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involved in generating the placebo response," says Don Price, an oral surgeon at the University of Florida
who studies the placebo effect in dental pain.
"But endorphins are still out in front." That case has been strengthened by the recent work of Fabrizio
Benedetti of the University of Turin, who showed that the placebo effect can be abolished by a drug,
naloxone, which blocks the effects of endorphins. Benedetti induced pain in human volunteers by inflating a
bloodpressure cuff on the forearm. He did this several times a day for several days, using morphine each
time to control the pain. On the final day, without saying anything, he replaced the morphine with a saline
solution. This still relieved the subjects' pain: a placebo effect. But when he added naloxone to the saline the
pain relief disappeared. Here was direct proof that placebo analgesia is mediated, at least in part, by these
natural opiates.
Still, no one knows how belief triggers endorphin release, or why most people can't achieve placebo
pain relief simply by willing it. Though scientists don't know exactly how placebos work, they have
accumulated a fair bit of knowledge about how to trigger the effect. A London rheumatologist found, for
example, that red dummy capsules made more effective painkillers than blue, green or yellow ones.
Research on American students revealed that blue pills make better sedatives than pink, a colour more
suitable for stimulants. Even branding can make a difference: if Aspro or Tylenol are what you like to take
for a headache, their chemically identical generic equivalents may be less effective. It matters, too, how the
treatment is delivered. Decades ago, when the major tranquilliser chlorpromazine was being introduced, a
doctor in Kansas categorised his colleagues according to whether they were keen on it, openly sceptical of
its benefits, or took a "let's try and see" attitude. His conclusion: the more enthusiastic the doctor, the better
the drug performed. And this year Ernst surveyed published studies that compared doctors' bedside manners.
The studies turned up one consistent finding: "Physicians who adopt a warm, friendly and reassuring
manner," he reported, "are more effective than those whose consultations are formal and do not offer
reassurance."
Warm, friendly and reassuring are precisely CAM's strong suits, of course. Many of the ingredients of
that opening recipe—the physical contact, the generous swathes of time, the strong hints of supernormal
healing power—are just the kind of thing likely to impress patients. It's hardly surprising, then, that
complementary practitioners are generally best at mobilising the placebo effect, says Arthur Kleinman,
professor of social anthropology at Harvard University.