Magic mushrooms and mental health: could psychedelic drugs treat depression?

For the past decade, Prof David Nutt, the Edmond J Safra Professor of Neuropsychopharmacology at Imperial College London, has been investigating the therapeutic potential of psychedelic drugs.

He spoke to Jason Goodyer about his pioneering work on using psilocybin to treat depression and the effect that psychedelics have on other mental disorders.

Your work is centred on psychedelic drugs. What does the term ‘psychedelic’ actually mean?

Psychedelics was a term developed back in the 1950s by people like Aldous Huxley [the author of The Doors Of Perception]. Psychedelic means mind-manifesting.

Typically, we talk about psychedelic drugs as drugs that produce altered states of perception and consciousness, such as magic mushrooms, LSD, mescaline, peyote, DMT, ayahuasca. It turns out they all work on a particular receptor in the brain called the serotonin 5HT2A receptor.

What is the role of the serotonin 5HT2A receptor?

The human brain is loaded with them, all in the parts of the brain where you do your thinking and your analysis of yourself. They tie together your consciousness with your other senses. They’re really in that circuit that kind of defines what you are as a human being. When you stimulate those receptors with psychedelics, you change the way the brain processes things.

The brain is an amazing organ; it’s the most efficient computer, 10 times more energy efficient than any computer we’ve yet invented. One of the reasons that the brain is so efficient is that it learns very quickly what to predict. Brains make inferences and we live through those inferences because it’s just so much more efficient.

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If your brain had to update every, say, 15 milliseconds, everything that’s gone into it, that would consume enormous amounts of energy. So, the brain basically looks for change. It sees what’s there and listens to what’s there, and then when things change, it takes notice. The rest of the time, it just says that things haven’t changed.

That process is what we call a small world; the brain becomes very efficient at doing what’s just enough to make sure you can find your way home and you can do your homework and you can turn on the TV. You can do all the things you need to, but you do them almost in a reflex way. The brain develops these sophisticated habits and psychedelics disrupt those.

Can you give me an example?

One of the elegant things about our research – the thing that I find perhaps the most interesting of all – is that, we know from the physiology of the visual system that when people hallucinate under psychedelics, they see what we call geometric patterns.

They see squares, they see circles, they see rectangles and they see spirals. And the physics of visual perception tells us that that’s actually the first level of visual analysis. What you see is determined by the brain reconstructing electrical impulses from the eye, and it starts off by reconstructing those kinds of images.

Actually, what you’re seeing under psychedelics is the early working of your visual system, because the higher work in putting it all together into images has actually been disrupted.

Prof David Nutt © Imperial College London

Beyond that, one of the most common positive experiences of people under psychedelics is that they see the world differently. They get insights into their own behaviour – particularly their own behaviour but also into other people’s behaviour – which they didn’t get before, and they kind of understand things [better].

Those insights can be profound and people can change as a result – change their whole behaviour; change their way of life.

Many of our subjects would describe their body slowly disintegrating and their atoms floating out

How did you begin your work on psychedelics and depression?

The depression trial was driven in part by the brain imaging studies we did. When we started working with psychedelics, we had no inkling whatsoever that we would be studying psychiatric disorders. We were studying them [the drugs] because they needed to be studied.

No one else has studied them, because they’ve been illegal for 50 years. We were interested to know why they produced these really remarkable effects – both in terms of perceptions and hallucinations, but also the altered sense of self.

So, we started off doing neuroscience. And when we did the first imaging studies, we discovered some rather unexpected things.

The first was that even when you give [magic] mushrooms to people in a scanner, they often come out and say, “Wow! That was an interesting experience,” and they often say, “I feel better.”

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People would come back to us a week later saying, “It’s amazing, ever since you gave that to me in the scanner, the world seems like a better, brighter, nicer place.”

The second thing we noticed was that the parts of the brain that normally drive depression got switched off by psilocybin. So, we thought, well, that’s interesting, maybe this wellness feeling that people have has got something to do with switching off the negative mood.

And the third thing that happened was that there was some brain imaging data on depression coming out, suggesting that depression was an over-engagement. There’s a circuit in the brain, which is the circuit of the self, that gets over engaged. It’s called the default mode network.

It’s that internal network where you do your thinking about yourself. We noticed that psilocybin completely disrupted that network – it switched it off. And of course, that explains something that’s fundamental in psychedelics: the dissolution of the ego.

