Placebo may cause physical effects

How placebos work

Positive expectation dampens pain

As Tor Wager from the University of Colorado and Lauren Atlas from the National Institutes of Health in Bethesda (USA) confirmed in a 2015 review, those areas of the brain that are involved in positive expectations and in the evaluation of pain, in particular, drive their activity in the In the course of a sham treatment high. This includes parts of the prefrontal cortex and the nucleus accumbens, a central switching station of the reward system. Other regions that process the type and intensity of pain stimuli, on the other hand, are dampened. These include the insular cortex and the thalamus.

Another important field of application for sham treatments is the therapy of depression. Depending on the study, the share of the placebo effect in the overall effect of antidepressants is estimated at up to 50 percent. In a 2002 study by neuropsychiatrist Helen Mayberg, sugar pills produced an effect comparable to that of conventional antidepressants. In the brains of those patients who responded to placebo, brain metabolism in the prefrontal cortex changed in a manner similar to that in those who were relieved by a true selective serotonin reuptake inhibitor (SSRI) -type antidepressant.

In 2015, a team led by Jon-Kar Zubieta from the University of Michigan reported that depressed patients not only showed weaker symptoms after taking a placebo, but also released more endogenous opioids in the nucleus accumbens and amygdala. Both areas of the brain are involved in the regulation of stress and emotion.

Both pain and depression are disorders with a pronounced subjective component. Could that possibly favor the placebo effect? Not necessarily. As recent research shows, even people with severe neurological diseases like Parkinson's respond well to dummy drugs. The brains of Parkinson's patients release too little dopamine due to the massive cell death in the Substania nigra. One of the few effective treatments at least partially compensates for this loss by administering L-Dopa, a precursor of the neurotransmitter dopamine.

As subjective as the placebo effect may seem, it is anything but a pipe dream

In 2010, a team led by Sarah Lidstone from the University of British Columbia in Vancouver divided patients with moderately severe Parkinson's syndrome into groups. These, it was said, would be assigned to L-Dopa therapy with a chance of 25, 50, 75 or 100 percent, the rest being temporarily switched to a placebo. In fact, however, all participants received a dummy drug. Those who believed they had a 75 percent chance of being treated reacted the most: their motor skills recovered significantly. Lidstone and her colleagues also used positron emission tomography (PET) to register a dopamine surge in the basal ganglia, which is essential for movement control. If, on the other hand, the prospects for therapy were weak, the positive expectations were apparently lacking - and the placebo effect did not materialize.

A supposedly 100 percent guarantee, on the other hand, neither improved the symptoms nor brought the brain metabolism up to speed. How can this be explained? It is known from research on learning on animals that more dopamine is released when a reward is likely but not certain. Meanwhile, in addition to Lidstone's team, other researchers found that dopamine activity is most likely to increase when Parkinson's patients see an improvement in symptoms to hope instead of assuming it.