Brainology E-Book

Will Storr

• Herausgeber: Canbury
• Kategorie: Geisteswissenschaft
• Sprache: Englisch
• Veröffentlichungsjahr: 2018

Seitenzahl: 380

Beschreibung

16 revealing stories about the human brain Ever wondered how Scandinavians cope with 24-hour darkness, why we feel pain - or whether smartphones really make children stupid? Have you heard about the US army's research into supercharging minds? You need some Brainology. Written for Wellcome, the health charity, these stories follow doctors as they solve the puzzle of our emotions, nerves and behaviour. Discover fascinating and intriguing stories from the world of science. Contents - Ouch! The science of pain - John Walsh - Why doctors are reclaiming LSD and ecstasy - Sam Wong - Inside the mind of an interpreter - Geoff Watts - How should we deal with dark winters? - Linda Geddes - Smartphones won't* make your kids dumb (*Probably) - Olivia Solon - You can train your mind into 'receiving' medicine - Jo Marchant - Charting the phenomenon of deep grief - Andrea Volpe - The mirror cure for phantom limb pain - Srinath Perur - Can you think yourself into a different person? - Will Storr - How to survive a troubled childhood - Lucy Maddox - What tail-chasing dogs reveal about humans - Shayla Love - A central nervous solution to arthritis - Gaia Vince - Could virtual reality headsets relieve pain? - Jo Marchant - What it means to be homesick in the 21st Century - John Osborne - Lighting up brain tumours with Project Violet - Alex O'Brien - The US military plan to supercharge brains - Emma Young    EXTRACT  Ouch! The science of pain John Walsh One night in May, my wife sat up in bed and said, 'I've got this awful pain just here.' She prodded her abdomen and made a face. 'It feels like something's really wrong.' Woozily noting that it was 2am, I asked what kind of pain it was. 'Like something's biting into me and won't stop,' she said. 'Hold on,' I said blearily, 'help is at hand.' I brought her a couple of ibuprofen with some water, which she downed, clutching my hand and waiting for the ache to subside. An hour later, she was sitting up in bed again, in real distress. 'It's worse now,' she said, 'really nasty. Can you phone thedoctor?' Miraculously, the family doctor answered the phone at 3am, listened to her recital of symptoms and concluded, 'It might be your appendix. Have you had yours taken out?' No, she hadn't. 'It could be appendicitis,' he surmised, 'but if it was dangerous you'd be in much worse pain than you're in. Go to the hospital in the morning, but for now, take some paracetamol and try to sleep.' Barely half an hour later, the balloon went up. She was awakened for the third time, but now with a pain so savage and uncontainable it made her howl like a tortured witch face down on a bonfire. The time for murmured assurances and spousal procrastination was over. I rang a local minicab, struggled into my clothes, bundled her into a dressing gown, and we sped to St Mary's Paddington at just before 4am. The flurry of action made the pain subside, if only through distraction, and we sat for hours while doctors brought forms to be filled, took her blood pressure and ran tests. A registrar poked a needle into my wife's wrist and said, 'Does that hurt? Does that? How about that?' before concluding: 'Impressive. You have a very high pain threshold.' The pain was from pancreatitis, brought on by rogue gallstones that had escaped from her gall bladder and made their way, like fleeing convicts, to a refuge in her pancreas, causing agony. She was given a course of antibiotics and, a month later, had an operation to remove her gall bladder. 'It's keyhole surgery,' said the surgeon breezily, 'so you'll be back to normal very soon. Some people feel well enough to take the bus home after the operation.' His optimism was misplaced. My lovely wife, she of the admirably high pain threshold, had to stay overnight, and came home the following day filled with painkillers; when they wore off, she writhed with suffering.

Leseprobe

BRAINOLOGY

The Curious Scienceof Our Minds

First published by Canbury Press, 2018

Canbury Press,

Kingston upon Thames, Surrey

www.canburypress.com

Cover: Ruth Blackford

All of the stories in this book were first published by Mosaic (mosaicscience.com), an online publication that tells stories you can trust about the science you care about. They are republished here under a Creative Commons licence. Some edits have been made, including to the headlines. Mosaic is created by Wellcome, a global charitable foundation dedicated to improving human health.

ISBN

9781912454006 Paperback

9781912454013 Ebook

9781912454020 Audiobook

Legal Note:This book is designed to inform and entertain its readers.

Its contents are not intended to, nor shall they be taken to, constitute health advice of any kind. Neither the author(s) nor the publisher shall be held responsible for any damage or harm arising from the contents of this book. The content of each article is the sole expression and opinion of its author, and not necessarily that of the publisher. No warranties or guarantees are expressed or implied by the inclusion of any chapters. Neither the publisher nor the individual author(s) shall be liable for any physical, psychological, emotional, financial, or commercial damages, including but not limited to special, incidental, consequential or other damages.

Contents

Ouch! The science of pain

Why doctors are reclaiming LSD and ecstasy

Inside the mind of an interpreter

How should we deal with dark winters?

Smartphones won’t* make your kids dumb (*Probably)

You can train a body into ‘receiving’ medicine

Charting the phenomenon of deep grief

The mirror cure for phantom limb pain

Can you think yourself into a different person?

How to survive a troubled childhood

What tail-chasing dogs reveal about humans

A central nervous cure for arthritis

Could virtual reality headsets relieve pain?

