by Jo Marchant
He also points to the clinical trials of antidepressants carried out over the last 30 years. Over that time, drugs have become steadily more effective in treating depression, but so have placebos.6 Moerman attributes their growing power to media coverage and advertising that has boosted popular awareness and beliefs about the effectiveness of antidepressants. “Oprah’s talking about it, there are ads for antidepressants in every magazine that might be read by someone who is likely to be depressed,” he says. “Now everybody knows that you can cure depression with a pill.” When we focus on the personal meaning that placebos have for people, rather than on the inert treatments themselves, suddenly the shifting results make perfect sense.
But when Kaptchuk asked patients in clinical trials what they thought about the pills they were taking, he heard something that still didn’t quite fit. The central dogma running through all discussions of the placebo effect was that, in order for it to work, you have to believe that you are receiving a real treatment. Patients often experience large placebo effects in trials, where there’s a 50-50 chance of being on either the drug or a placebo. Scientists have always assumed, somewhat patronizingly, that this is because people simply forget that they might be on placebo. Yet Kaptchuk found that this wasn’t the case. “These people are going crazy on double-blind trials,” he says. “They really worry about whether they are on placebo. They think about it every day.” So how come they were still experiencing placebo effects?
That’s when he came up with his boldest—and perhaps most deviant—idea yet.
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“I WAS shocked!” says Linda, as I sip my tea and tuck into a second macaroon. She had enrolled in a clinical trial through her gastroenterologist, Harvard’s Anthony Lembo, who was collaborating with Kaptchuk. At the start of the trial, Lembo handed her a bottle of clear plastic capsules with beige powder inside. After so many years of IBS misery, Linda was excited about trying the latest experimental drug for the condition. Then Lembo told her that the pills were placebos, with no active ingredient whatsoever.
Linda knew all about placebos from her training as a medical assistant and thought that taking them was a dumb idea. “I said, ‘Come on, how is a sugar pill going to work?’ ” she says. “But I did anything he said, because I was desperate.” She took the bottle home and swallowed the capsules twice a day with a cup of tea.
“I just took it the first day and forgot about it,” she says. Then, something surprising happened. A few days later, she realized that she wasn’t sick anymore. “I felt fantastic,” she says. “No pains, no symptoms, no nothing. I thought, ‘Wait a minute, this thing works.’ ”
For the three weeks of the trial, Linda went back to living a normal life. She could eat what she wanted, and could go out without worrying about where the nearest bathroom was. She went to the movies with a friend, and for a celebration dinner at the Olive Garden. Then she started to dread the end of the study. “When it got to the third week I thought, ‘Oh no, I can’t go off these pills.’ ” She begged Lembo to give her more placebos, but he explained that he didn’t have ethical approval to prescribe them to her once the study was over. Three days after her course of pills ended, her symptoms returned.
Linda wasn’t the only patient to benefit from the placebos. Kaptchuk’s trial included 80 patients with long-term irritable bowel syndrome, of whom half received a course of placebo. The doctors told these patients that although the capsules contained no active ingredient, they might work through mind–body, self-healing processes.
“Everyone thought it was crazy,” says Kaptchuk. But the trial, published in 2010, found that those patients taking placebos did significantly better than those who received no treatment.7 Kaptchuk has since got similar results in a pilot study of 20 women with depression,8 and in a study of 66 migraine patients, who received either drug, placebo or nothing over a total of more than 450 attacks.9 Taking what they knew to be a placebo reduced their pain by 30% compared with no treatment, says Kaptchuk. “My team was totally taken aback.”
Linda is now back to square one, but placebo research has been changed forever. One of the big barriers to using placebos in medicine is the concern that it is unethical to deceive patients. Yet Kaptchuk’s studies suggest that honest placebos can work, as well.
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THE POSTMAN knocks at the door and when I open it he hands me a black cardboard tube marked “Fragile.” It rattles like a child’s toy. Inside, smothered in bubble wrap, is a small, clear plastic jar packed full of blue-and-white capsules, looking just like drugs you might get from the pharmacist. The label reads “Metaplacebalin Relaxant Capsules. ONE or TWO capsules to be taken THREE TIMES per day.” My very own placebos.
