So, if the placebo effect in humans is also a conditioned response, then the explanation for its effectiveness would be that a patient simply associates getting better with, for example, seeing a doctor or taking a pill. After all, ever since childhood a patient will have visited a doctor, received a pill and then felt better. Hence, if a doctor prescribes a pill containing no active ingredient, a so‑called sugar pill, then the patient might still experience a benefit due to conditioning.
Another explanation for the placebo effect is called the expectation theory. This theory holds that if we expect to benefit from a treatment, then we are more likely to do so. Whereas conditioning would exploit our unconscious minds to provoke a placebo response, the expectation theory suggests that our conscious mind might also be playing a role. The expectation theory is supported by a host of data from many lines of research, but it is still poorly understood. One possibility is that our expectations are somehow interacting with our body’s so‑called acute phase response.
The acute phase response covers a range of bodily reactions, such as pain, swelling, fever, lethargy and loss of appetite. In short, the acute phase response is the umbrella term used to describe the body’s emergency defensive response to being injured. For instance, the reason that we experience pain is that our body is telling us that we have suffered an injury, and that we need to protect and nurture that part of the body. The experience of swelling is also for our own good, because it indicates an increased blood flow to the injured region, which will accelerate healing. The increased body temperature associated with fever will help kill invading bacteria and provide ideal conditions for our own immune cells. Similarly, lethargy aids recovery by encouraging us to get much‑needed rest, and a loss of appetite encourages even more rest because we have suppressed the need to hunt for food. It is interesting to note that the placebo effect is particularly good at addressing issues such as pain, swelling, fever, lethargy and loss of appetite, so perhaps the placebo effect is partly the consequence of an innate ability to block the acute phase response at a fundamental level, possibly by the power of expectation.
The placebo effect may be linked to either conditioning or expectation or both, and there may be other even more important mechanisms that have yet to be identified or fully appreciated. While scientists strive to establish the scientific basis of the placebo effect, they have already been able to ascertain, by building on Haygarth’s early work, how to maximize it. It is known, for instance, that a drug administered by injection has a bigger placebo effect than the same drug taken in pill form, and that taking two pills provokes a greater placebo response than taking just one. More surprisingly, green pills have the strongest placebo effect on relieving anxiety, whereas yellow pills work best for depression. Moreover, a pill’s placebo effect is increased if it is given by a doctor wearing a white coat, but it is reduced if it is administered by a doctor wearing a T‑shirt, and it is even less effective if given by a nurse. Large tablets offer a stronger placebo effect than small tablets…unless the tablets are very, very small. Not surprisingly, tablets in fancy branded packaging give a bigger placebo effect than those in plain packets.
Of course, all of the above statements refer to the average patient, because the actual placebo effect for a particular patient depends entirely on the belief system and personal experiences of that individual. This variability of placebo effect among patients, and its potentially powerful influence on recovery, means that it can be a highly misleading factor when it comes to assessing the true efficacy of a treatment. In fact, the placebo effect is so unpredictable that it could easily distort the results of a clinical trial. Therefore, in order to test the true value of acupuncture (and medicines in general), researchers somehow needed to take into account the quirky, erratic and sometimes strong influence of the placebo effect. They would succeed in this endeavour by developing an almost foolproof form of the clinical trial.
The blind leading the double‑blind
The simplest form of clinical trial involves a group of patients who receive a new treatment being compared against a group of similar patients who receive no treatment. Ideally there should be a large number of patients in each group and they should be randomly assigned. If the treated group then shows more signs of recovery on average than the untreated control group, then the new treatment is having a real impact…or is it?
We must now also consider the possibility that a treatment might have appeared to be effective in the trial, but only because of the placebo effect. In other words, the group of patients being actively treated might expect to recover simply because they are receiving some form of medical intervention, thus stimulating a beneficial placebo response. Hence, the straightforward trial design can produce misleading results, because even a useless treatment can give positive results in such a trial. So the question arises: how do we design a clinical trial that takes into account the confusion caused by the placebo effect?
A solution can be traced back to eighteenth‑century France and the extraordinary claims of Franz Mesmer. Whilst Mesmer is nowadays associated with hypnotism (or mesmerism), in his own lifetime he was most famous for promoting the health benefits of magnetism. He argued that he could cure patients of many illnesses by manipulating their ‘animal magnetism’, and one of the ways of doing this was to give them magnetically treated water. The remedy was very dramatic, because sometimes the supposedly magnetized water could induce fits or fainting as part of the alleged healing process. Critics, however, doubted that water could be magnetized and they were also dubious about the notion that magnetism could affect human health. They suspected that the reactions of Mesmer’s patients were purely based on their faith in his claims. In modern parlance, critics were suggesting that Mesmer’s remedies were exploiting the placebo effect.
In 1785, Louis XVI convened a Royal Commission to test Mesmer’s claims. This Commission, which included Benjamin Franklin, conducted a series of experiments in which one mesmerized glass of water was placed among four glasses of plain water–all five glasses looked identical. Unaware which glass was which, volunteers then randomly picked one glass of water and drank it. In one case, a female patient tasted her glass and immediately fainted, but it was then revealed that she had drunk only plain water. It seemed obvious that the fainting woman thought that she was drinking magnetized water, she knew what was supposed to happen when people drank such water, and her body responded appropriately.
After all the experiments had been completed, the Royal Commission could see that patients had responded in a similar way regardless of whether the water was plain or magnetized. Therefore, they concluded that magnetized water was the same as plain water, which meant that the term magnetized water did not really mean anything. Moreover, the Commission stated that the effect of supposedly magnetized water was due to the expectation of patients; today we would say that it was due to the placebo effect. In short, the Commission accused Mesmer’s therapy of being fraudulent.
The Royal Commission did not, however, speculate about the widespread effects of placebo throughout medicine, which is why Haygarth’s research on tractors fourteen years later is credited with formally recognizing the role of the placebo effect in medical practice. On the other hand, the Royal Commission did make a major contribution to the history of medicine, because it had designed a new type of clinical trial. The key breakthrough in the Royal Commission’s experiment was that the patients were unaware of whether or not they were receiving the real or fake treatment, because the glasses of mesmerized water and plain water were identical. The patients were said to be blind.