The straight case for mind bending

By Jerome Burne

Last year Andrew Thayer, a 63-year-old materials scientist, who had suffered from untreatable depression for nearly two decades, arrived at Imperial College in London. He was led into a room with subdued lighting and smelling of incense, swallowed a pill and lay down on a couch covered with a colourful Mexican rug.  

For the next seven hours he had an experience that was the most wonderful and the most terrifying of his life. ‘My ideas about the world swung through 180 degrees,’ says Andrew who lives in Shropshire. ‘At one point my mother, who had died some years ago, appeared as a demonic eagle. Later I experienced my ego dissolving. I became part of the universe but with no form. It was so beautiful.’  

Those two paragraphs were the start of a feature I wrote last year about the imaginative and courageous (because it is odd and hard to fund) research being done at Imperial College in London which showed that the mushroom-derived hallucinogen psilocybin was able to provide relief for months to people with depression who had not responded to any treatment for at least 18 years. Andrew was one of the subjects. For various reasons the article was never published (an updated version continues below) but first a little more introduction and background.

It’s no secret that psychedelic drugs are making a comeback as a possibly effective treatment for a range of psychological disorders and not before time. Last week the New Scientist magazine ran a feature saying that these drugs are returning to academic respectability 50 years after they were made illegal on the grounds that they were highly dangerous and had no medicinal value.

Psychiatric drug disaster

It is also no secret that psychiatric drugs have been a disaster for decades – highly addictive sleeping pills and tranquilizers, marginally effective anti-depressants with long-denied serious withdrawal problems and brain numbing antipsychotics that include weight-gain and diabetes among a long list of highly unpleasant side effects.

I felt it was worth publishing now because it includes details of what taking the drug is like, which is important for appreciating what a game changer it could be, and to remind people of the crucial but largely unappreciated role played by a friend of mine Amanda Feilding in shepherding this research out of the backwaters and into the mainstream – to mix metaphors.

I knew Amanda in those distant days when these drugs, which we both found fascinating, were legal. While I went on to writing Amanda stuck to experimenting with them on the perfectly rational grounds that a basic scientific principle is that to understand something you need to perturb it. Consciousness is a big and fascinating mystery and one of the best ways dramatically to perturb it is with hallucinogenic drugs.

She kept faith with this approach during all the years when such research was a deeply unfashionable hippy hangover. She gradually moved on to a more formal approach, funding a few like-minded mavericks interested in scanning brains of those on drugs or testing the effects of hallucinogens as a way to cut smoking addiction. She also helped fund the early research at Imperial that began in 2010.

Fewer nightmares and less distress

For a few years before they were outlawed in the early 1970’s the American government spent four million dollars funding 116 LSD studies many with positive results. The drugs seemed not to cause the wide range of physical side effects associated with the approved treatments. Now a number of the expensive larger scale RCTs required for licensing are underway.

The strange and extraordinary visions that Andrew reported are similar to ones described by others taking psilocybin or LSD. Psilocybin is the active ingredient in around 200 species of mushroom, known as magic mushrooms, while LSD is a synthetic version of a compound found in a fungus called ergot that can grow on rye.  

Three months after his two trips (the article continued) Andrew’s intractable depression had been transformed. ‘It’s not gone but I have a different way of thinking about it,’ he says. ‘It is now a part of me but it no longer defines me.  

‘I used to have nightmares and wake feeling certain the day would be bad and it was. Everything became felt flat and pointless. Now the bad dreams are fewer and they don’t trigger same despairing response. The depression is still there but it’s as though it’s in the next room. I’m off the antidepressants I took for 18 years.’   

Nearly half depression free after three months

Andrew was one of 20 patients in a trial being run by a team of neurologists at the Centre for Neuropsychopharmacology at Imperial College London, headed by Professor David Nutt.  

‘Both compounds target a receptor in the brain for serotonin’, says Nutt. ‘The familiar SSRI anti-depressants also target serotonin, which comes in 14 different varieties. But while SSRIs weakly affect all of them, these drugs strongly affects just one, the 2a receptor.’ 

The results of the trial, published last year in Lancet Psychiatry, were remarkable – 67 per cent were depression-free one week after treatment and 42 per cent were still in remission three months later.  

‘Research in the last few years has shown that properly handled these drugs can have remarkable beneficial effects on a number of serious psychiatric disorders,’ says Amanda Feilding one of the authors of this study. Feilding heads the Beckley Foundation in Oxford which worked on it jointly with Imperial College.  

So far over 500 doses of psilocybin have been safely given to people at two leading America universities – New York (NYU) and Johns Hopkins. They were patients with end-stage cancer, taking part in studies to see if the drug could help with their severe anxiety. 

Fear of death fades away

‘These were patients who were palpably afraid of death,’ says Stephen Ross an associate professor of psychiatry at NYU. ‘They just lost their fear and returned from their trips far calmer and more loving. They stayed that way till they died. We have never had anything like that in the psychiatric field before.’ 

