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EVERY SPOKEN WORD
95 min read · 18,889 words- 0:00 – 0:10
intro
- PAPeter Attia
[upbeat music] Hey, everyone. Welcome to the Drive podcast. I'm your host, Peter Attia. [upbeat music] Hey,
- 0:10 – 8:00
David’s early interest in the brain and experience in psychiatry
- PAPeter Attia
David. Thank you so much for making time, uh, in your evening, my afternoon here today. Uh, very, very much looking forward to speaking with you about a topic that I think is on a lot of people's minds lately.
- DNDavid Nutt
Well, thanks for the invite. I'm looking forward to it too.
- PAPeter Attia
Let's start a little bit with your, your background. You-- It, it sounds like based on what I've read, uh, going back to your early teen years, you, you've always had an interest in the brain, whether it be through the lens of neuroscience or psychiatry. What, what, what do you think sparked that interest?
- DNDavid Nutt
Uh, well, thinking about things. [chuckles] Yeah, yeah, I guess it was, uh, understanding that, um, I don't know, uh, I think when I was probably four or five, I suddenly kind of realized that actually thinking was what actually made things make sense. And then I realized that thinking came out of the brain, and I've always been fascinated by the brain. And actually, I went to university to Cambridge to do brain science. I wanted to be a physiologist, you know, like Hodgkin and Huxley do, do physiology. And then I kind of realized [chuckles] actually that some-- that, that was, you know, and single cells are interesting, but, uh, but the-- y-you gotta put the two, you know, the two hundred billion together and make sense of those. And actually, that's where then I went and did neurology, and that got a little bit boring because it's mostly people kind of dying slowly from diseases like amyotrophic lateral sclerosis. So then I moved to psychiatry, and then it became really wonderful because you see every aspect of the brain in psychiatry.
- PAPeter Attia
Well, it's so funny you say that because I'm not making this up, but this, this morning, my, uh, six-year-old son w- uh, was in my office, and he-- we were sort of fumbling around, and I, I have a whole bunch of racing helmets in my office. And so he's putting them on, and that, that got him talking about why we're wearing helmets to protect the brain and blah, blah, blah. And, and then I said, "Well, do you wanna see what a..." Well, he said, "What does a brain look like?" So I pulled up, you know, on Google, I pulled up some images of brains, but actual anatomic images. And, and again, he's only six, but he's looking at this, and he's thinking like, "That's very unimpressive." And, and he, he sort of says, "It just looks like a slimy thing." And I said, "Yep, that's true. That's what it looks like." And he says, "But is this where my thoughts come from?" And I said-
- DNDavid Nutt
There you go
- PAPeter Attia
... I said, "Yes. That's where your thoughts originate." And he said, "Well, how?" And I gotta tell you, it was very difficult for me to explain how electrical impulses work, and of course, I'm not gonna get into action potentials and neurotransmitters. But what's funny is it then took me down a rabbit hole of spending thirty minutes on YouTube trying to find good videos of this for kids. And I-- if anybody can find one, please send it. But I couldn't find great videos 'cause the, the videos that I found were more anatomic, like, "This is the part of your brain that controls movement. This is where memories are stored." But he was asking a deeper question, which was, "How does this blob make me think?" Uh, which, uh, it sounds like you were asking that same question as a four or five-year-old.
- DNDavid Nutt
Exactly. But what's amusing, even more amusing, is my new book, which is coming out, uh, later this year, is called Brain and Mind Made Simple. It won't be simple enough for a six-year-old unless he's very precocious, but I have written a book for the general public to try to explain that, that, that this peculiar phenomenon that how lots and lots of single nerves can actually turn into all the complexity of, of the different forms of consciousness and the different experiences that humans have. And at some point, and I think what you, you know, the point you raise is a really good one, it'd be really nice to then to migrate that down t- for, for children, maybe, you know, as a series of sort of comics or graphics 'cause I think, you know, the, I mean, it is the most wonderful thing in the, in the universe, the human brain. There's no argument about it. So let's get communicating as soon as we can.
- PAPeter Attia
Yeah. A-and, and I do think that, like for me personally, it's not a question I ever contemplated early. So it made me very happy that he was asking this question at the age of six in a, in a deep enough way. And, and look, even if the book is not written for a six-year-old, I'm sure it will help me do a better job explaining it to a six-year-old. Um, so, so coming back to your career, so now you've migrated into psychiatry, which of course, uh, on some levels is really about understanding pathology of the mind, which is effectively what all parts of medicine are, whether it be neurology or otherwise. Um, what were some of the first things that stuck out to you about the, the pathology of the mind through the lens of a psychiatrist?
- DNDavid Nutt
Well, the fir- the first patient I saw-
- PAPeter Attia
Hmm
- DNDavid Nutt
... who, uh, I was dropped into, there was a, a, a doctor didn't turn up. I'm a medical student, so one said, "Oh, please go, go and interview. Go and clerk this, this new m- this new patient." So I'm sitting there, I'm talking to this person who's not making any sense whatsoever, and kept talking about there being a smell of fish in the room and, and, and rambling on about the smell. And after about an hour of trying to get some sense, I say, "Well, thank you. I, I'll just... I, I have to go. I'll be back in a minute." And I go out, and I talk to the consultant. And, uh, and he says, "Oh, well, he's clearly psychotic." [chuckles] And I thought, "Oh, that makes a lot of sense. That's why he doesn't make sense, and that's why I didn't understand what was going on." So and, and what was very interesting actually about that is that the relationship between temporal lobe disorders, those, those parts of the brain which are intimately involved in, in aspects of consciousness and also smell, and there was this peculiar overlap between temporal lobe disorders where, where, you know, you can be psychotic, but you also have these olfactory hallucinations, and that's what he had. So he was hallucinating rather than in his ears, which most people with schizophrenia do. He was, uh, he was hallucinating in, in, in terms of smell. So yeah, I've never forgotten that, uh, [chuckles] 'cause it, it was just such a kind of completely bizarre experience. And it, and it made me realize I got a lot to learn, you know? [chuckles]
- PAPeter Attia
Now, for most people, when they go into psychiatry, um, and, and I'm sure this was the case with you, you spend a lot of time learning the neuropharmacology of the agents that are going to be used to help treat patients with psychiatric illness. And for many people, that's sort of where it stops. But you've also generated or developed this other interest, which is in the neuropharmacology of, um, these regulated substances, you know, call them illegal or recreational drugs and otherwise. Where did, where did that interest stem from?
- DNDavid Nutt
Wow. Well, so, uh, yes, I, I am, uh, I am a professor of neuropsychopharmacology, uh, at Imperial College London, and, uh, neuropsychopharmacology is, is really the use of drugs to study the brain and to study the effects of, of treatments for brain disorders, particularly in the case of psychiatry, uh, psychotropic drugs. Uh, my PhD was on the GABA system, on drugs m- m- manipulating the GABA system. As an undergraduate, I think, you know, the big influence on me, I was extraordinarily fortunate. So I, I'm at university in Cambridge in the 19... early 1970s, when people are discovering that the brain is a chemical organ. Up till that point, it was thought the brain was an electrical organ. It w- You know, it was like a very complicated computer or, you know, like a, you know, some kind of complex telephone exchange. But then the, the, the concept of chemical transmission came along, uh, and, uh, now we know that there are at least 80 different chemicals, neurotransmitters, hormones, neurohormones. And seeing that transformation from electricity to chemistry, uh, made me realize, you know, the way you study the brain now is through drugs which affect the chemistry of the brain. And then they, there, there are these therapeutic agents which are obviously very important, antidepressants, antipsychotics, anticonvulsants. But then that raises the next question, you know, but people use other drugs to change the brain. They, and they use them recreationally for, you know, like drugs like cocaine or crystal meth or the, or they use them to deaden pain or, or to get insights
- 8:00 – 11:20
David’s brief work on government drug policy in the UK
- DNDavid Nutt
like psychedelics. And, um, after a while, because I'd done so much research on drugs, I was asked by the British government to help them think through drug policy. Well, actually, that was, that was not true. They asked me to help them justify drug policy. But when I started working for them, I realized that the drug policy wasn't in any way evidence-based, and, and when I tried to bring evidence to bear on drug policy, they sacked me [chuckles] because it, because it's much more convenient to have a political decision-making about drugs than it is to have an, uh, an evidence-based one.
- PAPeter Attia
What year was that, that you got involved in that?
- DNDavid Nutt
Well, I started working on the principles of assessing drug harms really back in the 1990s, and it actually came with the rise of ecstasy and, and the, and people supposedly, or seemingly, getting harm from ecstasy. And I th- I, I was one of the p- uh, one of the experts who was asked by the government to come up with a policy which would reduce the harms from ecstasy. Yeah. And [chuckles] and it became very clear when we were researching those that, uh, the harms of ecstasy aren't from the drug at all. They're actually from the, uh, what you do when you're on the drug. They're either from the fact you dehydrate because you dance all night, uh, or you over, over... You, you get hypothermic because you're in an environment where you can't cool down. And so we said, and actually we brought in a, what in legislation in Britain, which said any club which is serving drinks, which is where most people were going to have their ecstasy, they're going to clubs, they must serve free water. 'Cause what the clubs were doing were, were actually forcing people to drink alcohol, uh, or pay for water in order to, to, to dr- get hydrated after using ecstasy. And that... And so, and in fact, they were doing worse. They were turning off the taps in the... They were even turning off the toilets so people couldn't drink water. So we f- we made it law that people had to get access to water. And we also recommended a good policy would be to have chill-out rooms, and of course, a lot of clubs do have chill-out rooms. And those just, those two simple, um, environmental approaches effectively, you know, there were very, very few deaths from ecstasy since then, until we got to the modern day when v- a variety of international policies have now made ecstasy considerably more harmful than it used to be.
