Subjects completed the experiment while in a PET scanner, allowing Petrovic to track their brain activity as they experienced both pain and pain relief.
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As hypothesized, the brain activity of those in the placebo group resembled those that got the drug, especially in a region called the anterior cingulate cortex, or ACC. This region in the middle of the brain is important in processing emotion, anticipating rewards and registering pain. Then psychologist Tor Wager, at the time a graduate student at the University of Michigan, took placebo imaging one step further. Raised in Christian Science, Wager had an enduring curiosity about mind-body connections.
The placebo effect was not one of them. So he set up a side project attempting to map the placebo effect as it was happening. In one experiment, he and colleagues had 24 subjects lie in an fMRI machine, an imaging device that tracks the blood flow and oxygen use that accompany brain activity. While subjects were in the scanner, the researchers administered a series of electric shocks to their wrists, each time warning them by showing them either a blue or a red cue on a screen whether the next shock would be mild or intense.
After each shock, subjects described their pain. In reality it was all placebo cream. A third of subjects who got what they thought was the painkilling cream reported less pain, showing a clear placebo effect. It was a measurable brain event and reflected an actual reduction in the experience of pain. Even more interestingly, Wager and his colleagues saw that when their subjects were anticipating pain relief, activity spiked in the more evolutionarily advanced prefrontal cortex, a region in the front of the brain that is central to generating expectations, and in a section of the midbrain that is key to the release of opioids.
Normally, pain signals begin somewhere in the body and work their way to the thalamus, deep in the brain, and then to the prefrontal cortex, producing conscious perception of pain. Like many in the field of placebo research, neurologist Luana Colloca has a practiced calmness about her. Her bedside manner is a sort of bashful nerdiness punctuated by sudden mischievous smiles. That manner, coupled with a level gaze and warm eyes behind glasses that slip down her nose, inspires both comfort and confidence. Perhaps that is how she persuaded me one cold, clear January day to strap a painful electrode to my left hand for half an hour.
Her lab is tidy, containing her electric chair, in which I will be shocked, and a few odd little instruments, like a bike helmet that blows air on your face to make you anxious. Soon an assistant is sticking sensors below my eye, on my chest and on my hand to measure my reactions — sweating, flinching, heartbeat. Alone in the room, I quickly learn to hate the red screen. We go three rounds of 18 shocks each. Finally, the session is done and Colloca returns. As before, she wears a long lab coat and a deadpan expression.
She starts by telling me that I have a decent tolerance to pain, which is deeply gratifying. Less gratifying. Then Colloca points to the results of the third round and says something that nearly topples me out of my chair. For that one, she fired every shock at full blast. Yet the shocks that came after a green screen felt far less painful — barely a 2 on my pain scale. Colloca flashes a mischievous smile. Colloca smiles at this. She says not to think of myself as gullible, but rather as a good learner. In two rounds of shocks, my brain learned to activate complex pathways — starting in my prefrontal cortex and trickling through to more primitive parts — every time I saw a green screen.
Theoretically, with lots more time in her terrible chair, the effect could be cemented in my brain for years. Until recently, most scientists thought the placebo effect was all about tricking gullible patients into responding to fake drugs. Today, placebos are widely recognized not as a psychological mirage, but as a potent inner pharmacy that we might someday even harness. In practice, though, unlocking that inner pharmacy presents an ethical challenge.
It may be possible to sidestep that ethical roadblock, however. In a study, Harvard medical researcher Ted Kaptchuk showed that some patients with irritable bowel syndrome improved even when they knew the treatment they were being given was a sham, suggesting that deception could, at least in some cases, be unnecessary. And Harvard University neuroscientist and placebo researcher Karin Jensen has found a way to elicit a placebo response without giving patients any conscious expectation at all.
Jensen got hooked on studying placebos while researching fibromyalgia, a condition involving muscle and joint pain without any observable injury, at the Karolinska Institute in the mids. She had learned that fibromyalgia patients struggled to access certain opioid-related brain regions, including the ACC — the center of emotion, reward and pain that Petrovic had found played a role in placebos.
Petrovic happened to sit in the chair next to Jensen. To study this question, Jensen decided to separate placebos from deception and expectation. To do this, she needed to create a placebo that subjects would not consciously detect. But instead of tying the pain stimuli to blue or red cues, she used images of two similar-looking men. Then she added a major wrinkle to the procedure, flashing the faces on the screen for just 12 milliseconds, too fast for subjects to tell which was which.
There is no Metro to White Oak, and it takes half an hour to drive from the sprawling campus to the National Institutes of Health, in Bethesda. The F. There will be no prescriptions for any placebo, either, unless clinical trials have demonstrated its effectiveness to the satisfaction of the F. Temple, who has for many years run the F. His office is so filled with towering stacks of files that, after you enter, it takes a moment to find him.
And that is absolutely not true. Temple, who has worked at the F. He has been regarded as a meddlesome reactionary by H. The more conservative medical establishment frequently accuses the agency of endorsing the wishful thinking of drug manufacturers. And to the large and growing community that supports alternative approaches to medicine Temple is Dr. Temple said that he understands why placebos attract people who become frustrated when science fails to provide definitive answers.
