly between inactive placebo and MDMA and usually the subjects guessed correctly a couple times they were wrong but that was that's a challenge we're trying to work with now in our current studies this is where we do the sessions the therapists sit on either side and the participant either/or eyes or sits on the futon it's a nice kind of aesthetically pleasing very private room there's a bathroom right behind that blue chair so people don't have to interact with any other people or spaces whether having your MDMA or placebo you know we call it placebo session this kind of as a shorthand it really should be called therapy only you know this is not just a drug trial it's a drug assisted psychotherapy trial so when I say placebo I mean therapy only because all the people who got besito got all the same all day session is the same follow-up sessions so the therapeutic approach was a non directive approach and supporting the emerging experience of the person you know and what happens somebody asked last night well what about do you ever do prong exposure the answer is prolonged exposure imaginal exposure almost always happens but we don't do it we don't decide now you should tell us that the trauma script or read the trauma script we encourage people to see what's going to come up for them and at some time inevitably they start processing the trauma and there'll be periods of time they're sort of like spontaneous prolonged exposure happening there will be other times when there's kind of spontaneous psychodynamic therapy happening people will start talking about their childhood and things that made them susceptible to PTSD perhaps and they'll make connections and interpret those things for themselves you know sometimes certainly we interact and give them a little guidance or suggestions but we don't direct it to go in one direction or the other but what happens as many of the elements of existing therapies tend to happen on spontaneously people have you know cognitive restructuring happens spontaneously people will have just suddenly realized that their view of something was didn't make sense and they're able to think of it a different way so it's actually in some ways not so foreign to people who have done other therapy because a lot of the elements that you recognize as being important in other therapies 10 happens on taneous Lee with the MDMA but they seem to often happen in in kind of a deeper way or they come more quickly than they might otherwise and you know the it's we're not talking to them all the time we encourage people to spend part of the time focusing inward without talking usually with eye shades and headphones listening to music if they're comfortable with that and then we alternate that with periods of talking to us and we don't have any set schedule for that but a rhythm kind of develops for each person and you know sometimes if we've been talking for a while we might say to somebody you know if it feels right to you this might be a good time to go back inside for a while or sometimes they will have been talking for us of course talking to us for a while and they'll say I think this would be a good time to go back inside now and they'll pull their eye shades back down lie down and go inside so it seems to be a good way of working that sort of unfolds spontaneously we've now written a treatment manual describing this it's quite different from a lot of treatment manuals in that it's there's more leeway for the therapists own intuition and and particular ways of working but there are certain elements that are essential that we've described in the manual and we have adherence measures and we now have independent raters watching our videos use video tape everything and now we can establish whether we are actually following our manual uniformly across sessions and across different studies this is an important point a number of people said think this exact thing or something like this I don't know why they call this ecstasy so the point is as I said before people didn't just come in and have a blissful experience and then everything was fine usually people had some periods of very affirming experiences sometimes you might call them blissful but much of the time of his hard work and painful you know people were there to process their trauma they would encounter a lot of of difficult emotions you know rage shame fear grief so the MDMA didn't spare them from that in fact it often helped them reach those feelings when they had previously been emotionally numbed but when they did come the MDMA has a tendency we think to give people the sense that okay this is hard but I can do it in a way that they often reported they'd never been able to do before in therapy our outcome measures are all done by a psychologist not involved in the treatment phase these are our outcome measures the primary outcome measure was the clinician administered PTSD scale the caps I'm sure you're all familiar with that that was the primary outcome measure for the paroxetine and sertraline trials that led to FDA indication so we thought it was important to use that it's also probably the best measure and then we also did the IES SEL 90 and the Neo and in a nutshell here's what we found in this first study these are the mean cap scores two-month from baseline which is time measurement one to two months time measurement for time two is four days after the first MDMA placebo session time three is four days after the second session the cap scores on the vertical axis the score 50 or more was required for study entry so you can see the placebo group in blue actually had this was statistically significant decrease in cap scores from they both had almost identical scores are just under 80 and the placebo group with these all-day sessions and all the therapy did improve but they still had significant symptoms whereas as you can see the MDMA group as soon as four days after the first session had a dramatic drop in caps which increase to maintain the spread of about 33 points better than placebo 50-plus points better than baseline and that P was 0.015 between group difference then stage two as I said people would cross over to open label MDMA if they got placebo with all this all the integration sessions that go with it seven of eight per SIBO people like you to do this the one who didn't was a placebo responder who got a good response to the placebo sessions and didn't feel she needed anymore here's what we found with that crossover cap score on the