PAREA Event in the European Parliament Meeting

PAREA organised a meeting in the European Parliament to launch the initiative to get psychedelic-assisted therapies (PAT) going in Europe.

Here are the presentations and a transcript from the meeting.

Presentations

• Full Appeal from PAREA (launch blog)
• The Time is Now – Tadeusz Hawrot
• PAT for mental illness – David Nutt
• PAT in substance use disorders – Anton Gomez-Escolar
• PAT in neurological condition – Jan Ramaekers

Transcript of PAREA Event

This transcript has been slightly edited for clarity (but not heavily, so do check the video to check if you want to quote the speakers).

[00:00:00] Frédéric Destrebecq: I think today mark’s a really important moment with the first meeting of the PAREA alliance, the Psychedelic Access and Research, European Alliance, and with the line-up of speakers, we really wanted to give a first insight on the potential for new therapies in this domain. Another host of today is MEP Saliba, and I know we’ve got a video message from him.

[00:00:30] Alexander Matthew Agius Saliba: Good afternoon, everyone. I regret that I cannot be with you today in person. Since this week. I am attending the external meeting in Vienna. Good mental health and well-being have been among my key priorities since day one. As a member of the European Parliament for several years, I have been co-chairing the m p Alliance for Mental Health.

The Alliance secretaries is provided by GA Europe, and I was pleased to learn that GA is one of PAREA’s founding members at one of the M A P Alliance meetings. Just before Covid, I called upon European Commission to prioritize mental health and also develop a European Union mental health strategy. The commission started to listen earlier this year, it’s President the commission.

President Vandelay announced that mental health will become an EU health priority and will see a comprehensive approach in the years to come. I’m encouraged by these developments in much the same way that I’m encouraged by the scientific progress surrounding using psychedelic compounds to treat mental health conditions.

In conjunction with proper psychological support, they hold the potential to provide safe reproducing. And robust clinical improvements and durable effects. And I do not have to convince anyone that we badly need more treatment options for people affected by mental health. My understanding is that it is likely that psychedelic-assisted therapies might be approved by regulators in the US as soon as 2024, and approvals in Europe will follow suit.

In this context, the EU prioritization of mental health couldn’t be timelier, and you can rest assured that I will be actively calling upon the EU institutions to include the area of psychedelic novel therapies and the wider mental health agenda. The European monitoring centre for drugs and drug addiction should be included in those efforts.

And together with my other MEP colleagues, we are working on a cross-party request to the European Monitoring Center for drugs and drug addiction to provide us with an evidence-based assessment of the current state of play and the field of psychedelic science to inform us about further direction. I wish you a successful event and you can count on my support.

[00:03:10] Frédéric Destrebecq: Thank you. Okay. And obviously thanks to MEP Saliba for the support that you, you just expressed. I just would like to invite our first speaker after this round of introduction who is Pedram Dara. Pedram participated in a Phase II clinical trial for PTSD with psychedelic [MDMA]-assisted therapy.

[00:04:07] Pedram Dara: Thanks everyone for being here. First of all, thank you to Tadeusz for organizing this and giving importance to the voice of patients and participants. My name is Pedram, and my story begins when I came to Canada in 2004 as a refugee. And during that experience of coming to Canada and also my entire life, prior to that, I experienced many traumatic events.

Unfortunately I didn’t seek any sort of treatment. And I lived on for about 15 years with different coping mechanisms started by, work and success and money, and then, you know, changed to, you know, relationships and, you know, I just changed different coping mechanisms rather than actually going after the root cause.

And that kept on until I was 34, 35 when I became a father. I think the lack of sleep and just having that life-changing experience really pushed my mental health even further down to the level that I couldn’t maintain work. So I would change jobs from jobs.

EDITING STOPS HERE (for now)

I couldn’t stay really productive. My, all of my relationships started hurting including the mom with my wife, my parents you know, all friends eventually became very isolated. You know, experiencing. , what I thought was depression to the level that I completely lost hope, and I would say definitely became suicidal.

I just couldn’t see a way through this. And on one hand, I’m a new father. I have this beautiful little girl, and I’m supposed to enjoy this experience. And everything on the outside looked good. But inside I was kind of dead. I, I couldn’t really even experience joy. Situation kept getting worse, unfortunately.

And one day which was I think probably my bottom , I would say my rock bottom moment where I, I used to experience a lot of rage episodes. I would just get really angry over small things and one day, I exploded so badly that unfortunately I never, fortunately I didn’t become that violent, but this time I think I, I met the border of that and I got so mad at home that I just threw a plate of food to the wall and just broke the pieces.

And then my wife just grabbed my daughter and ran away from the house to find safety and . I think that was a kind of like wake up moment for me where I felt like, okay, like I’m definitely in trouble and I need to seek help as a way to distract myself from sitting with those feelings and, and, and doing anything.

I started looking at my phone and I’m scrolling through. I randomly see an article about M D M S is a therapy for P ts d. Back then I thought M Mdm a was a party drug and p t was for soldiers. I didn’t see the connection between the two. Next thing you know, I learned more about it and I found out there was a study happening in the city that I was living.

And story short, that processed took four or five months, but eventually I was lucky enough to be accepted at that, that study. Only six other people before me had received this treatment before. So I felt very lucky to be accepted in this study. Changed my life, to say the least. Definitely gave me a new sense of hope that I was looking for and a, and a potential for healing.

Study ended in early 2019. Then from there on, I kind of went beyond the diagnosis. I took charge of my own healing journey especially because the current research protocols really lack post-treatment support, which was something that I was missing a lot. So I had to kind of take charge of that on my own.

And journey still continues. I mean, I’m here, I can speak about this experience, but by all means, you know, I still have my issues. I still struggle from time to time and I have moments that I fall down. But I definitely get up quick here. I, you know, I somehow haven’t lost that hope, so it’s kind of an upward spiral, I would say.

I’m happy to report that. Then I wanna share a few lessons that I learned through. This experience is I think psychedelics are kind of like tools and technologies. My own background is in technology, so this is how I made sense of my healing journey that I think they’re great for solving problems, especially they have massive potential for the speed and the scale of the mental health crisis that we’re all f facing.

And you know, obviously with covid things are even worse now. Yet at the same time, I don’t think it’s a one size fits all solution. I also don’t think it’s for everybody. And I think one of the first things we need to figure out is who are the best people for this sort of treatments? And and lastly it’s not a cure.

It’s a catalyst. That’s how I see it. It definitely initiated my own healing journey by, but it’s not a magical pill you take and all your problems go away. A few things that we lack, in my opinion and experiences that we lack infrastructure and accessibility and sufficient after curve. We also lack public f.

Be very relevant for the room we are in because, you know, we, like it or not, it has already attractive extracted capitalism because of the hype. And I think more public funding could could tackle that. Lastly, a few things that I think action points. I think definitely there’s still a stigma both around mental health conditions talking about it as well as psychedelics themselves.

So I think if one thing we could all do is by kind of like removing that stigma, it’s okay to not be okay. It’s okay to seek alternative treatments, and I hope we can do more in that. So we definitely need more resources. I my hope is that we make mental healthcare a fundamental human right and making it accessible to everybody.

And I say that because at this given moment in my home country back in Iran, people are being traumatized in, in number of thousands and a given moment. Because of the uprising. And I hope Europe doesn’t continue to be a garden and leave the jungle alone. And I hope that what happens in Europe could have an impact outside of Europe also.

Lastly, I think the voice of PAR patients and participants definitely need to be at rest. And it, we at the center of this innovation I had a opportunity of actually organizing a participant panel at the I C P R conference this year, which was very well received. And I think the, the lived experience is something that we need to share more of.

And then last, lastly, I hope we can transform the society also that is actually causing the trauma and suffering. Because if we only focus on, on the trauma and suffering alone, then, then yeah, we might improve our treatments. But, but if the world is still an unsafe place, we then will continue to have people becoming traumatized and having mental health conditions.

And kind of the analogy that I used to like to use is that Let’s assume we are having a lot of car accidents and people show up in the emergency rooms with broken limbs and arms, and, and if all we are doing is improving the treatments, but leaving the roads unsafe, then are we really solving the problem?

And my hope is that we do both. That while we continue to improve our treatments, we also make the world a safer place to begin with.

[00:11:04] Frédéric Destrebecq: Thank you.

Thank you. Thank you very much, Pedro. And particularly for conveying this let’s say very personal token and and your lived experience. I also wanted to reflect on what you said about it’s not a cure, but a catalyst. In your case, you were saying it was life changing to, to go through this this experience.

Still, I mean, were there any challenges that you faced in, in the process or what would be, let’s say, the most challenging, let’s say, step that you had to go through even with the psychedelic support in your, in your therapy?

[00:11:40] Pedram Dara: Yeah, absolutely. I think the biggest challenge was this notion of, it’s not my fault, but it’s my responsibility.

