 I'm Jo Neal, Professor of Psychopharmacology at the University of Manchester. I'm also Chair of Drug Sciences Medical Psychedelics Working Group and a trustee for Heroic Hearts UK. Drug Science is the UK's leading independent organisation providing evidence-based information about drugs. So we're all about education and research, but the ultimate aim of the working group is to enable patient access on the NHS. And this is a much needed medicine for people. So I am a scientist. I'm a drug discovery scientist. And I've worked all my career to develop better medicines for psychiatry. And this is through animal work. So it's very early stage drug discovery. And I've worked on many different illnesses. So it's modelling in the animals for addiction, for depression, for schizophrenia, for anxiety, OCD, for all the sort of significant mental disorders. And in all that time we have come nowhere. So we have not developed any new medicine or therapy through my work at least, that's made a difference to patients. And in fact the original medicines for psychiatry, so the original antidepressant and the original antipsychotic, the original mood stabilisers, they were discovered by serendipity, which is kind of typical of kind of drug discovery research. And that was in the 1950s. And we're still using medicines based on those today. So compared to cardiovascular medicine or cancer biology, really psychiatry has not come very far. And there is an enormous need for better treatments for mental health. We're in a mental health crisis. The COVID-19 pandemic has exacerbated that. And current treatments do not work well for people, particularly with severe mental health disorders, like severe depression, like post-traumatic stress disorder. Addictions, anorexia. These disorders are very hard to treat. And with the traditional antidepressants, for example, what we call the SSRIs, the selective serotonin reuptake inhibitors, a third of people do not respond at all. And they might try up to six different antidepressants and they're treatment resistant, then they're still not responding. A third of people will go into remission, but these are people who are not severely unwell. And a third of people have a response, but it doesn't last. And it costs the economy about 100 billion in the UK, and that's in terms of people not being able to work, lack of productivity, and as well all the kind of attempts at treatment. So psychedelic medicine is a complete paradigm shift, and it's a revolution in psychiatry, and it could not have come at a better time. And of course, this is not new. Indigenous people have known that psychedelics have healing powers. They've been using them for thousands of years in cannabis. So these are plant medicines. So we're talking about salicybin, a component of magic mushrooms. DMT, the active ingredient of ayahuasca, which comes from the banisteriopsis vine that grows in South America, and they brew this to make ayahuasca. And in fact, DMT has just been put through a clinical trial in London for severe depression, and the results are absolutely extraordinary. So it was a small trial, 35 people, but after two doses of DMT, 50% of people were in remission after 12 weeks. And that's not the kind of results that we get in psychiatry trials in drug discovery. In fact, these trials have been largely unsuccessful, the clinical trials for new drugs in psychiatry. And Big Pharma pulled out of this area 15 years ago, so there is no big industry working for new medicines for psychiatry. It's all smaller biotechs, universities. And that's, again, that's left patients bereft of new treatments. So again, psychedelics. The psychedelic industry is now booming, and many people who were working for traditional pharma are now working for these psychedelic companies, which is great because they are hugely experienced scientists and doctors. And of course LSD. So LSD was discovered by Albert Hoffman in 1938, quite well-known history now. He was working for Sandals, a big pharmaceutical company. They knew this was important, but they didn't know what to do with it. They didn't know what it would treat. So they handed it, it wasn't illegal in those days. They handed it out to psychiatrists, psychologists, anybody equipped to do studies. And there were over a thousand research publications before 1971 on LSD and its medicinal properties. So for addictions, Humphrey Osmond treated 2,000 people with substance use disorder with LSD, and he got a 45% abstinence rate. Alcoholics anonymous is seven. So extraordinarily beneficial for addictions, for tobacco addiction, for the existential anxiety and depression that occurs with a terminal diagnosis. There was a lot of work done in those days, and for neurological conditions as well. So for conditions like phantom limb pain. You know, this isn't completely new. There is a big literature on the medicinal benefits of psychedelics, but the counter-culture revolution appeared in the 60s. People like Timothy Leary wanting most people to take a psychedelic, the sort of tune in, drop out. The Nixon administration were fighting a war in Vietnam and they did not want people who would not, you know, the effect that psychedelics have in the brain on your subsequent behavior, connectedness to nature, empathy, connectedness to other people. That was not a mindset that the government wanted. So they ramped up the war on drugs in 1971, and they put psychedelics into schedule one of the UN Convention and made it a class