The Peter Attia Drive - #182 - David Nutt： Psychedelics & Recreational Drugs

00:00:00.000 Hey, everyone. Welcome to the drive podcast. I'm your host, Peter Atiyah. This podcast,

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00:00:41.320 now, head over to peteratiyahmd.com forward slash subscribe. Now, without further delay,

00:00:47.740 here's today's episode. My guest this week is professor David Nutt. David is a psychiatrist

00:00:54.420 and a neuroscientist who studies medicine at Downing College, Cambridge. And he completed

00:00:58.940 his clinical training at Guy's College in central London. David's had a lifelong interest in the

00:01:03.400 brain. And we discussed that in his path to where he is today. In particular, we focus on molecules,

00:01:09.620 molecules that affect the brain. And we break this into drugs of all sorts, but go through it in a

00:01:14.820 framework that David has been an advocate of and proposed, which looks at the risk of harm to the

00:01:21.100 individual, by the use of drugs, the risk to society, and the potential for addiction. And we

00:01:26.320 get into quite a bit of nuance around this. And we really cover a broad range of drugs. And I find

00:01:31.540 this to be a very helpful discussion because it's rather than just being sort of a moral discussion

00:01:35.480 of drugs, it actually gets into the neurobiology of them. And of course, the risks. But the real focus

00:01:40.840 of this discussion is actually around a class of drugs that many of you are well aware of and have a

00:01:45.800 growing interest in, which are these drugs referred to as psychedelics. And more broadly,

00:01:49.700 really, we get into not just psychedelics, but at least in the classical sense, such as psilocybin

00:01:54.160 and LSD. But we talk more broadly about empathogens, dissociative agents, and even atypical

00:01:59.980 psychedelics. So the only thing I'll say about this episode that kind of bummed me out is because

00:02:05.360 David had a hard stop, we were not able to go as long as either of us would have liked. So I can say

00:02:12.260 without reservation that this will be part one of more. When that second part will be, I'm not sure.

00:02:18.260 But please be patient with us as I accept the fact that we probably only covered about a third to a

00:02:23.740 half of the content that we wanted to get into. And my hope is that this whets your appetite for what

00:02:28.500 will be a part two and potentially a part three. So as you're listening to this, keep us posted of

00:02:32.740 your thoughts and what you would like us to go deeper in the next time. Because as I said, there's

00:02:36.740 pretty much no question in my mind, we will go into that. So without further delay,

00:02:40.600 please enjoy my conversation with David Nutt.

00:02:48.240 Hey David, thank you so much for making time in your evening, my afternoon here today. Very,

00:02:53.360 very much looking forward to speaking with you about a topic that I think is on a lot of people's

00:02:57.280 minds lately. Well, thanks for the invite. I'm looking forward to it too.

00:03:01.340 Let's start a little bit with your background. It sounds like based on what I've read,

00:03:04.960 going back to your early teen years, you've always had an interest in the brain,

00:03:08.800 whether it be through the lens of neuroscience or psychiatry. What do you think sparked that

00:03:12.720 interest? Well, thinking about things, I guess it was an understanding that when I was probably

00:03:18.720 four or five, I suddenly kind of realized that actually thinking was what actually made things

00:03:23.680 make sense. And then I realized that thinking came out of the brain. And I've always been fascinated

00:03:28.460 by the brain. And actually, I went to university to Cambridge to do brain science. I wanted to be a

00:03:33.260 physiologist, you know, like Hodgkin and Huxley to do physiology. And then I kind of realized

00:03:38.740 that some single cells are interesting, but you've got to put the 200 billion together and

00:03:45.340 make sense of those. And actually, that's where then I did neurology. And that got a little bit

00:03:49.920 boring, because it's mostly people kind of dying slowly from diseases like a myotrophic lateral

00:03:54.800 sclerosis. So then I moved to psychiatry. And then it became really wonderful, because you see every

00:04:00.360 aspect of the brain in psychiatry.

00:04:01.820 Well, it's so funny you say that, because I'm not making this up. But this morning,

00:04:06.600 my six-year-old son was in my office. And we were sort of fumbling around. And I have a whole

00:04:12.540 bunch of racing helmets in my office. And so he's putting them on. And that got him talking about

00:04:16.860 why we're wearing helmets to protect the brain and blah, blah, blah, blah. And then I said, well,

00:04:21.300 you want to see what, well, he said, what does a brain look like? So I pulled up, you know,

00:04:24.420 on Google, I pulled up some images of brains, but actual anatomic images. Again, he's only six,

00:04:29.460 but he's looking at this. And he's thinking, like, that's very unimpressive. And he sort of says,

00:04:34.920 it just looks like a slimy thing. And I said, yep, that's true. That's what it looks like. And

00:04:40.200 he says, but is this where my thoughts come from? And I said, yes, that's where your thoughts

00:04:46.840 originate. And he said, well, how? And I got to tell you, it was very difficult for me to explain

00:04:52.640 how electrical impulses work. And of course, I'm not going to get into action potentials and

00:04:56.740 neurotransmitters. But what's funny is it then took me down a rabbit hole of spending 30 minutes

00:05:01.600 on YouTube, trying to find good videos of this for kids. And if anybody can find one,

00:05:07.600 please send it. But I couldn't find great videos because the videos that I found were more anatomic,

00:05:12.920 like this is the part of your brain that controls movement. This is where memories are stored.

00:05:17.620 But he was asking a deeper question, which was, how does this blob make me think? Which it sounds

00:05:24.920 like you were asking that same question as a four or five-year-old.

00:05:27.980 But what's amusing, even more amusing, is my new book, which is coming out later this year,

00:05:32.840 is called Brain and Mind Made Simple. It won't be simple enough for a six-year-old unless he's very

00:05:38.420 precocious. But I have written a book for the general public to try to explain this peculiar

00:05:44.480 phenomenon that how lots and lots of single nerves can actually turn into all the complexity of

00:05:50.740 the different forms of consciousness and the different experiences that humans have.

00:05:55.900 And at some point, and I think the point you raised is a really good one, it'd be really

00:05:59.640 nice to then migrate that down for children, maybe as a series of comics or graphics.

00:06:07.740 Because I think, I mean, it is the most wonderful thing in the universe, the human brain.

00:06:12.020 There's no argument about it. So let's get communicating as soon as we can.

00:06:15.360 Yeah. And I do think that, like for me personally, it's not a question I ever contemplated early. So

00:06:22.520 it made me very happy that he was asking this question at the age of six in a deep enough way.

00:06:28.620 And look, even if the book is not written for a six-year-old, I'm sure it will help me do a better

00:06:33.660 job explaining it to a six-year-old. So coming back to your career, so now you've migrated into

00:06:37.920 psychiatry, which of course, on some levels is really about understanding pathology of the mind,

00:06:43.240 which is effectively what all parts of medicine are, whether it be neurology or otherwise.

00:06:47.920 What were some of the first things that stuck out to you about the pathology of the mind through

00:06:52.860 the lens of a psychiatrist?

00:06:55.740 Well, the first patient I saw, who I was dropped into, a doctor didn't turn up. I'm a medical student.

00:07:04.180 So I said, oh, please go and interview, go and clerk this new patient. So I'm sitting there,

00:07:10.420 I'm talking to this person who's not making any sense whatsoever, and kept talking about

00:07:15.180 there being a smell of fish in the room and rambling on about the smell. And after about

00:07:19.780 an hour of trying to get some sense, I say, well, thank you, I'll just, I'll be back in

00:07:23.860 a minute. And I go out and I talk to the consultant. And he says, oh, well, he's clearly psychotic.

00:07:30.120 And I said, oh, that makes a lot of sense. That's why he doesn't make sense. And that's

00:07:34.520 why I didn't understand what was going on.

00:07:36.000 So, and what was very interesting actually about that is that the relationship between

00:07:41.880 temporal lobe disorders, those parts of the brain, which are intimately involved in aspects

00:07:46.860 of consciousness and also smell. And there was this peculiar overlap between temporal lobe

00:07:51.680 disorders where you can be psychotic, but you also have these olfactory hallucinations.

00:07:57.020 And that's what he had. So he was hallucinating rather than in his ears, which most people with

00:08:01.160 schizophrenia do, he was, he was hallucinating in terms of smell. So yeah, I've never forgotten

00:08:06.140 that because it was just such a kind of completely bizarre experience. And it, and it made me realize

00:08:11.680 I got a lot to learn, you know.

00:08:13.660 Now, for most people, when they go into psychiatry, and I'm sure this was the case with you, you spend

00:08:18.140 a lot of time learning the neuropharmacology of the agents that are going to be used to help

00:08:23.500 treat patients with psychiatric illness. And for many people, that's sort of where it stops.

00:08:28.040 But you've also generated or developed this other interest, which is in the

00:08:32.820 neuropharmacology of these regulated substances, you know, call them illegal or recreational drugs

00:08:38.720 and otherwise. Where did that interest stem from?

00:08:41.680 Wow. Well, so yes, I am a professor of neuropsychopharmacology at Imperial College London.

00:08:49.240 And neuropsychopharmacology is really the use of drugs to study the brain and to study the effects of

00:08:56.820 of treatments for brain disorders, particularly in the case of psychiatry, psychotropic drugs.

00:09:02.520 My PhD was on the GABA system, on drugs manipulating the GABA system. As an undergraduate, I think,

00:09:08.280 you know, the big influence on me, I was extraordinarily fortunate. So I'm at university

00:09:12.360 in Cambridge in the 19, early 1970s, when people are discovering that the brain is a chemical organ.

00:09:20.960 Up to that point, it was thought the brain was an electrical organ. Yeah, it was like a very

00:09:26.540 complicated computer or, you know, some kind of complex telephone exchange. But then the concept

00:09:33.220 of chemical transmission came along. And now we know that there are at least 80 different chemicals,

00:09:40.160 neurotransmitters, hormones, neurohormones. And seeing that transformation from electricity to

00:09:45.580 chemistry made me realize, you know, the way you study the brain now is through drugs which affect

00:09:51.820 the chemistry of the brain. And then there are these therapeutic agents, which are obviously very

00:09:56.240 important, antidepressants, antipsychotics, anticonvulsants. But then it raises the next

00:10:01.720 question, you know, but people use other drugs to change the brain. And they use them recreationally

00:10:06.780 for, you know, like drugs like cocaine or crystal meth, or they use them to deaden pain or to get

00:10:12.200 insights like psychedelics. After a while, because I've done so much research on drugs, I was asked by

00:10:17.000 the British government to help them think through drug policy. Well, actually, that was that was not

00:10:22.160 true. They asked me to help them justify drug policy. But when I started working for them, I realized that

00:10:29.100 the drug policy wasn't in any way evidence based. And when I tried to bring evidence to bear on drug

00:10:34.780 policy, they sacked me because it's much more convenient to have a political decision making about

00:10:42.040 drugs than it is to have an evidence based one. What year was that that you got involved in that?

00:10:47.980 Well, I started working on the principles of assessing drug harms really back in the 1990s. And

00:10:55.280 it actually came with the rise of ecstasy. And people supposedly were seemingly getting harm from

00:11:00.800 ecstasy. And I was one of the experts who was asked by the government to come up with a policy which

00:11:05.880 would reduce the harms from ecstasy. And it became very clear when we were researching those,

00:11:12.720 that the harms of ecstasy aren't from the drug at all. They're actually from what you do when you're

00:11:18.360 on the drug. They're either from the fact you dehydrate because you dance all night, or you get

00:11:23.280 hypothermic because you're in an environment where you can't cool down. And so we said, and actually,

00:11:28.240 we brought in what in legislation in Britain, which said any club which is serving drinks,

00:11:33.820 which is where most people were going to have their ecstasy, they're going to clubs,

00:11:37.480 they must serve free water. Because what the clubs were doing were actually forcing people to drink

00:11:42.760 alcohol or pay for water in order to get hydrated after using ecstasy. And in fact, they were doing

00:11:49.920 worse. They were turning off the taps. They were even turning off the toilet so people couldn't drink

00:11:53.880 water. So we made it law that people had to get access to water. And we also recommended a good

00:12:00.680 policy would be to have chill out rooms. And of course, a lot of clubs do have chill out rooms.

00:12:03.820 And those two simple environmental approaches, effectively, very, very few deaths from ecstasy

00:12:10.520 since then, until we got to the modern day when a variety of international policies have now made

00:12:16.740 ecstasy considerably more harmful than it used to be. How much did this coincide with or follow in

00:12:22.000 lockstep with drug policy in the United States, which really seemed to get a real boost in the arm

00:12:27.100 in the early 80s? Was the UK leading or following? Oh, every country in the world follows you.

00:12:33.820 The United Nations is, and probably still is, paid for by the US. And it does what the US

00:12:40.520 tells them. Every single British drug law until 2016 was made at the behest of the Americans. 0.84

00:12:48.600 So, you know, America basically, you know, they say America sneezes, the world catches cold.

00:12:53.120 America defined drug policy. It started in 1934 with the attack on, you know, the liberalization of

00:12:59.080 drinking and the attack on cannabis. And it continued. And I mean, of course, the big inflection

00:13:03.780 was when Nixon decided that the war on drugs was actually a better vote getter than the war in

00:13:09.720 Vietnam. So he switched people's attention to drugs. And the world has been fighting a war on drugs,

00:13:14.820 largely funded, but certainly politically driven by America since then.