Mm-hmm. , because it was so easy to just blame everyone, you know, started by blaming my parents for everything you know, and then the society as a whole and all that. And then eventually I had this cold heart truth of like, okay, you know, like definitely was a lot of things that happened to me wasn’t my fault, but the healing is my responsibility.

Mm-hmm. . And I think just accepting that and really owning it and, and almost becoming interested in my own healing. So rather than like, here’s this mental health conditions that is, Is really like, you know, almost rather than seeing it as an enemy, I was like, okay, like let me just actually grow some interests and make this the biggest project of my life.

And that, that was perhaps the most challenging thing actually to go to. Yeah.

[00:12:27] Frédéric Destrebecq: Thank you. We’d like this this meeting to be a lively one and one where you have your say also and where you can contribute. So participants online are really welcome to put their questions into the chat. We have a way here to to collect questions, sorry in advance if we cannot deal with all of them given how attended or how well attended this afternoon is.

But if in the room anyone would like to, to speak up, simply wave at me and I’ll give you the floor. But otherwise I’ll I’ll move on with our speakers and feel free to come back also to bedroom. Whenever you’d like to to ask a question to to one of our next speakers, because next is pa, founder and the executive director ta sha and your task to introduce to us what pa stands for.

So you’ve got the flow.

[00:13:19] Tadeusz Hawrot: Great. Thank you, Fred. Let’s see, just if this will work, a few more tries. Maybe this,

so I might need to have the slides changed by the magic word next. Okay. So if we come back to the previous one,

So we come back to the pre covid time, COVID learned. You are on mute and before Covid it was next. So true. We’re back to normal then. Yeah. Okay. So good to be back in normal. And I will speak about pare obviously, and also about why we think that the time is now to start preparing for safe and effective psychedelic assisted therapies in Europe.

So I think a good place to start is with massive unmet needs that we see in the area of psychedelic assisted therapies and in, in the area of brain disorders. And I think that brain disorders really are unmet needs, perhaps alone. We can go next, please.

Next, let’s see if this works. . Well anyway, I’ll speak and well maybe we’ll catch up with slides. So we, in fact when we look at just the prevalence of mental health conditions, over 8,000 80 million and alcohol use disorder, 23 million Europeans being addicted, this is already more than 100 million Europeans.

And, you know, there are more conditions. And at the same time, we haven’t really seen a lot of really breakthrough innovation in the area. For instance, since 2015, there were only seven new neuropsychiatric drugs approved, whereas we’ve seen some eight drugs approved in oncology. And in the last few decades, really mostly what we’ve been doing is tweaking existing molecules.

So there was a slow, kind of painfully slow pharmaceutical innovation happening. So against this backdrop next Against this backdrop, we see this really truly groundbreaking scientific advances that are related to both psychedelic compounds and psychedelic assisted therapies. And we’ll hear more about that from, from Speakers today, LA later on.

And it’s not just science, but also, so, and, and you can see here on the slide just how many clinical trials are happening now in the last 10 years, they had, there has been this tremendous increase, though it’s always worth adding that this research started already in the 20th century and then went into a deep freeze because of the war on drugs, which as some say was the biggest kind of censorship of science next.

And it’s not just science, but there is also a lot of regulatory progress happening all over the world. And ex one example is that US Food and Drug Administration granted so-called breakthrough therapy designation for free psychedelic assisted therapies in. Few years. Next. So with all this still these, these treatments are not approved because we do need more research, bigger, bigger sample sizes.

We need really to use rigorous methodologies so that we can further understand and confirm safety and efficacy of those compounds. And also looking to other treatments parameters such as the, the therapy itself. Next. So with this, while we are not sure about the treatment parameters, we are sure about one thing or about the, the research we are sure about one thing, and that is that European health systems are not prepared for these treatments yet.

Next. And we are here as Parra to change it and to really offer advice and expertise of our members to EU policy makers so that we can start preparing for that. So, PARRA stands for Psychedelic Access and Research, European Alliance. And it’s also a Greek word, which means to be in the company of friends or to do something together.

And in the Greek culture, Parra is a venue for the growth of the human spirit and the development of ideas to enrich our quality of life. And these are values that also guide our joint collaboration to change perceptions, to educate to scale up and accelerate action, and of course, ultimately to bring better health to European citizens.

Next. So Per is all about our members. This is really our strength. We, we are this incredible partnership of a lot of groups. Many of them are active in Europe. Most importantly, we have several patient advocacy groups that are our funding members, patients covering the, the area of mental health, neurology, chronic pain.

We also have psycho professional associations like European College of Neuropsychopharmacology and European Psychiatric Association as a, as a member as well as a number psychedelic patient organization, cyan. And if we go next several, several associate members of servers and industry partners.

So with this, we are becoming this collective voice of , all kind of con concerned psychedelics and, and mental health and brain disorders in Europe, and the one-stop shop for the EU policy makers next. Our vision is a world in which brain health is valued, preventable, suffering is avoided and psychedelic novel, novel treatments help people to heal and enhance their sense of wellbeing.

And this brings us to our mission which you can see on the next slide. And this is safe, modern. And as an ethically responsible integration of those treatments into European mainstream health services, people should have them available within their existing healthcare, healthcare frameworks at the place where they live from the doctor and therapies they trust and paid by health insurance.

And on the next slide, you’ll see objectives that drive our progress. This is research supporting drug reform educating to decrease stigma, building capacity, collaboration, equitable, timely, affordable, safe, and legal access to those therapies, promoting meaningful engagement and safeguarding optimal care and safety for patients and child participants, and contributing to a diverse and equitable psychedelic ecosystem.

Now I guess now you can just click a few times because there will be animations. Yes. So I want to speak about a tremendous progress that has been happening in terms of policy and regulation in the last few years. Unfortunately, mostly outside Europe. And these are just examples. From this year we’ve seen this letter from National Institute of Health and Food and Drug Administration.

Earlier this year we spoke about NIH funding in 2021 for psychedelics amounting to 35 million. There were a couple of workshops organized at the federal level by, by federal agencies two day workshops each A few weeks ago, there was this initiative in the US Congress where they formed this bipartisan s which is, I guess a, a kind of equivalent to the m e p interest group here in Europe where they will explore psychedelic research, still the congressional conversation, and serve as an educational resource.

Also in closer to, to us, in, in, in the uk, we’ve seen some regulatory incentives and developments such as this innovation passport granted to M D M A assisted therapy for P T S D and also a grant from NICE to fund phase three trial for the ketamine use for the treatment of alcohol use disorder.

So with this, I, I, I like to think about this saying that the future is already here. It’s just unevenly distributed and I think we have a bit of work to do in Europe to catch up and actually take the lead. I think we, we should aim at taking the lead in terms of policy and regulation in this area.

And one more thing I want to mention on the next slide is another thing that was announced. So if you go next earlier this year in the US there was this letter from the us president’s Biden administration, which Speaks about an anticipation of an approval of M DMA and cell psilocybin therapies within the next two years.

And they are considering establishing a federal task force to address the numerous complex issues that are surrounding this therapeutic area and establishing public-private partnership where there will be a collaboration both across federal agencies as well as outside stakeholders. Next.

So I think this is really something that we should get inspired by in Europe because we have this unparalleled opportunity to address an area of such huge unmet needs. But you know, it also comes with with a lot of work and preparations we need to put, so we should formulate a, a similar initiative in the eu.

And if you go next, again more concretely. At Parra, we believe that we, we need to start preparing to develop infrastructure for the highest quality, safe, affordable, and equitable access, good standards of practice, training of specialized therapists, their credentialing and licensing, safe and ethical use more supporting people with challenging experiences as we know there, there will be.

Is engaging with communities and peer support networks so that once people go treatments, they also have them a possibility to carry through with their healing process with their communities and developing data standards. And this, it will be really best if we address this at the level of the European Union, rather than having individual countries working on this one by one and, you know, wasting resources, duplicating their efforts.

We believe that EU should provide a platform for member states to work together on developing these solutions. And also, very importantly, as we foreseen that there will be a bottleneck in terms of. Available therapist will be trained to assist people with these therapies. We might need to look at a phased rollout so that we can balance and need for widespread access with safety monitoring and supervision.

And on the last slide, I just want to thank you and invite you to get involved, join us, support us stay updated. Thank you.

[00:24:05] Frédéric Destrebecq: Thank you very much. That it’s very clear in terms of presenting the alliance vision objectives, but also on the as you said, the major unmet medical need that is actually insight in, in developing those activities. If, if there are no questions, I’m, I’m quite eager to take the next three presentations in a row and then open the discussion instead of having the q and a one by one.

And that would certainly help. Having a more animated discussion particularly yes. David, I would like to, to hear from you what it means in, in relation to mental health conditions. So Professor David Nuz is probably one we no longer need to introduce. You are the chair of barrier your former president of the Yin Brain Council, but you also Professor Timpe College in Neuropsychopharmacology and founder of drug science.

So David, please you have the floor.