What it means to be homesick in the 21st Century

Lighting up brain tumours with Project Violet

The US military plan to supercharge brains

Acknowledgements

Ouch! The science of pain

John Walsh

One night in May, my wife sat up in bed and said, ‘I’ve got this awful pain just here.’ She prodded her abdomen and made a face. ‘It feels like something’s really wrong.’ Woozily noting that it was 2am, I asked what kind of pain it was. ‘Like something’s biting into me and won’t stop,’ she said.

‘Hold on,’ I said blearily, ‘help is at hand.’ I brought her a couple of ibuprofen with some water, which she downed, clutching my hand and waiting for the ache to subside.

An hour later, she was sitting up in bed again, in real distress. ‘It’s worse now,’ she said, ‘really nasty. Can you phone the doctor?’ Miraculously, the family doctor answered the phone at 3am, listened to her recital of symptoms and concluded, ‘It might be your appendix. Have you had yours taken out?’ No, she hadn’t. ‘It could be appendicitis,’ he surmised, ‘but if it was dangerous you’d be in much worse pain than you’re in. Go to the hospital in the morning, but for now, take some paracetamol and try to sleep.’

Barely half an hour later, the balloon went up. She was awakened for the third time, but now with a pain so savage and uncontainable it made her howl like a tortured witch face down on a bonfire. The time for murmured assurances and spousal procrastination was over. I rang a local minicab, struggled into my clothes, bundled her into a dressing gown, and we sped to St Mary’s Paddington at just before 4am.

The flurry of action made the pain subside, if only through distraction, and we sat for hours while doctors brought forms to be filled, took her blood pressure and ran tests. A registrar poked a needle into my wife’s wrist and said, ‘Does that hurt? Does that? How about that?’ before concluding: ‘Impressive. You have a very high pain threshold.’

The pain was from pancreatitis, brought on by rogue gallstones that had escaped from her gall bladder and made their way, like fleeing convicts, to a refuge in her pancreas, causing agony. She was given a course of antibiotics and, a month later, had an operation to remove her gall bladder.

‘It’s keyhole surgery,’ said the surgeon breezily, ‘so you’ll be back to normal very soon. Some people feel well enough to take the bus home after the operation.’ His optimism was misplaced. My lovely wife, she of the admirably high pain threshold, had to stay overnight, and came home the following day filled with painkillers; when they wore off, she writhed with suffering. After three days she rang the specialist, only to be told: ‘It’s not the operation that’s causing discomfort – it’s the air that was pumped inside you to separate the organs before surgery.’ Like all too many surgeons, they had lost interest in the fallout once the operation had proved a success.

During that period of convalescence, as I watched her grimace and clench her teeth and let slip little cries of anguish until a long regimen of combined ibuprofen and codeine finally conquered the pain, several questions came into my head. Chief among them was: Can anyone in the medical profession talk about pain with any authority? From the family doctor to the surgeon, their remarks and suggestions seemed tentative, generalised, unknowing – and potentially dangerous: Was it right for the doctor to tell my wife that her level of pain didn’t sound like appendicitis when the doctor didn’t know whether she had a high or low pain threshold? Should he have advised her to stay in bed and risk her appendix exploding into peritonitis? How could surgeons predict that patients would feel only ‘discomfort’ after such an operation when she felt agony – an agony that was aggravated by fear that the operation had been a failure?

I also wondered if there were any agreed words that would help a doctor understand the pain felt by a patient. I thought of my father, a GP in the 1960s with an NHS practice in south London, who used to marvel at the colourful pain symptoms he heard: ‘It’s like I’ve been attacked with a stapler’; ‘like having rabbits running up and down my spine’; ‘it’s like someone’s opened a cocktail umbrella in my penis...’ Few of them, he told me, corresponded to the symptoms listed in a medical textbook. So how should he proceed? By guesswork and aspirin?

There seemed to be a chasm of understanding in human discussions of pain. I wanted to find out how the medical profession apprehends pain – the language it uses for something that’s invisible to the naked eye, that can’t be measured except by asking for the sufferer’s subjective description, and that can be treated only by the use of opium derivatives that go back to the Middle Ages.

§ § §

When investigating pain, the basic procedure for clinics everywhere is to give a patient the McGill Pain Questionnaire. This was developed in the 1970s by two scientists, Dr Ronald Melzack and Dr Warren Torgerson, both of McGill University in Montreal, and is still the main tool for measuring pain in clinics worldwide.

Melzack and his colleague Dr Patrick Wall of St Thomas’ Hospital in London had already galvanised the field of pain research in 1965 with their seminal ‘gate control theory’, a ground-breaking explanation of how psychology can affect the body’s perception of pain. In 1984 the pair went on to write Wall and Melzack’sTextbook of Pain, the most comprehensive reference work in pain medicine. It’s gone through five editions and is currently over 1,000 pages long.

In the early 1970s, Melzack began to list the words patients used to describe their pain and classified them into three categories: sensory (which included heat, pressure, ‘throbbing’ or ‘pounding’ sensations), affective (which related to emotional effects, such as ‘tiring’, ‘sickening’, ‘gruelling’ or ‘frightful’) and lastly evaluative (evocative of an experience – from ‘annoying’ and ‘troublesome’ to ‘horrible’, ‘unbearable’ and ‘excruciating’).

You don’t have to be a linguistic genius to see there are shortcomings in this lexical smorgasbord. For one thing, some words in the affective and evaluative categories seem interchangeable – there’s no difference between ‘frightful’ in the former and ‘horrible’ in the latter, or between ‘tiring’ and ‘annoying’ – and all the words share an unfortunate quality of sounding like a duchess complaining about a ball that didn’t meet her standards.