00:13:18.060 So let's talk a little bit about the framework through which one can think about drugs. I'm a

00:13:23.740 framework junkie. Everything I think about, whether it's how to order dinner, comes down to

00:13:28.280 sort of a framework. Some parameters that people might think of, how harmful is this? And again,

00:13:33.740 you know, I think the goal of frameworks is to have them be as unemotional as possible

00:13:37.460 and to have them whenever possible to be objective. So how harmful is something would be part of it.

00:13:43.800 How addictive is something? What's the physiologic dependence? And then even within harm, you could

00:13:50.600 sort of talk about the harm to the individual and then the harm to society as that individual acts.

00:13:56.600 Are there any other things you would include or do those three things largely encompass

00:14:00.080 what you think of as a good way to think about molecules?

00:14:05.340 That is quite a succinct way. So I started off with something somewhat similar to that.

00:14:10.800 But more recently, we've developed what's called multi-criteria decision analysis.

00:14:16.420 And it turns out actually there are 16 different ways in which drugs can do harm.

00:14:21.900 There are nine harms to the user and there are seven harms to society. And the societal harms range

00:14:28.200 from international damage, you know, like the US spraying Agent Orange in Colombia to kill

00:14:34.820 to kill cocoa plants, through to economic damage, through to health costs, through to damage to families, etc.

00:14:43.660 So there's seven harms to society and nine harms to the user. And each of those can, you can scale drugs

00:14:50.240 on each of those 16 scales of parameters of harm. And if you do all that and pull it all together

00:14:55.580 and then do a weighting, because obviously not every single one of those scales is equally important.

00:15:01.340 If you do all that, then you can actually very, very transparently and very reliably rate the harms

00:15:10.400 of different drugs. And we've used this procedure in Britain. We've used it in Europe and most recently

00:15:16.400 in Australia. And pretty much all the drugs always rank the same in all those, you know,

00:15:21.980 there's three sort of groups of Western jurisdictions.

00:15:25.560 So based on that type of a framework, what are the drugs that consistently come to the top of the list

00:15:31.460 in terms of harm, aggregate harm?

00:15:34.840 So the most harmful drug overall in all in Europe, in Britain, in Australia is alcohol.

00:15:41.140 And alcohol is the most harmful drug because it has way more social impact, more harms to others

00:15:47.480 than any other drug. And that, of course, is because it's much more widely used.

00:15:52.680 You know, 80% of American adults and British adults drink alcohol.

00:15:56.740 Pretty much every family in your country and my country knows someone that's been harmed by alcohol,

00:16:02.260 either through themselves getting in difficulties, having accidents, getting addicted,

00:16:07.000 or they've been harmed by other ones, someone who's drunk or drunk driver or someone who's drunk and violent.

00:16:12.040 But if you look at the harm to the user, alcohol is not number one, alcohol is about number four.

00:16:17.540 The drugs which are really harmful to the user are opiates, crack cocaine, and also crystal meth.

00:16:25.500 That's super interesting, right? Because those drugs have very different scheduling.

00:16:31.180 So heroin would be a schedule one drug, correct?

00:16:35.460 Cocaine would be a schedule two drug.

00:16:37.800 I guess crystal meth would be schedule one or would it be schedule two?

00:16:42.520 I'm not sure. In Britain, it's one, but I think I'm not sure in the US, to be honest.

00:16:47.640 And then, of course, alcohol is not even scheduled in that sense.

00:16:51.040 It's regulated only by the age at which you can legally consume it.

00:16:54.660 And also by taxation.

00:16:56.560 Right. So what we didn't talk about was tobacco. Does tobacco fit into this framework?

00:17:01.840 Yeah, tobacco, yeah. We always do tobacco because tobacco is...

00:17:05.900 This is an interesting paradox. When we first did this, tobacco came out at about number six or seventh.

00:17:11.280 And the tobacco, anti-tobacco brigade got very agitated.

00:17:14.060 They say it is the most harmful drug because it kills more people.

00:17:18.220 And we said, yeah, but that's right. It kills more people. 0.92

00:17:20.420 But they often die in their 50s and 60s.

00:17:23.280 Alcohol is killing people in their 20s.

00:17:25.120 And that's more important, we think.

00:17:26.820 Our valuation was that the harms of alcohol are considerably greater than the harms of tobacco.

00:17:32.480 And I think most people would agree that tobacco does, in the end, kill half of the people who smoke.

00:17:37.680 But it does it later in life.

00:17:39.460 And tobacco also causes relatively little damage to other people, unlike alcohol.

00:17:44.300 I mean, this is such an interesting question, and I don't even know how one would think about it, because you could also take the flip side, which is there's probably nobody who's benefited from tobacco.

00:17:55.740 I shouldn't say that.

00:17:56.660 There is a benefit to tobacco, which is that probably it helps some people calm down.

00:18:00.740 It probably helps cope with nerves.

00:18:02.080 But there's no moderate use of tobacco, like smoking only 10 cigarettes a day is protective, or the harm doesn't really kick in until you're at a pack a day.

00:18:12.340 No, that's not really true.

00:18:14.000 Any amount of tobacco is going to take some toll on your pulmonary system and your cardiovascular system.

00:18:20.780 Alcohol, conversely, you could say, well, look, a person who drinks responsibly, who has three drinks a week, bears no cost of the consumption of alcohol from a relative standpoint.

00:18:31.560 I mean, we could debate that.

00:18:32.700 I would argue that there's no dose of alcohol that's healthy, but there are probably doses that don't rise to the level of toxicity.

00:18:39.680 Yet, to your point, it's much easier to cross the line into acute toxicity, which also gets to another challenge here.

00:18:47.260 Tobacco has no acute toxicity.

00:18:49.320 It's 100% chronic toxicity.

00:18:51.300 Alcohol has both acute toxicity and chronic toxicity.

00:18:54.560 And it's that acute toxicity that results in incredible loss of life, both to the individual and to society.

00:19:02.260 Yes.

00:19:02.760 Does the framework allow you to measure these things?

00:19:06.040 Yes, it does.

00:19:06.660 Yes.

00:19:06.860 We can give you absolute ratings and rankings on both of those variables, acute toxicity versus chronic toxicity.

00:19:13.500 And, of course, you know, the drugs which really do badly on both of the opiates, which could kill you instantly when you take them, but also kill you quite quickly over time as well.

00:19:22.840 But there is another angle, and that's, I think, an important angle which our analysis doesn't bring in because it's difficult and challenging.

00:19:29.920 And I'd love to.

00:19:30.580 And, you know, maybe at some point we can do this.

00:19:32.480 And that's the benefits.

00:19:34.400 You pointed out quite clearly that generally tobacco doesn't bring many benefits.

00:19:38.520 You see, nicotine is a funny drug, though.

00:19:40.300 It's the only drug we know of that both calms people but also improves attention.

00:19:46.960 And so there are people who smoke, you know, generally, although they're addicted, they do get a benefit at least when the nicotine's in the brain.

00:19:54.880 But alcohol has a much broader kind of social.

00:19:57.300 I mean, alcohol is one of the most social drugs.

00:19:59.520 I mean, after ecstasy, it probably is the most social drug.

00:20:02.200 And that's why people use it.

00:20:03.640 So there are unquestionably psychological or social benefits from alcohol.

00:20:08.520 And that goes back to pre-Christian times with, yeah, that's right.

00:20:14.260 You know, you've got, you know, Jesus turning water into wine at the wedding at Canaan.

00:20:19.080 Why?

00:20:19.340 Because wine was what the Jews used to celebrate weddings.

00:20:24.140 And it's been used ever since.

00:20:25.900 We all use it.

00:20:26.480 We still use it today to celebrate.

00:20:27.620 So alcohol has a very powerful pro-social effect, which I think is why it's so widely used and why it's been, apart from that little aberration of American prohibition,

00:20:38.520 why it's actually been stable in our society for many millennia.

00:20:42.380 And do you think that that's the fundamental reason why, despite the sort of, I mean, hypocrisy of it, if we're going to be blunt,

00:20:53.300 we would make something like cannabis illegal while having something like alcohol be legal?

00:21:00.460 Does it basically come down to our social dependence on alcohol?

00:21:06.140 Now, that's a great question.

00:21:09.720 And I think, and it's a very interesting, I haven't thought about those two in that context before.

00:21:17.000 But I think that's a very interesting point you make.

00:21:19.500 Because cannabis is not a particularly social drug.

00:21:22.800 So people, when they get stoned, they tend to be quieter.

00:21:26.600 They're not, it's not the party drug cannabis, is it?

00:21:29.800 And it might, you might be right, it might be that people are less positive towards cannabis because it isn't so socially enabling as alcohol.

00:21:40.660 That's a very interesting point.

00:21:42.400 I take a different view up till now, until you said that.

00:21:44.700 I've taken a different viewpoint, which is that people have been very anti-cannabis because the alcohol industry and the drug enforcement agency have seen cannabis as the enemy.

00:21:53.840 And the disinformation that's been produced, you know, the hatred of cannabis, which started with Harry Anslinger trying to keep the DEA functioning after alcohol prohibition was disbanded.

00:22:06.500 You know, that 100 years almost, 90 years of disinformation has actually poisoned a lot of people's minds to cannabis.

00:22:13.200 So cannabis has been vilified.

00:22:15.140 And alcohol has been celebrated.

00:22:16.300 I mean, it's been celebrated throughout history in terms of art and culture and music and television.

00:22:21.940 You know, one of the staggering things, because of lockdown, I've been watching a lot of Netflix, and I've been seeing these disclaimers at the top saying, this program contains product placement, by which they mean usually, this program shows people drinking an awful lot of wine.

00:22:42.520 Yeah, we've come a long way.

00:22:44.780 It's an interesting point you raise.

00:22:45.960 I guess I hadn't thought of it, that the DEA needs a reason to exist, and therefore you need boogeymen.

00:22:52.060 Right?

00:22:52.200 If your business is smashing boogeymen, you need boogeymen.

00:22:55.200 Don't we have enough boogeymen with other drugs like heroin or methamphetamine or cocaine?

00:23:02.260 Like, I guess I'm confused as to, and I don't want to, this is not going to be a discussion about the legalization of cannabis, because it seems to me that that train has left the station.

00:23:10.020 I'm just amazed that there was such a lack of study, because I'll tell you where it's frustrating for me as an outsider.

00:23:18.940 I have a lot of questions.

00:23:20.820 My patients ask me questions, such as, if my 16-year-old son is smoking pot, is that going to have a negative consequence on his or her brain development?

00:23:31.740 And I wish I could answer that question, but I can't really point to rigorous studies one way or the other.

00:23:37.880 And to me, that's a failure of not having studied this drug the way we should have been studying it for the past hundred years.

00:23:44.760 Because you want to talk about a drug that probably has lots of benefits, but also potentially harms, cannabis would be a case study in that.

00:23:53.660 And I find it very frustrating as someone who prides himself in caring about data and trying to not have an emotional discussion about something, that I don't have answers to those questions.

00:24:04.080 And it seems like a real missed opportunity.

00:24:07.780 Well, it's worse than that.

00:24:08.740 I mean, the reason that the studies have not been done is because almost all the funding for that kind of research in America comes through the government, through NIDA.

00:24:18.980 And essentially, NIDA has not been funded to study the benefits of cannabis, even when, and this is the real missed opportunity, even when California voted to make medical cannabis legal.

00:24:33.340 What an opportunity.

00:24:34.300 You're going to have, we know, 20 million people using it.

00:24:36.860 You could have, within a couple of years, worked out its utility and its harms.

00:24:40.840 But the federal law, because cannabis was illegal under federal law, and it still is, they could not fund research.

00:24:46.660 So it's one of the many examples of the perverse negative consequences of this prohibitionist approach to drugs.

00:24:56.380 So let's talk about a few other drugs that we haven't mentioned.

00:24:58.520 We've talked about basically things that are not particularly harmful.

00:25:01.360 We've certainly talked about things that rise to a level of harm.

00:25:03.880 Where do the classic psychedelics, LSD, psilocybin, fit in, along with some of their more distant cousins, ayahuasca, DMT, 5-MeO-DMT?

00:25:16.140 And of course, we haven't, we've talked around it, but we haven't explicitly asked, where does MDMA fit on this list of harm in the aggregate sense, according to this sophisticated model?

00:25:24.260 Well, that's why I kind of started off talking about MDMA, because that was my first introduction to policy decisions.

00:25:31.620 And when I started working for the government back in 1994, I'd assumed that what they told me about the harms of drugs was right.

00:25:40.260 And then I discovered that when I did and my team did the more detailed and sophisticated analysis, they were completely wrong.

00:25:48.200 I'd been lied to.

00:25:49.780 The real paradox of doing this really in-depth multi-criteria decision analysis is it turns out that the drugs that have been most vilified and which we've been taught are the most dangerous turn out to be the least dangerous.

00:26:02.100 So at one end, the most harmful drug is alcohol, and at the least harmful drugs are magic mushrooms and LSD and MDMA.

00:26:10.040 So it's almost as if the whole law is completely on its head.

00:26:14.520 So let's now simplify and talk about only harm to the individual.

