Placebos, the Mystery of Medicine

 By now, most people have heard of the "placebo effect", whereby participants in the control group of a new drug trial who get a dummy medication often report the same effects as those receiving the real thing. This result is usually attributed to the power of suggestion, in the sense of the mind playing a trick on the body. Subjects believe they've been dosed with the actual drug, so they think they're getting better.

The placebo effect can even extend to surgery, as shown in a noted 2002 study conducted at Houston VA Medical Center and Baylor College of Medicine. There, patients suffering from osteoarthritis in their knees were divided into three groups. The first group underwent the most common surgery, in which damaged cartilage is removed; the second got arthroscopic lavage, which flushes loose cartilage away from healthy tissue; and the control group got some small incisions, but no actual surgery.

None of the groups knew which one they belonged to, nor were they told during a two-year follow-up period. The surprising result: Researchers found no differences among the three groups. All patients reported improvement in their symptoms of pain and ability to use their knees.

When asked why patients responded so strongly to the placebo surgery, Dr. Bruce Moseley, who performed the various procedures, said they believed they had been helped by surgery, which seemed to make a difference in their perception.

Now, however, a new University of Michigan study reveals that people exhibiting the placebo effect don't just think they're getting better. They really are getting better.

In an article published in the August Journal of Neuroscience, scientists at Michigan's Molecular and Behavioral Neurosciences Institute detail the results of an experiment carried out on 14 healthy males between the ages of 20 and 30. The young men agreed to allow researchers to inject their jaw muscles with a concentrated salt water solution to cause pain.

While being injected, the subjects had their brains scanned by a positron emission tomography (PET) scanner. The scans lit up those areas of the brain associated with the experiencing of pain.

Then, every four minutes, researchers turned on an IV drip that, they told the subjects, was delivering a drug that might help relieve their pain. In reality, though, all they were getting was a small amount of hydrating solution, a placebo.

In order to correct for the natural tendency to become acclimated to pain over time, the researchers slowly increased the amount of concentrated salt water being injected in the muscle as the scans continued, in order to keep the participants' rating of their pain within the same point range throughout the experiment. This was checked at 15-second intervals during the scans, as subjects were asked to rate the intensity of their pain sensations on a scale of 0 to 100. They also contributed more detailed first-person ratings after it was all over.

During the experiment, the verbally conveyed information was compared with the ongoing PET scans, which clearly showed the brain releasing its natural painkilling endorphin chemicals, known as "mu opioids". The appearance of the mu opioids correlated directly with the placebo drip and a resultant personal perception of lessened pain on the part of all participants. Even when the injection dose was increased, the effect held. If the subject believed that he was receiving pain relief, his brain released mu opioids and he was able to tolerate a higher level of pain.

Of the 14 participants, nine were classified as "high placebo responders" because they had more than a 20% difference between pain and placebo scans in their average pain ratings per volume of saltwater infused. The other five exhibited lesser but still noticeable effects. They were classified as "low placebo responders."

The subjective ratings were consistent with previous findings, according to lead researcher Jon-Kar Zubieta. But the simultaneous imaging of the participants' endogenous pain-reducing opioid systems sheds new light on why the placebo effect occurs.

Further research is needed to determine whether the same results will be obtained with women and older subjects. But Zubieta is confident in his conclusion that "this deals another serious blow to the idea that the placebo effect is a purely psychological, not physical, phenomenon. We were able to see that the endorphin system was activated in pain-related areas of the brain, and that activity increased when someone was told they were receiving a medicine to ease their pain. They then reported feeling less pain. The mind-body connection is quite clear."

The extent to which the placebo effect will work is still unknown, of course, but the Michigan study indicates that there may be a lot of interesting work still to do on it.

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Posted 10-04-2005 2:13 PM by Doug Casey
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