But Melzack’s grid of suffering formed the basis of what became the McGill Pain Questionnaire. The patient listens as a list of ‘pain descriptors’ is read out and has to say whether each word describes their pain – and, if so, to rate the intensity of the feeling. The clinicians then look at the questionnaire and put check marks in the appropriate places. This gives them a number, or a percentage figure, to work with in assessing, later, whether a treatment has brought the patient’s pain down (or up).

A more recent variant is the National Initiative on Pain Control’s Pain Quality Assessment Scale (PQAS), in which patients are asked to indicate, on a scale of 1 to 10, how ‘intense’ – or ‘sharp’, ‘hot’, ‘dull’, ‘cold’, ‘sensitive’, ‘tender’, ‘itchy’, etc – their pain has been over the past week.

The trouble with this approach is the imprecision of that scale of 1 to 10, where a 10 would be ‘the most intense pain sensation imaginable’. How does a patient ‘imagine’ the worst pain ever and give their own pain a number? Middle-class British men who have never been in a war zone may find it hard to imagine anything more agonising than toothache or a tennis injury. Women who have experienced childbirth may, after that experience, rate everything else as a mild 3 or 4.

I asked some friends what they thought the worst physical pain might be. Inevitably, they just described nasty things that had happened to them. One man nominated gout. He recalled lying on a sofa, with his gouty foot resting on a pillow, when a visiting aunt passed by; the chiffon scarf she was wearing slipped from her neck and lightly touched his foot. It was ‘unbearable agony’. A brother-in-law nominated post-root canal toothache – unlike muscular or back pain, he said, it couldn’t be alleviated by shifting your posture. It was ‘relentless’. A male friend confided that a haemorrhoidectomy had left him with irritable bowel syndrome, in which a daily spasm made him feel ‘as if somebody had shoved a stirrup pump up my arse and was pumping furiously’. The pain was, he said, ‘boundless, as if it wouldn’t stop until I exploded’. A woman friend recalled the moment the hem of her husband’s trouser leg snagged on her big toe, ripping the nail clean off. She used a musical analogy to explain the effect: ‘I’d been through childbirth, I’d broken my leg – and I recalled them both as low moaning noises, like cellos; the ripped-off nail was excruciating, a great, high, deafening shriek of psychopathic violins, like nothing I’d heard – or felt – before.’

A novelist friend who specialises in World War I drew my attention to Stuart Cloete’s memoirA Victorian Son(1972), in which the author records his time in a field hospital. He marvels at the stoicism of the wounded soldiers: ‘I have heard boys on their stretchers crying with weakness, but all they ever asked for was water or a cigarette. The exception was a man hit through the palm of the hand. This I believe to be the most painful wound there is, as the sinews of the arm contract, tearing as if on a rack.’

Is it true? Looking at the Crucifixion scene in Matthias Grünewald’s Isenheim Altarpiece (1512–16), you take in the horribly straining fingers of Christ, twisted around the fat nailheads that skewer his hands to the wood – and oh, God yes, you believe it must be true.

It seems a shame that these eloquent descriptions are reduced by the McGill Questionnaire to words like ‘throbbing’ or ‘sharp’, but its function is simply to give pain a number – a number that will, with luck, be decreased after treatment, when the patient is reassessed.

This procedure doesn’t impress Professor Stephen McMahon of the London Pain Consortium, an organisation formed in 2002 to promote internationally competitive research into pain. ‘There are lots of problems that come with trying to measure pain,’ he says. ‘I think the obsession with numbers is an oversimplification. Pain is not unidimensional. It doesn’t just come with scale – a lot or a little – it comes with other baggage: how threatening it is, how emotionally disturbing, how it affects your ability to concentrate. The measuring obsession probably comes from the regulators who think that, to understand drugs, you have to show efficacy. And the American Food and Drug Administration don’t like quality-of-life assessments; they like hard numbers. So we’re thrown back on giving it a number and scoring it. It’s a bit of a wasted exercise because it’s only one dimension of pain that we’re capturing.’

§ § §

Pain can be either acute or chronic, and the words do not (as some people think) mean ‘bad’ and ‘very bad’. ‘Acute’ pain means a temporary or one-off feeling of discomfort, which is usually treated with drugs; ‘chronic’ pain persists over time and has to be lived with as a malevolent everyday companion. But because patients build up a resistance to drugs, other forms of treatment must be found for it.

The Pain Management and Neuromodulation Centre at Guy’s and St Thomas’ Hospital in central London is the biggest pain centre in Europe. Heading the team there is Dr Adnan Al-Kaisy, who studied medicine at the University of Basrah, Iraq, and later worked in anaesthetics at specialist centres in England, the USA and Canada.

Who are his patients and what kind of pain are they generally suffering from? ‘I’d say that 55 to 60 per cent of our patients suffer from lower back pain,’ he says. ‘The reason is, simply, that we don’t pay attention to the demands life makes on us, the way we sit, stand, walk and so on. We sit for hours in front of a computer, with the body putting heavy pressure on small joints in the back.’ Al-Kaisy reckons that in the UK the incidence of chronic lower back pain has increased substantially in the last 15–20 years, and that ‘the cost in lost working days is about £6–7 billion’.

Elsewhere the clinic treats those suffering from severe chronic headaches and injuries from accidents that affect the nervous system.

