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| Archive : Summer
2006 |
YOU, A RESEARCH SUBJECT:
Take the pill the pleasant doctor gives you // Feel better, just as you thought you would // Suffer the side effects she warned you about // Confuse trial results because your sugar pill works just as well as the genuine article.
The Placebo Problem [page 2]
 By
Rachael Moeller Gorman // Illustrations by Leigh Wells
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Before WWII, physicians chose treatments based on expert opinion, and science largely stayed in the laboratory. But by mid-century, many doctors had begun to recognize the need to denounce quack treatments and validate new drugs. They came up with a human trial in which they compared results from a randomly assigned test group to results of a group that received sham treatment—a control, or placebo, group.
Old-school physicians denounced the random assignment of patients to untested treatments and no treatment at all (the placebo group) as unethical. In a letter to the British Medical Journal in 1951, one physician wrote, “Patients [are being] degraded from human beings into bricks in a column, dots in a field, or tadpoles in a pool; with the eventual elimination of the responsibility of the doctor to get the individual back to health.”
Then, in an influential paper, “The Powerful Placebo,” published in the Journal of the American Medical Association in 1955, Henry Beecher of the Massachusetts General Hospital and Harvard Medical School swung the debate toward the modern point of view. Beecher showed that in 15 of the first RCTs, which tested treatments for a variety of diseases, a certain percentage of people in the control group actually got better. RCT proponents used this to argue that without putting half the subjects from any trial into a control group, no one would ever know whether a treatment inherently worked or whether the placebo effect—the combination of expectation, physician care and nature just taking its course—experienced by those receiving the actual treatment as well, was responsible for the improvement. Beecher believed that the effectiveness of any drug resulted in part from its active ingredients and in part from a placebo effect, and that remains the prevailing view.
With support from Beecher’s persuasive arguments and the momentum of post-WWII science—in which research was venturing out of the laboratory and into the clinic—the randomized controlled trial became the gold standard. But this powerful new research tool was based on the assumption that there was a static placebo baseline that varied little across trials. Now, half a century later, Kaptchuk’s study and other recent work suggest there’s a lot more to the story.
Modern placebo research began with the study of pain. In 1978, Jon Levine, a researcher at the University of California at San Francisco, gave a placebo painkiller to patients after dental surgery, and some felt better. To those subjects he then gave naloxone, a drug that prevents the body from sensing a class of naturally occurring painkillers known as endogenous opioids. The patients’ pain increased significantly, suggesting that the placebo effect was being transmitted through a specific chemical pathway in the brain—the endogenous opioid system. Naloxone, by blocking that route, apparently eliminated the placebo effect.
But other pain studies found placebo responses that weren’t negated by naloxone, indicating that the effect must also work through non-opioid brain pathways. One possible route is the body’s conditioning response. Like Pavlov’s dog, which salivated when a bell rang because researchers had previously paired a ringing bell with food, we may be conditioned to respond in a certain way to an expected stimulus. In studies published in the late 1990s and early 2000s, Parkinson’s disease patients who took a powerful anti-Parkinsonian drug saw their motor skills improve even when the drug was replaced by a placebo. The study’s authors concluded that the patients’ brains had been conditioned to release dopamine, and continued to do so even when the placebo was substituted. |
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Illustrations by Leigh Wells
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