Since Kaptchuk provided scientific backing for the idea of open-label placebos, it hasn’t taken long for a smattering of private companies to start selling them online. A quick Google search turns up Placebo World, Universal Placebos, and Aplacebo, a company based in Chelmsford, U.K. Aplacebo’s website links to media coverage of Kaptchuk’s research and offers a range of products including empty bottles and sprays packaged in different colors for different desired effects (you add your own water), a homeopathic placebo and even a virtual placebo sent by text message.10
The products aren’t cheap at between £10 and £25, but as the website points out, studies show that the more a placebo costs, the better it works—probably because we instinctively believe that expensive treatments are more effective. When my capsules arrive, I put them in the kitchen cupboard next to the other drugs and they look reassuringly powerful, candy blue, so brightly colored they almost glow.
A few weeks later, I spend a fraught day looking after two sick children. I finally get them to bed and desperately need the rest of the evening to work, but a throbbing headache is taking hold. I open the kitchen cupboard and take out the jar. Are Kaptchuk’s results a fluke, I wonder? Or can placebos really help us in daily life?
Of course, doctors and drug companies already use placebo effects. As Benedetti’s experiment with the open and hidden infusion of painkillers shows, we experience placebo effects every time we receive a drug. Any benefits we ultimately feel are a combination of the active effect of the drug, plus its placebo effect. For some medications, the effects are almost entirely a result of their chemical components—placebo statins have little if any effect on cholesterol levels, for example. For others, like antidepressants, it’s mostly our minds doing the work.
One approach to harnessing placebo effects, then, is to boost the placebo effect associated with the active drugs we take. One problem with placebos is that they don’t work well on everyone (for reasons we’ll look at later in this chapter). But there are ways of designing drugs to trigger larger placebo responses in more people. Studies suggest that anything that helps to create the impression of a powerful, potent medication will produce a stronger effect.
Big pills tend to be more effective than small ones, for example. Two pills at once work better than one. A pill with a recognizable brand name stamped across the front is more effective than one without. Colored pills tend to work better than white ones, although which color is best depends upon the effect that you are trying to create. Blue tends to help sleep, whereas red is good for relieving pain. Green pills work best for anxiety. The type of intervention matters too: the more dramatic the treatment, the bigger the placebo effect. In general, surgery is better than injections, which are better than capsules, which are better than pills.
There are cultural differences, however, emphasizing the point that any effects depend not on placebos themselves, but on what they mean to us. For example, although blue tablets generally make good placebo sleeping pills, they tend to have the opposite effect on Italian men—possibly because blue is the color of their national football team, so they find it arousing, not relaxing.11 And although injections make better placebos than pills in the U.S., this is not necessarily true in Europe, where there is a stronger cultural belief in the effectiveness
of pills.
All fascinating stuff, but can we take the findings on honest placebos to their logical conclusion? Could we knowingly take dud pills to trigger our minds to solve problems such as depression, indigestion, pain or sleeplessness?
Kaptchuk says he loves the idea. “I certainly think people are overmedicated,” he says. He suggests a good place to start might be conditions where people tend to be on medication long-term, and where the drugs themselves have been shown to have little active effect beyond placebo—such as pain or depression. Then, for those patients who want it, he suggests that they could try a course of placebo first, before progressing if necessary to an active drug.
He doubts whether the idea will catch on with doctors, however. Sometimes in lectures, he says, he asks an audience of physicians whether, given undeniable evidence that honest placebos worked for a particular condition, they would prescribe them. “Not a single hand goes up.” One such skeptic is Edzard Ernst, professor of alternative medicine at Exeter University, U.K., who campaigns against the use of unproven medicines such as homeopathy. He says he is against the idea of using open-label placebos, even if they were shown to help. “We should always maximize the placebo effect in conjunction with effective treatments,” he explains.12 Using placebos on their own would mean that patients miss out on the extra therapeutic effect of active drugs.