Do they still use the McGill Questionnaire? ‘Unfortunately yes,’ says Al-Kaisy. ‘It’s a subjective measurement. But pain can be magnified by a domestic argument or trouble at work, so we try to find out about the patient’s life – their sleeping patterns, their ability to walk and stand, their appetite. It’s not just the patient’s condition, it’s also their environment.’

The challenge is to transform this information into scientific data. ‘We’re working with Professor Raymond Lee, Chair of Biomechanics at the South Bank University, to see if there can be objective measurement of a patient’s disability due to pain,’ he says. ‘They’re trying to develop a tool, rather like an accelerometer, which will give an accurate impression of how active or disabled they are, and tell us the cause of their pain from the way they sit or stand. We’re really keen to get away from just asking the patient how bad their pain is.’

Some patients arrive with pains that are far worse than backache and require special treatment. Al-Kaisy describes one patient – let us call him Carter – who suffered from a terrible condition called ilioinguinal neuralgia, a disorder that produces a severe burning and stabbing pain in the groin. ‘He’d had an operation in the testicular area, and the inguinal nerve had been cut. The pain was excruciating: when he came to us, he was on four or five different medications, opiates with very high dosages, anticonvulsive medication, opioid patches, paracetamol and ibuprofen on top of that. His life was turned upside down, his job was on the line.’ The utterly stricken Carter was to become one of Al-Kaisy’s big successes.

Since 2010, Guy’s and St Thomas’ has offered a residential programme for adults whose chronic pain hasn’t responded to treatment at other clinics. The patients come in for four weeks, away from their normal environment, and are seen by a motley crew of psychologists, physiotherapists, occupational health specialists and nursing physicians who between them devise a programme to teach them strategies for managing their pain.

Many of these strategies come under the heading of ‘neuromodulation’, a term you hear everywhere in pain management circles. In simple terms, it means distracting the brain from constantly brooding on the pain signals it’s getting from the body’s ‘periphery’. Sometimes the distraction is a cunningly deployed electric shock.

‘We were the first centre in the world to pioneer spinal cord stimulation,’ says Al-Kaisy proudly. ‘In pain occasions, overactive nerves send impulses from the periphery to the spinal cord and from there to the brain, which starts to register pain. We try to send small bolts of electricity to the spinal cord by inserting a wire in the epidural area. It’s only one or two volts, so the patient feels just a tingling sensation over where the pain is, instead of feeling the actual pain. After two weeks, we give the patient an internal power battery with a remote control, so he can switch it on whenever he feels pain and carry on with his life. It’s essentially a pacemaker that suppresses the hyperexcitability of nerves by delivering subthreshold stimulation. The patient feels nothing except his pain going down. It’s not invasive – we usually send patients home the same day.’

When Carter, the chap with the agonised groin, had failed to respond to any other treatments, Al-Kaisy tried his box of tricks. ‘We gave him something called a dorsal root ganglion stimulation. It’s like a small junction-box, placed just underneath one of the bones of the spine. It makes the spine hyperexcited, and sends impulses to the spinal cord and the brain. I pioneered a new technique to put a small wire into the ganglion, connected to an external power battery. Over ten days the intensity of pain went down by 70 per cent – by the patient’s own assessment. He wrote me a very nice email saying I had changed his life, that the pain had just stopped completely, and that he was coming back to normality. He said his job was saved, as was his marriage, and he wanted to go back to playing sport. I told him, ‘Take it easy. You mustn’t start climbing the Himalayas just yet.’’ Al-Kaisy beams. ‘This is a remarkable outcome. You cannot get it from any other therapies.’

§ § §

The greatest recent breakthrough in assessing pain, according to Professor Irene Tracey, head of the University of Oxford’s Nuffield Department of Clinical Neurosciences, has been the understanding that chronic pain is a thing in its own right. She explains: ‘We always thought of it as acute pain that just goes on and on – and if chronic pain is just a continuation of acute pain, let’s fix the thing that caused the acute and the chronic should go away. That has spectacularly failed. Now we think of chronic pain as a shift to another place, with different mechanisms, such as changes in genetic expression, chemical release, neurophysiology and wiring. We’ve got all these completely new ways of thinking about chronic pain. That’s the paradigm shift in the pain field.’

Tracey has been called the ‘Queen of Pain’ by some media commentators. She was, until recently, the Nuffield Professor of Anaesthetic Science and is an expert in neuroimaging techniques that explore the brain’s responses to pain. Despite her nickname, in person she is far from alarming: a bright-eyed, enthusiastic, welcoming and hectically fluent woman of 50, she talks about pain at a personal level. She has no problem defining the ‘ultimate pain’ that scores 10 on the McGill Questionnaire: ‘I’ve been through childbirth three times, and my 10 is a very different 10 from before I had kids. I’ve got a whole new calibration on that scale.’ But how does she explain the ultimate pain to people who haven’t experienced childbirth? ‘I say, ‘Imagine you’ve slammed your hand in a car door – that’s 10.’’

She uses a personal example to explain the way perception and circumstance can alter the way we experience pain, as well as the phenomenon of ‘hedonic flipping’, which can convert pain from an unpleasant sensation into something you don’t mind. ‘I did the London Marathon this year. It needs a lot of training and running and your muscles ache, and next day you’re really in pain, but it’s a nice pain. I’m no masochist, but I associate the muscle pain with thoughts like, ‘I did something healthy with my body,’ ‘I’m training,’ and ‘It’s all going well.’’