[00:24:56] David Nutt: Thank you, Fred. Next slide please.

Sorry. It might be just helpful to give a, a very brief historical overview of this field because it today, as has already mentioned, it’s there was a lot of data collected in the last century and that data was actually quite helpful to us currently, which I’ll explain in a little while, but we just start with.

The graph on the left hand side, it shows the number of publications each year for L s D, the psychedelic LSD in Blue and Slobin. The active ingredients in magic mushrooms in pink. And you can see there’s a massive increase in the number of publications going from the 1950s when these drugs were made available to 1970 and that the blue arrow below shows cytosine was introduced into medicine a as a, as a therapy by, by Sando in 1959.

And L S D was made available in the little box that’s a box of L S D tablets made available for researchers by Sando back in 1953. And that massive increase in publications, which covered over 40,000 patients being studied was fueled by. Reed by the US government, and at that time in the fifties and sixties, psychedelics were seen as the great revolution in psychiatric research and therapy.

For the first time, we had tools that we could use to both explore the brain and also change the brain. And then the arrow points to the 1971 UN Convention, psychotropics Convention, which effectively stopped all this research and. You can see there was a precipitate fall in the number of publications.

And for some years there were parti for side ibin. There were no publications at all. And this was a, I think, a deliberate attempt by the international community, driven by the American War on Drugs to actually eliminate or knowledge of these drugs. Funding stopped, and even if you could get support from charities, access to the drugs became virtually impossible.

And the driver for that was actually the war in Vietnam. And psychedelics, particularly L s D, were associated with the anti-war movement. You can see in the, the picture in the bottom right. And because the anti-war movement couldn’t be banned itself, the drugs got banned. And what was really perverse, and there is no sensible explanation for this, is that they were banned for.

In as well as being banned for recreational use that I think is the worst censorship of research and certainly of clinical practice in the history of world because that ban still persists today. There is no country in the world that’s signed up to the 1971 convention that has undone it.

Although, as you know, we are getting around it in research terms, but it’s still, all these drugs are still illegal internationally. Next slide.

Now one of the justifications for putting psychedelics into schedule one of the conventions was that they were very harmful as well as having no medical value. Well in the last 10 years, there have been three very detailed systematic reviews of the harms of a range of different drugs, including psychedelics and also M D M A, which I’ll talk about in a minute.

The first one was the, the one published by Drug Science in the Lancer in 2010, and that’s been replicated by a group of European experts funded by the department of Justice in Europe in 2014, and a group of Australian experts in 2018. And you don’t need to look at the, where the most, oops.

Could you go back please? But in the red circles, you see the drugs we’re talking about. You see Ls d salide, magic mushrooms and M D M A, and they all fall in the red circles. And you can see the red circles are the at the lower end of harm. So these are harm scores. The, the taller the bar, the more harmful the drug is.

And we have three independent groups of people estimating the harms of these drugs when used recreationally, and they turn out to be amongst the least harmful of all recreational drugs. And we know that when these drugs are used clinically using one or two or three doses at the most, the risks are even less.

So the myth of harms have really been exploded over the last 10 years, and this is given an underpinning to the resurrection of research that many groups are doing now. Next slide, please. So those are the psychedelics. And this, this just, this slide just looks at the history of M D M A, which is not, well, it’s not a psychedelic, it’s been similarly censored for research because of recreational use.

And that image, there is a a stylized picture of the man who reinvented and rediscovered, M D M A, Sasha Shige, there’s the molecule in his hand, and he’s with his wife. And, and Shulgin made a whole range of different amphetamine derivatives as well as other psychedelic tryptamines. But when he tested M D M A on himself, like all good chemists do, he, he realized it had a, a peculiarly discreet, and.

Effect to any other drug he’d ever tried. And he said it produced a clarity of thought and an empathy, which made it very different. So he shared it with his wife, who was a therapist, and she said, yes, this drug could be potentially a very useful tool for psychotherapy. And it was widely used by therapists, particularly in the west coast of the USA for about 10 years.

And tens of thousands of people were given it in therapy because it was a legal drug. But then two things happened. The first is it started being sold in clubs as a legal alternative to amphetamine, which was illegal. And en encouraged people to, to, you know, to dance and to become more, more empathetic with each other.

But the worst thing of all was its name was changed cuz originally it was called empathy because that’s what it does. But its name was changed to ecstasy to make it more appealing to, for recreational use. And of that then made it become very popular. It moved from Texas, it moved into many parts of the states.

It moved to ia, the rave scene in Europe started and there was a hysterical backlash, particularly because the media hated the idea that young people were having ecstasy and it was made illegal. But there was one group of therapists in the States who carried on trying to resurrect it and they’re called maps.

And they’re now, after 30 years, they’ve managed to raise enough funding to take M D M A through into clinical trials. And that was one of the trials the early trials that Hedron was talking about. The next slide, please. So let’s just look at the latest clinical data because there’s been a tremendous explosion of really high quality data in the last few years.

Next slide, please. And, and this I think, is probably the seminal study. The really kickstarted this whole field. And this is a study we did and published in 2016. We started in 2012. It took a long time to get the drug. It was that the study was delayed by the bureau. It. We achieved this output, and this is a trial of Abin, a single dose 25 milligram dose of Cylo ibin given to people with resistant depression.

They’d all failed on at least two antidepressants. Some had failed on over 10, they’d all failed on psychotherapy, C B T. And you can see they all got better. In fact, some of them got so well, they moved from being depressed to undepressed into the yellow bar at the bottom with no depression. In fact, some of them are still, well now, 10 years later, not many, but a quarter stayed.

Well, three quarters. The depression started to creep back after three or six months. But nevertheless, if when you, even if you go out to the three month data, that is the most powerful single dose therapy. For resistant depression. There’s ever been, in fact, it’s so powerful. It’s initiated many of the companies that Tad showed you the graph ofs getting interested in this field because this is potentially a revolution for treatment resistant depression.

And the good news is that it’s been replicated. The next slide, please. And these are the data published just last month by Compass Pathways. So one of the. Companies that set up to, to try to take Cy Ibin from research into Medicine was Comfort Pathways. And here they did a remarkable study. This is a, a massive multi-center, a randomized controlled trial of three different doses of Cy Ibin, A tiny dose, a one milligram dose, a middle dose, a 10 milligram dose, and the dose we used the 25 milligram dos in blue.

And if you look at the, the top left-hand curve, you see that one day after the high dose of Cyto Ibin, there was a profound reduction. In depression scores in these treatment resistant patients. And you can see if you’ve got the blue line in the top left, it, it’s, there’s a significant benefit of that high dose over the lower doses that goes out to six weeks.

In fact, it to some extent continues up to 12 weeks. And look at the right hand side of the, of the slide. You see the percentage of people getting into what’s called remission. And these are people that are no longer have depression. They’re, they’re effectively cured of their depression. At week 12, you see a quarter of the people who had previously treatment resistant depression were actually cured by just one single dose of cyto ibin 25 milligrams three months before.

So that, again, is a remarkable finding, unprecedented really, in, in terms of psychiatry or psychiatric treatments of depression. The next slide please. Now while Compass Pathways were doing their work, we were doing a different study, which was to compare the efficacy of psilocybin V versus the gold standard antidepressant, ESCE, Talopram, and ssri.

And it’s a complicated design. I haven’t got time to go through it with you completely, but it, both groups got exactly the same amount of psychotherapy. Both groups got psilocybin, but the CY group in red got a high dose. The Ecet Prime group in blue got a tiny dose, but they all had the same level of preparation and therapeutic support afterwards.

And if you look at the top left-hand graph, You see the reduction in oppression scores following the first dose and then following the second dose three weeks later of Cylo Ibin. And you see that the red bars, the Cylo Ibin group did better across the board than the Esom group. But again, you see the profound immediate, almost immediate reduction in depression scores following the Cy Signin.

Anes Talopram did very well because there was a lot of psychotherapy around the start of the trial. What’s on the interesting though is on the right hand graph, this is the off the sort of the opposite of reductions in depression. This is increases in wellbeing. This uses a standardized scale called the Warwick Edinburgh Mental Wellbeing Scales.

And you see again, after the first dose of cyto ibin, there’s a massive increase in wellbeing. Cyto aside being much more powerfully increasing wellbeing than prim. And this persists and may even go up with the second dose. And wellbeing’s important cuz wellbeing probably protects against future risk of relapse.

And the bottom left hand table shows remission rates in this trial. Now that we, we use four separate scales, and you can see that the different scales give different remission rates for Simon and Prim. But when you compare the difference between the two, you see. Sabin is at least twice as good and sometimes four times as good as Esther Talopram.

Supporting the view that getting people fully well is more likely after Sabin next trial. Next slide please. Other trials in other jurisdictions, particularly this trials in the USA from Johns Hopkins and the graph at the top shows an interesting trial where people were randomized either to staying on a waiting list, which is the black blobs or going onto sidey, the orange blobs.

