He was at Unherd a while ago talking to Florence Read about psilocybin and depression, which is a subject I have touched on in different ways here before. For me, this is one of those signals of change which could suddenly move quite quickly. Yes, society has views on psilocybins, which were outlawed here 50 years ago, but it also has an increasingly big problem with depression.

Both the research, and the responses to it, are interesting. It’s also a long interview transcript, so I’ll have to be selective.

‘They all got better’

The headline on the piece was: “Can psychedelics cure depression?” But let’s do the science first.

Psychedelics switch off the parts of the brain that control your mind. There was a group at Yale doing work in depression. They showed that the default mode network — the part of the brain that was turned off by psychedelics — is overactive in depression. If you scan the brains of depressed people, a greater amount of their brain is engaged in this internal, reflective, self-referential thinking. We thought: “Let’s see if we can turn it off in depressed people, and will they be non-depressed?” And lo and behold, they were.

As Nutt observes, the 1960s radical Timothy Leary got it the wrong way round: psychedelics weren’t turning the brain on, they were turning it off.

The initial study group for Nutt’s research was people who were depressed, and who had failed with other treatments, whether anti-depressants or CBT (cognitive behavioural therapy). And: “They all got better”.

Lowering the barriers

But, reading the interview, it’s not just the psilocybin that’s doing this. The use of psychedelics is combined with therapy: what the psychedelics are doing is (as I understand it) lowering the barriers to engaging with the trauma that is causing the depression. The reason that this might work:

(O)ne of the theories about why your mind is so preoccupied in depression — is that you’re trying to resist re-engaging with those traumas. But we encouraged them to do that. It’s challenging, it’s difficult, they find it distressing — but they often get fundamental insights.

There seems to be something about psilocybin that makes the medical establishment a little jittery, though. Having got a grant in response to a Medical Research Council call for research on new treatments for depression, it took a years and three re-designs to get the research design past the Ethics Committee. For example:

The ethics committee said: “It’s too dangerous; you can’t give depressed people psychedelics.” Why not? “Well, they might die.” That’s pretty unlikely — no one’s ever died on psilocybin before — but why do you think depressed people might die? “Well, they’re depressed.”

Safety study

The Ethics Committee turned down the proposed random controlled trial—for the same safety reasons—and instead proposed that the researchers start with a safety study:

Give 12 people it, see how they go. If none of them are dead in six months then you can come back and do a controlled trial.” So we said yes — in fact, the original trial was to see if people survived, which they all did. And the secondary outcome was whether their mood had changed. They could have got worse. They all got better.

That was only one of the delays to the project. It took another year to get hold of the drug because there’s only one place in the world able to make it. And then it took another two months to get permission from the Home Office to use it.

Thinking differently

Nutt suggests that these delays are because of the way that psychedelics have been “vilified” (his word) over the last half a century. Of course, there’s a history here too:

The reason psychedelics were banned in 1967 in the US and in 1970 in the UK was simply because psychedelics were allowing people to think differently about how they wanted to run international relations. The war in Vietnam was being protested. There’s this amazing photograph I have, of someone holding a placard that says: “Drop acid, not bombs.” They couldn’t ban the anti-war protests so they banned the drugs instead.

Nutt observes that drugs laws are very hard to shift. They’re certainly not that responsive to evidence. But all the same, things are changing. In the US half of the states now permit the recreational use of cannabis, and two thirds medicinal use, even though its still illegal at a federal law. Canada and Uruguay have pulled canabis out of the UN conventions.

None of that has happened yet to psilocybins, but Oregon has now made magic mushrooms a legal medicine, and are allowing wellness centres across the state to prescribe mushrooms as part of a wellness therapy.

It’s the first time anywhere in America that there’s kind of socialised medicine — using what it is now, and will be even when the therapy centres are open, an illegal drug. The purpose is to improve wellbeing in communities, and I think it’s going to work.

Cultural responses

Nutt isn’t confident that British doctors will follow suit, or not yet. He describes healthcare in the UK as “top-down, paternalistic and autocratic.” But at the same time there is strong academic interest, and the research is being published in leading science journals. The medical response seems more cultural. In the interview, Nutt describes giving a talk on this about five years ago yo the Royal College of Psychiatry, as part of a discussion on the future of psychiatry. By his account, the room split into three groups.

The older group—who could remember psychedelics when they were still legal, were pleased that Nutt was bringing them back into medicine. The middle group (then 35 to 60, so Boomers and GenX doctors) were sceptical or hostile:

“This is rubbish. There’s no RCTs. They’re dangerous drugs.”

And the trainees—effectively the Millennials in the room:

“Fantastic — at last. Psychiatry has got something to offer me!”

And this age-related cultural point is another reason why I think this area could move quickly when it starts to move.

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A version of this article is also published on my Just Two Things Newsletter.