I ask her why there seems to be a gap between doctors’ and patients’ apprehension of pain. ‘It’s very hard to understand, because the system goes wrong from the point of injury, along the nerve that’s taken the signal into the spinal cord, which sends signals to the brain, which sends signals back, and it all unravels with terrible consequential changes. So my patient may be saying, ‘I’ve got this excruciating pain here,’ and I’m trying to see where it’s coming from, and there’s a mismatch here because you can’t see any damage or any oozing blood. So we say, ‘Oh come now, you’re obviously exaggerating, it can’t be as bad as that.’ That’s wrong – it’s a cultural bias we grew up with, without realising.’

Recently, she says, there has been an explosion of understanding about how the brain is involved in pain. Neuroimaging, she explains, helps to connect the subjective pain with the objective perception of it. ‘It fills that space between what you can see and what’s being reported. We can plug that gap and explain why the patient is in pain even though you can’t see it on your X-ray or whatever. You’re helping to bring truth and validity to these poor people who are in pain but not believed.’

But you can’t simply ‘see’ pain glowing and throbbing on the screen in front of you. ‘Brain imaging has taught us about the networks of the brain and how they work,’ she says. ‘It’s not a pain-measuring device. It’s a tool that gives you fantastic insight into the anatomy, the physiology and the neurochemistry of your body and can tell us why you have pain, and where we should go in and try to fix it.’

Some of the ways in, she says, are remarkably direct and mechanical – like Al-Kaisy’s spinal cord stimulation wire. ‘There are now devices you can attach to your head and allow you to manipulate bits of the brain. You can wear them like bathing caps. They’re portable, ethically allowed brain-simulation devices. They’re easy for patients to use and evidence is coming, in clinical trials, that they are good for strokes and rehabilitation. There’s a parallel with the games industry, where they’re making devices you can put on your head so kids can use thought to move balls around. The games industry is, for fun, driving this idea that when you use your brain, you generate electrical activities. They’re developing the technology really fast, and we can use it in medical applications.’

§ § §

According to the International Association for the Study of Pain, pain is defined as ‘an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage’. It’s a broad-brush definition that hints at the holistic nature of pain and the range of factors that might influence our perception of it. If not all of its causes are directly physical, standardised drug treatments will always be something of a blunt instrument.

Researchers at the Human Pain Research Laboratory at Stanford University, California, are working to gain a better understanding of individual responses to pain so that treatments can be more targeted. The centre was created in 1995 by the pleasingly named Dr Martin Angst of the Department of Anesthesiology. Its first investigations were into finding reliable methods of quantifying pain. Then Angst (assisted by the equally pleasingly named Dr Martha Tingle) looked into questions of opiate pharmacology, such as how easily the body builds up toleration to drugs.

Pain has become a huge area of medical research in the USA, for a simple reason. Chronic pain affects over 100 million Americans and costs the country over half a trillion dollars a year in lost working hours, which is why it’s become a magnet for funding by big business and government.

The laboratory has several study initiatives on the go – into migraine, fibromyalgia, facial pain and other conditions – but its largest is into back pain. It has been endowed with a $10m grant from the National Institutes of Health to study non-drug alternative treatments for lower back pain. The specific treatments are mindfulness, acupuncture, cognitive behavioural therapy and real-time neural feedback. This may seem a very Californian range of pursuits, but the lab takes them very seriously and is enlisting an army of patients to build up a massive database.

They plan to inspect the pain tolerance of 400 people over five years of study, ranging from pain-free volunteers to the most wretched chronic sufferers who have been to other specialists but found no relief. Subjects are all called in, given screening tests (to exclude those with abnormal drug regimens or excessive ‘suicidality’) then subjected to several quantitative sensory tests: participants are asked to immerse one naked foot in a bucket of iced water until they feel pain; then one arm is subjected to a ‘contact heat evoked potential simulator’, which gradually heats up small-diameter nerve fibres until the patient feels pain; then they have ‘pressure needles’ poked onto their skin without breaking it until they report discomfort.

In all three cases, the idea is to find people’s mid-range tolerance (they’re asked to rate their pain while they’re experiencing it), to establish a usable baseline. They then are given the non-invasive treatments – mindfulness, acupuncture, etc – and are subjected afterwards to the same pain stimuli, to see how their pain tolerance has changed from their baseline reading. MRI scanning is used on the patients in both laboratory sessions, so that clinicians can see and draw inferences from the visible differences in blood flow to different parts of the brain.

A remarkable feature of the assessment process is that patients are also given scores for psychological states: a scale measures their level of depression, anxiety, anger, physical functioning, pain behaviour and how much pain interferes with their lives. This should allow physicians to use the information to target specific treatments. All these findings are stored in an ‘informatics platform’ called CHOIR, which stands for the Collaborative Health Outcomes Information Registry. It has files on 15,000 patients, 54,000 unique clinic visits and 40,000 follow-up meetings.

The big chief at the Human Pain Research Laboratory is Dr Sean Mackey, Redlich Professor of Anesthesiology, Perioperative and Pain Medicine, Neurosciences and Neurology at Stanford. His background is in bioengineering, and under his governance the Stanford Pain Management Center has twice been designated a centre of excellence by the American Pain Society. A tall, genial, easy-going man, he is sometimes approached by legal firms who want him to appear in court to state definitively whether their client is or isn’t in chronic pain (and therefore justified in claiming absentee benefit). His response is surprising.