vertical axis baseline post for SIBO so after two therapy only all day sessions plus the other therapy the mean caps was sixty five point six two months again over thirty point drop to thirty three point nine so having not responded to therapy only they responded to MDMA with therapy in a similar way as the other people had responded so when we looked at clinical response which we defined is greater than 30% reduction in caps it's a pretty common way to find that the psychotherapy only had a twenty five percent response MDMA eighty three percent and then the cross over the sea boat to MDMA it was a hundred percent we did neuropsychological testing before and after and we may have a see Bo the main one was our bands the results for all three were similar about the same here the our bands results our band score on the vertical axis where higher is better MDMA dark bars before light bars after the SIBO before and after no sign of any neuropsychological problems from MDMA so then we went back and we had obviously good results at two months we wondered are these going to last so we went back and did a long-term follow-up one year or more after completion we repeated the caps IES neo and gave people a questionnaire the caps was administered by the same psychologist that did the original caps and here's what we found there this was the baseline caps this was the two-month caps and this was the 45 month caps it because we started the long term follow-up at the end and our recruitment had happened over more than four years it ended up being a range of 74 to 417 to 74 months after the last MDMA session meaning of 45 months so this was very encouraging but there is a caveat you'll notice the N is 24 these two in the end of 16 here because not everyone did the calves you know the first thing was not only 19 people were included in long-term follow-up because one person had never gotten MDMA so other 19:16 did the caps they all did the questionnaire but only 16 ended up doing the caps for various reasons so if you just look at the 16 it's about 87% of people maintain their scores two people did relapse the caps are over 50 but it's fair to say well how do you know that the three that didn't take the caps didn't relapse and we don't we do have an indication that they didn't because they did the questionnaire and they their response is about benefit and maintain maintenance of benefit we're very similar to the overall group but that's not a standardized measure but even if you assume that those three relapse so you had five people relapsing and the rest maintaining that's still 74 percent of people maintaining their benefits three and a half years later so our current activities we now have a training program for research therapists people who are working on other studies and it's based on the manual and we use a lot of video from our sessions and we thought because now we do I'll show you this other studies that Maps has going on that we're involved in but we thought it would be really good if if the therapist had a chance to their own experience with MDMA so they understand better what's going on so we got FDA permission for a phase one trial that's enrollment is limited to people who have finished our training program and are working or going to work on research projects but they're allowed to have their own MDMA session in the same setting that same room with us there so that they have experience so far we've had two therapists have been through that we're also doing a relapse study we thought we wondered whether those people that relapsed three-and-a-half years later in the first study would respond to kind of like a booster session so we have permission to give them one session to see if they can regain their their gains and one person has done that so far and she in fact did have a very good response to that and now we're applying our manual and adherence measures to all our current studies so the other things that are happening in the Maps MVM a PTSD world is a study very much like ours in Switzerland a little bit smaller numbers it's been completed and it's being written now for publication a study in Israel was recently initiated these are all MDMA PTSD studies studies in Colorado Vancouver and Australia are in the approval process so is one in Jordan and there's activity in England to try to develop a protocol there so those are all nvm a PTSD studies and there is a open protocol now at Harvard for mdma-assisted psychotherapy for end-of-life anxiety and then this is what we're mainly working on now our new study of veterans with PTSD that's currently underway in Charleston and this time it's a dose-response design attempting to deal with that blinding problem that we were talking about so it's comparing three different doses and it's actually open now to veterans firefighters and police officers although so far it's been all veterans and it's very much like the first study except for the change in the doses it's open to 24 veterans firefighters police officers same cutoff they have to have a caps of greater than 50 this time instead of being after psychotherapy and drug treatment it has to be either or psychotherapy or medication for PTSD part of the reason for that is it seems that in VA in the VA system a lot of times people don't get a lot of psychotherapy is that true here anyway the veterans we've encountered usually haven't had much psychotherapy but they usually add psychopharmacology so we're using 30 75 and 125 milligrams each followed by half of that dose in the same eight hour and the MA sessions the same very similar schedule of preparation integration sessions is the same first study and this is an attempt to find a level of dose of MDMA that will act as an active placebo basically to see if we can fool ourselves better but still have a dose that doesn't work so well but we get fooled by I'm not sure we're doing that but that's what we're trying to do and then we do after the second session similar to the first design stage one we measure the outcome measures after the second session and break the blind and then stage two looks like this if they got full dose twice in the first and stage one then they get a third full dose session if they got lower medium dose in the stage one they get three full dose sessions so everybody ends up with three full dose sessions and we do follow-up measures two months in one year and so far we've enrolled nine veterans five have completed all the sessions we've had two dropouts