And you could see the sidey worked much better than waiting list and their waiting this group within switch to cyto ibin, that’s the right hand graph and they all got better. And there are also trials going on and you’ll hear a bit more about trials in addiction for smoking and alcohol dependence.

And there are trials also going on in anorexia. O c d and in pain syndromes. And you might say, why would a treatment with a psychedelic work across such a range of different disorders? And the answer is because they’re all what we call internalizing disorders. They’re all disorders in which individuals get locked into a, a ruminative way of thinking that they can’t escape from.

And I’ll show you at the end, the brain changes which underpin recovery from that. Thanks Slide.

What about the latest data with M D M A? So these are the data from the first of the maps phase three trials, and the second one has just been finished and we’re reporting later next year. But if it’s as good as this one, which is likely, then it, there will be it’s almost certain that M Dmma will be a medicine because you can see in the left hand box the remarkable difference between standard therapy, which is established therapy for P T S D in the blue line, and the same therapy in the red line with three doses of M D M A.

And those three doses produce much greater reductions in the scores for P T S D than the therapy with placebo, which was say like, and you can see this on the right hand image. So you see three circles on the right hand side, you see an image. The black circle or the proportion of people who met criteria for P T S D before treatment, and everyone did because that’s how they got into the trial.

They were, they had P T S D and they had not responded to previous therapy. And then you see the, the red part of a circle. That’s the proportion of people who got M D M A who still had P T S D after treatment and it’s less than a quarter. So three quarters got into remission, whereas the light blue circle, you see the opposite.

You see over three quarters stayed ill, they stayed having the diagnosis. So the difference between the red and the light blue is profound and it’s a such a powerful effect. It, it’s likely to be clinically really very important. Next slide.

We’ve been able to ask the question using brain imaging of how these treatments work. And this is the data we have on how M D M A works in P T S D and P S D is a disorder where the emotional response to a memory of trauma becomes overwhelming. And it’s recently that the emotion of P T S D is located in a different brain region to the factual memory of the trauma.

And that allows us to selectively deal with the emergent memory, the emergent emotions and the therapy with m with M D M A therapy and P T S D is designed to. Allow people to reengage with the emotional memory, but control the emotions. And often before M D M A it was difficult for them to do that.

They would often dissociate or faint or just run out the room. But M D M A allows them to stay in the therapy long enough to get well. And the images on the right hand side, the brain scans show why those, the blue blobs in the brains on the right are areas of the brain where the activity is reduced, suppressed by M D M A.

And those blue blobs are in what we call the emotional center, the limbic system, the amygdala and M D M A depresses activity in the emotional center. Enough for people to be able to stay in therapy and get better from therapy. So now we have a, an imaging correlate of the clinical outcome. Next slide please.

what about psychedelics? Well, psychedelics produce profound alterations in brain function, which is why they produce such profound changes in consciousness. But what’s particularly relevant for the therapeutic benefit is that they change connectivity in the brain. And these two images on the normal brain under placebo, the cyto, ibin treated brain, they’ve got the same number of connections.

There’s 7,200 connections in each. But you see in under the psychedelic, the connections are much broader, much more across the brain. The brain becomes hyperconnected under psychedelics, and that we think allows people to understand why they get depressed but also to come up with new solutions to how they might deal with their depression.

And so this catalytic process that you heard Pedra talk about initially, these facilitate a path to recovery by giving people new insights into what they might do and how they might think differently. The next slide.

The question is do do those changes which we see during the psychedelic state, do they persist subsequently? And this is a recent paper of ours, which show they do. And Well, we’ve, we don’t scan depressed people during the trip because it would be unethical. But what we have done is scan them after they’ve had their, their psychedelic experience.

And we’ve shown that the brain has changed as a result of the psychedelic experience in a way which increases cognitive flexibility. So if you look at the bottom right hand image there, you see the red lines going up. Going up means more, a more flexible brain. You’re more able to, to change the way you think, and that occurs after cyto ibin, but not after prim.

And the images at the top are, are just schemas, which help you make sense of what’s going on. The way we’re conceptualizing disorders like depression now is shown in the top left hand image. That’s what we call the energy landscape of the brain. The brain is very differentiated in depression. You have deep troughs and when people get locked into a deep trough, their thoughts go round and around and around with depressive content, but they can’t escape from them because the trough is too deep.

The middle image shows what happens during the psychedelic trip, which we know from studying healthy volunteers. The energy landscape of the brain is flattened, and that’s where that increased connectivity came from in the site I showed you previously. But we now know that persists and we can see it three weeks after the last psilocybin treatment.

There’s still greater flexibility, a flattened landscape, and that flattened landscape predicts outcome at three weeks and in one of the other studies, six months. So for the first time, now we can show a pattern of brain activity, which correlates strongly with clinical outcome and helps emphasize the the fact that what these drugs are doing is changing the functionality of the brain to make people able to escape from their depression.

The next slide, these. And just a couple of quotes from patients, just so to sum up the kind of experiences they describe. My outlook has changed significantly. I’m more aware now, it’s pointless to get wrapped up in ender’s negativity. I feel as if I’ve seen a much clearer picture. My mind works differently.

I ruminate much less and my thoughts feel ordered, contextualized, rumination was like thoughts out of context, out of time. Now my thoughts feel they like they make sense with context and logical. So these descriptions are very common. Patients often talk about these drugs as if they are reformatting their hard drive or defragging the hard driver for the computer and allowing the computer to work more smoothly and more fluently.

And that’s what the brain imaging shows. It shows that their brains are more more flexible. And just to finish with this quote from this philosopher and playwright George Bernard haw, those who cannot change their minds cannot change anything. Actually, we are now reframing that we think psychedelic treatments change the minds of our patients through changing their brains.

And the next.

And what we need to do now, and that’s why we’re here today, is change the minds of many healthcare professionals, some politicians and scientists about these therapies. We should bring them back into medical practice because we know they’re safe and we know they’re effective, but they’re still very hard to access.

Thank you.

[00:46:33] Frédéric Destrebecq: Thank you, Dave. I just would like to, to ask you a very quick question because you said new solution to old problems, but actually from the graph, the first graph that you showed with the, the, the surge of actually psychedelic use and psychedelic research in the sixties, seventies, it seems. It’s not that new.

But how that period where intense research in the field was actually going on how does that inform your work of, of today and would there be any findings out there, any evidence that is helpful to you today?

[00:47:04] David Nutt: Well, you absolutely. So the, I mean, one of the reasons it was easy to dismiss and to ban psychedelics was cuz no one knew how they worked.

Now we’ve got brain science. It’d be much harder for people to say, whoa, it’s just some kind of myth. It’s some kind of happy hippie kind of trippy thing. So we, the science helps us now make it our, our case stronger. But the nine, the early data is fantastic. You’ve got 40,000 patients. You’ve got an analysis of many of them showing enormous safety.

Yeah, with levels, you know, risks of psychosis. Risks of suicide, much lower than people would’ve assumed. And so, and I say to you now, you know, we, there are never has a, a medicine ever been put on the market with clinical safety data on 40,000 patients. That’s why I’m very reassured we can use this medicine because cuz we’ve got, that’s historical data that bolsters the, wait, we’ve got a thousand current patients, but we’ve got 40 thou.

So we know it. The, the safety data is really very, very helpful to us. So there is no more magic. And it, it gives a new light to this saying that science is basically responding to the educated guests for the last four, 400 years. So yeah, but it’s unfortunate it’s been 50 years since we’ve been able to do this and that, you know, there’s hundreds of millions of patients who have been denied access because the dec of the dis, the arbitrary decision to say they had no medical value even then, they though they did.

And that’s why it is, it’s in air. It’s a, it’s a very inhumane that that decision was very inhumane, that so many people have suffered. And, and there’s, and we, you know, we still haven’t brought it back. As I say, there’s no country in the world that has yet rescinded a signature on the Ewing convent. .

[00:48:56] Frédéric Destrebecq: Thank you Dave.

And am eager to move to our next speaker and we shall certainly come back as we are collecting questions in the, in the chat. And our next speaker is Anton Gomez Escola an Antonio psycho-pharmacology researcher and ota and you’re going to talk to us about the use of psychedelic assisted therapies in substance abuse disorders onto you.

[00:49:22] Anton Gomez-Escolar: Good afternoon, everyone. It’s okay. Okay. Our presentation

Okay. So I’m, I’m gonna talk about the use of psychedelics in the treatment of substance use disorders. Next, please. I’m gonna very briefly review a little bit the, the state of the, of this field and the possible implications for future research and for, and for implementation in national health services.

So, just to mention that we’re talking about psychedelic substances that were formally, formally known as hallucinogens. These substances include psilocybin, L S D D, MD meline, but there’s also other substances with psychedelic properties like M D M A, ketamine, Igan. They are all considered to be like psychedelic substances, even though they’re purely, not all, all of them are psychedelics, but they also, they all have psychedelic properties.