‘In 2008, I was asked by a law firm to speak in an industrial injury case in Arizona. This poor guy got hot burning asphalt sprayed on his arm at work; he had a claim of burning neuropathic pain. The plaintiff’s side brought in a cognitive scientist, who scanned his brain and said there was conclusive evidence that he had chronic pain. The defence asked me to comment, and I said, ‘That’s hogwash, we cannot use this technology for that purpose.’

‘Shortly afterwards, I gave a talk on pain, neuroimaging and the law, explaining why you can’t do this – because there’stoo much individual variability in pain, and the technology isn’t sensor-specific enough. But I concluded by saying, ‘If you were to do this, you’d use modern machine-learning approaches, like those used for satellite reconnaissance to determine whether a satellite is seeing a tank or a civilian truck.’ Some of my students said, ‘Can you give us some money to try this?’ I said, ‘Yes, but it can’t be done.’ But they designed the experiment – and discovered that, using brain imagery, they could predict with 80 per cent accuracy whether someone was feeling heat pain or not.’

Mackey finally published a paper about the experiment. So did his findings influence any court decisions? ‘No. I get asked by attorneys, and I always say, ‘There is no place for this in the courtroom in 2016 and there won’t be in 2020. People want to push us into saying this is an objective biomarker for detecting that someone’s in pain. But the research is in carefully controlled laboratory conditions. You cannot generalise about the population as a whole. I told the attorneys, ‘This is too much of a leap.’ I don’t think there’s a lot of clinical utility in having a pain-o-meter in a court or in most clinical situations.’

Mackey explains the latest thinking about what pain actually is. ‘Now we understand that pain is a balance between ascending information coming from our bodies and descending inhibitory systems from our brains. We call the ascending information ‘nociception’ – from the Latin nocere, to harm or hurt – meaning the response of the sensory nervous system to potentially harmful stimuli coming from our periphery, sending signals to the spinal cord and hitting the brain with the perception of pain. The descending systems are inhibitory, or filtering, neurons, which exist to filter out information that’s not important, to ‘turn down’ the ascending signals of hurt. The main purpose of pain is to be the great motivator, to tell you to pay attention, to focus. When Martin was doing the pain lab, we had no way of addressing these two dynamic systems, and now we can.’

Mackey is immensely proud of his massive CHOIR database – which records people’s pain tolerance levels and how they are affected by treatment – and has made it freely available to other pain clinics as a ‘community source platform’, collaborating with academic medical centres nationwide ‘so that a rising tide elevates all boats’. But he’s also humble enough to admit that science can’t tell us which are the sites of the body’s worst pains.

‘Back pain is the most reported pain at 28 per cent, but I know there’s a higher density of nerve fibres in the hands, face, genitals and feet than in other areas. And there are conditions where the sufferer has committed suicide to get away from the pain: things like post-herpetic neuralgia, that burning nerve pain that occurs after an outbreak of shingles and is horrific; another is cluster headaches – some patients have thought about taking a drill to their heads to make it stop.’

Like Irene Tracey, he’s enthusiastic about the rise of transcranial magnetic stimulation (‘Imagine hooking a nine-volt battery across your scalp’) but, when asked about his particular successes, he talks about simple solutions. ‘Early on in my career, I used to be very focused on the peripheral, the apparent site of the pain. I was doing interventions, and some people would get better but a lot wouldn’t. So I started listening to their fears and anxieties and working on those, and became very brain-focused. I noticed that if you have a nerve trapped in your knee, your whole leg could be on fire, but if you apply a local anaesthetic there, it could abolish it.

‘This young woman came to me with a terrible burning sensation in her hand. It was always swollen; she couldn’t stand anyone touching it because it felt like a blowtorch.’ Mackey noticed that she had a post-operative scar from prior surgery for carpal tunnel syndrome. Speculating that this was at the root of her problem, he injected Botox, a muscle relaxant, at the site of the scar. ‘A week later, she came up and gave me this huge hug and said, ‘I was able to pick up my child for the first time in two years. I haven’t been able to since she was born.’ All the swelling was gone. It taught me that it’s not all about the body part, and not all about the brain. It’s about both.’ How counterintuitive to discover that, after centuries of curing pain with opiates, the mind can give the morphine a run for its money.

This story was first published on 10 January 2017

by Wellcome on mosaicscience.com

Why doctors are reclaiming LSD and ecstasy

Sam Wong

At 6.30am on Thursday 29 October 2009, Friederike Meckel Fischer’s doorbell rang. There were ten policemen outside. They searched the house, put handcuffs on Friederike – a diminutive woman in her 60s – and her husband, and took them to a remand prison. The couple had their photographs and fingerprints taken and were put in separate cells in isolation. After a few hours, Friederike, a psychotherapist, was taken for questioning.

The officer read back to her the promise of secrecy she had each client make at the start of her group therapy sessions. ‘Then I knew I was really in trouble,’ she says.

‘I promise not to divulge the location or names of the people present or the medication. I promise not to harm myself or others in any way during or after this experience. I promise that I will come out of this experience healthier and wiser. I take personal responsibility for what I do here.’

The Swiss police had been tipped off by a former client whose husband had left her after they had attended therapy. She held Friederike responsible.

What got Friederike in trouble were her unorthodox therapy methods. Alongside separate sessions of conventional talk therapy, she offered a catalyst, a tool to help her clients reconnect with their feelings, with people around them, and with difficult experiences in their lives. That catalyst was LSD. In many of her sessions, they would also use another substance: MDMA, or ecstasy.