But I have no idea what that means in practical terms. How would it work? There are several studies, though, that illustrate the basis for his skepticism. A placebo effect is commonly observed during trials of blood-pressure medications. To qualify for such studies, subjects are supposed to have blood pressure that exceeds a hundred and forty over ninety in at least one of the two measurements. When a drug or a placebo is under study, subjects are usually divided into two groups.
Neither group knows exactly what it is getting nor do the doctors , but one group generally receives the drug and the other a placebo. If there is no difference, then what are we talking about? It turns out that there have been many trials of the type Temple mentioned. The researchers attempted to assess the combined impact of many different kinds of trials using meta-analysis, a statistical technique for extracting information from studies that are not statistically significant by themselves.
In almost every case, the researchers reported, there was essentially no difference between the placebo group and the openly untreated group. There were particular exceptions in studies of pain, where there was a slight but measurable placebo effect. Since we are physiologically capable of manufacturing our own painkillers—endorphins—the result may not have been surprising. Expectations and suggestion clearly influence behavior, and when we expect to receive medicine our bodies often begin to prepare for it.
The Danish researchers repeated the study in , and again last year, incorporating new data each time.
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The results and their conclusions remained the same. That was the point of his study of irritable-bowel syndrome, in which some subjects were told that they would not be treated. Effective long-term therapies have proved elusive. Patients in the first group received a placebo pill twice a day; those in the second received nothing. There were also statistically significant differences in the severity of symptoms.
Although a group of eighty patients is too small to draw definitive conclusions, honesty seemed to work. Great methods, very careful. Drugs do, too. Opiods, for example, increase pain in about ten per cent of those who take them.
Meta-analyses are useful to help understand large amounts of data from different trials. But statistical results that combine information from a variety of medical centers, with different kinds of patients, often in different countries, administered under different conditions, cannot be uniform and therefore cannot be conclusive. Like Wayne Jonas, they agree that the medical system needs to change.
There is an anti-technological, anti-science feeling in the West. We constantly see frustration with the limits of medicine. The placebo can be seen in some sense as a logical avenue for those frustrations. Everyone wants a simple, pain-free solution. That has always been true. After all, for many people a placebo is just a sugar pill. For others, the definition includes the entire ritual of treatment, the complete interaction between doctor and patient.
Increased attention has mostly raised new questions: What are the physical and psychological mechanisms that produce placebo effects? What are the conditions they most easily affect? And can we actually identify people who respond to placebos? Scientists now have bits of answers to some of those questions, but to reach their goal, and introduce placebos into clinical practice, they will need to answer all of them.
Ted Kaptchuk gets a great deal of pleasure from focussing on what other people reject. Indifference seems to motivate him. My father was a Red, so I have a tendency to get pleasure from subversiveness. A particularly radical son of the sixties, Kaptchuk was one of the founders of the Columbia University chapter of Students for a Democratic Society, in , but the organization was soon dominated by a faction that became the Weather Underground.
That was too radical even for Kaptchuk. He fled to the West Coast. But at some point I said, Ted, this is not being human. Kaptchuk decided to pursue studies in Chinese philosophy and medicine at the source. Beijing had yet to open its borders to Americans, but Kaptchuk hoped that his revolutionary bona fides would prompt the leadership to make an exception. The Chinese denied the request, and Kaptchuk spent much of the next decade studying in Macau.
Today, it is hard to imagine Ted Kaptchuk as a radical, let alone a fugitive. As a devotee of Eastern thought, he bars shoes from his house and speaks in a hushed, measured voice. David Carradine would have played him beautifully. Kaptchuk is the first prominent professor at Harvard Medical School since Erik Erikson with neither a medical degree nor a doctorate, and it would be easy to dismiss him as a signature representative of the unsubstantiated-alternative-health-care movement.
But he has published scores of books, articles in highly regarded peer-reviewed journals, letters, and review notes—on subjects ranging from placebo research to exorcism, from cancer treatment to shaman rituals among Navajo Indians. The data, compelling but so far preliminary, suggest that the answer is yes. Miller is a senior faculty member in the Department of Bioethics at the National Institutes of Health. He told me that he spent years seeking the advice of the most highly respected and rigorous medical statisticians. Because what do I really want?
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Anything that gets people away from the conveyor belts that move from the pharmaceutical houses to doctors and on to patients is worth considering. The question is this: Could the 1 exist without the 0, and vice versa?
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The answer, of course, is no. Remove either the 0 or the 1, and the digital age is a goner. Oh boy, this is really tricky. Because eventually it gets you to the final question: Could there be nothing at the beginning of everything without there being something? Or could there be something without there being nothing? I will refrain from answering these crazy questions. I am just dropping them at your feet to do with as you please. As for me, I am happy to know that asking these kind of questions is extremely satisfying and enjoyable, even as I am convinced that the answer is worth absolutely nothing.
At least if the answer is a product of the mind and subsequently accepted or rejected by said mind. All the brain power in the world can't produce the answer because it doesn't exist in the world of zeroes and ones, or any other number. It never will. This is one question to which the answer cannot be spoken or thought or expressed or judged or touched or even imagined. That's not where the answer exists. What you can do though, is look around. See the way a father holds his child, watch a teenager risk his life to save a dog from drowning, recognize the depth and sacred consciousness in the eyes of a horse, smell the smells of a wet forest, look at the oon and the stars on a clear night, sit on a terrace with a double espresso and feel the sun on your shoulders.
You can let your heart be touched by the generosity of strangers or the bravery of a soldier.