Scientists are learning to harness the power of sham treatments -- without the trickery. By Emily Singer, Special to The Times WHEN Haley Mack of Long Beach participated in a clinical trial testing new treatments for depression last November, she was told she would get either a real medicine or a placebo. But Mack was sure she was taking the real pill. She could do things that had been very difficult since she was diagnosed with clinical depression — she could shower and get dressed, and she actually looked forward to going to the clinic. "It had been difficult to look forward to things at all," she says. At the end of the trial, Mack was surprised to find out she had, in fact, been taking a fake pill. "My boyfriend joked . . . that I should go back on the placebo," she says. "He thought I seemed much better." Mack's boyfriend may have a point. Sham treatments, medical science is learning, can have a powerful effect on health. Researchers have found that administering sugar pills and saline injections can ameliorate pain, depression and anxiety. Such treatments can reduce tremors and other symptoms in Parkinson's patients, lower blood pressure in those with hypertension and open up airways in people who suffer from asthma. Researchers have even shown that sham knee surgery can alleviate arthritis pain and sham chest surgery, angina pain. Now doctors want to harness that power as a tool for treatment — without resorting to trickery. This is not as far-fetched as it sounds. Scientists are learning more about the response of the brain to placebos and about the various elements of treatment that help a patient feel better. Say you go to the doctor with a headache, and your doctor secretly gives you a candy mint rather than an aspirin. That fake pill gives you an expectation that you will feel better — and the so-called placebo effect kicks in, and you do. If that were all the placebo effect was about, doctors would be stuck. Deceptively prescribing a candy instead of medicine to a patient in pain is not considered ethical behavior. Luckily, other aspects of the doctor's visit — such as the whole doctor-patient interaction — play a role in placebo healing as well. "The response to placebo is not just a response to an inactive pill, it's a response to the entire treatment situation," says Dr. Walter Brown, a psychiatrist at Brown University in Rhode Island. "It's everything: going to an expert, talking about the problem, getting a diagnosis and a plausible treatment." Researchers are studying the best ways to capitalize on these cues. The modern study of the placebo effect started in 1955, with a scholarly paper by Harvard physician Dr. Henry Beecher, titled "The Powerful Placebo." Beecher reviewed 15 studies of conditions such as pain, anxiety and seasickness and concluded that, on average, about one-third of the people in the studies benefited from sham medicine. More recent studies have reported sometimes greater, sometimes lower, percentages of responders, depending to some extent on the medical condition. Debates about placebos continue to simmer. Some scientists argue that the placebo effect doesn't exist or has been greatly exaggerated — that the effects of sham medicines can be explained away by, for example, faulty statistics or health improvements that would have occurred anyway. Other scientists suggest (also controversially) that the placebo's clout can be impressively strong. A 1998 analysis of 19 clinical trials of antidepressants concluded that nearly half of these drugs' efficacy is linked to the placebo effect. Brain imaging studies have lent credence to the placebo effect as a real physiological phenomenon. For example, in two studies published in 2002, clinically depressed patients who responded to placebos showed dramatic changes in activity in the same areas of the brain that respond to antidepressants: the prefrontal cortex and the cingulate cortex. (The nature of these changes wasn't identical in those who took medicine versus placebo.) Other imaging studies have shown that the prefrontal cortex is active during the placebo response. This is the same part of the brain that lights up when you try to make yourself feel better or worse — rather as if the placebo response is similar to your ability to cheer yourself up, to regulate your mood if you've had a bad day by telling yourself that things aren't so terrible. "Things like pain don't just happen to you; your brain has to interpret the meaning and value to you," says Tor Wager, a psychologist at Columbia University in New York and author of some of the brain-scanning research. "Those circuits are partly under our control. The placebo is a way to [control] it beyond what we can do voluntarily." Studies are also revealing the chemical changes that occur when placebos are given to people. A study by Dr. Jon-Kar Zubieta of the University of Michigan in August showed that sham injections of pain medicine blocked pain by activating the brain's natural painkillers, known as endorphins. (Scientists are now doing studies to see whether sham injections or sham pills work better for treating pain.) In a report by University of British Columbia researchers published in 2001, Parkinson's patients given a fake treatment (and who experienced improvements in tremors and other symptoms) exhibited a change similar to that seen with drugs used to treat the condition: an increase in the brain chemical dopamine. Scientists don't know how placebos trigger the release of these substances. One theory holds that we learn to respond to placebos much like Pavlov's famous dogs learned to salivate at the sound of a bell signaling dinner. Initially, our bodies may respond to a specific pain medication by releasing molecules — such as endorphins in the brain. But as