00:26:20.080 So purely physiologic risk to self.

00:26:23.640 If I heard you correctly earlier, heroin and fentanyl and its cousins occupy the top spot, correct?

00:26:29.800 So aggregate greatest risk of acute and chronic mortality, yes?

00:26:36.000 And then second, you're putting the cocaine derivatives.

00:26:39.360 And then third would be the amphetamine derivatives.

00:26:42.680 So if we just look harm to the user, yes.

00:26:44.840 I mean, crack cocaine.

00:26:46.300 Crystal meth is probably more harmful than crack because it lasts longer in the body and the brain.

00:26:53.000 So I would generally, crystal is probably a bit more harmful to the user.

00:26:56.880 So it would be opioids, crystal, crack.

00:27:01.020 Let's talk a little bit about mechanism of action.

00:27:03.140 I'm very familiar with how opiates kill, but let's just briefly summarize it.

00:27:07.900 Is it mostly the respiratory depression?

00:27:09.740 Is that the fundamental issue in the short term?

00:27:13.760 Yeah.

00:27:14.560 They kill you in overdose.

00:27:15.900 You take just too much.

00:27:17.000 You don't know what you're taking.

00:27:18.280 Someone spiked your heroin with fentanyl, and you stop breathing, and you die.

00:27:21.480 Yeah, you want to talk about, you mentioned earlier, almost nobody in America doesn't know

00:27:27.060 somebody whose life has been destroyed by alcohol.

00:27:29.880 We're getting pretty close to that with opioids.

00:27:32.760 I mean, I personally know three people, is it four?

00:27:38.240 Maybe four, who have lost a child or relative to an opioid overdose.

00:27:45.420 Think about that.

00:27:46.580 I don't know that many people, David.

00:27:47.720 It is terrifying, and I'm sorry to say, guys, but you kind of got it wrong, and then you

00:27:54.420 got it wrong again, and you're still getting it wrong, and shall I just briefly go through

00:28:01.160 that?

00:28:02.020 Sure.

00:28:02.700 So the fentanyl crisis is very much an American problem, and it's not just because there's

00:28:09.680 obviously a lot of you.

00:28:10.500 The more people there are, the more likely it is that people will die, but it's a disproportionate

00:28:16.880 number of deaths.

00:28:17.480 So now, I think last year, more people died of opioid overdose than died in the whole of

00:28:21.340 the Vietnam War.

00:28:22.540 Yeah, and last year, we set here in the United States a record for the most overdose deaths

00:28:28.660 ever.

00:28:29.800 So it wasn't just the year of the most deaths due to COVID, but the real record, the story

00:28:34.260 behind the story is the most overdoses.

00:28:36.600 And the answers are complicated, and it's like a perfect storm of things going wrong.

00:28:44.600 So the first perfect storm was the excessive rollout of strong morphine derivative painkillers,

00:28:53.540 which were heavily promoted by some pharmaceutical companies, and you all know they've been sued,

00:28:58.900 et cetera.

00:28:59.120 So I think the doctors also, some doctors were to blame.

00:29:02.540 I mean, you know, some were clearly overprescribing, but there's also the problem that chronic

00:29:06.580 pain is very common.

00:29:08.480 You know, perhaps a quarter of the country have chronic pain.

00:29:12.640 When doctors are faced with no treatment, no physiotherapy, no occupation, all they had

00:29:18.820 was prescription pad, then they tended to veer towards prescribing opiates, which are

00:29:23.160 not good for chronic pain.

00:29:24.240 And it's interesting also, you see the states, which had the highest prescription levels of

00:29:29.040 opiates for chronic pain, are the ones actually that don't have medical cannabis.

00:29:32.880 Medical cannabis is the best treatment for chronic pain, better than any other drug.

00:29:38.360 But if you haven't got that, then you can't have it.

00:29:40.420 So that was the first thing.

00:29:41.420 Big increase in prescription, you know, partly driven inappropriately, partly out of just a

00:29:47.520 concern to help chronic pain.

00:29:48.680 The second thing was then the rise, the dispersion of that into society, you know, parents, kids

00:29:57.100 were taking it and taking their parents' oxycodone and dying.

00:30:00.680 So you have the crisis, you have the concern, and then you have the reaction.

00:30:04.000 The reaction then was to stop prescribing.

00:30:07.520 But when you stop prescribing to someone who is dependent on an opiate, they don't, unless

00:30:13.380 you provide them with something else like medical cannabis, they are in withdrawal.

00:30:18.760 And so they go and get an opiate.

00:30:20.960 And if you're not prescribing it, they go and get it from the black market.

00:30:24.220 And then you see this complete paradox.

00:30:26.380 You see this rise of heroin deaths, rise of fentanyl deaths, because that's what the black 1.00

00:30:30.300 market provides.

00:30:31.800 And then you get into this really, the most damaging cycle, or part of this cycle, is the

00:30:37.740 rise of fentanyl.

00:30:39.100 Because until there was a huge increase in black market demand from the people on oxycodone,

00:30:45.760 fentanyl wasn't a big issue.

00:30:47.760 But for various international reasons, the United Nations limiting the access of heroin,

00:30:53.000 the amount of poppies it could be grown in a so-called attempt to prevent heroin misuse.

00:30:59.640 15 years ago, particularly the Mexican cartels realized if they couldn't make heroin because

00:31:04.540 they couldn't get enough morphine, then they would make something else.

00:31:07.980 And they discovered fentanyls.

00:31:10.540 And fentanyls are so much more potent.

00:31:12.120 And there's so much more value for money, economic, you know, even the simplest fentanyl,

00:31:16.920 fentanyl, you know, it's 50 times more potent than heroin and twice as cheap to make.

00:31:21.000 So you don't have to be an economist to realize it's better to do that.

00:31:24.100 And then you get to the super fentanyls like carfentanil, which are a thousand times more

00:31:27.680 potent.

00:31:28.280 They're so potent, no one knows how to measure them.

00:31:30.160 And so you don't know how much you're giving to it.

00:31:32.100 So we've, you know, you see it's a cycle, a series of mistakes, which has actually just

00:31:35.780 led to this terrible tsunami of deaths.

00:31:38.460 And the only way to deal with it really is to have lots of testing to allow people to

00:31:42.540 take anything they've got and get it tested so they know what it is, eliminate fentanyls, 1.00

00:31:46.480 and start to bring in much safer treatments for people in chronic pain like medical cannabis.

00:31:51.820 I want to talk a little bit about the opiates before we leave it and come talk about a drug

00:31:57.680 called ibogaine, a derivative of iboga.

00:32:00.680 You know, I have read quite a bit about it and a lot of it's anecdotal, but it seems that

00:32:04.880 there's something very interesting going on there where you have this alkaloid that while

00:32:10.780 it comes with its own dangers and it's not clear how over or understated they are relative

00:32:15.160 to cardiac toxicity, it seems to have quite an efficacious punch when it comes to

00:32:21.760 relieving people from the throes of opioid addiction.

00:32:25.140 Do you have experience with it, at least scientifically, if not through experimental

00:32:28.840 collaboration?

00:32:30.840 Well, we're in the process of trying to do a study.

00:32:33.080 I would dearly love to understand the nearest science of ibogaine.

00:32:38.940 And it's been difficult to do that study because of the cardiac risks.

00:32:43.880 So, but we're in the process of working with a company that's developing a derivative

00:32:48.460 of ibogaine called noribogaine, which may be less cardiotoxic.

00:32:52.980 And we're working with them to do some brain imaging to see whether we can, if it is, is

00:32:59.520 it a normal psychedelic or not?

00:33:01.660 Because no one's ever studied it yet.

00:33:04.320 But the evidence, as you see, from, from it's used widely in some third world countries

00:33:09.760 as a, as a therapy for, for opiate withdrawal.

00:33:12.080 It's also a licensed medicine, interestingly, in New Zealand.

00:33:14.300 And, but they've stopped using it in New Zealand because of, of one death.

00:33:17.920 Which strikes me as a little bit odd, right?

00:33:19.840 When you consider, so based on some of the literature I've read, you know, the risk of

00:33:25.160 a fatal arrhythmia might be one in a thousand.

00:33:27.520 And that's, depending on what you're talking about, one in a thousand is an enormous risk.

00:33:32.020 But if you're weighing it against a person remaining addicted to opioids, what's the natural

00:33:37.680 history of that?

00:33:38.760 I mean, that might be 300 out of a thousand.

00:33:42.740 Yes, about that.

00:33:43.400 Yeah, so do you have a sense of what the true risk of ibogaine use is and how much of

00:33:47.800 that risk could be mitigated if it were administered in a proper setting, which would be a setting

00:33:52.040 with cardiac monitoring, for example, versus someone's house?

00:33:55.800 Well, one thing's for sure.

00:33:56.720 We're going to administer a cardiac monitoring.

00:33:58.900 Yeah, of course.

00:34:00.480 Yeah, exactly.

00:34:01.500 So, and there are plenty of other drugs which do have cardiac effects.

00:34:04.780 I mean, you know, usually they're used by cardiologists.

00:34:08.520 So the answer, you're right.

00:34:09.720 I mean, that's why I want to study it, because if we could get more clarity on its mechanism,

00:34:15.720 that I think would at least then reassure people there was a science behind it.

00:34:18.740 Because currently it's, well, you go to West Africa or you go to Vietnam and you get ibogaine

00:34:22.580 and your brain is shaken up and you come back cured.

00:34:25.920 And I think we could probably improve on that.

00:34:27.740 I think there's also, your point you make, doing it in a hospital setting, I think makes

00:34:32.000 more sense because, not just for safety, but also because I'm not sure it should be given

00:34:37.220 during withdrawal.

00:34:38.260 That's when it is being given.

00:34:40.180 And I think withdrawal just, we have, you know, there are other treatments which we have

00:34:44.560 given for opiate users, which have also been toxic in withdrawal.

00:34:49.420 You know, people, you know, withdrawal is a serious medical problem.

00:34:52.500 So, you know, they're ill.

00:34:54.380 They're physically struggling.

00:34:56.180 So, I think adding a burden to someone who's in withdrawal is not a sensible idea.

00:35:02.000 So, my thinking is that if we can restore a sensible balance with ibogaine, we could potentially

00:35:09.040 use it.

00:35:09.460 But also, I'm very interested in using other psychedelics, because I think the fundamental

00:35:13.920 principle is likely to be the same between ibogaine or psilocybin or DMT in addictions.

00:35:20.360 You're disrupting these over-learned, these persistent patterns of over-attention and

00:35:26.800 over-increased, you know, enhanced love for drugs.

00:35:30.080 You can perhaps break down those habit circuits and then allow people to escape.

00:35:34.980 Meaning that things like the default mode network?

00:35:37.720 Yeah, that's right.

00:35:38.500 So, I mean, our current thinking about how psychedelics might be used in psychiatry is built from this,

00:35:45.420 you know, remarkable finding that, you know, the psychedelic state is a state which is where

00:35:51.420 you have completely disrupted the default mode network.

00:35:53.660 This is the network in the brain which, in which your main sense of self, the core of

00:35:59.540 you is in the default mode network.

00:36:01.600 And embedded in that, of course, is whether you are, you know, your depressive thoughts or

00:36:06.240 whether you're love objects, you know, your heroin addict, anything that's really related

00:36:10.120 to you is embedded in the default mode network.

00:36:12.060 And if we can disrupt that with psychedelics.

00:36:14.140 How innate is that versus how formed is that?

00:36:17.320 The default mode network, I think, exists in children and babies.

00:36:20.500 And it is what you are.

00:36:22.180 It is the part of the brain in which where you encode yourself, your referential memories,

00:36:27.720 your plans, your retrospect, you know, looking back, looking forward, putting everything.

00:36:31.820 It is where you are.

00:36:32.980 We know that.

00:36:33.580 You know, if you damage the frontal part of the default mode network, your personality changes.

00:36:37.360 You damage the posterior part of the default mode network.

00:36:39.520 You kind of, you become a very strange person who really struggles with coordination and

00:36:44.320 integration.

00:36:45.380 So the default mode network is a fundamental part of orchestrating what you are.

00:36:51.700 But in that, of course, are all the things that you have been.

00:36:54.920 So in the default mode network coordinates your access to good memories, to bad memories, to

00:37:00.200 use of drugs, to resisting the use of drugs, et cetera.

00:37:03.060 But in a very simplistic way, the sort of current thought thinking is that some elements of the

00:37:09.580 default mode become misaligned or malignantly overengaged with negative thinking in depression

00:37:17.120 or compulsive attitude to the seeking of drugs in drug use.

00:37:22.280 And if we can disrupt those with psychedelics, then potentially people can kind of restore

00:37:27.200 a normal balance in that network and have a more rational approach, you know, a less determined.

00:37:34.700 So the brain is kind of determining things like addiction.

00:37:37.660 And even though people don't want to use the drugs, they often find themselves doing it,

00:37:41.920 even though they don't want to, because their brain is kind of driving them that way.

00:37:45.460 And we're going to come back and talk about the impact of psilocybin on the default mode

00:37:49.040 network.

00:37:49.380 But I guess to your point, this might be one of the ways in which ibogaine or iboga kind

00:37:55.260 of help rewire a brain for an individual who is opioid addicted, which isn't in itself kind

00:38:01.840 of an interesting thing, isn't it?