No. So in this in the drugs wheel we could. could say that we’re talking about the substances in the area of empathogens. That is the yellow, the psychedelics, that is the green and the blue part that is the dissociatives. Psychedelics assisted therapies are those that combine common psychotherapy with a psychedelic.

And as it was mentioned before, the psychedelic is not used to minimize the symptoms of the illness. It’s used to catalyze or to accelerate the efficacy of the, of the psychological intervention. So In this model of treatment, we don’t need to use a lot of substance. We don’t need to, to give the person the psychedelic substance every day as it is done now with and with all the antidepressants or analytics.

But in this case, we use it just in a few times, one, two, or three. And then results of that intervention are long lasting. The important thing about this kind of intervention is that it has to be given under direct supervision, so the substance is not given to the patient to take home. The substance is taken by the patient under the direct supervision of a therapist.

The patient should have some preparation before the, the session should have some monitoring during the session and should have some integration after the session. So it is very different to, to how some of the current pharmacotherapies are used nowadays in mental health. Please, next

So when we are talking about substance use disorder, we’re talking about a problem that is very important. So nowadays there is 11.8 million deaths a year that are related with substances like tobacco, alcohol, and other drugs. And we lose 130 million life adjusted years of disability, meaning that, that all the problems derive from the, from the abuse of these substances make the society lose a lot of healthy and productive years of life.

In, in the population. Tobacco, just tobacco is the single largest cost of preventable death. Worldwide, we’re talking about 6.6 million deaths a year. Alcohol is re responsible for 3.3 million deaths a year. So problem, not all of these deaths are related with substance abuse, but are. Behavioral addictions.

On the other hand, it’s a growing trend these days, especially after the pandemic and with the development of all new technologies, social media, pornography sites. So we are getting more and more behavioral addiction problems that also carry their own problems. Not, maybe, not the toxicity of, of some substances, but they have a ma a massive problem in when it comes to this life quality loose in population.

Thanks, please.

So how can you, how, how can we use and how are we using psychedelics to try to treat these substance use disorders in this headlines? We can see that in the next, in the last few years, we have been having some important news in this field. So we have New York Times talking about the next big addiction treatment.

We have M N B C talking about the psychedelic drugs, helping people with alcohol disorders, reduce drinking. We have many other media talking about this results from clinical studies that we will review in a second.

So to start with alcohol. There was a recent study published by Michael Ganus in New York University with really good results in alcohol use. So in this case they put, they, they divide as a group of people of patient with alcohol use disorder into two groups. One was receiving two doses of psilocybin, and the other one was receiving an active placebo to try to make them believe that they were taking the, the substance so that that way you can compare what’s the effect of the substance as just by obstructing the effect of the placebo.

And in this study they were all receiving two 12 weeks of psychotherapy along with the, with the pharmaceutical intervention, the percentage of heavy drinking days for the people that got the psilocybin. Was decrease many very significant, very significantly. Yeah. And and all also the mean intake of alcohol of that people was also reduced compared with the drink in, with the other group that was receiving the active placebo, showing that there is a efficacy in this substances.

So there is a lasting improvement in their alcohol intake habits, meaning we are decreasing the, the danger of this alcohol use disorder in these patients. Some of them also gain sovereignty after, after the, the clinical intervention. Next one, please. There are also some other studies ongoing at the time with alcohol use disorder and psychedelics.

There is one in University of Zurich. There is another one in John Hopkins. University.

Also some in Europe, like cop having, cop having university, an alcohol use disorder, and university of Iowa and United States

when it comes to tobacco. The other big addiction or substance use disorder that we were talking about, there is a very interesting study being done in John Hopkins University by Matthew Johnson. It was published a few years ago, but the results are still very striking. So it’s an open label study, meaning that in this case, patients knew whether they were taking the substance or no, they were not taking the substance.

And in this case 12 among 15 long time smoking addiction people. So people having trouble stopping smoking with several several fail attempts. In the past, 80% of those were. Abstinent six months after the initial intervention. So in that time, there were no intervention. It was just single intervention with with psilocybin.

And the results persisted over six months for 80% of the sample. This is huge. If we compare with the actual efficacy of their current treatments that are being prescribed for tobacco addiction, that in most cases are just 30% effective. So it’s a huge efficacy. Of course, it’s a very small sample, so we cannot extrapolate very solid data from this, but it’s pointing to other direction.

It’s showing us that there is a big p opportunity here in this kind of treatments for a very wide and common addiction that is killing 6.6 million people every year in the world. This this same study had a follow up at a 12 month month, sorry, and 16 to 13 months. Sorry. Go back . Thank you. At 12 month point.

60% were still abstinent. Had hadn’t been smoking in that in one year. After that intervention months to 30 months, 60% still abstinent. So it’s very long-lasting results for a very fast intervention that is only once in in time. No, thank you. So now there’s more research going on in this specific indication.

Tobacco tobacco addiction or nicotine use disorder. SI facilitators, smoking cessation treatment. This is the pilot study I was just presenting. There is model studies from John Hopkins University School of Medicine going on at the time.

And also to mention that these studies have gone gained a big grant by the National Institute of Drug Abuse from the United States million dollars that are gonna be increasing the speed of development in this particular field of addiction in the next few years. There’s also studies with opioids.

Opioids, sorry.

Yes. There’s also some studies with opioids going on, particularly there’s one substance that is called Ivo, that is, looks very promising for opioid addiction treatment in Spain. There is a study with Ivo for long long consumers of methadone that were already made a transition among heroin to methadone, and now they want to stop methadone use.

And by taking doses of Ivo in, they can make that transition way easier and w with much more successfully, with really, really good preliminary results at the time, but also Psilocybin is being explored for this same indication for opioid due disorders and also with a Bren that is similar substitute to strong opioids like in the case of methadone was for, for heroin.

In, in the case of the spine study,

there’s also cocaine studies exploring the possibility of using psilocybin in particular to treating cocaine addiction with the same model as the one we were talking about, like interventions combined with psychotherapy that produce long-lasting effects and and sovereignty in many people like in death intoxication, sorry, this one for example, in University of Alabama, Birmingham.

And also there is some private companies that are developing these substances for, for medical use. Some of them are already in phase two clinical trials, meaning that they’re just one step before the medical authorization. Of course, the phase three is the most complex and long and expensive phase of the trial.

But it’s interesting to see that these treatments are proving efficacy and they’re proving safety. They just need to prove that they are they can be accessible for bigger populations and still being safe and being effective in bigger numbers. No, but for example, we have alcohol use disorder M D M A being explored for alcohol use disorder.

We have psilocybin for alcohol use disorder as well. D M T derive substances for opioid use disorder and another different substances, all of them like related with psychedelics. Of course, the thing when we’re talking about private development is, is that there is. Due regularly mark an interest in, in patentability.

So they try to look for versions of the substances that have some patentability potential, meaning that there might be same efficacy with classic psychedelics, but of course the market is not gonna be so much interested in these developments. They wanna want to have some capacity to have some patentability in the, in the, in the previous no, in the later, sorry market distribution of these substances.

Next, please. Just to tap in a little bit on the mechanisms. David not gave an amazing introduction to this. Just to say, to mention that in the case of addition treatment, we can find that the substances, that substances have three different levels of action in the brain. So first of all, we have neuronal level increasing, neuroplasticity making neurons Better, better reconnect with other neurons, making the, the, the brain more find more easy, the possibility of changing the pathways that has been very established by repetitive use of substances or repetitive behaviors that are in behavioral addictions.

Also, there is changes in the, at the level of the network, so at the level of the brain. So it reduces the AMY activation. You have a reduced in default mode network activation. There is an area of the brain that, that that is very important to deactivate in some mental problems like depression or addictions in this case because it helps to, to change the patterns in the brain.

It change, change this pathways that has been established through years and years of, of pathological consumption. It acts like a rust bottom, no as one once feature in the media. It’s a very interesting analogy. Also, there is this level of the. Of phenomenological experience. So the patient is subject to that allows them to have a new way to see the world, a new way to see the old problems that has been battling with in the, and trying to to treat this addiction.

And it also can bring this mystical experience an experience that can be very profoundly insightful and have long-lasting changes in the, in the way the person approach, the, the surroundings, the environment, the, the other people, these substances or these other addictions. Next one, please.

So why this psychedelic assisted therapist might have a promising future for treatment of substance use disorder? As we were mentioning before, they are looking pretty effective, at least with the sample sizes we’re having now. So we really need to explore this in bigger sample sizes, but we, we hope this is gonna be the next.

And it also looks like the effects are very long-lasting. Maybe not forever, but at least lasting enough to make the patient go back to a normal life for a certain period of time. That probably is gonna also help them to, to not go back to the same old habits. And all addictions that were in a problem in the beginning.

Also, they look that. They are very safe, at least in clinical settings because of course, outside of the clinical settings, we have less control over the variables of set setting, the purity of the substance, the preparation of the, of the participant. But in the case of clinical studies, we, we can have a very good control of these variables.