That certainly makes sense for acute conditions where drugs are proven to be effective. If my son has a serious infection, I want antibiotics for him, not a fake pill. But Kaptchuk argues that in some cases, such as pain, depression or IBS, using placebos on their own might be just as effective as available drugs, and could free people from negative side effects such as addiction. “I’m hoping that there’s going to be some kind of shift because patients want therapies that have fewer side effects,” he says. “People don’t want to go on drugs for long periods of time.”
Ernst counters that there are few conditions for which we have no good treatments at all, and says that where drugs aren’t effective there are usually other therapies patients can try (for example physiotherapy or cognitive behavioral therapy). But Kaptchuk’s faith in placebos is shared by Simon Bolingbroke, an intelligence analyst from Chelmsford in Essex, and co-founder of Aplacebo, the company that made my capsules.
When I ask Bolingbroke why he decided that trying to sell inert medicines was a good idea, he tells me that he used to be in the military. When serving in Rhodesia (now Zimbabwe) in the 1970s, he was bitten by a tick. After returning home to the U.K., he started to suffer from a range of symptoms, including headaches, tiredness and pain in his joints and muscles. His doctors were mystified. By the time his condition was diagnosed as Lyme disease, a bacterial infection spread by ticks, it had spread to his nervous system, damaging it incurably.
Bolingbroke is now in a wheelchair and in constant pain from nerves that fire when they shouldn’t. “It’s false pain,” he says. “My nervous system is not working properly. It’s also hard to tell if things are hot or cold. Doing things like cooking or taking a bath, I have to be careful what I touch, because I’m not sure if it’s going to burn me.”
He was prescribed multiple medications to deal with the symptoms—at one point he was taking nine different drugs at once, from painkillers to antidepressants. They helped with the pain but he says they started to take over his life and caused dramatic mood swings. “They were turning me homicidal and suicidal in turns,” he says. “I wasn’t a nice person.”
Inspired by research on placebos, Bolingbroke decided to wean himself off the drugs, slowly replacing them, dose by dose, with inert pills that he made himself. Now, he says, he takes “virtually no” active medication. When I ask if he is controlling the pain as well on placebos as he was on painkillers, Bolingbroke thinks for a moment, then says, “It seems apparent to me that I am.”
Now he runs Aplacebo with a friend, selling placebos online. The capsules he sends me are pharmaceutical-grade gelatin casings, the same as conventional medicine in every way except that they are empty. The label is cleverly designed, using jargon to create the impression of a potent, scientific medicine. There’s a warning to follow the instruction sheet closely, and the ingredient list looks reassuringly high-tech—nitrogen (78.084%); oxygen (20.946%); argon (0.934%); carbon dioxide (0.039%)—even though all it lists are the chemical components of air.
Despite the persuasive packaging, however, I find it hard to imagine people spending their hard-earned cash on something that openly admits to being nothing. Is Aplacebo really intended as a serious business? “It sort of started as a joke,” Bolingbroke says. “We were laughing at ourselves. But it’s a joke that’s real.” He admits that the company hasn’t had any significant sales yet, but insists that with mounting scientific results, and growing awareness of the power of placebos, his products could one day catch on.
Back in my kitchen, I open the placebo jar and down a couple of capsules with a glass of water, standing by the sink just as I do when taking over-the-counter painkillers. I think about Benedetti’s research, picturing his basement lab in Turin, and I try to imagine endorphins flooding my brain. Then I wait to see what happens.
It’s hardly a scientific trial, but within 20 minutes or so the pain really does dissipate. With my mini-crisis averted, I can get back to work. And I feel empowered, just a tiny bit, to know that all I needed to do it was my own mind.
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BIBI HAJERAH High School is a ramshackle, mudbrick building in Taluqan, northeastern Afghanistan. Its female students wear a uniform of black robes and white headscarves, and they take their classes at battered wooden desks lined up in the shade of a tree outside. On the morning of May 23, 2012, classes were progressing as normal when someone complained of a bad smell.