00:38:03.120 And that there's got to be a genetic susceptibility to this, because there are many people who take

00:38:07.020 tons of opioids during, you know, say a post-operative recovery from surgery.

00:38:11.780 And, you know, they take tons of the stuff.

00:38:14.620 And then when they have to stop it, they stop it.

00:38:16.920 And that's the end of it.

00:38:17.560 And yet there are other people for whom that's not true.

00:38:19.120 So do we have a sense of what that genetic susceptibility looks like?

00:38:22.960 And is it more importantly, is it possible to predict that a priori so that we would

00:38:27.540 understand, hey, this is a person who is at such high risk for opioid dependency that even

00:38:32.740 if they have to get their wisdom teeth pulled out, we are not giving them this medication.

00:38:36.640 We're going to come up with a totally different pain management strategy.

00:38:40.640 Yes, theoretically, it's unlikely to be in the genes.

00:38:44.760 Oh, well.

00:38:45.440 It's probably polygenic, I'm sure.

00:38:46.940 Yeah, exactly.

00:38:47.460 There's not going to be a gene.

00:38:49.120 What do we know about white people become addicted? 0.86

00:38:51.800 Well, we know social factors are hugely important.

00:38:55.820 You know, I mean, if you've seen The Wire, then you know that downtown Baltimore.

00:39:00.600 I lived The Wire.

00:39:01.940 Well, I mean, I did my residency in Baltimore.

00:39:03.780 So I took care of the patients in The Wire.

00:39:06.500 Yeah.

00:39:06.840 It's a frightening place, isn't it?

00:39:08.880 Unbelievable.

00:39:09.280 The book, The Corner, which The Wire was based on, was the book I, once I matched to do my

00:39:14.380 residency in Baltimore, a friend of mine who was a year ahead of me at medical school who

00:39:19.060 had already now spent a year in Baltimore, I was like, hey, do you have any advice for

00:39:23.440 what I can do to kind of get ready for it?

00:39:25.060 Because I'm moving from Stanford to Baltimore.

00:39:26.620 You can't go from the most posh place in the world to the least.

00:39:31.740 His only piece of advice was he said, read The Corner because it's literally what you're

00:39:36.460 going to be living in.

00:39:37.840 And it will give you a great sense of empathy for the patients that you're going to be taking

00:39:42.540 care of.

00:39:43.540 And it's a riveting book, which ultimately became a riveting series.

00:39:47.260 Absolutely.

00:39:47.940 And a couple of years ago, I was on my way to Philadelphia from Washington to give a lecture.

00:39:52.040 And as we pulled out of Baltimore, I was looking out the train window thinking, it's like a

00:39:57.660 war zone.

00:39:58.060 Is this Hiroshima?

00:39:59.360 Because the downtown, I hadn't realized quite how destroyed it had been.

00:40:03.820 And if you're living there and you've got no job, I mean, and the only thing you can

00:40:06.560 do is deal drugs.

00:40:07.400 You take drugs, you deal drugs.

00:40:08.420 And so a lot of drug use addiction comes because that's the one way people can actually achieve

00:40:15.480 both the sense, something that takes away the misery of their lives, but also in a way

00:40:20.180 if they become drug dealers, become some of a role.

00:40:23.600 So coping with life stress is one reason people use drugs.

00:40:27.480 But there are some people, you know, and there are very, the rich, successful people who still

00:40:31.800 use opiates and get into problems with opiates.

00:40:34.460 And I give two examples of this, two Oscar winners, Tatum O'Neill, youngest ever Oscar

00:40:43.200 winner, marries the best, greatest tennis player I can remember there's maybe ever been, you

00:40:48.760 know, got two wonderful kids, lives the life that everyone envies, you know, she's famous,

00:40:54.100 beautiful, everything there.

00:40:56.100 But when she comes out of heroin treatment, she says, the only time I felt whole was on

00:41:02.280 heroin.

00:41:04.580 I see that with patients, not just heroin patients, I see it with alcoholics.

00:41:06.840 There are plenty of people for whom alcohol makes them what they want to be.

00:41:12.100 It's only when they're drunk that they're actually functioning normally.

00:41:16.200 And why that is, we don't know.

00:41:18.440 And actually, one of the interesting things, you know, the reason I want to study psychedelics

00:41:22.340 is because I'm wondering whether that gap that can only be filled by drugs could actually

00:41:27.460 be kind of refilled or at least remodeled with psychedelics.

00:41:32.600 And then, of course, there are people who use drugs to get high and then they find somehow

00:41:37.480 that their brain becomes sensitized to the drug use so that they, you know, they lose

00:41:41.920 control.

00:41:42.560 And that's a more classic with people you use cocaine or crystal.

00:41:46.840 So let's talk about those two drugs just from a mechanistic standpoint and where the risk

00:41:50.200 actually comes from.

00:41:51.540 Take your choice which one you want to start with.

00:41:53.280 So let's start with cocaine because that was the first of, well, there were several

00:41:58.100 cocaine epidemics.

00:41:59.140 But, I mean, let's talk about that.

00:42:01.240 Yeah, I mean, cocaine, I give a lecture sometimes, which is, was Freud right to give up on psychopharmacology?

00:42:08.040 Because, of course, Freud was a great protagonist.

00:42:11.860 Freud used cocaine himself.

00:42:13.620 He thought cocaine was a very powerful drug for getting people of heroin.

00:42:16.260 He got one of his disciples off heroin by giving them cocaine.

00:42:20.820 He didn't realize that cocaine also caused dependence.

00:42:24.180 In fact, Freud and his protégé both became cocaine dependent.

00:42:28.640 That's another Hopkins link, by the way, in Baltimore was the, basically the father of

00:42:32.480 the surgical residency in the United States.

00:42:34.740 And the first chief of surgery at Hopkins, William Stuart Halstead, himself became addicted

00:42:40.400 to cocaine when he became obsessed with it as a local anesthetic.

00:42:43.860 And so in the process of experimenting with cocaine as a local anesthetic, which, of course,

00:42:49.200 it became a very potent and remarkable local anesthetic, he and many of his residents became

00:42:54.380 cocaine addicted.

00:42:55.720 It's a footnote to this story of the creation of the great American Surgical Institute.

00:43:01.500 Well, it hasn't stopped.

00:43:03.800 They don't get addicted to cocaine anymore.

00:43:05.160 They get addicted to remyfentanil, usually, the anesthetist.

00:43:07.760 But that's another story.

00:43:08.880 So let's get back to cocaine.

00:43:11.540 So I think the reason Freud went into psychology was because he got them, he became completely

00:43:16.640 terrified of pharmacology because he kind of assumed that any drug would have that problem.

00:43:21.380 So, you know, you can maybe give cocaine credit for the development of psychoanalysis.

00:43:25.860 But when we get to the modern era, you know, then cocaine is the ultimate fun drug.

00:43:30.240 It gives you energy and drive and an enormous sort of sense of focus and purpose.

00:43:35.620 And then a terrible crash.

00:43:38.400 And we now, you know, we know that it's due to the release of dopamine and noradrenaline

00:43:43.080 in the brain.

00:43:44.000 But it's very spiky.

00:43:45.900 And during the course of a binge over the weekend, you know, the brain gets perturbed and then

00:43:49.220 people start to get paranoid and withdraw.

00:43:52.100 And some of them will get sensitized and become addicted.

00:43:55.460 And some of them will die because, of course, there's a cardiac effect.

00:43:58.500 And also, there's this problem that if you mix cocaine and alcohol, you get a drug called

00:44:03.980 cocaethylene, which is a longer acting and more cardiotoxic version of cocaine.

00:44:08.960 You know, I have patients who, our patients are always going to disclose to us what they

00:44:13.380 use.

00:44:13.660 We ask this question point blank, which recreational drugs do you use?

00:44:17.020 And a number of them will say, hey, you know, two or three times a year, I use cocaine

00:44:21.140 and they want to know what I think.

00:44:22.820 And again, the goal in that situation is not to come across as preachy and dogmatic, but

00:44:27.640 it's to sort of have a point of view and have it be grounded.

00:44:30.620 And my point of view with cocaine has always been, I don't think it's worth the risk and

00:44:34.860 I don't think it's the right kind of drug because, you know, just as much as we're now

00:44:38.060 talking about a framework for drugs, I have a much simpler framework for drugs, which is

00:44:44.260 it's really only got two levers.

00:44:47.040 One is what is the physical risk of this drug to me as an individual?

00:44:51.220 So with cocaine, what is the true risk of cardiac toxicity?

00:44:55.560 What is the risk of deepening physiologic dependence over time, et cetera?

00:45:00.660 And then the second component to my framework is, is this a drug that only alters your state

00:45:07.720 or does it have the potential to alter a trait?

00:45:10.900 I'm borrowing that from the book called Altered Traits, which gets into this distinction.

00:45:16.800 And so the idea being is psilocybin for anybody who's ever taken it is clearly a drug that

00:45:23.280 alters your state.

00:45:24.740 But if it just altered your state, you probably wouldn't take it because it's really not that

00:45:29.120 pleasurable.

00:45:29.720 But the real benefit of is the potential to alter a trait, whether it be depression, smoking

00:45:34.920 cessation or something else.

00:45:36.240 And so if a drug can only alter your state, but it has no potential to really alter your

00:45:42.880 traits, i.e.

00:45:44.060 how you behave off the drug, is it worth it?

00:45:47.640 And so my the way I explain this to patients is I say, I don't think cocaine can do that.

00:45:53.260 So therefore, it has two strikes.

00:45:55.980 It's O for two in the Peter framework.

00:45:58.200 It's it has a physical risk that is non-trivial and it's not going to make your life better

00:46:05.080 when you're not taking it.

00:46:06.280 And therefore, I think cocaine makes no sense to take.

00:46:08.800 Do you agree or disagree with that?

00:46:10.720 That's a very interesting analysis.

00:46:12.260 I like that.

00:46:12.760 I might start using it.

00:46:13.780 Yes.

00:46:14.740 So do you agree that that basically there isn't a positive to cocaine that I'm missing?

00:46:21.620 There isn't a benefit to it?

00:46:23.120 So I certainly would would say absolutely, absolutely true for crack.

00:46:28.700 For cocaine, I'm not entirely sure.

00:46:30.940 I mean, I think there are people who can use it just once or twice a year without getting

00:46:34.560 into much difficulty, provided they don't have serious cardiac problems.

00:46:38.760 So I certainly wouldn't be using it at my age.

00:46:42.080 But then look at like there's the famous example, which basically accelerated the war on drugs

00:46:46.500 was the case of Len Bias in 1985.

00:46:49.380 Are you familiar with the story of Len Bias?

00:46:51.100 Oh, very, very, he was the probably the most famous high school, pardon me, college basketball

00:46:57.360 recruit.

00:46:57.900 So he played basketball at the University of Maryland, a complete superstar, basically on

00:47:02.880 the level of a Michael Jordan.

00:47:04.920 And he was drafted by the Boston Celtics and probably had he gone on to play for the Boston

00:47:10.980 Celtics would have altered the course of the NBA for the next 10 years.

00:47:14.260 The day following the NBA draft, he was back in Baltimore celebrating with friends.

00:47:19.420 They're at a party in their dorm room.

00:47:22.180 He's either using cocaine.

00:47:23.880 He has a sudden cardiac arrest and dies.

00:47:25.920 And this really, really shocked the nation.

00:47:28.780 This was a really big deal.

00:47:31.060 And certainly some would argue that that only reinforced and doubled down on sort of the

00:47:35.940 Nancy Reagan-esque, just say no mantra, which of course reinforced the war on drugs.

00:47:42.400 So again, when you can have this totally, you know, the healthiest 21-year-old in the country

00:47:47.680 can die. 0.66

00:47:48.400 And you don't know what, you don't know the details, right?

00:47:49.980 How much was he on?

00:47:50.800 Was it laced with something?

00:47:52.440 No, but you've got to remember that, you know, sudden death in athletes.

00:47:55.960 We just had the European football championships.

00:47:58.880 And one of the star players, Ericsson from Denmark, had a cardiac arrest on the pitch.

00:48:05.620 So super fit athletes-

00:48:07.520 Might be more susceptible, yeah.

00:48:09.120 Yeah, particularly if they've got, you know, if they're big and they've got to develop some

00:48:12.800 kind of cardiomyopathy.

00:48:13.720 So yeah, athletes are paradoxically more potentially, you know, at least as vulnerable as other people

00:48:19.900 to these effects.

00:48:21.820 So talk about methamphetamine, crystal meth, these drugs, which obviously the amazing Netflix

00:48:27.080 series Breaking Bad brought everyone awareness of what these drugs are.

00:48:30.860 But physiologically, neurochemically, what is it that they're doing and what is the danger?

00:48:34.220 Well, they're very similar to cocaine.

00:48:36.140 I remember as a junior doctor, my very first period as a junior doctor, giving methyl amphetamine

00:48:46.480 intravenously to a man who had serious status asthmaticus.

00:48:53.840 Amphetamines were developed as a treatment for asthma.

00:48:57.460 They were developed as an alternative to ephedra.

00:49:01.200 Ephedra is a natural plant product.