They are non-elective. They have a very low toxicity, and all these psychological risks that are often featured in media are quite manageable when the people, when the person is ready and and and is well monitored during the, the experience. Also, it looks that these substances could be very effective in the future for wider populations, for national health SY systems because we have lo lasting effects with a very small exposure.

We have those substances are cheap in general, and also they work for very debilitating and very incapacitating conditions because addiction is a very capitating condition. So if we have substances that have any, any effect on this condition we are having, we’re gonna have very big returns in quality of life, but also in, in, in social, I mean in work, working capacity of these individuals in taxes, in many other variables that can, that can give back a lot of the money that we may invest in the development of these new therapies.

please. So just a few conclusions and considerations for later the q and a that we will have and all the, all the sit chatting about this topic. I think this is a very big opportunity for European research and development and also implementation. We can have very big public health returns if we implement this new approaches fast.

And we have a, a good resource into the, the development of these substances and the, and the resource of the substances because a few doses of these substances under their supervision has have fast and lasting therapeutic effects. And since the traditional business model is not so much interested as at this point in the way this classic psychedelic may be working because there is this problem of the patent of substances that are very old and are natural in many cases, there is this need of a little bit more of public funding that maybe in other pharmaceutical areas is not as needed as in this one in particular.

this will never be, or at least it looks like it will never be a take home treatment. It’s a treatment that is gonna be given under supervision. It’s not gonna be sold in pharmacies, and it probably won’t will be sold only in specific clinical settings with a specific clinics and specific that have professionals that are used to it.

So meaning that the, the safety profile of the substances can be even increased by the way the substance could be given or delivered to the, to the patient. And this, the use of this partic, this specific therapies can also have great savings for the public health systems. So we’re taking chronic patients very expensive patients for the, for public health systems.

Also having major losses in life, quality variables. And we are helping them to transform into healthy subjects in a very fast In a very fast treatment intervention and with lasting results. So this is really, really worth it to be explored. This is really worth it to be founded and this is really worth it to be implemented in a future if things, if, if this clinical research still show us that the efficacy, the safety, and the efficiency are the ones that we are seeing so far in the clinical research.

Thank you.

[01:06:57] Frédéric Destrebecq: Thank you very much, Anton. And we’ve got a few questions coming in and I’m eager to to be able to address them in in our discussion afterwards, we complete this picture. I’d like to turn to from mare University and give us the light on psychedelic assisted therapies in in Neur. Over to you again.

[01:07:15] Jan Raemakers: Okay. Thank you very much. Can you hear me well? Like this? So psychedelic assisted therapy in neurological conditions. That’s a broad term I would say, and that would encompass neurodegenerative disorder like dementia or Alzheimer. But also chronic pain like headache or cluster headaches or fibromyalgia.

There hasn’t been a lot of work in this area, but still there is a confidence that psychedelics may actually be effective in this real as well. And I think there are two reasons for that. The first is the, the, the fact that we now know that psychedelics cause a neuroplasticity. So meaning there’s more interconnection between neuro.

And if there’s a repair of neurons in pathways that are involved in neurological disorders, then from that you could actually predict that, you know, from a physical repair there will be therapeutic efficacy. And second for most of the neurological conditions. There’s also the, the psychological component, it’s actually also very important I think, for example, about, about pain in general, right?

Pain thresholds differ between individuals. Some can take pain much better than others. So there’s a, a psychological component to it, how you, how you handle pain. And that is something that we now know we can actually address with a psychedelics as. . Next slide. Please. And this is not entirely new.

So again, referring to the old days back in the sixties and the, and the seventies, if you dive into the literature, you’ll find that, you know, within Europe, actually Italy to my surprise a little bit, but but also in the United States, there have been neurologists, psychiatrists that have been treating their patients with psychedelics.

And the diagnosis of the patients are varied a lot in, in terms of chronic pain. Either it could be migraine. Sometimes people were suffering from pain related to cancers or, or pain because they were in a terminally ill state. Phantom lymph pains have also been treated with with psychedelics in particular ls.

Because this was like the prime psychedelic back in the days that was under investigation. And here again, what has been reported in, in, in samples that, you know, sometimes were small like six, but sometimes very decent, like 380, and anything in between that that single doses of L s D varying in moderate doses to high doses could actually relieve the pain of patients quite dramatically on the day that people actually took a psychedelic.

But in some of the patients that. Efficacy actually lasted over time. So even three weeks later, there was a report on improvement in many of these patients. So this is a very yeah, interesting. And also you would say a stimulus to continue your research. But of course, that didn’t happen cause the un gathered in 1971, which stopped most of the research.

Next slide. Please. But that again, as or often is the case, you can prohibit drugs, but that doesn’t mean that people stop using drugs. And that is also the case with patients who suffer from pain, right? If they don’t receive any benefit from the traditional pain medication, they will look for other alternatives.

And that’s typically what chronic patients have been doing. Chronic patients, you know, from a, from a range of pain conditions. And the good thing about that is that you can, you can. Question them, right? You can set up surveys because you’re interested in what they use, how, what, what the dose that they use, how long they use, how they use it, and compare that subjective experience in terms of pain relief versus other conventional analgesic et that are on the market.

Because remember pain patients do not decide overnight to go for a psychedelic. They would’ve tried everything that’s already on the market. They could probably show you one or two slides with every compound that they’ve tried before they went on to, to psychedelic. So we set up a survey like this.

This is certainly not the only one. There are many more out there asking them how great the, the relief of pain when using a, a high dose or a microdose of a psychedelic a low dose of psychedelic, a microdose, and And how that related to when they used a conventional analgesic. So here you see this the result from that.

So typically the relief of pain would be highest when people took a high dose of, of psychedelic. That would be significantly better as compared to dose of psychedelic. But the lower dose will still be more efficient than taking a conventional compound. And with conventional compounds, I’m referring to insight, but also to opioids, but also, and also cannabis actually in that, was in that same category.

So this is a promising again, next slide. And but you know, if, if you read some of the old literature, people that were in internally ill state and who actually reported relief of pain. And then, and you would ask them, would you like to have another 200 milligram micrograms of lsd? They would often say no because they didn’t like the psychedelic state and they preferred not to go in there.

So one question that, that is really emerging in the field and that is very prominent and and relevant, I think, is whether you can actually replicate some of these analgesic effects with low, with doses that do not actually produce that hallucination. So leave the, sort of, leave out the psychedelic effects while still being active on a pharmacological basis.

So we were interested in this principle and we set up a study together with the Beckley Foundation where we invited healthy volunteers to go through four treatment conditions. So one was a placebo and, and the other three conditions, we gave them low doses. Of LSDs. So five, 10, and 20 micrograms.

And these, particularly five and 10 would be doses that would not be noticeable, right? You can take it you can drive a car, go to the groceries, go to work, right? There is no and nothing would notice and nobody would be able to tell that you are actually taking a microdose. So we asked them to come back to our lab in four days and we wanted to test whether they could bear pain better under L S D.

So we asked them to place their hand in a bucket of cold water, which is at a constant temperature of three degrees, which is pretty cold. And typically you can’t keep your hand in that cold bucket for a very long time. So we registered how many seconds people were able to keep their hand in the water.

And besides, and apart from that, you also have some subjective measures. Next slide. So here we are looking at the data in the left panel. In the left upper panel, there’s pain tolerance. So this is the number of seconds that people can stick their hand in the cold water, and we didn’t relative to the placebo.

So these are, these are the white bars. We did not notice any change after five and 10 micrograms, but we did notice that after 20 micrograms, people were able to keep their hand in the water for a longer time. And at that particular dose, we also those participants also reported that the, the feelings of pain were less unpleasant and also less painful.

So the object change in pain perception was also supported by a subjective change of, of pain. Next slide.

So, yeah, we also looked at whether at this these dose, there was really, really no no psychedelic of. Were people really not noticing that they were taking a psychedelic and well, there was some effect, but really, really very low that you particularly could see at the higher dose of 20 micrograms.

But again, there were very negligible, I would say. Next slide. What we did find and this isn’t this right, is that there was an increase in blood pressure at at anti dose, which is a well known fact for lsd. Nothing of clinical significance, nothing to worry about. It’s all very much within the normal range.

But we do know that the increments in blood pressure actually also correlate with with analgesic effects, with at times that, that’s related to the bio receptor reflex response. So with the regression model to find out whether some of these perceptual effects or the blood pressure changes actually contributed to some of these pain outcomes, and I did but they explained about 15% of the entire response.

So they probably contributed, but it’s not probably not the entire mechanism that we are looking for. And we know, for example, that the, the main receptor target five H two A is actually well prominent also in the pain pathways. So very much slightly that there will be a pharmacological mechanism as well.

Next slide. Yeah. So, but that’s in healthy volunteers. Well, it is a kind of proof of principle that shows that no, there is analgesic effect, that you can even find a low doses. But, but then, you know, we need to make this step to chronic patients. And there are not many studies out there at the moment.