we begin to associate the pill or doctor with that analgesic response, our brains may learn to respond to these factors rather than to the medication. Doctor-patient interaction Regardless of the mechanism, the responses can be impressive enough to make some patients and doctors wonder why our bodies have self-healing properties that are so hard to tap on demand. In earlier decades, U.S. doctors would routinely harness them — simply by ordering fake pills from medical supply houses and prescribing them to their unsuspecting patients. Doctors in some other countries still do this. An Israeli survey published in the British Medical Journal last year found that 60% of doctors surveyed used placebos, with 30% of users prescribing placebos once a month or more. Another survey found that nearly 50% of Danish doctors had regularly used placebos. In the U.S. these days, however, placebos are used only in clinical trials to test new drugs. But researchers are hoping that the pills themselves aren't needed. They point to alternative medicine treatments, such as acupuncture, that they suspect are effective largely because of the hope they engender and the elaborate interaction between patient and healer. Acupuncture sessions last longer than a typical doctor's appointment, and practitioners discuss patients' symptoms and lifestyle at length. A large-scale trial of acupuncture for migraines published in May in the Journal of the American Medical Assn. showed that real and sham acupuncture treatments both could cut migraine pain as much as popular drugs, implying that the key to the treatment's successes doesn't depend on the precise placement of a needle — or perhaps on any needle at all. "We're learning that the context under which healthcare is delivered, such as how doctor interacts with patient, is important," says Ted Kaptchuk, an assistant professor of medicine at Harvard Medical School. Mack, whose depression improved while she was taking a placebo, thinks that these scientists are on the right track. "A lot of what was great about the study was that I was having sympathetic people spend time with me on a weekly basis," Mack says. "I'm sure that had a profound effect." Scientists are now trying to quantify those effects. At UCLA, Dr. Andrew Leuchter, vice chairman of the department of psychiatry, is leading a federally funded study to more precisely measure the importance of doctor-patient interaction in self-healing. In it, 140 people with major depression will receive one of three treatments during a nine-week period. Some will get an antidepressant pill plus regular evaluations and interactions with doctors and nurses; others will get the evaluations but no antidepressant, just a sugar pill. The third group will get only the evaluations — no pill, fake or real. The patients will be assessed for their mood, their anxiety levels and their day-to-day functioning. Their brains will be scanned and monitored for changes. The goal will be to find out whether merely visiting the clinic makes a patient feel better and, if so, how much of a contribution it makes. "One of the major unanswered questions is the role of interpersonal interaction," Leuchter says. "If the doctor and patient get along better, is the patient more likely to improve and more likely to show a placebo response?" Faith and expectations A patient's level of expectation may also be a key factor in enhancing the placebo response. Last year, Leuchter's group showed in a small study that people with depression who expressed strong faith that an antidepressant drug would help them responded better under therapy than patients whose faith was less strong. Building on this feeling of faith, he suspects, may be a fast route to helping patients heal themselves. Some researchers are already trying to put the power of the placebo into practice: Brown gives occasional seminars to doctors on how to do this. The key, he says, is to accentuate the many elements that make a visit to a doctor special and powerful-seeming — such as the knowledge that one is visiting a recognized healing authority, the careful discussion of ailments, and all those medical office accouterments such as the white coat, stethoscope, weigh scales, medical diplomas and busy nurses bustling down hallways. Research has shown that if doctors write down instructions (say, to exercise regularly) on a prescription pad instead of plain paper, the patient is more likely to follow a directive. Research has also shown that patients with unspecific chest pain fared better when given simple diagnostic tests in addition to merely discussing the symptoms with the doctor. Talking the right way about treatments is key, Brown says. "Doctors should give people an appropriate and optimistic expectation about their treatment," he says. "For example, say, 'This is a powerful painkiller' rather than 'This may help.' " On the flip side, care should also be taken to be honest about but not overemphasize possible side effects. Studies show that cancer patients who expect to suffer nausea with chemotherapy are more likely to experience it. Doctors aren't suggesting we toss out our real pills. Placebo effects are said to fade away over time, whereas a drug would continue to work. And the placebo effect seems mostly to help for conditions such as pain and mood disturbances in which there is a strong subjective component to symptoms. But the doctors do hope that ultimately the placebo effect can be harnessed to enhance the effectiveness of a wide array of conventional treatments. "What we're doing is trying to reconfigure the science of medicine and the art of medicine," Kaptchuk says. "The pendulum has gone way to science, but the placebo is about the healing context … how that remedy gets communicated to the patient."