00:49:02.920 It was discovered to have this bronchodilating properties back in the 1800s.

00:49:08.840 There was a huge demand.

00:49:10.580 The plant couldn't supply the demand.

00:49:12.440 So German pharmaceutical companies went away and made a synthetic ephedra, which they called

00:49:18.220 amphetamine.

00:49:19.520 And it was used largely for the treatment of asthma, really to the Second World War, when

00:49:26.000 people realized it could actually be used to keep soldiers awake.

00:49:31.320 And it's another interesting aside.

00:49:33.620 But I'm very interested in the history of drugs in war because they tell us quite a lot about

00:49:38.980 the consequences of drug use.

00:49:41.800 And what I often give I often give a talk when I talk about amphetamines, I compare the the

00:49:48.260 allies.

00:49:49.140 So the Brits and Americans, we use amphetamine sulfate, whereas the Germans and the Japanese 1.00

00:49:53.940 thought they were really clever because they had this super amphetamine called

00:49:57.940 methamphetamine, which lasts a lot longer.

00:50:00.500 But what they didn't realize was that longer is not better.

00:50:05.460 And the turning point of the war was actually the North Africa campaign when the Germans

00:50:11.020 were pushed back when they got to Egypt.

00:50:13.480 So Rommel was pushed back by...

00:50:14.800 Rommel's last end, yeah.

00:50:15.720 That's right.

00:50:16.400 Absolutely.

00:50:17.040 By the Desert Rats, the Allied troops, the Australians. 0.55

00:50:21.240 And the way the Desert Rats used to work was that they would be up all night working 0.88

00:50:25.920 around the Germans, harrying them, blowing them up. 1.00

00:50:28.420 And then they'd go back, they'd be up all night on amphetamine sulfate.

00:50:32.980 And then they'd go back and they'd sleep all day.

00:50:35.480 But the Germans would take methyl amphetamine to stay up to defend themselves against the 0.94

00:50:40.020 Desert Rats.

00:50:40.720 But they couldn't sleep in the daytime.

00:50:42.060 And eventually they became sleep deprived and paranoid.

00:50:45.260 And the same with Japanese. 0.99

00:50:46.260 You know, these descriptions of how the Japanese became, had these terrible hallucin, sensory 0.63

00:50:52.300 somatic hallucinations from using large doses of crystal meth for long periods.

00:50:56.600 So crystal meth is longer acting and probably more neurotoxic than amphetamine sulfate.

00:51:04.140 Talk about the neurotoxicity.

00:51:05.460 What actually happens to the person's brain?

00:51:09.020 Because you certainly have this meme of the crystal meth user, right?

00:51:13.700 No teeth, bruised, pin skinny, emaciated.

00:51:20.080 But that meme doesn't actually tell me about their brain.

00:51:23.680 What's actually happening to them?

00:51:25.640 Well, they're certainly pushing their dopamine system to a point where it's probably depleted.

00:51:31.640 And that seems to then lock them into a state where they can't really function normally in

00:51:37.280 the world without taking the drug.

00:51:39.300 There's also a bit less good evidence that it might also damage the dopamine pathways to

00:51:44.300 the frontal cortex, which impairs their ability to make judgments to executive function, etc.

00:51:50.520 But I have to caution it.

00:51:52.220 I mean, the big concern about crystal meth actually came as a result of the Japan, after the Second World War,

00:52:00.980 there were, you know, factories, crystal meth factories in Japan.

00:52:05.480 You know, there were barrels of the stuff.

00:52:07.280 And there were a lot of Japanese soldiers who had nothing else to do.

00:52:10.100 And they used to use huge doses of crystal meth, often intravenously.

00:52:14.480 And the evidence for brain damage really comes from that population.

00:52:18.260 There's not so much evidence from it when it's being used, as it tends to be used now,

00:52:23.080 orally without, you know, in more prolonged periods.

00:52:26.080 So I'm not sure that you get a lot of what you might call cortical damage with crystal meth.

00:52:31.500 But I think it definitely does distort the dopamine pathways in your brain and will affect

00:52:36.640 your motivation and your ability to sort of get activated, etc.

00:52:42.140 So now let's talk a little bit about these drugs that, unfortunately, or they seem to have

00:52:47.320 the same scheduling and therefore they're viewed by the DEA as both as dangerous in terms

00:52:53.960 of harm or risk of addiction and as medically useless.

00:52:58.760 Because really that's the criteria for Schedule 1, right?

00:53:01.240 Is high potential for addiction and no medical use.

00:53:05.640 And so cocaine does not fit in Schedule 1 because while it is highly addictive, we at

00:53:10.900 least have one appropriate medical use for it, which is, and it's a great anesthetic, especially

00:53:15.460 in the nose.

00:53:17.020 Obviously, fentanyl is not Schedule 1 because even though we acknowledge it's highly addictive,

00:53:22.120 it has this pain blunting effect.

00:53:25.560 Remarkably, psilocybin is Schedule 1.

00:53:29.240 MDMA is Schedule 1.

00:53:31.900 LSD is Schedule 1.

00:53:33.660 So let's talk about these three, which are, if you believe the DEA scheduling, the worst

00:53:39.560 possible drugs imaginable because by definition, they must have a high addiction for potential

00:53:45.340 and they serve no medical benefit whatsoever.

00:53:48.540 So take them in any order you like.

00:53:50.520 Well, let's take the psychedelics first because that's how it all started.

00:53:55.040 I mean, these drugs were banned not because they had any negative impact.

00:53:59.740 They were banned in the face of opposition.

00:54:03.040 Bobby Kennedy confronted the DEA and the FDA when they said, we want to ban LSD.

00:54:10.120 And he said, hang on a second.

00:54:11.860 Hang on.

00:54:12.320 We spent billions of dollars researching LSD up till this time and we got loads of positive

00:54:18.880 results.

00:54:20.480 In fact, his wife was being treated.

00:54:21.980 Was he still the AG when he was having this discussion with them?

00:54:25.280 Was he still the Attorney General of the United States?

00:54:26.900 No, no, no.

00:54:27.380 He was Secretary of State.

00:54:29.020 He was about to get elected as president.

00:54:30.840 Yeah, yeah.

00:54:31.720 This was later on.

00:54:32.720 Just before he was assassinated.

00:54:34.740 Yeah, yeah.

00:54:35.260 Okay.

00:54:35.620 And he's saying to these, come on guys, we've had 15 years of this remarkable research which

00:54:40.520 we've invested.

00:54:41.480 NIH in the States funded over 130 grants to study the therapeutic use of LSD.

00:54:47.780 And they found it was very therapeutic and very little harms.

00:54:50.380 And then the DEA come and the CIA come and say, we've got to ban it.

00:54:53.720 He's saying, what are you talking about?

00:54:56.060 And of course, what they were talking about was the fact that the hippie movement was starting

00:55:01.700 and the hippie movement was anti the war in Vietnam.

00:55:05.240 And LSD was seen as fueling the hippie movement.

00:55:08.340 But also worse than that, it was changing music and people were dressing differently and putting

00:55:13.680 flowers in their hair and they were sticking flowers down the guns of the soldiers that were 0.97

00:55:18.180 trying to stop them protesting the war.

00:55:20.120 It was changing the whole tenor of, I suppose, what you might call sort of intellectual debate

00:55:26.460 in America, particularly amongst students.

00:55:28.880 And it was seen as a real threat to the American way of doing everything, which was basically

00:55:33.220 having bigger and better bombs and guns.

00:55:36.140 And so LSD got banned because it was essentially changing the way people voted.

00:55:43.040 People didn't want to vote for war.

00:55:45.000 But they couldn't ban it.

00:55:46.160 In those days, there were rules which said, basically, you had to find harms.

00:55:51.420 And those harms could be physical harms or they could be social harms.

00:55:54.320 And it's very easy to find social harms because you just get a few editors of your National

00:55:58.440 Inquirer or similar rags to just invent stories about the harms, you know, and the way people

00:56:04.700 have been corrupted by using LSD.

00:56:06.260 And there's these wonderful, I mean, it's sad, but it's amusing now, but of course, very damaging.

00:56:13.220 It's front covers of these magazines or newspapers making absurd claims about LSD, usually with

00:56:19.720 semi-naked women. 1.00

00:56:21.220 And that was enough concern.

00:56:23.880 If editors are socially concerned, then we can ban the drug.

00:56:26.140 And it got banned.

00:56:26.720 And once LSD got banned, all the other serotonergic hallucinogens that were known about at the

00:56:32.580 time, and actually, in America, you did know about quite a lot.

00:56:35.320 A lot of countries didn't know there were more than LSD and psilocybin.

00:56:38.040 So some countries didn't ban DMT or 5-methoxy.

00:56:41.480 But you Americans, you just banned it all because you had good scientists.

00:56:44.700 So LSD was banned for political and social reasons.

00:56:48.180 No, not because of any harms.

00:56:50.800 If Tim Leary had not been around, would it still have been banned, in your opinion?

00:56:55.960 Probably not.

00:56:57.860 I think the fact that he was encouraging a fundamental change in the American way of life through

00:57:05.720 using drugs, I think he certainly compounded the problem.

00:57:09.220 And he certainly popularized LSD and encouraged people to think differently about society.

00:57:14.660 There was a genuine fear that Americans would actually cease to want to fight wars and actually

00:57:20.840 want to have peace.

00:57:21.640 And that was just seen as being extremely bad for the American economy and, of course,

00:57:27.100 the American presence internationally.

00:57:29.680 So prior to the scheduling of LSD, you mentioned over 130 grants had been issued to study it.

00:57:37.600 This was a drug that had been manufactured in the late 1930s by the pharmaceutical company

00:57:41.880 Sandoz.

00:57:42.960 What were some of the things that they had learned about LSD under that period of time in which

00:57:48.060 it was studied rigorously?

00:57:50.320 So there were 40,000 patients studied.

00:57:53.920 A thousand papers were published.

00:57:56.480 And there have been analyses of many of these groups of patients.

00:57:59.700 And they discovered that it actually was very safe.

00:58:03.380 If anything, it reduced suicide rates compared with non-treatment.

00:58:07.600 And you've got to remember at the time, in the 50s and 60s, there were very few alternatives.

00:58:11.560 We hadn't modern, so-called modern, particularly antidepressants, hadn't been really invented

00:58:16.240 until the 1960s.

00:58:18.460 It was shown to be effective.

00:58:20.260 And it was shown to be safe.

00:58:21.400 And it didn't cause psychosis.

00:58:23.200 So actually, this was the revolution.

00:58:26.100 This was the beginning, the dawning of real psychiatry.

00:58:30.660 Psychiatry was becoming like the rest of medicine.

00:58:32.940 We had tools that we could help people with other than talking.

00:58:37.100 And in what context, David?

00:58:38.300 So would that be like a single dose of LSD combined with a prolonged period of psychotherapy

00:58:45.380 during the period of time under which the individual is under the influence?

00:58:49.640 Or did it require multiple treatments?

00:58:51.780 I mean, do you have a sense of what was required for that efficacy?

00:58:54.360 But it was used in two different ways.

00:58:56.380 So in the States, the typical use was how we're using it today, which is give people a

00:59:01.520 big-ish dose, give them a big trip, a few-hour trip.

00:59:03.880 And then afterwards, help them work out what the trip meant.

00:59:09.100 So it was always done in the context of psychotherapy, because in those days, all American psychiatrists

00:59:14.160 were actually effectively, mostly Freudian analysts.

00:59:18.360 So it was always done in the context of psychotherapy.

00:59:20.600 And it was allowed.

00:59:21.460 But in Britain, we often use lower doses.

00:59:25.180 And we use that repeatedly to try to break down psychological resistance to actually engaging

00:59:30.020 in psychotherapy.

00:59:31.060 And what was the difference in those doses, David?

00:59:32.740 So the big trip dose would be how many micrograms?

00:59:35.900 So for LSD, it would have been 100 or 125.

00:59:39.140 And then for reducing the resistance, we would say, in psychotherapy, breaking down the resistance,

00:59:44.000 it would be perhaps 25 micrograms.

00:59:46.280 And is 25 micrograms perceptible?

00:59:48.600 Or is that considered a microdose for the individual?

00:59:50.980 No, no, that's perceptible.

00:59:51.900 Anything over 10 micrograms is perceptible.

00:59:54.680 Even 10.

00:59:55.760 A lot of people can discriminate 10.

00:59:57.300 Not in the sense, not because they're psychedelic, but they can feel.

01:00:00.620 Something's different.

01:00:01.040 Yeah, feel things.

01:00:01.840 And in the case that you describe in the UK, how many treatments at that lower level and

01:00:08.760 at what interval were typically necessary to produce the benefits?

01:00:11.980 Well, they'd be weekly and they'd be maybe for 10, 15, 20 treatments.

01:00:16.280 So it's just an unbelievable loss to the scientific community when LSD becomes scheduled.

01:00:22.140 Absolutely.

01:00:23.660 Perhaps the biggest loss of all is relation to alcoholism.

01:00:27.860 A lot of people don't realize that the founder of Alcoholics Anonymous, Bill Wilson, he escaped his alcoholism.

01:00:35.780 He broke free from the chains, as he described it.

01:00:38.300 He escaped the chains of his alcoholism through a psychedelic experience.