- PAPeter Attia
How much did this coincide with or follow in lockstep with drug policy in the United States, which really seemed to, um, get a, get a real boost in the arm in the early '80s? Um, w- was, was the UK leading or following?
- DNDavid Nutt
Oh, every country in the world follows you. The United Nat- United Nations is, uh, uh, probably still is, paid for by the US, and it does what the US tells them. Uh, every single British lu- drug law until 2016 was made at the behest of the Americans. So, you know, America basically, you know, you know when they say, "America sneezes, the world catches cold." America defined drug policy. It started in 1934 with the, the attack on, you know, the liberalization of drinking and the attack on cannabis, and it continued. And, I mean, of course, the big inflection was when Nixon decided to, that the war on drugs was actually a better vote-getter than the war in Vietnam, so he switched people's attention to drugs. And, and, you know, the world has been fighting a war on drugs, largely funded, but certainly politically driven by America since then.
- 11:20 – 17:44
A scale for rating the relative harm of certain drugs
- PAPeter Attia
So let's talk a little bit about the framework through which one can think about drugs. Um, I, I'm a framework junkie. I, everything I think about, whether it's, you know, how to order dinner, comes down to sort of a framework. Um, so, so w- you know, some parameters that people might think of, right, th- are, you know, how harmful is this? And again, you know, the, I think the goal of frameworks is to have them be as unemotional as possible and to have them when- whenever possible, to be objective. Um, so, so how harmful is something would be part of it. How addictive is something? What's the physiologic dependence? Um, a- and then even within harm, you could sort of talk about the harm to the individual and then the harm to society as that individual acts. Are there any other things you would include, or do those three things largely encompass what you think of as, as a, as a good way to think about molecules?
- DNDavid Nutt
Well, that's, yeah, that's, that's, uh, is quite a succinct way. So I started off with something somewhat similar to that. Uh, but more recently, we've developed what's called multi-criteria decision analysis, and it turns out actually there are 16 different ways in which drugs can do harm. There are nine harms to the user, and there are seven harms to society. And the societal harms range from international damage, you know, like the US s- spraying Agent Orange in, you know, in Colombia to kill, to kill coca plants, through to economic damage, through to s- health costs, through to s- damage to families, et cetera. So there's seven harms to society and nine harms to the user, and each of those can, uh, you can scale drugs on each of those, um, those, uh, 16 scales of parameters of harm. And if you do all that and put it all together and, and then do a weighting, because obviously not every single one of those scales is equally important, if you do all that, then, um, you, you can actually very, very transparently and, and very reliably rate the harms of different drugs. And, and we've used this procedure in Britain, we've used it in Europe, and most recently in Australia, and pretty much all the drugs always rank the same in all those, you know, those three sort of groups of Western, um, jurisdictions.
- PAPeter Attia
So based on that type of a framework, what are the drugs that consistently come to the top of the list in terms of harm, aggregate harm?
- DNDavid Nutt
So the most harmful drug overall in all, in, in Europe, in Britain, in Australia is al- is alcohol. And alcohol is the most harmful drug because it's, has way more social impact, more harms to others than any other drug. And that, of course, is because it's much more widely used. You know, 80% of American adults and British adults drink alcohol. Pretty much every family in your country and my country knows someone that's been harmed by alcohol, either through thems- themselves getting in difficulties, having accidents, getting addicted, or they've been harmed by other ones, someone who's drunk, a drunk driver or, or someone who's drunk and violent. But if you look at the harm to the user, alcohol is not number one. Alcohol is about number four. The drugs which are really harm to the-- harmful to the user are opiates, uh, crack, uh, uh, crack cocaine, and also crystal meth.
- PAPeter Attia
So th- that's super interesting, right? Because those drugs have very different scheduling, right? So, so heroin would be a Schedule I drug, correct? Cocaine would be a Schedule II drug. I guess crystal meth would be Schedule I, or would it be Schedule II in the US?
- DNDavid Nutt
I'm not sure in the... In, in, in Britain it's I, but I'm, I think, I'm not sure in the US, to be honest.
- PAPeter Attia
And then of course, alcohol is not even scheduled in that sense. It's regulated only by the age at which you can legally consume it.
- DNDavid Nutt
And also by taxation, yes.
- PAPeter Attia
Right. So, um, what we didn't talk about was tobacco. Where-- Does tobacco fit into this framework?
- DNDavid Nutt
Yeah, tobacco, yeah. We always do tobacco because tobacco is-- [chuckles] This is an interesting paradox. When we first did this, we, tobacco came out at about number six or seventh, and the tobacco, anti-tobacco brigade got really agitated. They said, "It is the most harmful drug because it kills more people." And we said, "Yeah, but it-- That's right, it kills more people, but they often die in their 50s and 60s. Alcohol is killing people in their 20s, and that's more important, we think." Our evaluation was that, that the harms of alcohol is considerably greater than the harms of tobacco. And, uh, and I think most people would agree that, you know, tobacco does, in the end, kill half of the people who smoke, but it does it later in life, and, uh, it doesn't... Tobacco also c- causes relatively little damage to other people, unlike alcohol.
- PAPeter Attia
I mean, this is such an interesting question, and I, I don't even know how one would think about it because, um, y- you could also take the flip side, which is there's probably nobody who's benefited from tobacco. I, I shouldn't say that.
- DNDavid Nutt
Yes, there is.
- PAPeter Attia
There is a benefit to tobacco, which is that probably it helps some people calm down. It probably helps cope with nerves. But there's no moderate use of tobacco, like smoking only 10 cigarettes a day is protective, um, or the harm doesn't really kick in until you're at a pack a day. No, that's not really true. Any amount of tobacco is going to, to take some toll on your pulmonary system and your cardiovascular system. Alcohol, conversely, you could say, well, look, a person who drinks responsibly, who has, you know, three drinks a week, bears no cost of the consumption of alcohol from a relative standpoint. I mean, we could debate that. I, 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, of toxicity. Yet, to your point, um, it's much easier to cross the line to, into acute toxicity, which also gets to another challenge here. Tobacco has no acute toxicity. It's 100% chronic toxicity. Alcohol has both acute toxicity and chronic toxicity, and it's that acute toxicity that results in incredible loss of life, both to the individual and to society. Does the framework-
- DNDavid Nutt
Yes
- PAPeter Attia
... allow you to, to measure these things?
- DNDavid Nutt
Yes, it does. Yes, we can give you absolute ratings and rankings on both of those variables, acute toxicity versus, uh, chronic toxicity. And of course, you know, the drugs which really do badly on both are the opiates, which can kill you instantly when you take them, but also gradually kill you quite quickly over time
- 17:44 – 23:35
The contrast in regulation between cannabis vs. alcohol and why research on potential benefits of cannabis is lacking
- DNDavid Nutt
as well. But there is another angle, and that's I think an important angle which our analysis doesn't, um, bring in because it's, it's difficult and challenging, and I'd love to, and, you know, maybe at some point we can do this, and that's the benefits. The, the, the, y- you pointed out quite clearly that generally tobacco doesn't bring many benefits. It-- Nicotine is a funny drug, though. It's the only drug we know of that both calms people but also improves attention. And, and so there are, you know, people who smoke, you know, generally, although they're addicted, they do get a ben- a benefit at least, uh, when the nicotine's in the brain. But alcohol has a much broader kind of social... I mean, alcohol is one of the most social drugs. I mean, after ecstasy, it probably is the most social drug, and that's why people use it. So there, so there are unquestionably psychological or social benefits from alcohol. A- and that goes back for sin- well, that goes back [laughs] that goes back to pre-Christian times with-
- PAPeter Attia
Millennia. Yeah, yeah
- DNDavid Nutt
... Yeah, that's right. You know, you've got, you know, Jesus turning water into wine at the wedding at Cana. Why? Because wine was what the Jews used to celebrate weddings, and it's been used ever since. We all use it. We still use it today to celebrate. So, 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, why it's actually been stable in our society for, for many millennia.
- PAPeter Attia
And do you think that that's the fundamental reason why despite the sort of, I mean, hypocrisy of it, if we're gonna be blunt, we would make something like cannabis illegal while having something like alcohol be legal? Is it, does it basically come down to our social dependence on alcohol?