The brain is an amazing organ; it’s the most efficient computer, 10 times more energy efficient than any computer we’ve yet invented

Many of our subjects in the scanner would describe their body slowly disintegrating and their atoms floating out. They’d float out beyond the scanner and then float into space, and some would go into other dimensions and some would go into mountains and see God. You know, they would be somewhere else other than the scanner.

That sense of disorganisation of where you are in space we can explain now in terms of the brain’s circuits. It’s because you’ve disrupted the default mode, which essentially anchors you in normal space.

Now, when we discovered that this other group had shown that the default mode network was overactive in depression, we put two and two together and thought, well, if it’s overactive in depression and we can disrupt it completely – that’s what psychedelics do – maybe we should be trying it in depression.

How did you set up your experiments?

Depression is the largest cause of disability in the western world, in Britain certainly. Current treatments are, you know, they’re not bad but they’re not brilliant. A lot of people have residual depression and a lot of people have resistant depression. They don’t get completely well when they’re treated.

So, there was a call put out and we argued the case I just told you – that there are three reasons for trying psychedelics in depression – and we got funded.

Actually, that was the easy bit. It was extremely difficult to get permission to do this study. Ethics committees were very cynical.

It took us years to get hold of the drug because we had to get it made and imported from overseas. And they would only allow us to study people with what we call ‘treatment-resistant depression’, so people who had failed on at least two treatments – two drug treatments – and also had failed on cognitive behaviour therapy (CBT). It turned out some people had failed on 15 or 20 or more different drugs.

Depression is the largest cause of disability in the western world

It was a simple trial. We gave people a low dose to make sure there was no paradoxical reaction in depressed people to psilocybin, and then we gave them a decent dose, a 25mg dose, which gave them a decent trip. And then we looked to see what happened.

I think it’s important to say one other thing. When this was done, there were two therapists with the each person all the way through the trip. We prepared them carefully for what might happen, the good effects and potentially the negative effects of the trip.

And then the next day, we did what’s called an integration session, which is where the therapists try to help the person make sense of what they’ve experienced. Because often with depression people have had quite nasty experiences [while tripping].

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They relive traumas that they’ve been trying to repress, and those traumas are in their brain and they’re eating away and causing the depression. But then, very often, they made sense of why they were depressed, and then they had to deal with that.

In the trip it’s difficult to deal with it; you get insights, but afterwards you need to talk through what they mean with the therapists. We found that from almost the next day, their mood was improved and most people had a benefit for several weeks or months.

In fact, even at six months, there was a significant positive impact of this treatment, after just a single dose for most people.

Could this effect also be potentially used to treat addiction?

This is where our research is at present. So, what pulls all these things together? It’s what we call internalising disorders – addiction, depression, anorexia and also obsessive-compulsive disorder (OCD). These are disorders where people are engaged internally with thinking that’s not useful.

In depression, people are thinking about things they’ve done wrong; in OCD they’re thinking about contamination; in anorexia they’re obsessed with food and weight; and in addiction, they’re obsessed with alcohol or tobacco or heroin.

This point I was making about the brain being very efficient, one of the reasons the brain is efficient is that it lays down habits. Think about riding a bike. You start off and my goodness, you’re using probably every bit of your brain to balance and to see where you’re going and to work out you’ve got to hold this and push that pedal.

At six months, there was a significant positive impact of this treatment, after just a single dose for most people

It’s an enormous amount of conscious effort. But then, after a few days, it’s nothing at all. And then for the rest of your life, you can ride bikes. Why? Because your brain has downloaded all the conscious efforts into a habit, a behaviour that is fully acquired and in fact, it’s almost impossible then not to ride a bike when you’re put on a bike.

So, that process of making the brain do its own thing free from conscious control is fabulous for most of life and very necessary.

But suppose your brain gets you locked into something that isn’t useful, such as drinking too much or taking heroin. Then it’s difficult to unlock that, because the brain is about locking you in.

So, what we’re hoping is that psychedelics can, by fragmenting that ongoing, habitual process of behaviour and thinking, free people up enough so that they can escape from the addictions.

WARNING: Psychedelic drugs are a Class A drug according to UK law. Anyone caught in possession of such substances will face up to seven years in prison, an unlimited fine, or both. Info and support for those affected by substance abuse problems can be found at bit.ly/drug_support

David Nutt’s latest book, Drugs Without The Hot Air: Making Sense Of Legal And Illegal Drugs, is out now (£18.99, UIT Cambridge).