"I aim to please" - The Extent of the Placebo Effect

             Many people have heard of the ‘placebo effect.’ Placebo pills, sometimes known as sugar pills, are the gold standard control used to demonstrate the effectiveness of drug treatments for conditions like depression, ADHD, anxiety, and so on. These pills carry no useful medication, but can affect change solely through suggestion. However, a placebo must not always come in pill form. The placebo effect can be seen in injections and, perhaps more surprisingly, surgical procedures. This, coupled with the fact that the placebo effect can occur for a range of mental health and medical conditions, illustrates that even a simple sugar pill, and the expectation that it brings, can alter both our brain and physiological state.

            Since its initial use, placebo surgery has demonstrated a startling point—that no actual medical procedure, only the guise of one, can lead to patient recovery. In 1939, Dr. Feischi demonstrated that a surgical procedure for agina pectoris that involved increasing myocardium blood flow was successful for the majority of patients. But, twenty years later, a paper published in the New England Journal of Medicine showed that a fake operation worked just as well (1). The “sham surgery” patients showed decreased angina symptoms. More recently, a controlled study looking at arthroscopic surgery for osteoarthritis in the knee showed similar findings. The sham procedure group had no more pain, and no less motion than the actual surgery group. Both groups were significantly better than prior to surgery (2). Therefore, the results cannot be explained away by saying that the surgery simply does not work.

            Yet another medical procedure showed similar results. Half the patients in a Parkinson’s study received human neuron grafts on their brains—the other half just had the placebo surgery. Moreover, the study had a double-blind; the doctor did not know which procedure he was performing until he walked into the operating room and opened up an envelope. A significant number of participants experienced an “improved quality of life” after the surgery. Remarkably, half the placebo surgery patients reported the same thing (2). Somehow, the belief that they had received neuron grafts alleviated some of their Parkinson’s symptoms.

Someone on the web forum commented that how large the placebo effect is depends on how subjective the illness is. And while there are no cases of someone willing themselves back from a broken leg, there are other instances where a clear objective, physiological change takes place. In one experiment, researchers put a colored substance on patients’ warts, covering the warts. They told the subjects that the substance would alleviate their warts over time. And when the substance wore off a few weeks later, the majority of the warts were gone (3). The kicker? The substance was just dye—it had no real curative powers. An actual, visible, physiological change took place because the patients thought they were getting an actual treatment.

Logically, it seems that the placebo effect must be regulated by the brain. But how does this happen? How can the brain will itself to get better? One theory is that of classical conditioning—that the medical setting has primed people to experience relief. Another theory, however, directly relates to changes in the brain (6). The placebo effect may be caused by the release of endorphins (which are endogenous opiates) in individuals’ brains when they believe they are getting treatment.

Current research seems to support the endorphin theory. Donald Price found that placebo-induced analgesia can be reversed by naloxone, an opioid antagonist (5). In other words, when endorphin release is blocked the placebo effect ceases to exist. Therefore, even though people still had the same expectations and hopes about treatment, their brain failed to create physiological changes based on these expectations. Another experiment used PET scans in order to look at brain functioning in subjects given placebo pills. The PET scan demonstrated that placebo use led to increased endorphin release in the patients’ brains (7).

Other studies have demonstrated brain activity changes due to placebo use that correspond to specific illnesses. For example, another PET scan study found that taking placebos for pain maintenance activated the rostral anterior cingulate cortex in subjects(6). This area (the rostral anterior cingulated cortex) of the brain is associated with levels of pain. In a similar study, researchers looked at Pakinson’s patients who received a placebo saline injection. Just like the actual treatment, the placebo led to decreased neuronal firing in the subthalamic nucleus (6). High levels of firing in this area are associated with the tremors brought on by Parkinson’s.

Our expectations of treatment seem to cause the release of endorphins that increase overall mood, at least in some circumstances. But it also seems to lead to changes in specific brain areas/function, depending on what the placebo is being used for. So the placebo effect appears to be specific, not just a general sense of feeling better or feeling less pain. The brain is capable of responding to the placebo in a similar way to how it responds to the actual drug—without even necessarily knowing how the drug is supposed to work. This placebo effect also seems to be fairly successful for a wide range of illnesses and disorders. Which makes me wonder—is it ethical to give placebos as medication? 

Citations:

 1) The Placeo effect and placebos: what are we talking about? Some conceptual and historical considerations

2) The Placebo Perscription

3) Sham surgery in research: ethics

4) The Mysterious Placebo Effect

5) Fields, H. L.; Price, D. D. Toward a Neurobiology of Placebo Analgesia. In The Placebo Effect: An Interdisciplinary Exploration; Harrington, A., Ed.; Harvard University Press: Cambridge, MA, 1997; pp 93–116.

6) Pulling Apart the Placebo

 7) Placebos trigger an opioid hit in the brain