- DNDavid Nutt
Now, that's a great question, and I think, and it's a very interesting-- I h- haven't thought about those two in that context before, but I think it, that's a very interesting point you make because cannabis is not a particularly social drug. So people, when they get stoned, they tend to be quieter. They're not, it's not the, the party drug, cannabis, i- is it? 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, um, as alcohol. That's a very interesting point. I take a different view. Up till now, until you said that, I've taken a different viewpoint, which is that p- people have been very anti-cannabis because the alcohol industry and, and the Drug Enforcement Agency have seen cannabis as the enemy. And, and the disinformation that's been produced, you know, the, the hatred of cannabis, which started with Harry Anslinger trying to keep the DEA functioning after alcohol prohibition was, uh, disbanded. You know, that 100 years almost, what, 90 years of disinformation has actually poisoned a lot of people's minds to cannabis. So cannabis has been vilified, and alcohol's been celebrated. I mean, it's been celebrated throughout history in terms of art and culture and music and television. You know, one of the staggering things, I, I, I, I've, I s- [laughs] because of lockdown, I've been watching a lot of Netflix, and I, and I've been seeing, 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." [laughs]
- PAPeter Attia
[laughs] Yeah. We've come a long way. Um, it's an interesting point you raise. I guess I hadn't thought of it, um, that, that, that part of the DEA's re- you know, the DEA needs a reason to exist, and therefore you need boogeymen, right? If your, if your, if your business is smashing boogeymen, you need boogeymen. Don't we have enough boogeymen with other drugs like heroin or methamphetamine or cocaine? Like, I, I guess I'm confused as to... And I don't wanna, this is not gonna be a discussion about the legalization of cannabis, um, because it seems to me that that train has left the station. I'm just amazed that, um, that there was such a lack of, of study. Because I'll t- I'll tell you where it's frustrating for me as an outsider. I have a lot of questions. I g- 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?" And I wish I could answer that question, but I can't really point to rigorous studies one way or the other. And to me, that's a failure of not having studied this drug the way we should have been studying it for the past 100 years. Because you wanna talk about a drug that probably has lots of benefits but also potentially harms, cannabis would be a case study in that, 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, and it, it, it seems like a, a real missed opportunity.
- DNDavid Nutt
Well, it's worse than that. [laughs] I mean, the reason it, it's, you haven't, 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. And, uh, e- essentially, uh, this 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 canna- medical cannabis legal. What an opportunity. You're gonna have, we know, 20 million people using it. You could, you could, you could have within a couple of years worked out its utility and its harms. But the federal law, because cannabis was illegal-
- PAPeter Attia
Right
- DNDavid Nutt
... under federal law, and it still is-
- PAPeter Attia
Still is, yeah
- DNDavid Nutt
... they could not fund research. So it, it's a, it's an, it's one of the many examples of the perverse negative consequences of this prohibitionist approach to drugs.
- 23:35 – 33:11
The opiate crisis and rise of fentanyl: the cause and potential solution
- PAPeter Attia
So let's talk about a few other drugs that we haven't mentioned. We've talked about basically things that are not particularly harmful. We've certainly talked about things that rise to the level of harm. Um, where do the classic psychedelics, uh, LSD, uh, psilocybin fit in, along with some of their more distant cousins, you know, ayahuasca, DMT, 5-MeO-DMT? Um, 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, of harm in the aggregate sense according to this sophisticated model?
- DNDavid Nutt
That's why I kind of started off talking about MDMA because that was my first introduction to policy decisions. And, and when I started working for the government back in, you know, 1994, I'd assumed that what they'd told me about the harms of drugs was right. And then I discovered that when I did and my team did the more detailed and sophisticated analysis, they were completely wrong. I'd been lied to. And, uh 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. So at one end, the most harmful drug is alcohol and at the least harmful drugs are magic mushrooms and LSD and MDMA. So it's almost as if the whole law is completely on its head.
- PAPeter Attia
So let's now simplify and talk about only harm to the individual. So purely physiologic risk to self. If I heard you correctly earlier, heroin and fentanyl and its cousins occupy the top spot, correct? So aggregate greatest risk of acute and chronic mortality, yes?
- DNDavid Nutt
Correct. That's right.
- PAPeter Attia
And then second, you're putting the cocaine derivatives and then third would be the amphetamine derivatives.
- DNDavid Nutt
So if we just look harm to the user, yes. I mean, crack cocaine, crystal meth probably more harmful than crack.
- PAPeter Attia
Okay.
- DNDavid Nutt
Because it lasts longer in the body and the brain. So I would generally, crystal's probably a bit more harmful to the user. So it would be opioids, crystal, crack.
- PAPeter Attia
Let's talk a little bit about mechanism of action. I'm very familiar with how opiates kill, but let's just briefly summarize it. Is it mostly the respiratory depression? Is that the fundamental issue in the short term?
- DNDavid Nutt
Yep. Yeah. They kill you in overdose. Yeah, you take just too much, you don't know what you're taking. Someone spiked your heroin with fentanyl and you stop breathing and you die, yeah.
- PAPeter Attia
Yeah. You want to talk about, you mentioned earlier, almost nobody in America doesn't know somebody whose life has been destroyed by alcohol. We're getting pretty close to that with opioids.
- DNDavid Nutt
You are, you are.
- PAPeter Attia
I mean, I personally know three people, is it four? Maybe four who have lost a child or relative to an opioid overdose. Think about that. I don't know that many people, David.
- DNDavid Nutt
It is terrifying. And I'm sorry to say guys, but you kind of got it wrong and then you got it wrong again and you're still getting it wrong. And shall I just briefly go through that?
- PAPeter Attia
Sure.
- DNDavid Nutt
So the fentanyl crisis is very much an American problem. And it's not just because there's obviously a lot of you, the more of you, the more people there are, the more likely it is that people will die. But it's a disproportionate number of deaths. So now I think last year more people died of opiate overdose than died in the whole of the Vietnam War.
- PAPeter Attia
Yeah. And last year we set here in the United States a record for the most overdose deaths ever. So it wasn't just the year of the most deaths due to COVID, but the real record, the story behind the story is the most overdoses.
- DNDavid Nutt
And the answers are complicated and it's like a perfect storm of things going wrong. So the first perfect storm is the excessive rollout of strong morphine derivative painkillers, which were heavily promoted by some pharmaceutical companies and you all know they've been sued, et cetera. So I think the doctors also, some doctors were to blame. I mean, some were clearly over-prescribing, but there's also the problem that chronic pain is very common. Perhaps a quarter of the country have chronic pain. When doctors are faced with no treatments, no physiotherapy, no occupation, all they had was prescription pad, then they tended to veer towards prescribing opiates, which are not good for chronic pain. And it's interesting also, you see the states which had the highest prescription levels of opiates for chronic pain are the ones actually that don't have medical cannabis. Medical cannabis is the best treatment for chronic pain, better than any other drug. But if you haven't got that, then you can't have it. So that was the first thing. Big increase in prescription, partly driven inappropriately, partly out of just a concern to help chronic pain. That was the first. The second thing was then the rise, the dispersion of that into society. Parents, kids were taking it and taking their parents' oxycodone and dying. So you have the crisis, you have the concern, and then you have the reaction. The reaction then was to stop prescribing. But when you stop prescribing to someone who is dependent on an opiate, they don't, unless you provide them with something else like medical cannabis, they are in withdrawal. And so they go and get an opiate. And if you're not prescribing it, they go and get it from the black market. And then you see this complete paradox. You see this rise of heroin deaths, rise of fentanyl deaths because that's what the black market provides. And then you get into this really, the most damaging cycle or part of this cycle is the rise of fentanyl. Because until there was a huge increase in black market demand from the people on oxycodone, fentanyl wasn't a big issue. But for various international reasons, the United Nations limiting the access of heroin, the amount of poppies that could be grown in a so-called attempt to prevent heroin misuse. 15 years ago, particularly the Mexican cartels realized if they couldn't make heroin because they couldn't get enough morphine, then they would make something else. And they discovered fentanyls. And fentanyls are so much more potent and there's so much more value for money, economic. Even the simplest fentanyl, fentanyl, it's 50 times more potent than heroin and twice as cheap to make. So you don't have to be an economist to realize it's better to do that. And then you get to the super fentanyls like carfentanil, which are a thousand times more potent. They're so potent, no one knows how to measure them. And so you don't know how much you're giving them. So you see it's a cycle, a series of mistakes, which has actually just led to this terrible tsunami of deaths. And the only way to deal with it really is to have lots of testing to allow people to take anything they've got and get it tested so they know what it is, eliminate fentanyls and start to bring in much safer treatments for people in chronic pain like medical cannabis.
- PAPeter Attia
Um, I wanna talk a little bit about the opiates before we leave it and come talk about a drug called ibogaine, a derivative of iboga. Um, you know, I have read quite a bit about it and, and a lot of it's anecdotal, but, um, it seems that there's something very interesting going on there where you have this alkaloid that while it comes with its own dangers, and it's not clear how over or understated they are relative to cardiac toxicity, it, it seems to have quite an efficacious punch when it comes to, uh, relieving people from the throes of opioid addiction. Do you have experience with it a- at least scientifically, if not, uh, through experimental, uh, collaboration?
- DNDavid Nutt
Well, we're in the process of trying to do a study. I, I would dearly love to understand the neuroscience of ibogaine, and we're... But it's been difficult to do that, uh, study because of the cardiac risks. So, but we're in the process of, of working with a company that's developing a derivative of ibogaine called noribogaine, which may be less cardiotoxic. Uh, and we're working with them to do some brain imaging to see whether we can... If it is, is it a normal psychedelic or not? Because, um, we don't... No one's ever studied it yet. By, um, the evidence, as you see from, from... It's used widely in, um, some, uh, third world countries as a, as a therapy for, for opiate withdrawals. Also a licensed medicine, interestingly, in New Zealand, but they've stopped using it in New Zealand because of, of one death. Now that, you know, that's, that's probably a bit of an overreaction.
- PAPeter Attia
Which strikes me as a little bit odd, right? When you consider, um... So, so based on some of the literature I've read, you know, the risk of a fatal arrhythmia might be one in 1,000, and that's depending on what you're talking about, one in 1,000 is an enormous risk. Um, but if you're weighing it against a person remaining addicted to opioids, what's the natural history of that? I mean, that might be 300 out of 1,000.
- DNDavid Nutt
Yes, about that.