One by one, the girls started to feel sick and dizzy, and to faint. Within hours, more than 100 pupils and teachers had been admitted to the hospital. Pictures broadcast by the media showed armed guards outside the hospital and chaos inside. The crowded wards overflowed with distressed girls, apparently struggling to breathe, being fanned by female relatives.
Khalilullah Aseer, spokesperson for the local police, was sure of the culprit. “The Afghan people know that the terrorists and the Taliban are doing these things to threaten girls and stop them from going to school,” he told CNN.13 “That’s something we and the people believe. Now we are implementing democracy in Afghanistan and we want girls to be educated, but the government’s enemies don’t want this.”
Girls had been strictly forbidden from attending school under the previous Taliban regime, but Afghan women won back the basic right to education when Western forces ousted the extremists in 2001. Attending school still took courage, however. Several schoolgirls had suffered acid attacks by the Taliban. Hundreds of girls’ schools in Taliban-influenced areas had been closed for safety reasons, and according to one survey, more than half of Afghan parents kept their daughters at home to protect them.
And then, it seemed, there was the poison. The incident at Bibi Hajerah school was the sixth such outbreak in Afghanistan that year. Since 2008, more than 1,600 people from 22 schools across the country had fallen ill in similar circumstances. The poisoning was thought to be a systematic campaign of terror by the Taliban. The Afghan authorities announced several arrests and confessions, and suggested that the victims had succumbed to either toxic gas or a poisoned water supply. Meanwhile local and international media broadcast alarming pictures of victims being carried on stretchers and hooked up to drips.
The symptoms were short-lived, however. The girls all recovered. And although hundreds of samples of blood, urine and water were tested, they came back clear. After interviewing girls and teachers at Bibi Hajerah, staff from the World Health Organization (WHO) concluded that there was no poisoning.14 The entire outbreak—and probably all of the other episodes too—had been caused by a “mass psychogenic illness.”
So be warned: the placebo effect has a dark side. The mind might have salu
tary effects on the body, but it can create negative symptoms too. The official term for this phenomenon is the “nocebo effect” (Latin for “I will harm,” just as “placebo” is Latin for “I will please”) and it hasn’t been much studied because of ethical concerns. But from what we know about the biology of placebo effects, the Afghan schoolgirls weren’t faking it. Fearing or believing that they were about to become ill created real, physical symptoms, even causing some to briefly lose consciousness.
Similar events have been reported throughout history. It may have been mass hysteria that triggered the seventeenth-century witch trials in Salem, Massachusetts. More recently, a fainting epidemic among schoolgirls in the West Bank in 1983 was widely attributed to mass poisoning, with Israel and Palestine blaming each other until official investigators concluded that the symptoms had a psychological cause.
Nocebo effects are even one explanation for the power of voodoo curses. Clifton Meador, a physician at the Vanderbilt School of Medicine in Tennessee, has spent years documenting examples of the nocebo effect. In his book Symptoms of Unknown Origin (2005) he tells the story of an Alabama man, 80 years ago, who was cursed with voodoo. By the time the unfortunate patient was seen by a doctor, Drayton Doherty, he was emaciated and apparently close to death. Concluding that nothing he could say would shift the patient’s unshakeable belief that he was about to die, Doherty resorted to trickery. With the family’s consent, he gave the man a strong emetic then slyly produced a green lizard from his bag, pretending it had come out of the man’s body. The witch doctor had magically hatched the lizard inside him, Doherty told his patient. Now that the evil animal was gone, the man would get well again. And so he did.
It’s impossible to confirm Doherty’s dramatic account, but these effects aren’t only relevant to impressionable schoolgirls or gullible voodoo victims. Anyone can be affected, although who or what can make you feel ill is highly dependent on your social and cultural background, and on what you find believable. If a witch doctor curses you, you might laugh, but if the TV news reports a terrorist gas attack nearby, or a medical doctor in a white coat tells you that you’re dying of cancer, you’ll be more inclined to take the threat seriously.