01:00:42.280 That was before LSD.

01:00:44.240 And then when LSD came along and it was legal, he tried it and he said, wow, this drug could help lots of alcoholics escape from this belief that the only thing that matters to them is alcohol.

01:00:57.140 It could give them a sense that there is more.

01:00:59.600 It is possible to change.

01:01:00.760 And he persuaded or was instrumental in six trials of LSD for alcoholism that were conducted in the States.

01:01:08.800 So one or two doses in people with alcoholism.

01:01:12.580 And a few years ago, a couple of Norwegians went back and they dug out the old data and they did it, put it through a modern meta-analysis, collate all the data.

01:01:21.840 You've got an effect size of one, which is twice that of any subsequent treatment for alcoholism.

01:01:28.740 LSD was a revolution in the treatment of alcoholism.

01:01:33.360 Now, in the 50 years since LSD has been banned, you know, you can make a rough calculation worldwide.

01:01:40.720 Over 100 million people have died prematurely from alcohol use disorder.

01:01:46.320 And if LSD helped perhaps just 10% of them, that would be 10 million lives saved.

01:01:54.480 Now, you ask the question, well, how many lives have been saved from the ban?

01:01:59.960 Well, I'm not sure.

01:02:02.100 Maybe let's say, let's say globally, maybe, maybe 50, 50 lives a year have been saved because fewer people took it possibly.

01:02:10.500 So then you say, you know, we've got 50 years.

01:02:12.380 There's 2,500 lives saved and 10 million lives lost.

01:02:17.160 So the equation is so balanced against the decision that was made.

01:02:22.440 It really, I think it's the worst censorship of research in the history of the world.

01:02:27.720 And what are the typical harms of LSD?

01:02:30.280 Is it basically self-harm inadvertently through people who are tripping to such an extreme level that they, you know, you hear these stories.

01:02:38.360 Well, this guy thought he could fly and he jumped off a building.

01:02:41.660 Sure.

01:02:42.320 Well, the CIA were very good at promoting those stories.

01:02:45.380 But there are, well, okay.

01:02:48.280 Unquestionably, people do dangerous things when they're taking LSD in dangerous places.

01:02:54.440 And we should mitigate against that.

01:02:56.100 And I can promise you, when we do psychedelic therapy, we lock the door so they can't judge.

01:03:03.060 Okay.

01:03:04.380 How many, here's a statistic.

01:03:06.560 In Britain, and I imagine it's even way worse in the States, each year in Britain, probably 20 to 30 people die jumping, usually drunk, from piers or breakwaters or even from hotel balconies into the swimming pool.

01:03:24.660 So probably more people die each year jumping from alcohol.

01:03:28.040 Which says nothing of automotive accidents and liver toxicity and respiratory depression.

01:03:34.100 Just the jumping.

01:03:35.540 Okay.

01:03:35.880 So LSD, if you take LSD in a dangerous situation with people who are also tripping and you've not got someone to look after you, then, of course, it's, you know, there is a risk.

01:03:45.220 But when LSD was used in these 40,000 patients in hospitals, there was very little evidence of any harm at all.

01:03:52.440 Okay, let's talk about its cousin, psilocybin.

01:03:58.360 Yes, psilocybin, of course, has been around a lot longer.

01:04:00.980 Psilocybin is present in mushrooms.

01:04:03.440 There are about 200 species of magic mushrooms, different ones in different parts of the world.

01:04:07.160 And it was really the beginnings of the psychedelic revolution where LSD and Hoffman and Gordon Wasson, the American mycologist, who discovered a tribe in Mexico that were using mushrooms for psychedelic experiences.

01:04:24.880 And actually went and exposed them and actually rather destroyed their culture by making it a target for tourism.

01:04:32.440 So psychedelic mushrooms have been around forever because mushrooms have been around way before humans.

01:04:38.720 One of the interesting theories about Hinduism, you often wonder, you know, why do Hindu gods have so many arms?

01:04:44.600 Probably because the first people that became Hindus have been using this cocktail called Soma, which, of course, was the term was adopted by Aldous Huxley in Brave New World.

01:04:57.880 But the real Soma was a powerful mixture, probably, of magic mushrooms, of ephedra, and cannabis.

01:05:05.320 You mix that a lot together, it's not surprising your elephants have five heads and four arms.

01:05:10.180 So magic mushrooms have been around in many cultures for millennia.

01:05:13.540 That active ingredient was discovered, the psilocybin as being the active ingredient, was also discovered by Hoffman.

01:05:20.220 Because Wasson went to him and said, why is this causing hallucinations like LSD?

01:05:23.700 And he said, oh, well, because it looks a bit like serotonin, a bit like LSD.

01:05:27.640 And we've been working now with psilocybin for a number of reasons.

01:05:31.180 The main one is that it doesn't have the stigma.

01:05:34.240 LSD, you say LSD to a politician and they immediately turn off.

01:05:39.460 You know, LSD is a bad thing.

01:05:41.860 Whereas psilocybin, they don't know how to say it, they don't know how to spell it, they don't know what you're talking about.

01:05:46.460 And how can you be worried about magic?

01:05:48.480 It's only a mushroom.

01:05:50.280 The second reason we started using psilocybin was because we didn't have safety, really good safety data on any of these.

01:05:57.020 But we did know that in Britain, magic mushrooms were legal until 2005.

01:06:00.740 And we knew that about a million young people a year were using mushrooms.

01:06:05.680 And we persuaded our regulators they could let us use mushrooms because that body of evidence of safety was adequate.

01:06:12.500 And they said, okay, yeah.

01:06:13.320 What led to the scheduling only 15 years ago?

01:06:16.040 I mean, what was happening that in 2005 they said we've got to ban this thing?

01:06:20.080 It's complicated.

01:06:20.800 So the active ingredient psilocybin was banned in 71 alongside LSD, DMT.

01:06:27.580 But the mushrooms weren't banned.

01:06:29.080 Why would you ban the mushroom?

01:06:30.100 They don't have much of it.

01:06:31.160 And who cares if people are going to go and lie on the side of a mountain and, you know, see pretty pictures in the sky.

01:06:37.040 But what happened was that a couple of head shops in Camden Town, North London, started selling freeze-dried mushrooms.

01:06:45.240 So they would concentrate the dose?

01:06:47.160 Well, it's not just that.

01:06:48.240 Like you could take more of it?

01:06:49.420 Or was it just the fact that it was being sold commercially in the head shops?

01:06:51.580 It could be sold in London.

01:06:53.300 And so no one really cares if people go on a hillside in Devon.

01:06:58.040 That's quite fun.

01:06:58.880 But if someone's selling a dangerous psychedelic drug to our young people in London, the right-wing press just went ape.

01:07:06.780 These were probably the same shops that sold Doc Martens, by the way, because I know those head shops.

01:07:11.420 They're very dangerous places.

01:07:12.700 Yeah, absolutely.

01:07:13.500 And it was a classic example of political expediency.

01:07:19.420 The Tory party had lost the third election in a row to the Labour Party, Tony Blair's Labour Party.

01:07:26.120 And they brought in a new guy called David Cameron.

01:07:29.040 And David Cameron had spoken previously about, you know, he'd used drugs and he was in favor of drug reform.

01:07:35.760 But as soon as he became leader of the Tory party, he became anti-drugs because that's what he was told to do.

01:07:40.440 And he saw these newspaper headlines, head shops corrupting our young people.

01:07:45.960 And he started goading the Labour Party that, yeah, soft on drugs, you're soft on drugs.

01:07:52.520 You know, look, they're selling this illegal.

01:07:54.620 The drug wasn't illegal, but the mushrooms weren't illegal.

01:07:56.480 But they made out they were. 1.00

01:07:57.920 And Tony Blair, instead of saying, don't be stupid, he did what many liberal-leaning politicians do. 1.00

01:08:07.520 In fact, exemplified in your country by Clinton. 1.00

01:08:10.600 Clinton was the guy that was told the Democrats had to be harder on drugs than the Republicans.

01:08:16.380 And he's the guy with the three strikes and you're in prison forever.

01:08:19.980 And the same with Labour.

01:08:20.900 They were told, if you're not tougher on drugs or as tough as the Tories, you're going to lose the election.

01:08:26.460 So he goaded Blair into making the mushrooms illegal.

01:08:31.300 And he did it without consulting us and without – he actually broke the law.

01:08:34.880 But we discovered that actually governments are allowed to do that.

01:08:39.020 Even if you take them to court, they can just change the law to prove it, you know, to allow them to have done what they did.

01:08:44.680 And so, yeah, so the mushrooms are now illegal as well as the active ingredient.

01:08:49.480 And then MDMA itself is not really a classic psychedelic.

01:08:53.620 You know, there's sort of a framework for these psychedelics where you've got the kind of the typical, the atypical.

01:08:58.820 But sort of if you have sort of psilocybin LSD here, you've got MDMA here, more of an empathogen.

01:09:03.920 And then you have ketamine as more of a dissociative.

01:09:06.700 And then these really atypical ones like ibogaine, which we've already talked about.

01:09:09.720 So let's spend just a minute on MDMA because, again, I think it's one that – well, first of all, people confuse MDMA and ecstasy a little bit.

01:09:17.740 And it's probably worth clarifying the nuances there.

01:09:20.420 But also talking about the potential that it has.

01:09:22.360 I've had, you know, Rick Doblin on the podcast before.

01:09:24.620 So we've gone incredibly deep on the benefits of, you know, treatment for PTSD.

01:09:29.760 And we've talked a lot about MAPS.

01:09:31.120 We don't need to go that deep.

01:09:31.980 But just for someone who maybe hasn't heard that, what would be the overview?

01:09:35.340 Well, MDMA is a great American invention.

01:09:38.060 Yep.

01:09:38.260 Well, your top drug chemist, Sasha Shulgin, was interested in derivatives of amphetamines.

01:09:46.620 MDMA was made, you know, back in 1904 as a possible agent for blood clotting, but it never got used.

01:09:52.620 And Shulman made it in the 60s and said, wow, this drug is different from amphetamines.

01:09:58.080 It's not activating.

01:09:59.220 It's not driving me like amphetamines.

01:10:01.740 It's actually making – it's giving me a clarity of thought, but also a sense of warmness and empathy.

01:10:07.140 So he gave it to his wife.

01:10:09.120 And she said, wow, this is a very – this is empathy.

01:10:12.440 This would be really useful in psychotherapy, in couples counseling.

01:10:15.880 It would potentially help break down, you know, those layers of irritation and grit that build up in relationships sometimes.

01:10:23.000 Put people back into love.

01:10:24.660 And it was widely used for about 10 years by therapists, particularly in the West Coast of the States.

01:10:28.700 And it was called empathy.

01:10:30.020 And everything was fine.

01:10:31.740 And then some smartass in Texas decided this is a legal drug and we could sell this. 1.00

01:10:37.840 We can't sell amphetamines, but we can sell ecstasy because it's legal.

01:10:40.800 But who wants to buy ecstasy?

01:10:42.600 So they changed the name to ecstasy.

01:10:44.960 So they didn't want to buy empathy, sorry.

01:10:46.640 They changed the name to ecstasy.

01:10:48.220 You've got an amphetamine which can help keep you active but also make you much more in love with other people.

01:10:55.200 And it became, you know, widely used.

01:10:58.140 You know, it's the perfect drug for parties, isn't it?

01:11:00.420 You know, you've got energy but you're also happy.

01:11:02.560 You're not fighting people like you do if you're taking speed.

01:11:05.680 And it became hugely popular and it spread into Europe.

01:11:08.640 And then, of course, it just riled the Puritans.

01:11:12.220 It riled the right-wing press.

01:11:13.920 The idea that young people could have ecstasy when the newspaper owners never had it and didn't even know what it meant.

01:11:22.260 They just didn't – you had this moral outrage.

01:11:25.960 Which eventually got the drug banned.

01:11:27.760 But again, you couldn't – in America and Britain in those days, you couldn't ban a drug just because kids liked it.

01:11:32.480 You had to find evidence of harm.

01:11:34.380 And some of the worst science that's ever been done is the science proving or supposedly proving that MDMA is harmful.

01:11:42.180 And culminating in that amazing experiment that was done by Riccardi, which is really embarrassing for Johns Hopkins,

01:11:49.400 you know, when he claimed that taking MDMA and listening to the Poges overnight gave monkeys brain damage.

01:11:57.200 And we all said, well, hang on a second.

01:11:58.980 None of our kids are coming out of the clubs with brain damage.

01:12:01.960 I think your experiment's wrong, Riccardi.

01:12:04.180 He said, no, no, it's right.

01:12:05.200 Look, ecstasy causes brain damage.

01:12:07.480 And he got published in science despite the fact the referee said, this has got to be wrong.

01:12:12.140 And of course, eventually they went back and they audited what they'd done.

01:12:14.920 And instead of giving the monkeys MDMA, they'd given them crystal meth, which is way more toxic.

01:12:20.980 That paper was recall.

01:12:23.240 I mean, he did have to pull that paper, didn't he?

01:12:25.320 No, no, he didn't retract the paper.

01:12:27.320 He just put it.

01:12:27.880 It was never retracted?

01:12:28.720 I think you can still find it.