A drug. Even though we know that they are relatively safe and, you know, compared to alcohol, if you do the David Knutz done the analysis, the multi-cranteer decision analysis of all drugs, alcohol is what causes the most harm to yourself and to society. Heroin crack cocaine. These are all relatively harmful drugs, but psychedelics really are causing very, very little harm to people or to society. In fact, as we know, they're likely to be beneficial to society. At this time, we need more connectedness to nature. There are four aspects of psychedelic medicine that I think is really important for people to understand. So they heal people. And in psychiatry, we don't do that. That's not a word we use. We give people a medicine that they have to take every day, and we manage their symptoms and enable them to kind of cope with having this illness. And actually, psychedelics heal people and they no longer meet the criteria for having that disorder. For example, in the MAPS trial, the Multidisciplinary Association for Psychedelic Studies, led by Rick Doblin, a phase three trial, that's a big trial for PTSD. PTSD is extremely difficult to treat. Psychiatrists really don't have much in the way of medicines to treat this. There's a lot of therapy needed. Lots of people don't respond. 67% of people after three doses of ecstasy of MDMA, which is also a psychedelic, no longer met the criteria for having PTSD. As with the DMT results, these results are absolutely extraordinary. And that is because of the way psychedelics work in the brain. The effects are extremely long-lasting. So after the three doses of ecstasy, people six months later were still well. I spoke to a combat veteran who took two doses of psilocybin in Amsterdam in hotel room. Not the way you should. We would suggest you do this. I spoke to him in January 2019. Sorry, he had his experience in January 2019. I spoke to him in August 2019 and he was still well. And he's now in medical school and I speak to him quite regularly and he hasn't used psilocybin again. So that experience, that encounter with a strong pharmacological agent, we know that they interact with the serotonin 2A receptor. We know that they increase the release of glutamate in the brain. The mechanism is complicated. The pharmacology is extremely complicated but very, very exciting. And what happens is that the brain is reset. So we know that they switch off the default mode network because the brain is divided into a series of networks and this is kind of the top-down control of the brain. So that is turned off while the psychedelic is on board in the system and this enables bits of the brain to communicate with each other, other networks that are kind of prevented from talking to each other and it produces ego dissolution and people come out of that with a completely different perspective on their own behaviour, on their own mental state and the reason that they became unwell, it's usually some kind of trauma, they're able to see that and actually able to forgive perpetrators and it is the most extraordinary healing experience for people. So that's one thing. The effects are very long-lasting because of that release of glutamate. What we see is neuroplasticity. So that's an increase in connections between the neurons and increase in synapses. So those are the connections between the neurons. So you see more synapses, you see enhanced connectivity and those effects are very long-lasting and that probably explains why the effects persist for so long. So this is a complete paradigm shift. If you take a medicine every day, you will have a large side effect burden. That's just how it's going to work and clinicians always have to balance the benefits versus the side effects. But if you take a medicine once or twice or maybe you need it once a year, sort of refresher for your brain and your behaviour, you completely avoid side effects. So it's a complete paradigm shift in how we think about mental illness and how we treat it. The other thing is that these medicines are remarkably safe. So the way they work, they don't have a lot of effects all over the body that lots of other drugs have. That makes them very safe. It's, of course, an extreme psychological experience. Ego death is very frightening for people. But in the clinical setting with the psychologists there, with a great deal of preparation and integration, so we talk about set and setting. So the person must be in the right mindset to do this. They must be mentally very prepared because it's a very intense experience and they must be in the right setting with the right people in the right environment. That's extremely important. And then because when you're undergoing the psychedelic experience, you can't make any sense of it. You're not in that position. You're just going through this, but it's afterwards that you need an awful lot of integration and help with a trained psychologist to help you make sense. But it might be a while, I spoke to a combat veteran last week, it took him five months after the experience to really start to see all the benefits for his own mental health and his own healing. And we have done some analysis on the pharmacology and how safe these medicines are. When you take them, you get an increase in blood pressure and heart rate because of the effects of the serotonin system on the blood vessels. So you get constriction of the blood vessels, but that doesn't last very long and that resolves pretty quickly after you've taken the