- PAPeter Attia
Yeah. So, so do you have a sense of what the true risk of ibogaine use is, and, and if it, you know, uh, how much of that risk could be mitigated if it were administered in a proper setting, which would be a setting with cardiac monitoring, for example, versus, you know, someone's house?
- DNDavid Nutt
Well, one thing's for sure, we're gonna administer with cardiac monitoring.
- PAPeter Attia
Yeah, of course. [laughs]
- DNDavid Nutt
[laughs]
- 33:11 – 41:32
The science of addiction and the potential use of psychedelics for treating drug addiction
- DNDavid Nutt
Uh, yeah, exactly. So, and there are plenty of other drugs which do have cardiac effects and, you know, usually they're used by cardiologists.
- PAPeter Attia
Yeah. [laughs]
- DNDavid Nutt
Uh, so the answer... You're right. I mean, that's why I want to study it because, uh, I, I... If we could get more clarity on its mechanism, that I think would at least then reassure people there was a science behind it. 'Cause currently it's, "Well, you go to West Africa or you go to Vietnam and you get ibogaine and your brain is shaken up and you come back cured." And, uh, you know, I think we could probably improve on that. I think there's also... Your, your point you make that it, d- doing it in a hospital setting I think makes more sense because, um, not just for safety, but, uh, but also because I'm not sure it should be given during withdrawal. That's when it is being given.
- PAPeter Attia
Mm-hmm.
- DNDavid Nutt
And I think withdrawal just... We have, you know, there are other treatments which we have given for opiate, uh, uh, users which have also been toxic in withdrawal. You know, people, you know, withdrawal is a serious medical problem, so, you know, you know, they're ill, med- they're physically in str- struggling. So I think adding a, a burden to someone who's in withdrawal is not a sensible idea. So, so my thinking is that if once, if we can restore a sensible balance with ibogaine, we could potentially use it. But also I'm, I'm very interested in using other psychedelics 'cause I think the fundamental principle is likely to be the same between ibogaine or psilocybin or DMT in addictions. You're disrupting these, these overlearned, these persistent patterns of over-attention and over, uh, increased, you know, enhanced love for, for, for drugs. You can perhaps break down those habit circuits and then allow people to escape.
- PAPeter Attia
Meaning the things like the default mode network?
- DNDavid Nutt
Yeah, that's right. So I mean, uh, our current thinking about how psychedelics might be used in psychiatry is, is to, is built from this, you know, remarkable finding that the, you know, the psych- what's... The psychedelic state is a state which is where you have completely disrupted the default mode network. This is the network in the brain which, in which your s- your main sense of self, the, the core of you is in the default mode network. And, uh, and embedded in that, of course, is whether you are, you know, your d- your depressive thoughts or whether your love objects, you know, your, your heroin addict. Anything that's really related to you is embedded in the default.
- PAPeter Attia
And, and how, how, how innate is that, uh, versus how, uh, how formed is that?
- DNDavid Nutt
Well, the, the default mode network, I, I think exists in children and, and babies, and it, it's, it is what you are. It is the part of the brain in which, where you encode yourself, your ref- self-referential memories, your plans, your, your, your retrospect, you know, looking back, looking forward, putting every... It is where you are. We know that. If, you know, if you damage the frontal part of the default mode network, your personality changes. You damage the posterior part of the default mode network, you kind of, you become a very strange person who d- who really struggles with coordination and integration. So the default mode network is a fundamental part that, of orchestrating what you are. Um, but in, in that of course are all the things that you have been. So in the, the default mode network coordinates your access to good memories, to bad memories, to, to use of drugs, to resisting the use of drugs, et cetera. But, uh, in a very simplistic way, the sort of current thought thinking is that, that some elements of the default mode become, uh, misaligned or, or, or malignantly over-engaged with negative thinking and depression or, uh, compulsive attitude to the seeking of drugs in drug use. Uh, and if we can disrupt those with psychedelics, then potentially people can kind of restore a normal balance in that network and then, and have a more rational approach, you know, a less, a less constr- a less determined. So, so the brain is kind of determining things like addiction. And the, uh, uh, uh, and even though people don't wanna use the drugs, they often find themselves doing it even though they don't want to because their brain is kind of driving them that way.
- PAPeter Attia
And we're gonna come back and talk about the impact of psilocybin on the, on the default mode network. But, but I guess to your point, this might be one of the ways in which ibogaine or iboga kind of help rewire a brain, uh, for an individual who is opioid addicted, which is in and of itself kind of an interesting thing, isn't it? In that there's, there's got to be a genetic susceptibility to this because there are many people who take tons of opioids during, you know, say a post, you know, postoperative recovery from surgery and, you know, they take tons of the stuff, and then when they have to stop it, they stop it, and that's the end of it. And yet there are other people for whom that's not true. So do we have a sense of what that, what that genetic susceptibility looks like? And is it... more importantly, is it, is it possible to predict that a priori so that we would understand, hey, this is a person who is at such high risk for opioid dependency that even if they have to get their wisdom teeth pulled out, we are not giving them this medication. We're gonna come up with a totally different pain management strategy.
- DNDavid Nutt
Yes, theoretically, it, it is unlikely to be in the genes. I mean, well-
- PAPeter Attia
It's probably polygenic, I'm sure. Yeah.
- DNDavid Nutt
Yeah, exactly. There's not gonna be a gene. Um, uh, what, what, what do we know about why people become addicted? Well, we know, uh, uh, we know that social factors are hugely important. You know, I mean, if you've seen "The Wire," then you know that, uh, downtown Baltimore-
- PAPeter Attia
I lived "The Wire."
- DNDavid Nutt
You lived "The Wire."
- PAPeter Attia
Well, I mean, I did my residency in Baltimore, so I, I-
- DNDavid Nutt
So you know, I mean-
- PAPeter Attia
... I took care of the patients in "The Wire," yeah.
- DNDavid Nutt
It's a frightening place, isn't it? I mean, it's fra-
- PAPeter Attia
Un- unbelievable. The book, "The Corner," which "The Wire" was based on, was the book I... Once I matched to do my residency in Baltimore, a friend of mine who was a year ahead of me in, at medical school who had already now spent a year in Baltimore, I was like, "Hey, do you have any advice for what I can do to kinda get ready for... 'cause I'm moving from Stanford to Baltimore." You can't go from-
- DNDavid Nutt
[laughs]
- PAPeter Attia
... the most posh place in the world to the least. And he said, um, his only piece of advice was he said, "Read 'The Corner' 'cause it's literally what you're going to be living in, and it will give you a great sense of empathy for the patients that you're gonna be taking care of." Um, and it's a riveting book, which ultimately became a riveting series.
- DNDavid Nutt
Absolutely. And, and y- you know, I... A couple of years ago, I was on my way to Philadelphia from Washington to give a lecture, and as we pulled out of Baltimore, I was looking out the train window thinking, "This is like a war zone. Is this Hiroshima?" Because the, you know, the downtown Balti... You know, I hadn't realized quite how destroyed it had been. And if you're living there and you've got no job, I mean, and the only thing you can do is deal drugs, you take drugs and you deal drugs.
- PAPeter Attia
Absolutely.
- DNDavid Nutt
So, so, uh, a lot of drug use addiction comes because that's the one way people can actually achieve both a sense... something that takes away the misery of their lives, but also in a way, if they become drug dealers, become some, a, a role. So, so coping with life stress is one reason people use drugs. But there are some people, you know, and they're very, you know, you know, the rich, successful people and, um, who, who still use opiates and get, and get into problems with opiates. And, um, the example I, I give two examples of this, two, two Oscar winners. Tatum O'Neal, youngest ever Oscar winner, marries the best, greatest tennis player, Mike and Row, there's maybe ever been. You know, got two wonderful kids, lives, you know, the life that everyone envies. You know, she's famous, beautiful, everything there. But when she comes out of heroin treatment, she says, "The only time I felt whole was on heroin." And, uh, you see that... I see that with patients, not just heroin patients. I see it with alcoholics. There are plenty of people for whom alcohol makes them what they want to be.
- PAPeter Attia
Mm-hmm.
- DNDavid Nutt
Only when they're drunk that they're actually functioning normally. And it... And why that is, we don't know. And actually, one of the interesting things, you know, that I... and the reason I wanna study psychedelics, 'cause I'm wondering whether, whether that gap that can only be filled by drugs could actually be kind of refilled or at least remodeled with psychedelics. Yeah. So, um, yeah, so that's another... And then of course there are, there are people who, who get, you know, who use drugs to get high, and then they find somehow that the, the har- their brain becomes sensitized to the drug use so that they, you know, they lose control, and that's, like, more classic with people who use cocaine
- 41:32 – 48:38
Cocaine: mechanisms of action and risks
- DNDavid Nutt
or, or crystal.
- PAPeter Attia
So let's talk about those two drugs just, just from a mechanistic standpoint and where the risk actually comes from. Um, take your choice which one you wanna start with. [chuckles]
- DNDavid Nutt
Well, let's start with the earlier. Let's start with, uh, let's start with cocaine because that's the, that was the first of... [chuckles] Well, there were several cocaine epidemics, but I mean, let's talk about that. Um, yeah, I mean, cocaine. Uh, I give a lecture sometimes, which is, was, was Freud right to give up on psychopharmacology? 'Cause of course Freud was a great protagonist. Fr- Freud used cocaine himself. He thought cocaine was a very powerful drug for getting people off heroin. He, he got one of his, his disciples off heroin by giving them cocaine. He didn't realize [chuckles] that cocaine also caused dependence. In fact, Freud and his, um, his protege both became cocaine dependent.
