Lab Talk

Placebo in the Brain

The placebo effect can be large and can be measured as real changes in brain activity, confounding the effects of drugs and treatments.  How does simply the expectation of healing result in real physiological changes?

Discovering the placebo effect

In the 1700s, Dr. Elisha Perkins believed in the power of sticks. Metal-made healing sticks, he reasoned, could heal patients through their powerful magnetic properties when applied to the body. Though he didn’t quite understand the exact mechanism, the sticks did seem to work in some cases.

After Dr. Perkins’ death, Dr. John Haygarth became interested in this unique treatment method. In an attempt to better understand the mechanisms at work, he painted a number of sticks. Much as Dr. Perkins had claimed, these sticks did help some patients. The magnetic properties of metal, however, turned out to be unimportant. Some of Dr. Haygarth’s painted sticks had been metal, but others had been wood. Those patients who responded to the metal sticks, also responded to the wooden sticks.

Dr. Haygarth’s experiment was the first in a string of studies providing evidence of the placebo effect, the startling truth that what a person believes can have a very real impact on physical outcomes.

See related post Neurofeedback and ADHD

Controlling for Placebo Effects

This idea has become a cornerstone of medical research. No study testing a new drug or procedure is approved without evidence that it outperforms a control group. Much like Dr. Perkins’ understanding of his magnetic sticks, however, doctors and researchers have had trouble identifying the exact mechanisms at work. As a result, some scholars doubted the validity of the placebo effect. Instances of evidence were regarded as coincidental. Even when placebos gained mainstream acceptance and secured an important role in clinical trials, they were considered an annoyance to be taken into account, not a phenomenon worthy of study in its own right. This changed in the mid-1900s, with a seminal study in which Dr. Beecher argued, with evidence, that placebo was powerful enough to really matter. Our understanding of placebo has been improving ever since.  Indeed treatment of brain disorders are most susceptible to placebo effects.

Placebo effects arise from expectation

As our ability to monitor and read the human brain improves with new neuroscience methods and technologies, scientists are uncovering the physical mechanisms of placebo. Placebo, it turns out, can be found in your brain.

Perhaps the most startling placebo-related discovery is that placebo is not one mechanism. Instead, there are as many placebos as there are illnesses and treatments. They act in different ways, at different times, and even impact people differently depending on a number of factors, including genetics. Placebo exists beyond sugar pills and hypnosis. As a psychosocial contextual cue that elicits a biological response, placebos can be words, rituals, or any other input that creates expectation.

The very act of expecting changes your brain, but it doesn’t work alone. Memory and motivation also impact placebo. Modulation of anxiety, activation of the brain’s reward centers and learned responses play a role.

Measuring placebo effects and the placebo prone

Our best understanding of the placebo effect has been derived from studies related to pain and Parkinson’s disease. In these instances, scientists have identified the networks that are activated by placebo. In pain, opioidergic, dopaminergic and cholecystokinergic networks are activated. In Parkinson’s disease, it is neuronal changes in the basal ganglia and dopaminergic activation in the striatum. The changes seen in a patient’s brain who is experiencing a positive placebo effect is similar to that seen in patients given prescribed, effective pharmaceuticals.

Today, some studies conduct a placebo lead-in. This is a period of time when participants that are particularly susceptible to the placebo effect integrated into the study at hand can be identified, and potentially removed before the study begins. How are we able to identify these placebo-prone people?

One way is through EEG. A 2006 study, for example, looked at how quantitative EEG cordance in the placebo lead-in phase influenced treatment outcomes for major depression. In this case, they were more interested in bolstering the effectiveness of their treatment – medication – with placebo than in removing placebo-prone individuals.

See related post What does the EEG Signal Measure?

Effective medical treatment of major depression is often accompanied by decreases in prefrontal electroencephalogram (EEG) cordance. This can occur within forty-eight hours of receiving treatment drugs. In this study, researchers instead looked at changes in EEG during the placebo lead-in phase. Before any drugs had been administered, a number of patients were already showing decreased cordance in their prefrontal EEG. At the end of the study, it was these individuals who benefited from treatment most. Their post-study Hamilton Depression Scale Scores – a measure of major depression – were lower than patients who did not exhibit this placebo.

See related post  EEG and Major Depressive Disorder

Healing by placebo

The placebo effect can be just remarkably strong and unlike pharmaceuticals, placebos typically have no negative side effects. This begs the question of why we don’t spend more effort understanding how to treat by ‘placebo’ and why some of us are more capable of healing by expectation.

As we continue to uncover the mysteries of the human brain, previously unknown mechanisms and influences are becoming known. Armed with this knowledge, we may be able to use these mysteries to help cure diseases, increase longevity and improve the human condition. The placebo effect, far from being an annoying nuisance, may hold the secret to actively using our brain’s amazing talents to benefit our lives.

Leave a Reply