Friederike was accused of putting her clients in danger, dealing drugs for profit, and endangering society with ‘intrinsically dangerous drugs’. Such psychedelic therapy is on the fringes of both psychiatry and society. Yet LSD and MDMA began life as medicines for therapy, and new trials are testing whether they could be again.

§ § §

In 1943, Albert Hofmann, a chemist at the Sandoz pharmaceutical laboratory in Basel, Switzerland, was trying to develop drugs to constrict blood vessels when he accidentally ingested a small quantity of lysergic acid diethylamide, LSD. The effects shook him. As he writes in his book LSD,My Problem Child:

‘Objects as well as the shape of my associates in the laboratory appeared to undergo optical changes… Light was so intense as to be unpleasant. I drew the curtains and immediately fell into a peculiar state of ‘drunkenness’, characterised by an exaggerated imagination. With my eyes closed, fantastic pictures of extraordinary plasticity and intensive colour seemed to surge towards me. After two hours, this state gradually subsided and I was able to eat dinner with a good appetite.’

Intrigued, he decided to take the drug a second time in the presence of colleagues, an experiment to determine whether it was indeed the cause. The faces of his colleagues soon appeared ‘like grotesque coloured masks’, he writes:

‘I lost all control of time: space and time became more and more disorganised and I was overcome with fears that I was going crazy. The worst part of it was that I was clearly aware of my condition though I was incapable of stopping it. Occasionally I felt as being outside my body. I thought I had died. My ‘ego’ was suspended somewhere in space and I saw my body lying dead on the sofa. I observed and registered clearly that my ‘alter ego’ was moving around the room, moaning.’

But he seemed particularly struck by what he felt the next morning: ‘Breakfast tasted delicious and was an extraordinary pleasure. When I later walked out into the garden, in which the sun shone now after a spring rain, everything glistened and sparkled in a fresh light. The world was as if newly created. All my senses vibrated in a condition of highest sensitivity that persisted for the entire day.’

Hofmann felt it was of great significance that he could remember the experience in detail. He believed the drug could hold tremendous value to psychiatry. The Sandoz labs, after ensuring it was non-toxic to rats, mice and humans, soon started offering it for scientific and medical use.

One of the first to start using the drug was Ronald Sandison. The British psychiatrist visited Sandoz in 1952 and, impressed by Hofmann’s research, left with 100 vials of what was by then called Delysid. Sandison immediately began giving it to patients at Powick Hospital in Worcestershire who were failing to make progress in traditional psychotherapy. After three years, the hospital bosses were so pleased with the results that they built a new LSD clinic. Patients would arrive in the morning, take their LSD, then lie down in private rooms. Each had a record player and a blackboard for drawing on, and nurses or registrars would check on them regularly. At 4pm the patients would convene and discuss their experiences, then a driver would take them home, sometimes while they were still under the influence of the drug.

Around the same time, another British psychiatrist, Humphry Osmond, working in Canada, experimented with using LSD to help alcoholics stop drinking. He reported that the drug, in combination with supportive psychiatry, achieved abstinence rates of 40–45 per cent – far higher than any other treatment at the time or since. Elsewhere, studies of people with terminal cancer showed that LSD therapy could relieve severe pain, improve quality of life and alleviate the fear of death.

In the USA, the CIA tried giving LSD to unsuspecting members of the public to see if it would make them give up secrets. Meanwhile at Harvard University, Timothy Leary – encouraged by, among others, the beat poet Allen Ginsberg – gave it to artists and writers, who would then describe their experiences. When rumours spread that he was giving drugs to students, law-enforcement officials started investigating and the university warned students against taking the drug. Leary took the opportunity to preach about the drug’s power as an aid to spiritual development, and was soon sacked from Harvard, which further fuelled his and the drug’s notoriety. The scandal had caught the eye of the press and soon the whole country had heard of LSD.

By 1962, Sandoz was cutting back on its distribution of LSD, the result of restrictions on experimental drug use brought on by an altogether different drug scandal: birth defects linked to the morning-sickness drug thalidomide. Paradoxically, the restrictions coincided with an increase in LSD’s availability – the formula was not difficult or expensive to obtain, and those who were determined to could synthesise it with moderate difficulty and in great amounts.

Still, moral panic about its effects on young minds was rife. The authorities were also worried about LSD’s association with the counterculture movement and the spread of anti-authoritarian views. Calls for a nationwide ban soon followed, and many psychiatrists stopped using LSD as its negative reputation grew.

One of many stories in the press told of Stephen Kessler, who murdered his mother-in-law and claimed afterwards that he didn’t remember what he’d done as he was ‘flying on LSD’. In the trial, it emerged that he had taken LSD a month earlier, and at the time of the murder was intoxicated only with alcohol and sleeping pills, but millions believed that LSD had turned him into a killer. Another report told of college students who went blind after staring at the sun on LSD.

Two US Senate subcommittees held in 1966 heard from doctors who claimed that LSD caused psychosis and ‘the loss of all cultural values’, as well as from LSD supporters such as Leary and Senator Robert Kennedy, whose wife Ethel was said to have undergone LSD therapy. ‘Perhaps to some extent we have lost sight of the fact that it can be very, very helpful in our society if used properly,’ said Kennedy, challenging the Food and Drug Administration for shutting down LSD research programmes.