drug. So unless you have a heart, a serious heart condition, you won't experience any, you're unlikely to experience any adverse effects. And what something we're interested in is the drug-drug interactions because at the moment for the clinical trials, people have to give up their antidepressant before they can take the psychedelic because they also work on the serotonin system and there's a potential of a drug interaction there. But actually in the small trials where they've investigated this, there is no adverse interaction. And there is a possibility that the presence of an antidepressant could reduce the impact of the psychedelic because of pharmacological competition. But in fact, that doesn't seem to happen either. That's something we need to do more work on. But of course, there are probably 130 at least clinical trials registered for psychedelics for a range of disorders. Psychedelics also have a powerful anti-inflammatory effect and Charles Nichols is the expert on this. That is a complicated mechanism but it seems to be an inhibition of TNF-alpha. One of the main cytokines, it's a pro-inflammatory cytokine. So that gives you the potential for treating inflammatory disorders. So inflammatory viral disorder, asthma disorders characterised by an increase in inflammation and those are very difficult disorders to treat as well. So as well as psychiatric conditions, psychedelics have the potential to treat peripheral disorders like I said, inflammatory diseases. But also neurological conditions. There were a lot of studies done on LSD and pain seems to be remarkably effective at reducing pain and in some studies, more effective than opiates. Cluster headache is a condition they call suicide headaches and these are excruciating pain that come and go throughout your life and they can last for days or hours and psychedelics seem to have a beneficial effect on these and at the moment there's nothing to treat that. So the message really is that psychedelic medicine can heal people. The relatively few side effects, the side effect burden is very minimal because you don't take them very often. They're relatively safe. I mean no drug is completely safe without risks. It's an intense psychological experience for sure so people need to be ready for that and of course it's all about dose so nobody should be taking too much of anything. As a pharmacologist that's a really important message for people. You shouldn't take too much or too often. But the law is making it very difficult for people like me who want to research it in the lab, people who want to do clinical trials because it's in schedule one of the UN Convention. So the definition of a schedule one drug is no therapeutic indication. UK university academics and NHS scientists, clinicians have an exemption from the UK government to work with all schedule two drugs or drugs in lower schedule. And these are potentially far more harmful. So drugs like heroin, cocaine, amphetamine, fencycline, ketamine, these are all in schedule two. So I can use these experiments to do science with these drugs without needing any special permission from the UK government. But as soon as I want to work on some cannabis products or a psychedelic, I need to apply to our UK government for a controlled drugs license. And that's bureaucratic, it's time consuming, it costs a great deal of money. There are great time delays because the home office are understaffed and that is stopping people doing research. So I was doing an animal study with Silo Saiban and it took me a year to get my controlled drugs license. One of the concerns about psychedelic assisted psychotherapies that the price is quite high, it costs a lot because of the working hours for psychotherapists and all this stuff. How can we make sure that it will be mainstreamed or it will be accessible and available for the general public and also for the not so middle-classish people? Absolutely, because at the moment ketamine treatment is available in the UK and that's for severe depression and that has been shown to have good effects for people. £8,000, you can only go to a private clinic. So the government must fund the NHS and they must support the NHS to deliver this therapy. But the companies that are developing these medicines are potentially going to make a lot of profit. They also have to work with the NHS and enable this to be provided. We need training for psychotherapists. We're going to need a lot more and clinicians. So this must be a unified effort and it must come from the top. This has to come from the government. I know some of the companies are committed to reciprocity. That is kind of giving back to Indigenous people as well because these medicines have been used by them. We must protect where these medicines come from. You know, Peru and there is, of course, a psychedelic tourism industry building up, which is not particularly helpful and ethically, potentially not very desirable. But we must enable this to happen. Economically, though, the figures should stack up. We have done an economic analysis of psychedelic assisted therapy compared to antidepressant treatment as usual. Of course, antidepressant drugs are very cheap because they're off-patent now. But because they don't work very well, there are so many people that are not in work that psychedelic assisted therapy, because it heals people, it enables them to contribute and function in society. So the figures do stack up, but actually at the moment, because it costs