- PAPeter Attia
That, that's another Hopkins, that's another Hopkins link, by the way, in Baltimore, was the, the godfather of-
- DNDavid Nutt
Is that right?
- PAPeter Attia
Yeah, yeah. So the, basically the father of the surgical residency in the United States, um, and the first chief of surgery at Hopkins, uh, William Stewart Halsted, uh, himself became addicted to cocaine when he became obsessed with it as a local anesthetic. And so in the, in the process of experimenting with cocaine as a local anesthetic, which of course it became a very potent and remarkable local anesthetic, he and many of his residents became cocaine addicted. Um, so it's sort of, you know, it's a footnote to the, to the story of the, the creation of the great American Surgical Institute.
- DNDavid Nutt
Well, uh, it hasn't stopped. They don't get addicted to cocaine anymore. They get addicted to remifentanil usually, the anesthetist. But that's another story. [laughs] Um, let's get back to cocaine. So I, I think the reason Freud went, became a psych- into psychology was because he got, then became completely terrified of pharmacology because he kind of assumed that any drug would have that problem. So, you know, you can maybe g- maybe give cocaine credit for the development of psychoanalysis.
- PAPeter Attia
Mm-hmm.
- DNDavid Nutt
But, but when we get to the modern era, you know, then, you know, cocaine is, uh, is the ultimate fun drug. It gives you energy and drive and, uh, and, um, you know, an enormous sort of sense of focus and, and purpose. Uh, and then a terrible crash. And, uh, and, and we now, you know, we know that it's, that's due to the release of dopamine and noradrenaline in the brain. Uh, but it's very spiky and, uh, and during the course of a binge over the weekend, you know, the brain gets perturbed and then people start to get paranoid and, and withdraw. And some of them will get sensitized and become addicted. And some of them will die because of course there's a cardiac effect. And also there's this problem that if you mix cocaine and alcohol you get a, a drug called cocaethylene, which is a longer acting and more cardiotoxic version of cocaine.
- PAPeter Attia
You know, I have patients who... I mean, our patients are always going to disclose to us what they use. We ask this question point blank, "Which recreational drugs do you use?" And, um, a number of them will say, "Hey, you know, two or three times a year I use cocaine," and, and they want to know what I think. And, uh, again, the goal in that situation is not to come across as preachy and dogmatic, but it's to sort of have a point of view and have it be grounded. And, and my point of view with cocaine has always been I don't think it's worth the risk and I don't think it's the right kind of drug because, you know, just as much as we're now talking about a framework for drugs, I have a much simpler framework for drugs, which is, um, it's really only got two levers. One is what is the physical risk of this drug to me as an individual? So with cocaine, what is the true risk of cardiac toxicity? What is the risk of, um, deepening physiologic dependence over time, et cetera? And then the second component to my framework is, is this a drug that only alters your state or does it have the potential to alter a trait? I'm borrowing that from the book called Altered Traits, um, which, which gets into this distinction. And, and so the idea being is, you know, psilocybin for anybody who's ever taken it, is clearly a drug that alters your state. But if it just altered your state, you probably wouldn't take it because it's really not that pleasurable. But the real benefit of is, is the potential to alter a trait, whether it be depression, smoking cessation, or something else. And so if a drug can only alter your state but it has no potential to really alter your traits, i.e., how you behave off the drug, is it worth it? And, and so my... The way I explain this to patients is I say, "I don't think cocaine can do that." So therefore it, it has two strikes. It's O for two in the Peter framework. It's, it has a physical risk that is non-trivial and it's not going to make your life better when you're not taking it, and therefore I think cocaine makes no sense to take. Do you agree or disagree with that?
- DNDavid Nutt
That's a very interesting analysis. I like that. I might start using it. Yes.
- PAPeter Attia
So do you agree that, that basically there isn't a positive to cocaine that I'm missing? There isn't a benefit to it?
- DNDavid Nutt
Well, I, I certainly would s- would say absolutely, that's absolutely true for crack. For cocaine, I'm not entirely sure. I mean, I think there are people who can use it just once or twice a year without getting into much difficulty, provided they don't have serious cardiac problems. So I certainly wouldn't be using it at my age. [laughs]
- PAPeter Attia
But then look at like there's the famous example which basically accelerated the war on drugs was the case of Len Bias in 1985. Uh, are you familiar with the story of Len Bias? Oh, he was the, probably the most famous high school, uh, pardon me, college basketball recruit. So he played basketball at the University of Maryland. Um, a complete superstar. Uh, basically on the level of a Michael Jordan. Um, and he was drafted by the Balti- the, the, the Boston Celtics and, uh, probably had he gone on to play for the Boston Celtics would have altered the course of the NBA for the next ten years. Um, the day following the NBA draft, he was back in Baltimore celebrating with friends. They were at a party in their dorm room. He's... You know, they're using cocaine. He has a sudden cardiac arrest and dies. And this really, really shocked the nation. Uh, this was a really big deal. Um, and, and, and certainly some would argue that that was, that only reinforced and doubled down on sort of the, the, the Nancy Reagan-esque just say no, uh, mantra, which of course reinforced the war on drugs. Um, so, so again, when you can have this totally, you know, the healthiest twenty-one-year-old in the country can die and you don't know what, you don't know the details, right? How much was he on? Was it laced with something? You know, one doesn't know.
- DNDavid Nutt
No, but you've got to remember that, you know, sudden death in athletes. I know y- I don't... We just had the European Football Championships, and one of the star players, Eriksen from, uh, Denmark, had a cardiac arrest on the pitch. So super fit athletes-
- PAPeter Attia
Might be more susceptible. Yeah
- DNDavid Nutt
... have some... I th- yeah. Um, so particularly if they've got a, you know, if they're big-
- PAPeter Attia
Mm-hmm
- DNDavid Nutt
... and they've got developed some kind of cardiomyopathy. So, so yeah, I don't... Athletes aren't, aren't paradoxically more potentially, you know, at least as vulnerable as other, other people-
- PAPeter Attia
Yeah. Yeah
- DNDavid Nutt
... as to, to these,
- 48:38 – 53:12
Methamphetamine and crystal meth: mechanisms of action and neurotoxicity
- DNDavid Nutt
these effects.
- PAPeter Attia
So, so talk about methamphetamine, crystal meth, these, these drugs which obviously the, uh, the amazing Netflix series Breaking Bad, uh, brought everyone awareness of, of what these drugs are. But, but physiologically, neurochemically, what is it that they're doing and what is the danger?
- DNDavid Nutt
Well, they're very similar to cocaine. I, uh, s- I mean, I remember as a, um Junior doctor, my very first period as a junior doctor, giving methylamphetamine intravenously to a man who had serious status asthmaticus.
- PAPeter Attia
Hmm. Geez.
- DNDavid Nutt
Amphetamines were developed as a treatment for asthma.
- PAPeter Attia
Hmm.
- DNDavid Nutt
They were developed, um, as an alternative to ephedra. Ephedra is a, a natural plant product. It was discovered to have this, uh, bronchodilating properties back in the 1800s. There was a huge demand. The plant couldn't supply the demand, so German pharmaceutical companies went away and made a synthetic ephedra, which they called amphetamine. And it was used largely for, [chuckles] for the treatment of, uh, of asthma, really till the Second World War, when people realized it could actually be used to keep, um, soldiers awake. Uh, and, um, and, and here's another interesting aside. I f- I'm very interested in the, the history of drugs and war because they tell us quite a lot about the, the consequences of drug use. A- and well, I often give, I often give a talk where I talk about amphetamines. I, I compare the a- the Allies, so the Brits and Americans. We used amphetamine sulfate, whereas the Germans and the Japanese thought they were really clever because they had this super amphetamine called methylamphetamine, which lasts a lot longer. But what they didn't realize was that longer is not better. And, and the turning point of the war was actually the, the North Africa campaign, when the Germans were pushed back when they got to Egypt. Um, so Rommel was pushed back by-
- PAPeter Attia
Rommel's last stand, yeah.
- DNDavid Nutt
That's right. Absolutely, by, uh, the Desert Rats, the, the, the, the Allied troops, the Australians. And the way [chuckles] the Desert Rats used to work was that they would be up all night, hang, you know, working around the Germans, harrying them, blowing them up, and then they'd go back. Or they'd, that, they'd be up all night on amphetamine sulfate, and then they'd go back and they'd sleep all day. But the, so the Germans would take methylamphetamine to stay up to, to fight a- to defend themselves against the Desert Rats. But they couldn't sleep in the daytime, and eventually they became sleep deprived and paranoid. And the same with Japanese. You know, these, [chuckles] these descriptions of how the Japanese became compul- they had these terrible hallucin- s- sensory somatic hallucinations from using large doses of crystal meth for long periods. So, crystal meth is, it's longer acting and probably more neurotoxic than amphetamine sulfate.
- PAPeter Attia
Talk about the neurotoxicity. What, what actually happens to the person's brain? 'Cause we ... You, you certainly have this meme of the crystal meth user, right? No teeth, bruised, pin skinny, emaciated. But that meme doesn't actually tell me about their brain. What's, what's actually happening to them?