Smaller psilocybin pilot studies on patients with addictions have also had impressive results. Done at John’s Hopkins University in Baltimore and funded by the Beckley Foundation, they reported that 80% of the 12 subjects in the smoking trial were still abstaining six months later  

What’s new about this latest research is not just as a confirmation of the earlier positive results but that the new scanning technologies such as MRI allow researchers to peer into the brain and see the ways the brain gets rewired while patients take a trip and why it might lead to such dramatic changes in behaviour. 

What has become very clear is that because of the extreme states these drugs can create they can only be safely taken in a carefully controlled environment. All the while Andrew was on his roller-coaster inner journey on the couch, two psychiatrists were there to support and reassure him.  

Andrew and all the volunteers took two doses a week apart; a low one and then one that was much stronger. Andrew’s first trip was largely benign and he came to appreciate a special power the drug seemed to have. He saw himself, as if appearing in an internal movie. In one crucial scene he was in a safe place with a man he didn’t recognise who was guarding and protecting him.  

Andrew reconnects with his dead father

‘As I watched it seemed that the drug told me that the man was my father,’ he says. ‘My father had died when I was only 16 and losing him had affected me deeply. The feeling that he was still with me was like finding an internal teacher and protector.’    

On his next high dose trip, however, the scenes from his internal movie took a much darker turn when he met his mother who was also dead. He saw huge demonic mythic figures. ‘An ant, the head of a wasp and the head of black eagle,’ he says.  

‘All were trying to get into my body through my mouth which they forced open. The interior commentary told me that each was my mother. ‘It was terrifying and I was finding it very hard to breathe. But my helpers advised me to go towards the monsters not to fight them.’  

Terrifying as it was, afterwards Andrew found he had new insights into events in his early childhood and how they could have influenced his depression. 

Letting go of mean negative judgements of yourself

So what is going on here? How can these potent internal movies have an ultimately beneficial effect? This research is building a clearer picture of how the drug changes the way patients think about their condition and how the action it has on brain chemistry allows that to happen. 

Dr Camilla Day one of the psychiatrists who supported Andrew explains the changes in thinking. ‘The visions seem to allow you to understand that you have free will,’ she says.  

‘That you don’t have to keeping doing the same negative unproductive things. You don’t have to identify with the thoughts that come into your head. They are just thoughts.  You can let go of the hurt and resentment. Let go of the mean negative judgements of yourself.’  

 To find out what these hallucinatory drugs were actually doing to the brain, the Beckley/Imperial collaboration had run an earlier experiment, giving volunteers a dose of LSD and then watching the effect in an MRI brain scanner.  

Benefits of chemically shaking up your brain

The results, published last year in the Proceedings of the National Academy of Science, made it look as if the brain was weathering a storm of sorts, with brain networks disintegrating and losing their boundaries so that parts of the brain that normally barely communicated began to show much more active connections.  ‘It’s this ability of the drug to shake up long standing patterns that seems to be key to its effect.’ says Dr Robin Carhart-Harris, a neuroscientist and the lead author of the paper. 

‘It opens up the possibility of establishing new patterns which the patients experience being able to reassess old ways of thinking and behaving. Addiction and depression involve rigid patterns that become reinforced over time. Being able to break these patterns is probably why the drug can help.’ 

Fascinating and promising as this research is it is still in very early stages, and the scientists involved all agree larger proper trials with a placebo are needed. (This, the New Scientist article reports, is now happening)

Commenting on the research, professor of pharmacology at Oxford Philip Cowen described it as ‘ground breaking and important’ but points out that even if bigger trials are successful there are major obstacles to rolling it out across the NHS.  

SSRIs stops hallucinogens working

One of these is that most seriously depressed patients are on SSRIs. ‘These drugs reduce the effect of psilocybin,’ he says. ‘But coming off them can be very hard and take months or longer. And would the NHS have the resources to provide the support all the patients would need?’ 

Cowan’s concerns also illustrate two of the major problems with the existing system – the reliance on drugs with a range of nasty side-effects and insufficient resources for psychological support.

These “problems” should ensure a major upheaval in psychiatry if psychedelics are actually made widely available. They don’t work like other psychiatric drugs – tools to damp down mental distress – but by helping patients to understand why it happens. Also, crucially, they won’t work well without connecting with others. These two features could certainly turn psychiatry on its head.

 

Jerome Burne

Jerome Burne

Jerome Burne is the editor of HealthInsightUK. He is an award-winning journalist who has been specialising in medicine and health for the last 10 years and now works mainly for the Daily Mail. His most recent book “10 Secrets of Healthy Ageing” was written with nutritionist Patrick Holford. He blogs at “Body of Evidence” – jeromeburne.com. 2015: Finalist for 'Blogger of the Year' award from Medical Journalists' Association.

7 Comments

  • “I’m off the antidepressants I took for 18 years”: my first thought – what was the sequence of events here?