so much to run a trial, psychedelic assisted therapy is very expensive. One way to reduce the cost for the NHS is to have group therapy. And I think there are certain groups of people or types of patients who would prefer that. Certainly the combat veterans for that, it seems to suit them to go together. They have the same experience of Afghanistan, of Iraq. And that camaraderie that they had when they were at war, that's something that seems to be part of the healing process for them. But I think for many people, it's very important to have that group support. So that could reduce a therapist's time because you wouldn't need a therapist for every person. The other thing is the group integration. And I know that that has happened, that has been a patient-led development after some of the clinical trials. So that and peer-led support groups, I think that works very well for people. You want to discuss your experience with somebody who's had a similar experience and has maybe had a similar mental health issue to begin with. So there are lots of ways that we can reduce the cost. It's not just one person in a room for eight hours, psilocybin-assisted therapy with a clinician and a psychotherapist and then one-on-one psychotherapy for six months later. There are many, many ways that patients can lead on this. And actually that will reduce the cost. The other way is to use a shorter acting psychedelic like DMT. So the small pharma trial that I explained at the beginning, the results were... I mean, the chief medical officer running the trial did not expect the results to be as good, and I didn't. The results are absolutely extraordinary. Of course, we need bigger, bigger trials to confirm the results. That's a very short-acting psychedelic and they were giving it IV. So it's in and out of your system very quick. The whole experience probably takes about an hour. So you don't need to have somebody in the clinic for so long, although, well, you will need to keep them in to make sure that they are okay. It's quite a... It's potentially a much more intensive experience than psilocybin. But you won't need to have them in a room with one or two fully qualified practitioners for eight hours. So that's another way that we could potentially reduce the cost is having different psychedelics that don't last so long. Of course, there's interest in healing without the psychedelic experience, but I think that for some conditions for sure, for neurology, for inflammatory diseases, but for severe mental health, I don't really see that coming. But I know there are companies developing those drugs. What do you think about those efforts in the pharmaceutical industry that try to kind of reduce the experience itself and increase the neuroplasticity? Is it possible to have psychedelic medications minus the trip? Yes. Oh, yeah, the pharmacology is there. We probably understand enough about the neuroplasticity to be able to... or certainly reduce the psychedelic experience, I think. You're probably moving away from the 2A receptors that they do activate. I think it's a little way off, but the technology is there. And I know there are companies working on third-generation psychedelics that will have the neuroplasticity effects or will have the neurological... the anti-inflammatory effects for sure. I don't know about... I mean, neuroplasticity can be beneficial, I think, for people without that psychedelic experience. But for trauma, for addictions, for severe depression, I think the psychedelic experience is what really is working for people. Is there a lot of suspicion or negativity among how public health professionals in the UK if it comes to psychedelics? I think that's lessening. So psychedelics are massively stigmatized by the press, and they have been up until probably the last five years. But now there's probably an article in the papers or a documentary. Quite regularly, David Knutt will be interviewed some of the experts, Rick Doblin. HBO have got a series of Netflix, Michael Pollan. So certainly the public opinion is shifting. We conducted Up Drug Science, a YouGov survey. So that in the UK is all demographic. So it's people who voted Brexit, Remain, Labour, Tory, all over the UK geographically. And 55% of people supported bringing in psychedelic assisted therapy. 60% of people said that they would consider it if they were mentally very unwell. 68% of people wanted to see this coming in for people with a terminal diagnosis. And I think it was about 60% for combat veterans as well. So that shows you... What was interesting was that the people who didn't want to see it coming in were people who'd had bad trips and bad experiences themselves. And you can understand why they're very nervous about it coming in. You know, we need to be very careful. For the clinical trials, people are assessed extremely carefully. And many people don't get into a trial. So we need to be extremely careful. There'll be some people who really should not. People with a risk of psychosis, family history should not. Which is sad because the drugs for schizophrenia and psychosis have a heavy side effect burden. So healthcare professionals is an interesting one. When I speak to... Well, not being a clinician, I don't speak to them so much. Again, I think the situation is changing and people are becoming more accepting. But we've still a long way to go. I think the older guys who were there in the beginning in the 60s and remember all the research that was being conducted. And