- DNDavid Nutt
Well, they're certainly pushing their dopamine system to a point where it's probably depleted, uh, and that seems to then lock them into a state where they can't really, uh, function normally in the world without taking the drug. Uh, there's also a bit l- less good evidence that it might also damage the dopamine pathways to the frontal cortex, which impairs, uh, their ability to, to, to make judgments, to executive function, et cetera. But I have to caution it. I mean, the, the, the big concern about crystal meth actually came, uh, a- as a result of the Japen- after the Second World War. There were, you know, factories, crystal meth factories in Japan. You know, there were barrels of the stuff, and there were a lot of Japanese soldiers who had nothing else to do, and, and they used to use huge doses of crystal meth, often intravenously. And, and, and the evidence for brain damage really comes from that population. There's not so much evidence from it being, when it's being used as it tends to be used now, um, orally without, you know, in, in more prolonged periods. So I'm not sure that you get a lot of what you might call cortical damage with crystal meth, but I think it definitely does distort the dopamine pathways in your brain and, and will affect your motivation and your ability to, to sort of get up and a- get activated, et cetera.
- 53:12 – 1:09:45
How psychedelics came to be classified as schedule I drugs despite their numerous therapeutic uses
- PAPeter Attia
So now let's talk a little bit about these drugs that unfortunately, or, you know, for ... They, they seem to have the same scheduling and therefore they're viewed by the DEA as both as dangerous in terms of harm, uh, or risk of, of, of, of addiction and as medically useless. 'Cause really that's the criteria for Schedule 1, right, is high, high potential for addiction and no medical use. And so, um, cocaine does not fit in Schedule 1 because while it is highly addictive, we at least have one appropriate medical use for it, which is, and it's an, it's a great anesthetic, especially in the nose.
- DNDavid Nutt
Yeah.
- PAPeter Attia
Um, obviously fentanyl is not Schedule 1 because even though we acknowledge it's highly addictive, it has this pain blunting effect.
- DNDavid Nutt
Mm-hmm. Mm-hmm.
- PAPeter Attia
Um, remarkably, psilocybin is Schedule 1. Um, MDMA is Schedule 1.
- DNDavid Nutt
Mm-hmm.
- PAPeter Attia
So LSD is Schedule 1. So let's talk about these three, which are, if you believe the DEA scheduling, the worst possible drugs imaginable-
- DNDavid Nutt
Mm-hmm
- PAPeter Attia
... because by definition they must have a high addiction for potential and they serve no medical benefit whatsoever. So, uh, take them in any order you like.
- DNDavid Nutt
Well, let's take the psychedelics first because that's how it all started. I mean, these drugs were banned not because they had any negative impact. They were banned in the face of opposition. Bobby Kennedy confronted the DEA and the FDA when they said, "We want to ban LSD." And he said, "Well, hang on a second. Hang on. We spent billions of dollars researching LSD up till this time, and, [chuckles] and we got loads of positive results." In fact, his wife became intrigued-
- PAPeter Attia
Was he still the AG when he was having this discussion with them? Was he still the Attorney General of the United States?
- DNDavid Nutt
No, no, no. He was, um, he was Secretary of State.
- PAPeter Attia
Okay.
- DNDavid Nutt
He was about to get elected as president.
- PAPeter Attia
This was ... Yeah, yeah, this was, this was ... Okay. Later on, yeah.
- DNDavid Nutt
Just be- just before he was assassinated.
- PAPeter Attia
Yeah. Yeah. Okay.
- DNDavid Nutt
And he's saying to these ... "Come on, guys." [laughs] You know, "We've had 15 years of this remarkable research which we've invested..." NIH in the States funded over 130 grants to study the therapeutic use of LSD, and they found it was very therapeutic and very little harms. And, and then the DEA come and the CIA come and say, "We've got to ban it." He's saying, "What, what you talking about?" And of course, what they were talking about was the, was the fact that the hippie movement was starting, and the hippie movement was anti the war in Vietnam, and LSD was seen as fueling the hippie movement. But also worse than that, it was changing music and people were dressing differently and putting flowers in their hair and, and they were sticking flowers down the guns of the soldiers that were trying to stop them protesting the war. You know, it was changing the whole tenor of, I suppose, what you might call sort of int- intellectual debate in America, particularly among students. And it was seen as a real threat to the American way of, of doing everything, which was basically having bigger and better bombs and guns. And so LSD got banned because it was s- you know, essentially changing the way people voted. People didn't want to vote for war. And they had ... But they couldn't ban it. In those days, [laughs] there, there were rules which said basically you had to, you had to find harms, and those harms could be physical harms or they could be social harms. And, and it's very easy to find social harms because you just get a few editors of your National Enquirer or, or similar rags to just invent stories about the harms, you know, and, and the way people have been corrupted by using LSD. And there's these wonderful ... I mean, it's sad, but, you know, but, but it's amusing now, but of course, very damaging. These front covers of these m- magazines or newspapers making absurd claims about LSD, usually with semi-naked women, and, uh, and that was enough s- concern. If editors are socially concerned, then we can ban the drug, and it got banned. And once LSD got banned, all the other serotonergic hallucinogens that were known about at the time, and actually in America, you did know about quite a lot. A lot of countries didn't know there were more than LSD and psilocybin, so some countries didn't ban DMT or 5-methoxy. But you Americans, you just banned it all because you had good scientists. So LSD was banned bec- for political and social reasons, no- not because of any harm.
- PAPeter Attia
If Tim Leary had not been around, would it still have been banned, in your opinion?
- DNDavid Nutt
Probably not. I think the fact that he was encouraging a, a, a, you know, a fundamental change in the, the American way of life through using drugs, I think he certainly compounded the problem. Uh, and he certainly popularized LSD and encouraged people to, to, to think differently about society. I think that w- I think there was a genuine fear that Americans would actually cease to want to fight wars and actually want to have peace, and that was just seen as being extremely bad for the American economy and, of course, the American presence internationally.
- PAPeter Attia
So prior to the scheduling of LSD, you mentioned over 130 grants had been issued to study it. This was a drug that had been manufactured in the late 1930s by the pharmaceutical company Sandoz. What were some of the things that they had learned about LSD under that period of time in which it was studied rigorously?
- DNDavid Nutt
So there were 40,000 patients studied. A thousand papers were published, uh, and there have been analyses of many of these groups of patients and, and they discovered that it actually was very safe. If anything, it reduced suicide rates compared with non-treatment. And you've got to remember at the time, in the '50s and '60s, there were very few alternatives. You know, particularly antidepressants hadn't been in- really invented till the 1960s. It was shown to be effective, uh, and, and it was shown to be safe, and it didn't cause psychosis. So actually, it was ... This was the revolution. This was the beginning, the dawning of a new, uh, of ps- of real psychiatry. Psychiatry was becoming like the rest of medicine. We had tools that we could help people with other than talking.
- PAPeter Attia
And, and in what context, David? So, so would that be, like, a single dose of LSD combined with a prolonged period of psychotherapy, uh, during the period of time under which the influ- the, the in- the individual's under the influence? Or did it require multiple treatments? I mean, do you have a sense of what requi- what was required for that efficacy?
- DNDavid Nutt
Well, it was used in two different ways. So in the States, the, the, the typical use was, uh, what, how we're using it today, which is give people a, a biggish dose, give them a big trip, few-hour trip, and then afterwards help them work out what the trip meant. So it was always done in the context of psychotherapy 'cause it, 'cause it, in those days, all American, uh, psychiatrists were actually effectively Freud, were mostly Freudian analysts. So it was always done in the context of psychotherapy, and it was allowed ... But in Britain, um, we tended, we u- often used lower doses, uh, and we used that repeatedly to try to break down psychological resistance to actually engaging in psychotherapy. So there were these two-
- PAPeter Attia
And what was the difference in those doses, David? So the big trip dose would be how many micrograms?
- DNDavid Nutt
So for, uh, for LSD, it would've been 100 or 125.
- PAPeter Attia
Okay.
- DNDavid Nutt
And then for the, for the, uh, uh, you know, for, um, opening up the ... Reducing the resistance, we would say, in psychotherapy, which go- breaking down the resistance, it would be perhaps 25 micrograms.
- PAPeter Attia
And is 25 micrograms perceptible, or is that considered a microdose where the individual-
- DNDavid Nutt
No, no, that's perceptible. Anything over 10 micrograms is perceptible.
- 1:09:45 – 1:14:26
The history of MDMA and the bad science and political forces leading to its demonization
- PAPeter Attia
And then MDMA itself is not really a classic psychedelic. You know, I, I, I've-
- DNDavid Nutt
No, no
- PAPeter Attia
... there's sort of a framework for these psychedelics where you've got the, kind of the typical, the atypical, um, but, but sort of if you have sort of psilocybin, LSD here, you've got MDMA here, more of an empathogen, and then-
- DNDavid Nutt
Yes
- PAPeter Attia
... you have ketamine as more of a dissociative, and then these really-
- DNDavid Nutt
Yeah
- PAPeter Attia
... atypical ones like ibogaine, which we've already talked about. So-
- DNDavid Nutt
Correct. Correct
- PAPeter Attia
... s- so, um, let's spend just a minute on MDMA because again, I, I, I think it's one that... Well, first of all, people confuse MDMA and ecstasy a little bit, and I, it's probably worth clarifying the nuances there. Uh, but also talking about the potential that it has. I, I've had, you know, Rick Doblin on the podcast before, so we've gone incredibly deep on-
- DNDavid Nutt
Okay
- PAPeter Attia
... on the benefits of, you know, treatment for PTSD, and we've talked a lot about MAPS. We don't need to go that deep, but just for someone who maybe hasn't heard that, what would be the overview?
- DNDavid Nutt
Well, MDMA is a great American invention.
- PAPeter Attia
Yep.