which has been interesting one veteran dropped out early on after one medium dose session and the reason he dropped out as he said he didn't need any more because he was better and his caps was dramatically better and the other thing he said about it was during the session he got the insight that the oxycontin that he said he was using for his back he was actually using to make himself feel better emotionally and he didn't need or want to do that anymore so he came out of the session saying I realized I don't want anything from the outside to change my the way I'm feeling I can talk about this now I can deal with it by talking about it I don't need that and he stopped taking oxycontin that day and didn't want any more MDMA but he did agree to continue in the follow-up so I'll show you his follow-up results after one session the other dropout unfortunately was somebody who got low dose and had such a hard time being faced with all that time in which there was nothing happening except the possibility of him focusing on his inner experience it was too hard for him he wasn't willing to go on it's been six men and one woman with combat trauma all from Iraq to woman with women with military sexual trauma and now we're in that we're about to enroll a Vietnam veteran another man from Iraq and another woman with MST it's been in a way heartbreaking but good for recruitment that without having to without trying to recruit we've had 220 veterans call us asking about being in the study from all over the country I'm sure it's more now that was when I left home and it we usually most days we get at least one call so they're calling much faster than we can enroll them so it's way too early to draw any conclusions but I'll just give you a little flavor of what we're seeing so far you first six people you can see three people had response to quite low very low cap scores two people had a quite a big drop but still about 50 this is the one year this is baseline these are the intermediate Phillips and this is one year so we've only had two people do one year this Green Line is that the veteran who only had one dose so two months later his caps had gone from like 85 to just over 20 and when he came back from when your follow-up it was 24 and this one is that somebody who has had three sessions now but this is after his two sessions and we don't have this we're about to get his follow-up and what happened he reported that he was doing quite a lot better and then 10 days before he came back for his measures a number of people in his National Guard unit from his hometown were killed and a lot of people were wounded so he had just come from a funeral when he came back for his testing so we think maybe he's going to show improvement next time from what he's telling us we also did the back Depression Inventory this time and you see you can see what we found one person had a score of over 30 just under 40 and that didn't change the other two people with early high scores had considerable drops to 20 or below and the three people that were already stayed low there wasn't any sign it was increasing depression the GAF of assessment of functioning this is the same person that didn't improve on the back this is the same person that had just been to the funeral and the others had had some definite increase in their GAF we also in the first day we felt people were telling us about a lot of ways that helped them that weren't captured on the with the standard measure so we decided to add the post-traumatic growth inventory to see if we could capture some of this other change and one the same person did not have any increase in post-traumatic growth but everybody else had a rather robust increase in post-traumatic growth after their sessions so now you know all this is aimed at moving into phase 3 clinical trials which are what to the FDA requires to face clinical phase 3 trials which will have to be two or three hundred people each in order to apply for labeling for a new drug so that's what we're aiming for this is going to be a little while in the future at least one will be in the u.s. maybe two perhaps one will be in one of these other countries where we're doing studies but we're really hoping one might happen at a VA someplace so please keep that in mind so thank you very much I that's all I have to say and I'd like to have some discussion thank you and also Rick Doblin is here the president of maps and for questions about kind of the overall drug development strategy Rick is very good at answering those we're gonna open it up for for questions dr. Bucky thanks for a really very interesting presentation and I missed the first minute so you probably mentioned your funding but that was one question though the question is have you applied for federal funding for NIH funding specific and if you did what kind of reviews that you get were there critiques that we have interest the funding is all from maps and multidisciplinary Association for psychedelic studies which is a private nonprofit that gets money from membership individual donations and Family Foundation's we did apply for an inh grant for our manual development and we did not get that Rick do you have more details about their response yeah we were told that we didn't have enough pilot data at the time that we applied and David not who's the drug policy was the drug policy adviser in England has spoken to Tom Insel who's the head of NIH and Tom used to do MDMA neurotoxicity research like 20 years ago and he says that they might be open to considering something but we haven't got around to applying yet I'm aware some other groups that are psilocybin further for this type of treatment and was wondering if you could speak to the different types of psychedelics and you know which ones are indicated for certain disorders and couldn't speak more generally about that yeah well the there is a lot of exciting work quite a bit now with psilocybin psilocybin for end-of-life anxiety at UCLA and Johns Hopkins and NYU and also the suicide and spiritual experience Studies at Johns Hopkins there are no no psilocybin PTSD studies going on that would probably be interesting to do although our feeling is MDMA is probably better suited for PTSD but I think many of these compounds really deserve further study you know they were they were studied psilocybin and LSD were studied in the 50s and 60s and had some really good data so where that seems to be growing too I think that you know we talked quite a bit with