We’ll, I’ll show you in a minute that there is a lot of interest in it, but so far the clinical data out there is scars and there are basically conducted by IMA in I shink at Yale University in the US who looked at migraine patients. So that’s the data that we’re looking at here. So they received a single dose of psilocybin of 10, 10 milligrams, which is not a high dose, it’s, it’s a moderate dose, I would say, in 12 people.

And relative to the baseline level and relative to the placebo treatment that they also went through, they reported that the number of days that they days per week, that, that have felt a migraine actually reduced after the single dose of psilocybin. And also the intensity of pain reduced similarly as, as was the, the functional impairment that they that they experience while doing day-to-day operation, work on the school, things like that.

So that is was really the very first indication. I believe that in chronic patients, showing that a low to moderate dose of psilocybin can be actually beneficial acutely, but also on the longer term, and that same group also published another study in cluster headache just a couple of weeks ago.

Next slide. So in, in a, in a small sample, I must say but people, so patient with cluster headaches and sometimes patients have cluster headaches that they experience you know, throughout an episode. But sometimes cluster headaches can be chronic. I’ve been talking to patients who, who, who, who tell that, you know, if they have a, a cycle of, of cluster headache, it’s hard to imagine.

But that can actually last for three months. And they would re, they would report that with, with the treatment of psilocybin, that can actually reduce the cycle to a number of weeks, like two or three weeks, which for them, of course, is an enor advantage. So these anecdotal data is all out there but the clinical data is still waiting to be gathered.

And this is the very first attempt in small, in small samples. So three patients that that went through a placebo condition and through a condition where they had cycles of psilocybin. So just about 10 milligrams, again, over a period of of a year. And what they reported on average is that there was a reduction in the number of attacks that they experienced.

So there, there was a, a reduction that was evident from the means, but if you put statistics on them this did not actually reach statistical significance. And you can actually see also when you look at the, the, the bars that are surrounding the means that are quite wide. So probably meaning that some benefited an auto state note which is what we expect.

But in order to be, to get a better understanding of who’s responding and who’s not, we need really larger sample sizes to conduct Saudi slight Next slide. . Yeah. So I looked at the, the American Registry of now what are people doing right in terms of psychedelics, which studies are ongoing?

And the pink line I thought, I thought I was comforting in a way that this actually, that represents like fundamental studies. So academia driven work that is just interesting in psychedelics looking at fundamental mechanisms of action and maybe also clinical responses. And then the yellow line is mood disorders.

And that also makes a lot of sense. Dave talked about it. This is really the studies that are paving the way and that’s also the area where the much more, the most progress has been made so far. But you see that as the blue line, so headache and also where Spain, that’s, oh, that the light blue line, these are actually there that are increasing and If you search the web, you’ll find that there are actually, I dunno, somewhere between five and 10 companies at the least that have an interest in, in this in pain as an indication and that are developing formulations of psychedelics in the treatment of these indications.

And they could focus on headache, but they would also focus on chronic pain such as neuropathic pains. So for example so I think the field is opening up. The interest is there. The basic pharmacology behind it is not complete, but it’s it’s promising. And yeah, I’m expecting that in the next five years there will much more studies coming up with with data in this field.

Next. . Yeah. And that brings me, I think, to my final slide. So I mean, there was a lot of challenges still ahead of us, I think in general for the psychedelic field, but in, in, in terms of chronic pain and neurological disorders, you know, we need a lot of clinical trials to begin with, right? And they need large sample sizes.

The, the other issue here is that, you know, can we, how, how we will we treat them? Do we need a single dose or do we need to repeat it? And if so, then, you know, is there, will there be tolerance developing which indications which do we have to go through a for a personalized route? Could, if, if.

Patients, they would develop their own way of treatment. And some would take 10 milligrams out of profit only from 20. So there’s a lot of variation in there. So I think tailoring to, to patient needs will be very important, particularly in this in this area. And of course mechanisms of actions, you know, always important and we need to understand them much better.

And then in the ver in the, in the very few, you know, how do we implement these psychedelics in our healthcare system? And that’s a problem that’s not new to neurological disorders, but I think this applies to the entire mental health fields. And with that, you know, I would like to thank you

[01:22:13] Frédéric Destrebecq: well maybe Jan to open the discussion and on that particular last word you had in your conclusion, what would be for you, the key challenge, but also the key solution in addressing this? Let’s say implementation issue. Yeah. Well, so the one, so we we’re talking a lot about psych psycho, like assisted therapy, right?

[01:22:32] Jan Raemakers: So the, the therapy is of course a very important aspect to some of the, the treatments and the indications. I think we should first have a discussion when the this assisted therapy is actually needed. So I could imagine it’s very, very important in the context of the treatment of PTSD and also depression, but it might be less important, for example, in the treatment of chronic pain.

So I think we have to first have to have this discussion to when these assisted therapies should be, should be used and should be implemented as part of the overall of therapy. And if we do, I think we also need to prepare our mental healthcare system for that novel situation. Because I think at, at least in the Netherlands, I know your CCA could talk about it.

The, the, the. The, the medical world is not prepared for a combined package where you just not only give a pill and treatment, but also have psych psychological assessments to go along with that. So that needs to be prepared, I think. Thank you.

[01:23:31] Frédéric Destrebecq: I, I really wanted to push that a little bit further because we are in the European Parliament.

It’s time to come up with a, a very concrete policy, ask to or host of today, but also his his colleagues. And I’d like to come back to, to Yon and to, to you, Dave, to you, I mean, do you share yas conclusions and what you’d be your views on that? On let’s say the readiness of our system in terms of the implementation of psychedelic assisted therapies?

Dave, you’d like to go first?

[01:23:58] David Nutt: Yeah, I, I, I mean, I, as a psychiatrist, I see. Psychedelics is kind of putting the soul back into psychiatry because that the fact we have now tools to facilitate what psychiatrists do as what, which, which is, I mean, all doctors do psychotherapy, but psychiatrists supposed to do it properly, professionally, and now with, with, with, with psychedelics, you know, there’s a really incentive to, to regain those skills and to, or even to expand them.

So I think it’s going to, it’s gonna be really extremely exciting times for Young Psycho. I think we’re going to, it’s gonna help. Recruitment into psychiatry because I think we have young psychiatrists will see that there’s a chance to be part of a, a, a new wave of intervention. So what we do need though is obviously an awful lot of education because currently they’re not being trained in this at all.

And you, you know, they’re learning about it on the side. And and the big challenge is getting their teachers, the trainers to accept that they want to, they want to learn and then pass the messages down.

[01:25:04] Anton Gomez-Escolar: I totally agree. When it comes to implementation, the biggest challenge is training. We need like all the healthcare people involving healthcare, especially psychiatrists, psychologists, they want to know about these therapies, how they work, what they’re talking about.

Because sometimes you hear this criticism for psychedelics talking about the possibility of no, I don’t want patients to be like taking psychedelics everywhere. No, no, no, no. Because this is gonna happen in a very controlled environment, and this is very important for people to know that it’s just single or very few posters in a controlled environment by a very trained therapist that has all the important variables set, setting preparation.

Under control. And that is where the success in the long term is gonna, is gonna be like in really controlled environments with, with a very good preparation, very good training. And I agree with David that now, like being a teacher in this is probably challenging because you are gonna have like this interest from new generation of psychiatrists, new generation of psychologists, new new generation of people working with with psychological part of the brain, everything that are gonna be very interested in, in, in, in psychedelics.

And we really need to fill that gap and, and to provide that training to the people that is gonna be the future the future professional, delivering these treatments to the, to the patients in need.

[01:26:15] Frédéric Destrebecq: Thank you. I’d like to repeat my call for any questions or, or comments in this part of the meeting, but I mean, as I don’t see anyone raising a hand or, yes Sergio.

Go ahead. .

[01:26:28] Sergio Pérez Rosal: Thank you. So thank you for, for your presentation as an anesthesiologist, I think that chronic pain patients all actually react better to treatment when it is in a multi-model form a at an exercising psychotherapeutic aid, and so on and so on. So I do believe that even for chronic pain yeah, framework of a apply psychedelics within a psychotherapeutic or psychiatric contracts would be necessary, or at least yeah, that’s what what we have in evidence without a psychedelics during chronic pain.

And the other thing that I was thinking about is about microdosing. I didn’t saw the, the, the question mark about the safety of microdosing, since we know that in, in uses cardiovascular activation of five h t two one receptors and two B receptors, which might lead to heart valve conditions that are irreparable.

[01:27:24] Jan Raemakers: So to start with the first question. So what, what we do see with, with any treatments of psychedelics is that at some point the initial effect were off, right? And then the patient is confronted with this question, how do I are auto means alternative means that I can use to sort of sustain the, the therapeutic effect that I, that I had.