- DNDavid Nutt
One of your top drug chemists, Sasha Shulgin, w- was interested in derivatives of amphetamines, and, uh, he... MDMA was made, you know, back in 1904 as a possible agent for blood clotting, but it never, never got used. And, uh, uh, Shulgin made it in the, in the, in the '60s and said, "Wow, this drug is different from amphetamines. It's not activating. It's not, it's not driving me like amphetamines. It's actually making... It's giving me a clarity of thought, but also a sense of warmthness and empathy." So he gave it to his wife, and she said, "Wow, this is a very em- you know, this is empathy. This would be really useful in psychotherapy, in couples counseling. It would help, could potentially help break down, you know, those layers of irritation and grit that build up in relationships sometimes. Put people back into love." And it was widely used for about 10 years by therapists, particularly on the West Coast of the States, and it was called empathy, and everything was fine. And then some smartass in Texas decided this is a legal drug, and we could sell this. We can't sell amphetamines, but we can sell ecstasy 'cause it's legal. But who wants to buy ecstasy? So they changed the name to ecstasy. So they didn't wanna buy empathy, sorry. They changed the name to ecstasy. You got an amphetamine which can help keep you active, but also make you much more y- in love with, uh, with other people. And it became, you know, widely used. What... You know, it's the perfect drug for parties, isn't it? You know, you've got energy, but you're also happy. You're not fighting people like what you do if you're taking speed. And it became hugely popular, and it spread into Europe. And then of course, it just riled the right, the Puritans. It riled the right-wing press. The idea that young people could have ecstasy when o- when the newspaper owners couldn't even... Had never had it and couldn't even remem- didn't even know what it meant. They just didn't... It... You had this moral outrage which eventually got the drug banned. But again, you couldn't, in America and Britain in those days, you couldn't ban a drug just because kids liked it. You had to find evidence of harm. And some of the worst science that's ever been done is the science proving, or supposedly proving, that MDMA is harmful. And yet [laughs] culminating in that, an amazing experiment that was done by Riccardi, uh, [laughs] which is really embarrassing for Johns Hopkins, you know.
- PAPeter Attia
Yep.
- DNDavid Nutt
When he claimed that, uh, taking MDMA and listening to The Pogues overnight gave monkeys brain damage. And we all said, "Well, hang on a second. [laughs] None of our kids are coming out of the clubs with brain damage. I think your experiment's wrong, Riccardi." He said, "No, no, it's right. Look, ecstasy causes brain damage." And ev- and he got published in Science despite the fact the referees said, "This is, this has gotta be wrong." And of course, eventually they went back and they audited what they'd done, and instead of giving the monkeys MDMA, they'd given them crystal meth Which is way more toxic [laughs]
- PAPeter Attia
That, that paper, that paper was recall. I mean, he, he did have to pull that paper, didn't he?
- DNDavid Nutt
He didn't. No, no, he didn't retract the paper. He just put in-
- PAPeter Attia
It was never retracted?
- DNDavid Nutt
I think you can still find it. If you look in Science, you'll still find it's there. It's not struck out.
- PAPeter Attia
Oh.
- DNDavid Nutt
I think you'll just find there's a, there's a correction. "Sorry, guys, this wasn't MDMA. This was actually [laughs] methamphetamine."
- PAPeter Attia
Wow. So that's-
- DNDavid Nutt
Terrifying
- PAPeter Attia
... that's, that's our answer to Andrew Wakefield for you, huh?
- DNDavid Nutt
[laughs] Indeed.
- PAPeter Attia
Yeah.
- DNDavid Nutt
And it's, it's embarrassing really because... Well, for all sorts of reasons, because it's, uh, so much American science is paid by the government that it, it... Uh, apparently, I don't know, I heard that the editor of s- 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. Of course, all that happens is in the end, young people, young people think this doesn't make sense, and then they discover they've been lied to. So are they gonna listen to anything else the government tells them?
- 1:14:26 – 1:21:28
History of ketamine, medical use of esketamine, and the waning effects of psychedelics with increasing usage
- PAPeter Attia
Yeah. Um, let's talk briefly about ketamine before we come back to, to psilocybin 'cause I wanna, I wanna sort of double-click more on psilocybin, specifically with, um, w- with, uh, w- for the treatment of depression. But, uh, let, just to round out all of our sort of psychedelics, um, ketamine, of course, is the only drug on this list that is legal. Um-
- DNDavid Nutt
Mm-hmm
- PAPeter Attia
... so it's, I believe it's a Schedule 3, perhaps a Schedule 4, uh, used as an anesthetic typically, uh, and it's quite dissociative. So, uh, can you, 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, uh, research?
- DNDavid Nutt
Yes, a wonderful story, and, uh, and it goes back to, um, to John Krystal, who's a professor up at, uh, Yale, and he was using ketamine to model psychosis, and he was comparing ketamine and THC, um, uh, to model psychosis. And they both produce altered states of consciousness, which sort of, you know, have some overlap with psychosis. But he noticed that afterwards, uh, his volunteers often felt better. You know, they actually came out of the ketamine experience saying, "Well, that was weird," but they had an improved mood. And he thought, "Maybe this is mood-elevating." So then he and his colleagues went on and did a study. Yeah, ketamine elevates mood. And for a couple of days after a ketamine trip, your mood is definitely improved. And now there have been about 30 studies showing that ketamine can, um, have a, have a value, particularly if you add it on to other treatments of depression which have not, uh, been very successful. So if people are partially recovered, give a bit of ketamine, and their mood gets better. Um, the problem with ketamine compared with what we're gonna talk about in a minute with psilocybin is that the effect is very short-lasting. It lasts only two or three days. So currently what you have now is a licensed medicine. Janssen decided to, to pursue this 'cause this was the, the first real breakthrough in the treatment of depression for really for 50 years. So they w- so they... But you couldn't patent ketamine because ketamine has been, was being used back in the Vietnam War as a buddy drug when people were being blown up and having it as a, use it as an analgesic. So they took the enantiomer, one of the isomers of ketamine called S, the S enantiomer, and they call it esketamine, and they formulated it for nasal inhalation, so you don't have to inject it, which is better and easier for psychiatrists. And now that's sold as a, as a treatment, and it's called esketamine Spravato. And it works, and you take it a couple of times a week, and then gradually over time, you use, you dose less and less as the, as the-
- PAPeter Attia
So you don't develop a tachyphylaxis to it? It actually-
- DNDavid Nutt
If you do it twice a week, you don't. No, no.
- PAPeter Attia
And, and you are able to get patients off of it while still preserving the antidepressive benefits?
- DNDavid Nutt
That's less clear, but s- for s- in some, that's true. But it does have... There is an advantage of it over ketamine. Ketamine clinics tend to-
- PAPeter Attia
They give it intravenously or intramuscularly, right?
- DNDavid Nutt
They give it intravenously or in... Yeah, or intramuscularly. But als- the problem there is that, you know, ketamine is a dependence-producing drug. It's a drug, a recreational drug, um, you know, is relatively popular in Britain, is relatively popular in China, um, probably popular also in the States. I'm not sure what the stats are. Um, the problem is you do get tolerance, tachyphylaxis, if you use it regularly. So while it's relatively safe in the doses you might use, you know, maybe, you know, you know, 500 milligrams for, for, for depression, if people are using it recreationally and taking more and more, they're getting up to grams a day, and then you get into serious problems. You get bladder, um, problems. You get a... Basically, you get a, a s- a severe chronic cystitis which can cause bladder atrophy, needing bladder resection. And you also get a, a psychological state. You get a kind of... You can get brain damage, uh, or at least you can get a state of, of, of severe cognitive impairment, which actually rather mimics schizophrenia. So, so heavy use of ketamine is actually really to be avoided.
- PAPeter Attia
And what defines that? I mean, those are very scary things you just described. Obviously, the, the psychiatric component much more than the urologic. Um, what, what, what is too much? I mean, because I'll tell you, this is something I get asked a lot. Um-
- DNDavid Nutt
Uh-huh
- PAPeter Attia
... "Hey, you know, I'm, I'm going to this ketamine clinic once a month. It's, it's changing my life." Uh-
- DNDavid Nutt
Yeah
- PAPeter Attia
... you know, and I don't... Is... You know, at what point does that become too much?
- DNDavid Nutt
Oh, yeah, well, certainly daily use is too much.
- PAPeter Attia
Mm-hmm.
- DNDavid Nutt
So I mean, people who are addicted to ketamine are using it four or five times a day. They might be using five grams a day, and that, that's when you get into the serious brain damage. So I think twice a week ket- oh, I think we know from, from esketamine twice a week seems to be without, uh, uh, doesn't have any enduring-
- PAPeter Attia
But if you're not using the enantiomer twice a week, will probably still produce a tachyphylaxis and a, a diminishing return at some point?
- DNDavid Nutt
Yes, but this... One of the really interesting questions, and we don't understand this, why is it that when people use ketamine And they get tachyphylaxis. They can overcome it by taking more
- PAPeter Attia
By the way, I should explain to people what tachyphylaxis is 'cause we're using the term without me defining it. It's, uh, it's, 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. So for example, we don't generally get tachyphylactic to Tylenol, right? You have acetaminophen.
- DNDavid Nutt
Yeah.
- PAPeter Attia
If you take 500 milligrams and your headache goes away, you know, you'll-- the next time you take 500 milligrams, it, it does about the same thing. Um, so to your point, you can sort of over-- you can push the dose a little bit and, and, and stay ahead of it with ketamine?