01:12:30.160 If you look in science, you'll still find it's there.

01:12:32.280 It's not struck out.

01:12:33.740 I think you'll just find there's a correction.

01:12:36.520 Sorry, guys, this wasn't MDMA.

01:12:38.460 This was actually methamphetamine.

01:12:42.500 Wow.

01:12:43.480 Terrifying.

01:12:43.900 So that's our answer to Andrew Wakefield for you, huh?

01:12:47.420 Indeed.

01:12:47.860 And it's embarrassing really because, well, for all sorts of reasons, because so much American science is paid by the government.

01:12:58.180 Apparently, I don't know, I heard that the editor of the magazine Science was told by senators that the American Academy of Science, which runs a journal, would not get government funding if he didn't put that paper in and get it published to deter young people from using MDMA.

01:13:16.040 Of course, all that happens is, in the end, young people think this doesn't make sense, and then they discover they've been lied to.

01:13:22.060 So are they going to listen to anything else the government tells them?

01:13:24.720 Yeah.

01:13:24.840 Let's talk briefly about ketamine before we come back to psilocybin, because I want to sort of double-click more on psilocybin specifically for the treatment of depression.

01:13:34.880 But just to round out all of our sort of psychedelics, ketamine, of course, is the only drug on this list that is legal.

01:13:42.200 So I believe it's a Schedule 3, perhaps a Schedule 4, used as an anesthetic typically, and it's quite dissociative.

01:13:49.880 So can you talk, I guess, specifically about the use of ketamine in treatment-resistant depression, which seems to be one of the more promising areas of research?

01:14:00.680 Yes, a wonderful story, and it goes back to John Crystal, who's a professor up at Yale, and he was using ketamine to model psychosis, and he was comparing ketamine and THC to model psychosis.

01:14:14.780 And they both produce altered states of consciousness, which sort of have some overlap with psychosis.

01:14:20.520 But he noticed that afterwards his volunteers often felt better.

01:14:26.100 You know, they actually came out of the ketamine experience saying, well, that was weird, but they had an improved mood.

01:14:30.460 And he thought, maybe this is mood elevating.

01:14:31.980 So then he and his colleagues went on and did a study.

01:14:34.560 Yeah, ketamine elevates mood.

01:14:36.420 And for a couple of days after a ketamine trip, your mood is definitely improved.

01:14:40.720 And now there have been about 30 studies showing that ketamine can have a value, particularly if you add it on to other treatments of depression,

01:14:49.560 which have not been very successful.

01:14:51.240 So if people are partially recovered, give a bit of ketamine, and their mood gets better.

01:14:55.780 The problem with ketamine compared with what we're going to talk about in a minute with psilocybin is that the effect is very short-lasting.

01:15:00.820 It lasts only two or three days.

01:15:02.600 So currently what you have now is a licensed medicine.

01:15:06.980 Janssen decided to pursue this because this was the first real breakthrough in the treatment of depression for really for 50 years.

01:15:13.420 But you couldn't patent ketamine because ketamine was being used back in the Vietnam War as a buddy drug when people were being blown up and having used it as an analgesic.

01:15:23.380 So they took the enantiomer, one of the isomers of ketamine, called the S-enantiomer, and they called it S-ketamine,

01:15:29.660 and they formulated it for nasal inhalation so you don't have to inject it, which is better and easier for psychiatrists.

01:15:34.920 And now that's sold as a treatment, and it's called S-ketamine Spravate.

01:15:38.120 And it works, and you take it a couple of times a week, and then gradually over time you dose less and less as the patients recover from depression.

01:15:45.720 So you don't develop a tachyphylaxis to it?

01:15:48.100 If you do it twice a week, you don't.

01:15:49.480 No, no.

01:15:50.340 And you are able to get patients off of it while still preserving the antidepressive benefits?

01:15:56.600 That's less clear, but in some that's true.

01:16:00.060 But there is an advantage of it over ketamine.

01:16:04.200 Ketamine clinics tend to—

01:16:06.200 They give it intravenously.

01:16:07.480 They give it intravenously, yeah, or intramuscularly.

01:16:09.980 But also the problem there is that ketamine is a dependence-producing drug.

01:16:15.180 It's a drug, a recreational drug.

01:16:17.080 It's relatively popular in Britain.

01:16:19.680 It's relatively popular in China, probably popular also in the States.

01:16:22.940 I'm not sure what the stats are.

01:16:24.740 The problem is you do get tolerance, tachyphylaxis, if you use it regularly.

01:16:28.560 So while it's relatively safe in the doses you might use, maybe 500 milligrams for depression,

01:16:35.220 if people are using it recreationally and taking more and more, they're getting up to grams a day,

01:16:39.260 and then you get into serious problems.

01:16:41.320 You get bladder problems.

01:16:43.500 Basically, you get a severe chronic cystitis, which can cause bladder atrophy, needing bladder resection.

01:16:50.380 And you also get a psychological state.

01:16:53.600 You can get brain damage, or at least you can get a state of severe cognitive impairment, which actually rather mimics schizophrenia.

01:17:02.720 So heavy use of ketamine is actually really to be avoided.

01:17:05.860 And what defines that?

01:17:07.600 I mean, those are very scary things you just described.

01:17:10.080 Obviously, the psychiatric component much more than the urologic.

01:17:14.500 What is too much?

01:17:15.580 I mean, because I'll tell you, this is something I get asked a lot.

01:17:18.480 Hey, you know, I'm going to this ketamine clinic once a month.

01:17:21.600 It's changing my life.

01:17:23.540 You know, at what point does that become too much?

01:17:25.980 Oh, yeah.

01:17:26.320 Well, certainly daily use is too much.

01:17:29.180 So, I mean, people who are addicted to ketamine are using it four or five times a day.

01:17:32.500 They might be using five grams a day, and that's when you get into the serious brain damage.

01:17:37.340 So I think twice a week, oh, I think we know from S-ketamine, twice a week seems to be without, doesn't have any enduring problems with diabetes.

01:17:44.080 But if you're not using the enantomer, twice a week will probably still produce a tachyphylaxis and a diminishing return at some point.

01:17:51.500 Yes, but one of the really interesting questions, and we don't understand this.

01:17:55.120 Why is it that when people use ketamine and they get tachyphylaxis, they can overcome it by taking more?

01:18:03.460 By the way, I should explain to people what tachyphylaxis is because we're using the term without me defining it.

01:18:08.060 It's, of course, when the same amount of a medication produces a lesser and lesser effect or when you require more and more of a medication to produce the same effect.

01:18:17.140 So, for example, we don't generally get tachyphylactic to Tylenol, right?

01:18:20.920 You have acetaminophen. If you take 500 milligrams and your headache goes away, you know, the next time you take 500 milligrams, it does about the same thing.

01:18:28.720 So to your point, you can push the dose a little bit and stay ahead of it with ketamine?

01:18:33.420 Correct, you can. You can, like heroin, like fentanyl. You can overcome the tolerance.

01:18:39.220 But with psychedelics, you can't. And that's an interesting phenomenon.

01:18:43.920 And it's probably to do with subtle changes in the downstream mechanisms in the cells that, you know, you get an almost complete absence of effects of psychedelics after two or three doses.

01:18:56.340 And do you know who told us that?

01:18:57.640 No.

01:18:58.140 The U.S. government.

01:18:59.600 So the U.S. government were very interested in or fearful, actually, when psychedelics came around in the 50s.

01:19:06.120 They thought, well, maybe the Russians will be spraying LSD on our troops.

01:19:10.080 So how can we protect our troops from LSD?

01:19:12.540 So they started giving troops LSD to find out what the effects would be to see how they could abort them.

01:19:19.220 And they discovered by the third day of giving the troops LSD, LSD had no effect anymore.

01:19:23.440 Well, I didn't realize that was the case.

01:19:24.800 So if you're talking 250 micrograms of LSD, at some point, people are going to stop responding to that?

01:19:31.520 Yeah, but the second dose will be less than the first.

01:19:33.660 If you take it every day, the second dose is way less than the first.

01:19:36.240 But what if you're taking it once a month, for example?

01:19:38.380 No, no, no.

01:19:39.040 It takes about a week to recover.

01:19:41.720 The effect disappears between about one and two weeks, depending on how much you take.

01:19:45.320 I see.

01:19:45.580 So it's not a lifelong tachyphylaxis.

01:19:47.240 It's very temporal.

01:19:48.460 No, although some people do say, well, a lot of people say that for all drugs, that the first one's always the best.

01:19:52.940 Yes, yes.

01:19:53.560 So you can't overcome the tachyphylaxis with psychedelics, whereas you can with heroin and you can with ketamine.

01:20:03.100 And why that is, we're not so clear as to why that is.

01:20:07.060 All right.

01:20:07.640 Well, there's so many more questions I have about this, David, but I know we have a very hard stop today.

01:20:11.780 So I want to make sure we have some time to talk about your most recent work with psilocybin and depression.

01:20:18.540 About three months ago, a study was published in the New England Journal of Medicine.

01:20:21.700 You were the senior author on that paper.

01:20:23.460 I've written about it at length, which compared psilocybin to Lexapro, a very, very popular, commonly used, reasonably well-tolerated SSRI.

01:20:34.080 Do you want to just give people a quick overview of the study design and what you set out to test?

01:20:39.980 Oh, I'd be pleased to.

01:20:40.820 Yes.

01:20:41.060 So previously, we had done a study, an open trial.

01:20:45.480 We'd taken 20 people with resistant depression.

01:20:47.840 We'd given them a single psilocybin trip and found a very good outcome.

01:20:53.580 But the effect didn't last very long.

01:20:55.260 It lasted, you know, one to two months.

01:20:57.900 But for many of them, the depression came back.

01:21:00.700 Based on that and also some theoretical work I'd done with Robin Carhart-Harris, who was with me at the time.

01:21:05.880 He's now moved to UCSF.

01:21:07.180 We came to the conclusion that psychedelics treat depression in a different way to antidepressants.

01:21:15.000 And that paper's published in the Journal of Psychopharmacology.

01:21:17.340 It's called A Tale of Two Receptors.

01:21:18.540 It's a free download.

01:21:20.180 Feel free to read it because it conceptualizes that there are two ways you can lift depression.

01:21:24.040 One way is with Lexapro or other similar drugs that enhance serotonin in the limbic system.

01:21:32.740 And there, they basically block the stress response.

01:21:35.980 And we know that stress is a major cause of depression.

01:21:38.540 You block stress-induced depressive changes in that system.

01:21:42.900 And that allows the limbic system to recover.

01:21:46.760 So that it's a bit like if you have a broken leg, you set the leg in plaster so that the bone can heal itself.

01:21:52.940 SSRIs set the limbic system in plaster so over a period of six to eight weeks, they can heal and get you over your depression.

01:22:01.480 And that's through a particular subtype of serotonin receptors called the serotonin 1A receptor, which is very expressed in the limbic system.

01:22:09.480 But we think psychedelics, we know psychedelics work in the cortex.

01:22:12.320 And they disrupt cortical processing and disrupt, we think, the deep, persistent ruminations and negative thoughts of depression.

01:22:21.820 So we said, let's do a study where we take depressed people.

01:22:26.020 We scan them with fMRI before and after.

01:22:28.920 And then we see if we can look at if the brain changes are different with the escitalopram compared with the psilocybin,

01:22:38.420 predicting that we would see cortical differences, that the cortex would be changed by the psilocybin,

01:22:44.500 and the subcortical regions would be changed by the escitalopram.

01:22:47.860 So the primary aim of the study was to see if there were differences in brain mechanisms.

01:22:53.100 But, of course, we have to know whether there are differences in outcome.

01:22:56.240 So we compared the mood-changing effects of these two drugs.

01:23:00.500 But you couldn't just say, here, you're on Lexapro, here, you're on psilocybin.

01:23:04.120 We had to blind it.

01:23:05.740 And that's quite difficult with psychedelics.

01:23:07.240 So the way we did that was to tell everyone they were going to get psilocybin.

01:23:13.340 But half the group got a low dose, a placebo dose, a one milligram dose, and half got a high dose, a 25 milligram dose.

01:23:19.600 But they all went through the same psychotherapy.

01:23:23.260 It didn't matter what dose they got.

01:23:24.660 They all got all the same preparation and the psychotherapy that goes with a high dose of psilocybin.

01:23:29.540 And then they all got pills.

01:23:32.060 But the escitalopram group got escitalopram and the psilocybin group got placebo.

01:23:38.200 So they're both getting two pills.

01:23:40.400 One is getting a placebo plus a high dose of psilocybin.

01:23:43.940 The other, yeah.

01:23:44.720 And the point of that is what's called clinical equipoise.

01:23:47.220 People have to believe that they're getting the best they can.

01:23:51.320 And we gave them two doses of psilocybin, whether high or low.

01:23:54.880 One at the start and one after three weeks to see how long the effect would last.

01:23:58.020 And then we measured changes in mood and we measured side effects.

01:24:02.340 And we also looked at other aspects of depression.

01:24:05.000 Rather than just looking at depression scores, we also looked at things like well-being,

01:24:08.860 which is a different way of looking at how people are feeling.