    “there are major obstacles to rolling it out across the NHS … One of these is that most seriously depressed patients are on SSRIs. ‘These drugs reduce the effect of psilocybin,’ he says. ‘But coming off them can be very hard and take months or longer.’”

    Theodore Dalrymple (aka Anthony Daniels), a former GP and prison doctor, argues that the problems of coming off heroin, and its addictiveness, are greatly exaggerated. Is there any chance that the same is true of SSRIs?

    ‘And would the NHS have the resources to provide the support all the patients would need?’ Ah, the mandatory demand for money that infects every article mentioning the NHS.

    • Editorial

      The boring answer to question about whether SSRI side effects are exaggerated is: it depends. Certainly there are some people who have a dreadful time. Check out Luke Montague who suffered for years but had the resources to set up society for evidence based psychiatry or David Healey’s site (rxisk) -he is a psychiatrist who has been campaigning on behalf of people suffering side effect for at least three decades

      .On the other hand some may come off with little problem. What is certain is that no drug company has done research to discover whether more people suffer than don’t. for years they denied there were any side effects at all – long story of disreputable behaviour

      Problem of NHS resources very real. One answer is that to help people through a trip don’t need psychiatrists or even medical people at all could be done by supportive local people possible with medical person around. Would require a rather different model with more community support.

  • The fact that so few people have responded to this subject, should not, I think, be taken to mean that people do not care about depression, or are not interested in this subject. For example, I know someone who could definitely benefit from this treatment if it became widely available.

    I think it is that these drugs clearly operate on the mind in ways that nobody really understands, and that may relate more to the ‘soul’ than to the physical brain. For example, I know some people think that the brain normally traps the mind inside the body, and these drugs weaken that link for a while, allowing the person’s mind to expand out and view a larger reality.

    I hope this treatment becomes more widely available, but it is obvious why so many people are cautious about it!

  • How sad & simpistic. To this ret.mechanic, it’s akin to using a spanner or a screwdriver to mend an ailing auto…very difficult,indeed.Seriously, if our cars were at the mercy of allopathic doctors,we’d all be walking to work. More tools are needed…total diet change to restore the gut microbiome, vitamin [esp B complex] & mineral supplementation… In a nutshell-’… Magnesium is an old home remedy for all that ails you, including “anxiety, apathy, depression, headaches, insecurity, irritability, restlessness, talkativeness, and sulkiness.” In 1968, Wacker and Parisi reported that magnesium deficiency could cause depression, behavioral disturbances, headaches, muscle cramps, seizures, ataxia, psychosis, and irritability – all reversible with magnesium repletion…Let’s look at Eby’s case studies from his paper:

    A 59 y/o “hypomanic-depressive male”, with a long history of treatable mild depression, developed anxiety, suicidal thoughts, and insomnia after a year of extreme personal stress and bad diet (“fast food”). Lithium and a number of antidepressants did nothing for him. 300mg magnesium glycinate (and later taurinate) was given with every meal. His sleep was immediately restored, and his anxiety and depression were greatly reduced, though he sometimes needed to wake up in the middle of the night to take a magnesium pill to keep his “feeling of wellness.” A 500mg calcium pill would cause depression within one hour, extinguished by the ingestion of 400mg magnesium…’
    –Emily Deans, M.D.
    https://www.psychologytoday.com/blog/evolutionary-psychiatry/201106/magnesium-and-the-brain-the-original-chill-pill

    • Editorial

      Couldn’t agree more. The psychiatric/psychological assumption that the factors influencing mental states operate only from the neck up is clearly absurd. About 20 years ago a tightly controlled RCT was run in UK’s toughest young offenders prison. The two groups simply got pills of either Vitamin and mineral RDAs or a placebo. Supplemented group had 35% reduction in violent incidents – easy to rate as all incidents routinely recorded. Prison service never repeated it and spent at least 100 million testing a set of psychological interventions that produced little benefit.

      PPis are now an accepted cause of magnesium deficiency – GPs poor at spotting it – and something like 40% of elderly population are on these drugs often for years. Highly likely contributes to their depressive symptoms.

      Think ‘sad and simplistic’ a rather harsh way to describe the fascinating research being done on psychedelics. Multi-factorial approach to mental health – as with gut health, brain health. heart health and the rest – obviously way to go but that doesn’t exclude going into detail on why specific interventions make sense.

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  • On the subject of supplements, I know someone (aged 66) who suffered from lack of energy and depression over many years, with no help from doctors. She experimented with a whole range of supplements, and finally tried co-enzyme Q10. After a month of taking 120 mg of this per day, she found that her stamina increased markedly. She also says that her depression is starting to lighten – though it is hard to be totally certain yet.

    Presumably Q10 only makes a difference to people who are actually short of it – likewise with many other supplements. Therefore perhaps ideally patients complaining of problems with no obvious diagnosis could be given a list of supplements that might help and be encouraged to experiment.

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