And in, in terms of depression, people may turn to yoga, mindfulness, running, all kinds of things that, that, that sort of connect them to, to the response that they had in the beginning. And I think something similar could also work with neurological disorders such as pain. I think you gave some good examples of that.

There is some evidence indeed that there is particularly with lsd, there may some cardiac problems, even with microdosing. We don’t, we do not know how the, the, the frequency of that adverse events. And we don’t also, we also do not know how that actually will develop when people take it on a very frequent basis.

So I think, yes, there are some ground for worry there, and I think we need to monitor any complaint in that area. And but we need, we need long-term studies to, to get a better understanding of the actual magnitude or, or clinical relevance of that problem.

[01:28:35] Frédéric Destrebecq: Thank you, Jan. And Pedram, I would like to invite you to contribute to that part of the discussion.

We have a question in the chat actually, on the, the potential to launch a U P N Citizens Initiative. I won’t. Tale of of the technicalities of, of that process. But do you see there that from your perspective, there could be a kind of societally driven initiative to push for search options to be, to be made available?

What’s your, your point of view based on the discussion we just had for, you mean, you mean for psychedelic therapy to be available?

[01:29:05] Pedram Dara: I mean, yes, absolutely. I’m all for it. That’s probably why I’m here still. I, I think there’s massive potential, but I just think what’s missing the most is like, even here being in this room, I just feel like most of the attention goes to how you do this.

But really the voice of patient and the voice of participants still missing. Like, you know, like I feel like I spoke eight minutes and there’s two hours talk about everything else. And I think until we, we can include more of these voices and this leave the experiences and also the challenges really like, feel like with psychedelics we are so much focused on solution.

But I don’t think they actually understood the problem enough. And that’s one area that I’d like to see more. And the only way you do that is by doing qualitative research, by talking to people, by learning more about them and the cultural aspects of it. So very much missing in the current treatments.

[01:29:58] Frédéric Destrebecq: Okay. So actually, you, you are setting the agenda for the next para meeting in this in this house then? Yes, I would hope so. Yeah. , we need more of this. Absolutely. Yeah. No, absolutely. But I think, David, you, you mentioned ethical limitations in your in your presentation. I mean, from what Pedro is just saying is there anything you’d like to, to, to respond to that in terms of addressing the magnitude of the problem, if I understand correctly what you said?

[01:30:24] David Nutt: Yeah. But also being able to deliver on, on these kind of expectations. Well, I think the thing to say is we’re, we’re in quite an early stage and we’ve gone through and yet we’ve only been going for 10 years, really the modern field. And we’ve gone through a phase of enormous hope and hype and, and now there’s, there’s a lot of concerns as to whether there’s actually enough resources even to, to take perhaps any psychedelic through to, through to being sort of commissioned in a, in a, in a class as a regulated medicine.

So I, I’m absolutely with Petro and the, the, the driver hasn’t, is got to be more than just the, the, the traditional model of of make, of IP and, and, and, and commercialization and another patient voice is gonna be critical in, in making all resources available just so that the hope isn’t just, doesn’t disappear because it’s, because it doesn’t turn out to be satisfactory to, to companies.

And we know, I mean, you know, there are very, very few. Almost none of ’em, maybe none of the major pharma companies that still work in the brain space who are actually interested in psychedelic presence. And they’re the ones that do have a lot of resources. And if we can’t unlock those, we’ve gotta find other sources.

And, you know you know, maybe the EU is the, you know, that would be, you know, a fantastic opportunity for them to, to step up to that.

[01:31:50] Frédéric Destrebecq: Yeah. And the, we have another question in term of availability of those therapies and that maybe I’d, I’d like to, to jump in here practical question on how will Europe differ in terms of regulation and accessibility?

From the us, Asia, uk, Australia, any countries. Do you have a view on that?

[01:32:08] Tadeusz Hawrot: So I’ll start with one thing that we have in common. In common, that’s the how we approve these drugs, the regulation. You know, there is fda, there is ema. So they are kind of gatekeepers. Now, Europe is quite different from the states in that we are of course, very fragmented because countries have freedom to handle their healthcare delivery as they want.

And it results in huge access inequities. So we are first of all kind of we have to consider psychedelics in this wider context. What’s also different in Europe is that unlike the US one, where when the treatment, when the drug is being approved by a DA almost automatically you know, this will be somehow covered by, by private insurance.

In Europe, that’s not the case again I think In Italy, there will be eight out eight out of 10 of treatments approved by em. A will be available in Italy and in Romania, two out of 10 on average. So, huge differences again. So that’s another thing to keep in mind. And this also has to do of course, with the reimbursement landscape.

We have these complicated health technology assessment bodies which are looking at not just whether the intervention is safe and effic efficacious, but also they look at the value for money. So again, it’s a very fragmented light landscape. Every country has their own HTA machine. Luckily, the commission is working towards bringing these different assessments together through the pharmaceutical legislation that will be finalized in the next few years on the commission site through the hta directive from December, 2021 when the commission wants to create this coordination body bringing together representatives from member states.

So I think there are some real chances for us there to understand these processes and then to engage. And perhaps one idea that we have at Parra is us. This HTA collaboration at the U level is moving forward. We could have, so one of the collaboration schemes there is horizon scanning, and perhaps we could make a case to have psychedelic assisted therapies taken up as a, as a pilot by member states.

[01:34:24] Frédéric Destrebecq: Thank you ta. And I would like to, to really convey an apology because we need to, to bring this discussion and this event to, to a close. And I’m also conscious that me p Duda needs to also continuous day towards other meetings and other activities. And I’d like to to give him the opportunity to say a, a little word before having to leave and and before we run to the conclusion of of this meeting.

Thank you very much,

specialist.

Thank you. Thank you very much Mr. Duda. And actually it’s great to hear from you that the dialogue is taking shape and that we will have further opportunities to to engage into, into this. And something is really moving as of today. So I’m really pleased to turn to my colleague, co-chair of co vice chair should.

Of of pa Deirdre Ryan, who is the president of pen Alliance Europe for the concluding remarks of today, Deirdre over to you.

[01:36:56] Deirdre Ryan: Well, first of all, I’d like to take this moment to mark the milestone that is today and the initial support that we’ve already received from you, Emmy Pou. Thank you for that.

And from me, p Salma, who couldn’t be here today. We’ll look back in years to come and remember that we were all here. That these were the first steps that were taken in, introduced and psychedelic assisted therapies in Europe. We were before the FDA approval. We have the nod that the same will follow in the eu, and we have this unique opportunity to be ahead of the game.

We can see the tide that is coming. We know the unmet need. You can hear from all the research that was presented today that psychedelic assisted therapies are not only effective. They’re safe, but they’re efficient. But what we need to do in introducing this to a population is to develop the infrastructure for the highest quality, safe, affordable, and equitable access to these treatments so that they can benefit the greatest number of people in all conditions that involve mental health, chronic pain, neurological conditions, substance use disorders across the broad spectrum and the many areas that are un yet in not investigated that may benefit from these treatments.

So it’s so important. As we’ve mentioned today, regulators aren’t used to dealing with both the drug and the treatment. There’s infrastructure changes that need to happen at the EU level, and we need EU support. So that trickles down to the EU member states, and that’s why we have our appeal. You all have it in front of you, where we’ve detailed what it is that needs to happen to make sure that this becomes success.

Now, when we have the opportunity before things become introduced in America and we follow suit here, we have the chance to shape it ourselves. And it’s so important that this is a multi-stakeholder initiative, that the patients are central to this, that we ensure that their needs that are unmet at the moment are best represented by these treatments that we understand as petrin setting which patients.

The really best four. There’s so much yet to be discovered, but we need to do this in a safe and approachable way across Europe so that it’s not just in the top five countries, it’s also in Romania. And this fosters competitive clinical trials to boost EU based EU culture, EU funded research in this area to endorse these infrastructures and the structures that need to happen in healthcare, but also across other policy areas.

Health doesn’t only stay in health. There’s the whole societal impact. It affects how we work. It affects how we get to work. It affects the environment. It affects employment, it affects justice, it affects our security and our borders and how that impacts on our health. And it is multi policy area. And that is why we need the EU to lead on this.

And we are here saying we have the information, we have the energy, we know the need is there, so let’s do it. So in conclusion, the future is here. It may be disproportionate. We all have a part to play in moving forward. And may this be the catalyst, like psychedelic assisted therapies to shape the future.

Thank you.

Brilliant.

[01:40:52] Frédéric Destrebecq: And on this note, I’d like to bring the meeting to a close. And as it was said brilliantly by Dere the momentum is here, the time is right, and the dialogue is open. So please be in touch, convey any comment or questions to perk and will very happily respond. You know, the man now and whom to, to reach to.

Thank you to our virtual audience for staying with us. And also thank you again for host of today, the teams of assistance who have been really helpful. The interpreters the teams at Pen Alliance Europe, at the European Brain Council as well as Tarek and James for putting all of this together and see you at the next meeting.