the some of the researchers that are doing so Simon studies and the sessions are different in that there's less community less talking during the sessions but it's a very similar approach of preparing people and then helping them integrate it afterwards I think there's a lot of there are a lot of similarities there's one thing the the classic psychedelics are more likely to produce a spiritual experience and so that makes it more effective possibly for the people who have anxiety about dying in this particular study with MDMA we've noticed that some people still do have spiritual experiences and we did have an MDMA study Michael mentioned at Harvard with cancer patients and we also have recently completed an LSD study in Switzerland with end-of-life but what we've noticed is that the spiritual experience does not seem to be correlated with reductions in the caps so some people have had a spiritual experience some people have not and they both still seem to be better whereas with the psilocybin studies they use the states of consciousness questionnaire which were also using now and they did find a high correlation between results and strength of spiritual experience and we're tracking that formally now with the vet study but we don't think it's important in the same way with MDMA it may be very important for an individual but overall not necessary I was certainly impressed by the results in the long-term follow-up and I may have missed this but was too curious and what kind of treatment those patients were getting in between they've been the interval between the end of your study and the 45 months yeah and we didn't control for that but we did track that where that paper should be coming out soon we're about to send their final revisions in next week but that's a that's a good question what we found was that people some people were still in psychotherapy or taking psychopharmacology about the rate you know everybody had had both of those but a study entry a little over 80% of people were in psychotherapy and at long-term follow-up it was about 40% so then that the number in therapy had dropped to about half the number having psychopharmacology was about the same the average number of drugs was smaller but there still were people using any depressant sore and anxiety drugs and it you know I'm saying in our paper that perhaps that's analogous to the way you know people might be unresponsive to antidepressants they get ECT they're better but then they need any depressants to maintain it even though they didn't respond to him first so maybe it's kind of analogous to that I just find that I think there was a few other people that reported using marijuana yeah we were there so we actually have FDA permission for a study of marijuana and 50 US veterans for post-traumatic stress disorder but the National Institute on Drug Abuse which has a monopoly on the supply of marijuana has refused to sell us any so that that study won't be taking place but our general view is that marijuana is something that can help control symptoms but it doesn't really offer the possibility of a cure and it needs to be used chronically for an extended period of time whereas MDMA does have that potential of actually moving people past the PTSD hi Mike I enjoyed it so much I came back again right the your p-value is point zero one five on the initial control group and then point zero five do you have an effect size and number needed to treat yeah if X has just over one psychotherapy that comes closer well I should also add to that the effect size was almost exactly the same in the Swiss study as in the u.s. study I thank you very much for your research I appreciate the goals here for sure I was wondering the question you bring up around the placebo and the expectancy effect you know of having a deeply spiritual altered experience I mean I do some prolonged exposure work with veterans and certainly the more engaged they are emotionally you know the more impact that treatment has and I was wondering for the placebo folks what what were the sessions like knowing that they didn't get the magic pill yeah the sessions usually involved a period of a certain amount of disappointment except for a couple people who thought they'd gotten it and had quite deep experiences just from the set and setting and the expectancy effect but then they weren't as different as you might think they tend to be less deep and less intense but we really made an effort to work in the same way and encourage people to take advantage of the time and actually everybody you know in the first study with inactive placebo said in retrospect they were really glad they had those placebo sessions even though they were disappointed at the time they found them useful but not in the same way so with the low dose sessions we're actually finding people experience them as being more difficult the low dose seems to bring up a little you know be a little activating and bring up a little more material and a little anxiety without really helping them over the hump so to speak so we actually started out with three low dose sessions and we changed the protocol to two because we found people were finding them too difficult well but you did have one responder we had one person who responded not two but three after the by.ya responded to three love those sessions had a really difficult time with two but then in a way it was a different mechanism it brought up stuff it was very difficult there was a lot of intense transference anger about you know what we were doing to her and then we were able to work with that in therapy that the follow-up sessions were really aimed at processing that and and of course that was part of her overall process so that ended up being helpful so it was almost like a different mechanism not it not as appealing harder on people not as fast but maybe actually potentially useful thanks so much you

Author Since: Mar 11, 2019

  1. Don't Forget: HTTPS:////WWW.CREATESPACE.COM/7091427 
    As a Survivor, I wrote a perfect treatment, from a time when there was no treatment known! Keep it up! Proud of you & your help w/ Let's stop cruelty & Death by bath-chemsitry drugs.Demand drug
    Regulation. SUZANNA

  2. Imho MDMA goes deeper and has less psychotic side effects.
    Marijuana is often to heavy cultured and potent.

  3. Mdma sounds like it could help me with my ptsd. I am the creator of Dexter the serial killer and i have ptsd.

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