Johnson describes 19th century London as ‘a Victorian city with an Elizabethan infrastructure’ – a boom town than had grown from a million people in 1800 to three million in 1850. One of the results was to overwhelm the complex ecology of specialist labourers – from nightsoilmen to pure-finders to bone collectors to toshers to mudlarks – which had managed the disposal of the city’s waste. Cellars and gardens became cesspits. The smell was notorious.

Soho was a poor district in the heart of the city; families lived three to four to a room. Indeed, the present topography of Regent Street (big open streets running west to Mayfair, with limited access east to Soho) had been designed deliberately by Nash as a way to restrict the social exchange of rich and poor.

The invention of public health

John Snow, the scientific hero of the book, lived at the south edge of Soho. He had pioneered the effective application of chloroform so successfully that he had attended at the birth of one of the Royal children as anaesthetist. But – in his attempts to prove the link between cholera and infected water, which pre-dated the Broad Street [now Broadwick Street] outbreak – he would spend his evenings walking some of the roughest areas of south London collecting water samples from households for his research.

The prevailing scientific view at the time was that disease was transmitted by ‘bad air’ – the so-called miasmatic view that ‘all smell is disease’. One of the main protagonists of this theory was Edwin Chadwick, who did more than almost anyone to develop the idea of public health intervention, in a career that started as a Poor Law Commissioner and ended on the General Board of Health. As Johnson writes:

Chadwick helped solidify, if not invent, an ensemble of categories that we now take for granted: that the state should directly engage in protecting the health and well-being of its citizens, particularly the poorest among them”.

And that this required experts and institutions to address issues ignored or exacerbated bt the markets, and that doing all this can sometimes require huge investment.

But when it came to cholera, the obsession with smell produced precisely the wrong solution: sewage was piped into the Thames (Bazalgette’s monumental sewer programme came later). The official Board of Health enquiry into the Broad Street tested the water-borne theory, but concluded “After careful enquiry we see no reason to adopt this belief”. (The terms of reference didn’t help).

However, a second investigation, sponsored by the Parish, was more convinced, partly because Henry Whitehead, the curate at St Luke’s church, had been initially sceptical but was persuaded of Snow’s theory both by meeting him and reading his earlier work on the causes of cholera. More important, through, was Whitehead’s diligence as a social investigator, as he went round the parish knocking on doors and tracing the pumps which people took their water from.

A map of time and space

If this is a triumph for civil society, it is a triumph for something else as well: the invention of public health statistics, William Farr‘s “Weekly Returns of Births and Deaths”, which provided an evidence base for research. In some ways, Snow’s research method was the first time that an epidemiological approach had been applied to health research. But acceptance of Snow’s theory was not immediate; it took some years before it finally prevailed over miasma – helped by London’s Great Stink, which didn’t produce any surge in disease. Snow was dead before it was fully accepted. The map helped; the version that made the difference showed the distribution of deaths in the houses around the pump – and also the time taken to reach it, through the maze of Soho alleys and back streets, a map, as Johnson notes, of time as well as space.

The Ghost Map quotes a line from Jane Jacobs, that “cities were the most helpless and devastated victims of disease. but they became great disease conquerors”. In the face of climate change, the density of cities becomes an asset. But they are also vulnerable to disruptive attack, especially assymetric attack. A nuclear bomb in a suitcase could kill millions, and a chemical or biological attack would be worse.

But the microbes could have the last laugh. Although microbes have been managed through successive waves of public health reforms, “micobial life has an uncanny knack for mutation and invention”. Microbes modify and adapt rapidly. Unlike more complex forms, viruses can and do swap genes with other viruses, swiping lines of genetic code from one another, and creating the so-called ‘transgenic shift’. Public health professionals increasingly regard pandemics as inevitable, rather than being a risk or a ‘wild card’. In a world dominated by dense cities, many with poor public health systems, it’s probably only a matter of time before a microbe gets lucky – with effects which will be far devastating than the Broad Street cholera epidemic.

The picture at the top of the post, of one of the several ‘ghost maps’ is from a review of the book at dylanstiles.com.

The secret is in the economics apparently – which are driven largely by technology. This sounds a bit like one of those school maths problems, but at the moment it takes around 20 technicians eight or nine months to sequence a single person’s DNA. New technologies could replace the people, so that two or three people could do the job in a week.  Which on the back of my envelope sounds like it would be about 100 times cheaper.

From the perspective of genetic scientists this is largely a good thing. They can see applications will help diagnose the optimal response to a cancer or even spot people with cancers early. It could help those with genetic diseases, and so on. But once the technology is that widespread it clearly opens up the gates for all of the ethical issues which have been prefigured (insruance hazard and so on). Perhaps more interesting, if we do see a fell in cost and simplicity of that magnitude in a decade, is how it might look in twenty years. In a world where people already talk about a ‘lab on a chip’ one can envisage do it yourself DNA sequencing on one’s laptop – even a whole open source community.