The greatest wonder drug we know about is the placebo. A placebo is an inert substance, such as a sugar pill, that has no direct physiological effect. Placebos can cause research participants to report improvements in a variety of physical and mental conditions. For this reason, tests of the effectiveness of new drugs or medical treatments must include not only treatment and no treatment conditions but also a placebo condition. While the size of placebo effects varies, placebos can account for well over half the difference between treatment and no treatment groups, especially with subjective outcomes such as pain or depression. Placebo effects are part of a broader class of self-fulfilling prophecies in which the expectation that some event will occur sets in motion processes that result it actually occurring.

Placebo effects are often underestimated, since clinical trials seldom use active placebos. An active placebo is one that has a noticeable physiological effect that is irrelevant to the condition being measured. It is used to convince patients that they are receiving a real drug rather than a placebo. Of course, if they figure out that they are getting a placebo, they may not expect to improve and have, in effect, reassigned themselves to a no treatment condition. Studies show that active placebos are more effective than passive or inert placebos.

A new study by Kate Faasse and her colleagues in Health Psychology shows how subtle placebo effects can be. The participants were 81 New Zealand undergraduates who reported frequent headaches. They were given four doses of medication to treat their next four headaches. Two of them were labeled “Nurofen,” a common New Zealand brand name, while the other two were labeled “generic ibuprofin.” Within each of these conditions, one dose was active ibuprofin while the other was a placebo. Therefore, the study contained four conditions: branded active, generic active, branded placebo and generic placebo. To avoid order effects, each participant was asked to use the drugs in an assigned random order.

The students filled out a standard 6-point pain scale before taking each pill and again one hour later. Results showed that real ibuprofin reduced pain more than the placebo did. When participants received ibuprofin, it was equally effective no matter how it was labeled. However, the branded placebo was more effective in relieving pain than the generic placebo. In fact, branded placebos did not differ in effectiveness from real ibuprofin. Apparently these college students mistakenly believed brand-named drugs are more effective than generics.

This experiment had a within-subjects design; that is, participants received all four treatments in random order. This increases the statistical power of the data analysis, but it creates other problems. It allows the participants to compare the four conditions to one another. They probably assumed the researchers were comparing the effectiveness of brand name and generic headache remedies. It’s not clear to me whether the greater reported pain relief in the branded placebo condition was due to participants’ faith in brand names or their guess about what the researchers hoped to find.

This study is similar to an experiment by Alberto Espay and others published earlier this year. Twelve people with “moderate to severe” Parkinson’s disease were given two different placebos—two identical injections of a saline solution—in random order. They were told that one of them was an expensive new drug costing $1500 per dose, while the other cost only $100 per dose. Before and after each injection, participants completed three tests of motor skills used to measure the severity of Parkinson’s disease. While both placebos improved performance on the tests, the expensive placebo was more effective than the cheaper one.

Research shows that placebos can cause real, measurable physiological changes in the brain. Some have attributed the placebo effect to classical conditioning, in which the physiological response to effective drugs is generalized to ineffective ones such as placebos. However, the present results would seem to require a cognitive explanation. Classical conditioning also has difficulty explaining placebo effects that don’t involve habitual behaviors, such as the pain relief and increased mobility reported by patients who received sham knee surgery!

The effectiveness of placebos raises ethical questions. Should doctors be permitted to prescribe placebos? Since telling patients they are getting a placebo would reduce–but not completely eliminate–its effectiveness, should they be allowed to conceal from patients the fact that their treatment is a placebo? How much is our society willing to tolerate willful deception of patients by health care providers? (How much does it tolerate already?)

A literal reading of the results of these two studies suggests not only that doctors should prescribe placebos, but also that expensive placebos are more effective than cheaper ones. How much should drug companies and health care providers be allowed to charge for placebos? Of course, given what we know about placebos, the American public is already paying a considerable sum for both prescription and over-the-counter drugs whose effectiveness is partially or completely explained by the placebo effect.

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