I think the younger clinicians are very receptive. But my understanding it's the sort of middle age who have, of course, been indoctrinated in a way. Drugs are bad. Psychedelics make you lose your mind and do crazy things. Cannabis is bad. We'll give you psychosis. None of those things are true. So it's really about education. Psychedelics are also used outside of the medical realm by traditional healers or different kinds of communities. What do you think about that? How should the government regulate that if it should? Well, all governments are doing this in their own way, I think. And countries are doing this differently. So in the States, quite a few cities have decriminalized psychedelics. I mean, there should never be a class A drug. That's just crazy. We should at least... These are plant medicines. They're used for personal healing. And people should be allowed to do that safely. And our current drug laws are making it dangerous and difficult for people. People should not be in fear of making their own mental health better. And they should be able to access really evidence-based information. This should be publicly available for people. So in Alberta, they have legalized psychedelic assisted therapy. In Oregon, it is legal in the state. There are a couple of Colorado have voted to do this. Of course, Australia have just voted to do this as well, to legalize MDMA and psilocybin for assisted therapy. But we need to keep practitioners safe. We need to keep people who want to use these plants. I mean, psilocybin mushrooms grow all around us. Many, many people use these, drive them. You can buy spores. It's not illegal, as far as I understand it, to buy spores and preparing them. Then it's, of course, illegal. People should be allowed to do this. And if we change our laws, at least to decriminalize psychedelics. But we should state-regulate them. People should be allowed to buy them safely and use them safely. And to access good information and to access support. Because people who are using them for their own personal well-being How can we make sure that it is not charlatans who are kind of abusing these substances and abusing the naivety of some people? I mean, that is a very good question. And even in the trials there have been some, people are very vulnerable when they're in a psychedelic, having a psychedelic experience. And people have been taken advantage of. And on retreat centers as well. We're all responsible. Everybody who's involved in this field, I think, personal practitioners, people running clinical trials. Companies making these medicines because some companies will grow the product. But I think as it starts to become more widely available, it will not be sustainable and companies will be synthesizing. The companies have a big responsibility to indigenous people to give back to the people who are the experts. I don't know how we keep everybody safe. I don't know how you have a register, I think, of people who are qualified to practice in this area. We need more training. We'll have to have more experienced practitioners. My understanding is that the Scottish government, the Scottish government do have some independence and they do have some autonomy over their own constitution from Westminster, which is a very good thing. My understanding is that they have control of their own health system. And this is a health issue. So there will be ways that the Scottish government can approve... I don't know whether they can approve this as a medicine without going to Westminster. Certainly the police can de-prioritize for sure and can decriminalize without going through Westminster. The police commissioner is my understanding. But I think with the Scottish government having control of their own health system, they can probably enable this to happen sooner in Scotland. I mean, that is my hope, but I don't understand Scottish law well enough. The MSPs, though, can lobby Westminster and they need to be very proactive in getting the laws changed because minimum we need to reschedule, we need to decriminalize and we need to bring in psychedelic assisted therapy. People in the UK are dying. We have the highest rate of drug-related deaths in Europe. It's particularly high in Scotland. People need a medicine for addiction and severe people are killing themselves. Combat veterans kill themselves. Far more combat veterans kill themselves after combat than ever died in the wars. We need medicine that will help these people and we know from the trials and from the work that went on before in 1971 and from Indigenous people. We know a lot about these medicines. It's not like bringing a new drug onto the market. That's what's so exciting for me. We have so much information, medically, scientifically, personal use from people. We have a lot of people who use these drugs for their own spirituality, for their own wellbeing. It should be so much easier to bring this into practice than a new chemical entity, which, as I told you about at the beginning, I've spent all my life trying to get them into patients and we've never succeeded. I've worked on a drug that started in Glaxo and I worked on it for probably 10 years. This drug is probably 30 years old now and it's far too slow, people are dying. So I would like to think that Scotland, because they do have some control of their own constitution and their own laws, they should be leading the way on this and telling Westminster how to do this and I think they badly need to do this.