- DNDavid Nutt
Correct. You can. You can. Like heroin, like fentanyl.
- PAPeter Attia
Yep.
- DNDavid Nutt
You can, you can overcome the tolerance. But with psychedelics you can't, and that's an interesting phenomenon, and it's probably to do with subtle changes in the, in the downstream mechanisms in the cells that w- you know, you get an almost complete absence of effects of, uh, of psychedelics after two or three doses. And do you know who told us that?
- PAPeter Attia
No.
- DNDavid Nutt
Uh, the US government. So [chuckles] the US government were very interested in, or fearful actually, when psychedelics came around in the '50s. They thought, "Well, maybe the Russians will be spraying LSD on our troops, so how can we protect our troops from LSD?" So they started giving, uh, troops LSD to find out what the effects would be to see how they could abort them, and they discovered by the third day of giving the troops LSD, LSD had no effect anymore.
- PAPeter Attia
Wow, I didn't realize that was the case. So if you're ta- if you're talking 250 micrograms of LSD, at some point people are gonna stop responding to that?
- DNDavid Nutt
Yeah. Well, the, the second dose will be less than the fir- if you take it every day, the second dose is way less than the first
- 1:21:28 – 1:40:33
Psilocybin for depression: David’s promising research and the roadblocks to more robust experiments
- PAPeter Attia
All right. Well, there's so many more questions I have about this, David, but I know we have a very hard stop today, so I wanna make sure we have some time to talk about your most recent work with psilocybin and depression. Uh, about three months ago, a study was published in The New England Journal of Medicine. You were the senior author on that paper, I've written about it at length, which compared psilocybin to Lexapro, a very, very popular, commonly used, reasonably well-tolerated SSRI. Um, do you wanna just give people a quick overview of the study design and what you set out to test?
- DNDavid Nutt
Oh, I'd be pleased to. Yes. So previously we had done a study, an open trial. We'd taken 20 people with resistant depression, and we'd given them, uh, a single psilocybin trip and found very good outcome. Uh, but the effect didn't last very long. It la- it lasted, you know, one to two months. But for many of them, the depression came back. Uh, based on that and also some theoretical work I'd done with Robin Carhart-Harris, who was with me at the time, he's now moved to UCSF, we came to the conclusion that psychedelics treat depression in a different way to antidepressants. We... And that paper's published in Journal of Psychopharmacology. It's called "A Tale of Two Receptors." It's a free download. Uh, feel free to read it 'cause it conceptualizes that there are two ways you can lift depression. One way is with a, with, with Lexapro or other similar drugs that enhance serotonin in the limbic system, and there they basically block the stress response. And we know that stress is a major cause of depression. You block stress-induced depressive changes in that system, and that allows the limbic system to recover. So that it's a bit like a... If you have a broken leg, you set the leg in plaster so that the bone can heal itself. 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, and that's through a particular subtype of serotonin receptors called the serotonin 1A receptor, which is in the, very expressed in the limbic system. But we think psychedelics, we know psychedelics work in the cortex, and they disrupt cortical processing and disrupt, we think, the deep, persistent n- ruminations and negative thoughts of depression. So we said, "Let's do a study where we take depressed people, we scan them with fMRI before and after, and then we see if we can pr- look at the, if the brain changes are different with the escitalopram compared with the psilocybin," predicting that we would see cortical differences, that the cortex would be changed by the psilocybin and the subcortical regions would be changed by the escitalopram. So the primary aim of the study was to see if there were differences in brain mechanisms. But of course, we have to know whether there are differences in outcome. So we compared the, the, the mood-changing effects of these two drugs. But you couldn't just say, "Here, you're on Lexapro. Here, you're on psilocybin." We had to blind it, and that's quite difficult with psychedelics. So the way we got, we did that was to tell everyone they were gonna get psilocybin, 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. But they all went through the same psychotherapy depending... It didn't matter what dose they got. They all got all the same preparation and the psychotherapy that goes with a high dose of psilocybin. And then they all got pills, but the escitalopram group got escitalopram, and the, the, um, psilocybin group got placebo.
- PAPeter Attia
So they're both getting two pills. One is getting-
- DNDavid Nutt
That's right
- PAPeter Attia
... a placebo plus the high dose of psilocybin. The other-
- DNDavid Nutt
Exactly
- PAPeter Attia
Okay.
- DNDavid Nutt
And the point of that is what's called clinical equipoise. People have to believe that they're getting the best they can. And, and then, and, and we gave them two doses of psilocybin, whether high or low, one at the start and one after three weeks to see how long the effect would last. And then we measured changes in, in mood, and we measured side effects. And we also looked at other aspects of, of depression. Rather than just looking at depression scores, we also looked at things like wellbeing, which is a different way of, of, of looking at how people are feeling. And in the end, f- on the, the primary measure, there was no difference, that psilocybin at six weeks was as good, uh, as, um, or equal to as, uh, escitalopram on that particular measure, which was a, a particular self-report measure called the QUIDS self-report, which has been used quite extensively in research in the States, particularly in the STAR *D study. But when we looked at all the other measures, uh, actually psilocybin did rather well.
- PAPeter Attia
Yeah, so I wanna pause on that for a sec because, um, I, I think that the paper was undersold a little bit. I, I think it was... It, it, it read as a negative study, um-
- DNDavid Nutt
Yeah
- PAPeter Attia
... as opposed to a non-inferiority study. Um-
- DNDavid Nutt
Correct
- PAPeter Attia
... what, why do you think that happened? Do you, do you, do you think that there was a mistake in the way that, that either the journal treated that or even the way you treated that as the authors?
- DNDavid Nutt
Yeah, that's a great question, a very perceptive question. Uh, that's a question I think you should ask the editors of The New England Journal.
- PAPeter Attia
[chuckles]
- DNDavid Nutt
So the reality was w- it, the truth was it wasn't, it wasn't powered for non-inferiority. If you want a proper non-inferiority study in psychiatry takes 150 patients in each arm. We could never afford to do that. There's very few that have ever been done except by com- well, probably none have been done except by companies. We could not statistically do a non-inferiority study, so we had to just do a kind of comparison. And, uh, and the answer was that, well, we, th- we had to pre-- we, you know, you pre-specify. We pre-specified two outcomes, the QUIDS and the wellbeing, and it did brilliantly on the wellbeing. But because that's kind of not, uh, that's sort of soft, wishy-washy psychiatry, th- th- we, we, they insisted that we use the QUIDS as the primary. Now, when they, if you don't meet... This is a bit statistical sort of-
- PAPeter Attia
Mm-hmm
- DNDavid Nutt
... uh, jargon really, but if you don't meet your primary, you're not allowed to report the secondaries. It's kind of, it's absolute, it's, it's, it's purism. It's puristic statistics. But as you, as you say, it's kind of not very intuitive because when you look at it, actually it was very clear that the overall, the many m- well, there was not a single measure that favored escitalopram. [chuckles]
- PAPeter Attia
Well, that's, that's sort of the thing is, uh, you know, I, I read the paper in great detail, and my takeaway was this is very promising because I'm very familiar with, with Lexapro, and I'm very familiar with its efficacy, but I'm also very familiar with its side effects and the baggage that comes with it.
- DNDavid Nutt
Mm-hmm. Yes.
- PAPeter Attia
Most people, uh, you know, for the, for the listener, Lexapro is typically given at two doses, 10 milligrams or 20 milligrams. Going from 10 to 20, there is a su- sizable increase in the efficacy, but there's also a sizable increase in the side effects, many of them sexual. And when we're talking about treating young people, old people, middle-aged people, y- you fix their depression, but you destroy their libido. You're, you're, you're-
- DNDavid Nutt
Mm
- PAPeter Attia
... trading one problem for another often. And, uh, the, the, the list of patients I've, you know, taken care of who can't tolerate these drugs despite the benefit that they're receiving from an antidepressive or anxiolytic standpoint, uh, is significant. So, so to me, I read that study with enormous optimism, right? Which is if there is a way to give somebody 25 milligrams of psilocybin and get the same antidepressive benefits but without these other side effects, uh, this is very exciting. This needs to be explored a heck of a lot further. Do you think that the study at least accomplished that as, as, as an outcome?
- DNDavid Nutt
Yeah. So people have said, "Well, why didn't you fight back with a journal? Why didn't you demand, you know, that they were more positive?" And, and the answer is, from my perspective, being the first ever psychedelic study in The New England Journal of Medicine tells the world that psilocybin is a medicine, and it's as good as Lexapro. And if anyone who reads the paper can see that it does do better on sexual dysfunction, and it does do better on many of the other, uh, issues that Lexapro has a problem with. And that, it fits with the theory that one of the things, it's very... The reason Lexapro and other SSRIs dampen down sexual activity is because they dampen down the limbic system, which is the part of the brain which drives those behaviors. And also, people on these drugs often say, "Yes, I'm, I, I don't feel depressed anymore. I don't, I don't g- I don't cry. I, I, I don't have the, the distress that comes from seeing sad things on the TV." But they also say, "But also I don't enjoy life as much because I, I'm kind of... My, my pleasures are blunted."
- PAPeter Attia
Right. It's, it's-
- DNDavid Nutt
And that all fits with that theory
- PAPeter Attia
... blunting the top and the bottom.
- DNDavid Nutt
Exactly.
- PAPeter Attia
Yeah.
- DNDavid Nutt
Exactly. Whereas psilocybin is stopping the thinking and allowing the rest of your brain to work normally.
Episode duration: 1:40:33
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