Possession of LSD was made illegal in the UK in 1966 and in the USA in 1968. Experimental use by researchers was still possible with licences, but with the stigma attached to the drug’s legal status, these became extremely hard to get. Research ground to a halt, but illegal recreational use carried on.

§ § §

At the age of 40, after 21 years of marriage, Friederike Meckel Fischer fell in love with another man. Sadly, as she soon discovered, he was using her to get out of his own marriage. ‘I had a pain within myself with this man having left me, with my husband whom I couldn’t connect to,’ she says. ‘It was just like I was out of myself.’

Her solution was to become a psychotherapist. She says she never thought of going into therapy herself, which in 1980s West Germany was reserved for only the most serious conditions. Besides which, her upbringing taught her to do things herself rather than seek help from others.

Friederike was at the time working as an occupational physician. She recognised that many of the problems she saw in her patients were rooted in problems with their bosses, colleagues or families. ‘I came to the conclusion that everything they were having trouble with was connected to relationship issues,’ she says.

A former professor of hers recommended she try a technique called holotropic breathwork. Developed by Stanislav Grof, one of the pioneers of LSD psychotherapy, this is a way to induce altered states of consciousness through accelerated and deeper breathing, like hyperventilation. Grof had developed holotropic breathwork in response to bans on LSD use around the world.

Over three years, travelling back and forth to the USA on holidays, Friederike underwent training with Grof as a holotropic breathwork facilitator. At the end of it, Grof encouraged her to try psychedelics.

In the last seminar, a colleague gave her two little blue pills as a gift. When she got back to Germany, Friederike shared one of the blue pills with her friend Konrad, who later became her husband. She says she felt herself lifted by a wave and thrown onto a white beach, able to access parts of her psyche that were off-limits before. ‘The first experience was breathtaking for me,’ she says. ‘I only thought: ‘That’s it. I can see things.’ And I started feeling. That was, for me, unbelievable.’

The pills were MDMA, a drug which had entered the spotlight in 1976 when American chemist Alexander ‘Sasha’ Shulgin rediscovered it 62 years after it was patented by Merck and then forgotten. In a story echoing that of LSD’s origins, upon taking it, Shulgin noted feelings of ‘pure euphoria’ and ‘solid inner strength’, and felt he could ‘talk about deep or personal subjects with special clarity’. He introduced it to his friend Leo Zeff, a retired psychotherapist who had worked with LSD and believed the obligation to help patients took priority over the law. Zeff had continued to work with LSD secretly after its prohibition. MDMA’s potential brought Zeff out of retirement. He travelled around the USA and Europe to instruct therapists on MDMA therapy. He called it ‘Adam’ because it put the patient in a primordial state of innocence, but at the same time, it had acquired another name in nightclubs: ecstasy.

MDMA was made illegal in the UK by a 1977 ruling that put the entire chemical family in the most tightly controlled category: class A. In the USA, the Drug Enforcement Administration (DEA), set up by Richard Nixon in 1973, declared a temporary ban in 1985. At a hearing to decide its permanent status, the judge recommended that it should be placed in schedule three, which would allow use by therapists. But the DEA overruled the judge’s decision and put MDMA in schedule one, the most restrictive category. Under American influence, the UN Commission on Narcotic Drugs gave MDMA a similar classification under international law (though an expert committee formed by the World Health Organization argued that such severe restrictions were not warranted).

Schedule one substances are permitted to be used in research under the UN Convention on Psychotropic Substances. In Britain and the USA, researchers and their institutions must apply for special licences, but these are expensive to obtain, and finding manufacturers who will supply controlled drugs is difficult.

But in Switzerland, which at the time was not a signatory to the convention, a small group of psychiatrists persuaded the government to permit the use of LSD and MDMA in therapy. From 1985 until the mid-1990s, licensed therapists were permitted to give the drugs to any patients, to train other therapists in using the drugs, and to take them themselves, with little oversight.

Believing that MDMA might help her gain a deeper understanding of her own problems, Friederike applied for a place on a ‘psycholytic therapy’ course in Switzerland. In 1992, she and Konrad were accepted into a training group run by a licensed therapist named Samuel Widmer.

The course took place on weekends every three months at Widmer’s house in Solothurn, a town west of Zurich. Central to the training was taking the substances a number of times, 12 altogether, to get to know their effects and go through a process of self-exploration. Friederike says the drug experiences showed her how her whole life had been coloured by the loss of her father at the age of 5 and the hardship of growing up in postwar West Germany.

‘I can detect relations, interconnections between things that I couldn’t see before,’ she says of her experiences with MDMA. ‘I could look at difficult experiences in my life without getting right away thrown into them again. I could for example see a traumatic experience but not connect to the horrible feeling of the moment. I knew it was a horrible thing, and I could feel that I have had fear but I didn’t feel the fear.’

§ § §

People on psychedelic highs often speak of profound, spiritual experiences. Back in the 1960s, Walter Pahnke, a student of Timothy Leary, conducted a notorious experiment at Boston University’s Marsh Chapel showing that psychedelics could induce these.

He gave ten volunteers a large dose of psilocybin – the active ingredient in magic mushrooms – and ten an active placebo, nicotinic acid, which caused a tingling sensation but no mental effects. Eight of the psilocybin group had spiritual experiences, compared with one of the placebo group. In later studies, researchers have identified core characteristics of such experiences, including ineffability, the inability to put it into words; paradoxicality, the belief that contradictory things are true at the same time; and feeling more connected to other people or things.