01:24:12.720 And in the end, on the primary measure, there was no difference that psilocybin at six weeks

01:24:18.300 was as good or equal to as escitalopram on that particular measure,

01:24:22.920 which was a particular self-report measure called the QUID self-report,

01:24:26.460 which has been used quite extensively in research in the States, particularly in the STAR-D study.

01:24:31.880 But when we looked at all the other measures, actually psilocybin did rather well.

01:24:36.640 Yeah.

01:24:36.840 So I want to pause on that for a sec because I think that the paper was undersold a little bit.

01:24:42.940 It read as a negative study as opposed to a non-inferiority study.

01:24:48.720 Why do you think that happened?

01:24:50.060 Do you think that there was a mistake in the way that either the journal treated that

01:24:53.760 or even the way you treated that as the authors?

01:24:56.460 Yeah, that's a great question.

01:24:58.040 A very perceptive question.

01:25:00.080 That's a question I think you should ask the editors of the New England Journal.

01:25:02.880 The truth was it wasn't powered for non-inferiority.

01:25:09.940 If you want a proper non-inferiority study in psychiatry takes 150 patients in each arm.

01:25:17.100 We could never afford to do that.

01:25:19.260 There's very few of them have ever been done except by – well, probably none have been done

01:25:22.660 except by companies.

01:25:23.880 We could not statistically do a non-inferiority study.

01:25:27.240 So we had to just do a kind of comparison.

01:25:29.280 And the answer was that, well, we had to pre-specify.

01:25:35.720 We pre-specified two outcomes, the quids and the well-being.

01:25:40.660 And it did brilliantly on the well-being.

01:25:42.700 But because that's kind of not – well, that's sort of soft, wishy-washy psychiatry.

01:25:49.200 They insisted that we use the quids as the primary.

01:25:51.820 Now, if you don't meet – this is a bit statistical sort of jargon really.

01:25:56.740 But if you don't meet your primary, you're not allowed to report the secondaries.

01:26:02.160 It's purism.

01:26:03.300 It's puristic statistics.

01:26:05.640 But as you say, it's kind of not very intuitive because when you look at it, actually, it was

01:26:10.820 very clear that the overall – well, there was not a single measure that favored esitalopharm.

01:26:17.640 And there were like –

01:26:18.860 Well, that's sort of the thing is, you know, I read the paper in great detail.

01:26:24.080 And my takeaway was this is very promising because I'm very familiar with Lexapro.

01:26:30.400 And I'm very familiar with its efficacy.

01:26:31.840 But I'm also very familiar with its side effects and the baggage that comes with it.

01:26:35.280 Most people, for the listener, Lexapro is typically given at two doses, 10 milligrams or 20 milligrams.

01:26:40.580 Going from 10 to 20, there is a sizable increase in the efficacy, but there's also a sizable

01:26:46.340 increase in the side effects, many of them sexual.

01:26:49.800 And when we're talking about treating young people, old people, middle-aged people, you

01:26:55.220 fix their depression, but you destroy their libido, you're trading one problem for another

01:27:00.220 often.

01:27:01.240 And the list of patients I've taken care of who can't tolerate these drugs, despite the benefit

01:27:07.160 that they're receiving from an antidepressive or anti-anxiolytic standpoint, is significant.

01:27:12.340 So to me, I read that study with enormous optimism, right?

01:27:15.680 Which is, if there is a way to give somebody 25 milligrams of psilocybin and get the same

01:27:20.920 antidepressive benefits, but without these other side effects, this is very exciting.

01:27:27.120 This needs to be explored a heck of a lot further.

01:27:29.640 Do you think that the study at least accomplished that as an outcome?

01:27:34.120 Yeah.

01:27:34.260 So people have said, well, why didn't you fight back with a journal?

01:27:37.100 Why didn't you demand, you know, that they were more positive?

01:27:40.220 And the answer is, from my perspective, being the first ever psychedelic study in the New

01:27:46.680 England Journal of Medicine tells the world that psilocybin is a medicine.

01:27:53.060 And it's as good as Lexapro.

01:27:55.080 And anyone who reads the paper can see that it does do better on sexual dysfunction, and it

01:28:00.100 does do better on many of the other issues that Lexapro is a problem with.

01:28:05.320 And it fits with the theory that one of the things, it's very, the reason Lexapro and other

01:28:11.580 SSRIs dampen down sexual activity is because they dampen down the limbic system, which is

01:28:17.700 the part of the brain which drives those behaviors.

01:28:19.700 And also, people on these drugs often say, yes, I don't feel depressed anymore.

01:28:24.120 I don't cry.

01:28:26.020 I don't have the distress that comes from seeing sad things on the TV.

01:28:31.080 But they also say, but also, I don't enjoy life as much because my pleasures are blunted.

01:28:36.560 And that all fits with that theory.

01:28:37.840 It's blunting the top and the bottom.

01:28:39.340 Exactly.

01:28:39.980 Exactly.

01:28:41.260 Whereas psilocybin is stopping the thinking and allowing the rest of your brain to work normally.

01:28:46.020 A word on microdosing, David, I even had to go back and do the conversion.

01:28:50.620 So when I was reading the study, I was going, wait a minute, what does 25 milligrams of psilocybin

01:28:55.100 mean?

01:28:55.420 Because typically when people are taking psilocybin, we're giving it to them in the whole mushroom,

01:28:59.660 and that's typically like five grams.

01:29:02.140 So of course, then I had to get really deep in the weeds and figure out which species of

01:29:05.640 mushroom and what the conversion is.

01:29:07.620 But the point is 25 milligrams of pure psilocybin is on par with about four to five grams of

01:29:16.300 magic mushrooms, and therefore it is truly a psychedelic experience.

01:29:20.700 What is known about the imperceptible dose, like 100 milligrams of magic mushroom or one

01:29:29.120 to two milligrams of pure psilocybin and its potential for antidepressive benefits?

01:29:36.780 Well, loads of people use it.

01:29:38.720 Loads of people, you know, they go pick the mushrooms, they dry the mushrooms, and they

01:29:42.900 take them.

01:29:45.280 I'll give you a, I was talking at a festival a couple of years ago in Wales.

01:29:50.400 It's, you know, it's called How the Light Gets In, and it's a big intellectual music and

01:29:54.800 music festival.

01:29:55.620 And after my talk, a lady came up to me, she said, yeah, I've got to share you the, you know, 0.99

01:29:59.700 I'm a nurse, she says.

01:30:01.220 I've got a kid, it's difficult.

01:30:02.420 I mean, I'm not married, she says.

01:30:04.000 But I get up every morning, you know, and I get the kid to school, and I come back,

01:30:08.060 she says, I have a cigarette, a cup of coffee, and a mushroom, and I've been really good

01:30:11.860 for the last few years.

01:30:13.740 And there's, anecdotally, there's large numbers of people who are using these mushrooms.

01:30:18.740 Do they work or not?

01:30:19.860 We don't know, because it's almost, the rules around these drugs, the Schedule 1 status

01:30:24.940 means that a single mushroom is just as illegal as a bunch of mushrooms, or as pure cytosibine.

01:30:34.120 Four years ago, we got ethical permission to do a microdosing study with LSD.

01:30:41.360 But, they said, this is an illegal drug, a dangerous drug.

01:30:44.840 Every microdose had to be given in hospital.

01:30:46.860 And then we costed up what it would take to buy all that time in hospitals to do six weeks

01:30:54.300 of microdosing.

01:30:55.020 We couldn't afford it.

01:30:56.400 And so, there has never been a proper controlled microdosing study of any, repeatedly, of any

01:31:02.580 psychedelic.

01:31:03.760 But from a mechanism of action standpoint, David, do you see a plausible path to microdosing

01:31:09.800 being effective, given what you now know about macrodosing?

01:31:13.380 Well, it won't be as good.

01:31:15.220 Obviously, not a single microdose won't be remotely as good as a macrodose.

01:31:18.380 But say repeatedly, because I believe in your study, they were given this macrodose every

01:31:22.260 two weeks, correct?

01:31:23.180 Twice.

01:31:24.080 Three weeks apart, twice.

01:31:25.420 Yeah, that's right.

01:31:26.420 But if we were talking about microdosing three or four times a week at one to two milligrams,

01:31:33.260 and we're talking about this type of a treatment over the course of a year, so apples to apples

01:31:37.680 time-wise, is there a plausibility here that you can see from a mechanism standpoint?

01:31:42.580 Well, it'd be a great experiment to do.

01:31:44.880 I mean, I think it is, I mean, I think, and I think it's ethical to do that, because I

01:31:49.200 think it is plausible that microdosing over a long period might do two things.

01:31:56.540 I would be slightly surprised if it really elevated mood in depressed people.

01:32:01.540 But it might protect people against a lowering of mood.

01:32:06.500 And so, one of the interesting questions, in fact, in many ways, the fundamental question

01:32:10.260 we have now, as a result of our two depression studies, is not that we can get people better.

01:32:15.180 There's no question with psilocybin.

01:32:17.000 How can we keep them well?

01:32:19.100 And one of the great things we know about the SSRIs is that if you take them continuously,

01:32:24.060 they do protect against depression.

01:32:26.680 They do protect against the stresses of life causing depression at the cost of blunting.

01:32:33.720 So, the question is, what could we do other than give them an SSRI after the psychedelic

01:32:40.160 treatment?

01:32:40.560 And maybe microdosing would work.

01:32:42.540 But until we get it liberated, until we get it out of Schedule 1 and get it available, it's

01:32:47.840 impossible to do those studies.

01:32:49.960 Where do you think will be the thin end of the wedge to make that happen?

01:32:53.740 Obviously, Roland Griffiths has done great work at Johns Hopkins, someone I'd like to have

01:32:57.760 on the podcast as well, looking at psilocybin in end-of-life depression, though I don't

01:33:04.040 know where things are from a pathway perspective.

01:33:06.440 There's obviously efficacy with smoking cessation and alcohol cessation, and now your work with

01:33:12.420 depression.

01:33:14.000 Which of these will be the first domino that falls, in your opinion, to change the scheduling

01:33:18.740 of psilocybin?

01:33:19.420 I think depression.

01:33:20.800 Because a multi-center study is going on in Europe and the US by a company called Compass

01:33:26.840 Pathways, and they're doing a dose-finding study.

01:33:29.600 They've finished, they've recruited the last subject, they will get the results hopefully

01:33:34.080 by Christmas or the New Year.

01:33:35.900 And that's a high dose, 25 milligram dose, a placebo dose, a one milligram dose like we

01:33:40.500 did, and a 10 milligram dose in between.

01:33:43.200 I think if that's positive, then the floodgates will open to their second study and also to

01:33:49.220 funding of that research.

01:33:51.620 Now, Compass has come under great scrutiny from some in their effort to, you know, basically

01:33:56.820 do a land grab of intellectual property on a molecule that basically should be in the

01:34:01.400 public domain.

01:34:02.760 How do you think about that in terms of balancing the need to make something as widely available

01:34:08.100 as possible to the public, while at the same time needing to create an economic incentive

01:34:12.300 to do so?

01:34:13.100 Yes.

01:34:13.360 Well, of course, I have to express, and I've been helping them for a lot.

01:34:16.620 I mean, their Compass Pathways exists because of our first depression study.

01:34:20.900 You know, they basically took our data and went and tried to do research with it.

01:34:25.120 And they started off being a bit like maps.

01:34:27.180 They started off trying to raise money by being a not-for-profit.

01:34:32.960 Now, Rick Doblin is a phenomenon, but it has taken him 25 years to raise enough money

01:34:40.000 to do the maps phase three.

01:34:44.140 And after a year or so, Compass Pathways realized that they didn't have the resources or the skill

01:34:50.080 or the personalities that Rick has.

01:34:53.400 Yeah, Rick's a force of nature.

01:34:54.880 He is.

01:34:55.780 And they realized that they couldn't be a not-for-profit.

01:34:58.380 They had to get the money for this to happen.

01:35:00.080 They had to go down the more conventional route.

01:35:03.200 So, you know, much as I would like it not to be the case, you know, reality is, I think

01:35:08.320 if we want to see cytosibine with enough evidence in my lifetime to make it a medicine,

01:35:13.100 then I think that they are the people that are most likely to deliver that.

01:35:17.180 But on the other side, you've got Oregon.

01:35:20.300 You've got Oregon, which voted in November last year to make mushrooms a medicine in two

01:35:26.180 years' time.

01:35:27.440 So it's actually a bit of a race now to see who's going to win.

01:35:30.480 I don't know how Oregon are going to do it.

01:35:32.780 I just hope they do it carefully and sensibly.

01:35:35.100 But it might be that the mushroom ends up being the medicine rather than the cytosibine.

01:35:39.980 Exciting times.

01:35:40.780 David, I promised you that at 6 p.m.

01:35:45.400 I would draw to an end and we are at 5.59 p.m.

01:35:48.600 So I'm going to stick to my word despite the fact that we are only halfway through what

01:35:52.720 I wanted to talk about.

01:35:53.820 So I think the only logical conclusion here is that we will have to sit down and do this

01:35:58.180 again if you're willing.

01:35:59.340 I'd be delighted.

01:36:00.360 It's been a wonderful conversation.

01:36:01.920 Thank you so much.

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The Peter Attia Drive - November 01, 2021

#182 - David Nutt： Psychedelics & Recreational Drugs

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