cream protected them from feeling as much of a burn as a
control cream. Even when the researchers showed participants
that the active cream was just petroleum jelly, it made little
difference. The participants still reported less pain from the heat
when they were re-tested with it versus the control cream (The
Journal of Pain, 2015).
Welcome to the world of open-label placebo research, where
it’s not a question of whether placebos work, but how.
For decades, placebo response was generally seen as
“an uninteresting source of noise that interfered with
pharmacological research,” says Bret Rutherford, MD, assistant
professor of clinical psychiatry at Columbia University.
But these days, scientists are studying placebos as a
psychobiological phenomenon and the placebo response as
a potentially important part of the success of many medical
treatments. Researchers are using psychological assessments,
brain scans and genotyping to better understand how placebo
responses work and to identify who may be most likely to
respond to them.
The research could lead to changes in how psychologists and
others conduct research and in how health-care professionals
“Understanding the mechanisms underlying placebo effects
can shift our understanding of when and how treatments work
and how to use them — not in terms of giving people fake
drugs, but in terms of changing the principles by which we
learn to care for each other,” says Tor Wager, PhD, an associate
professor of psychology and neuroscience at the University of
Colorado at Boulder, who worked with Schafer on the open-label cream study.
Like cognitive therapies, Wager says, placebos tap into
How the mind makes medicine
people’s beliefs that there’s hope and that they can get better.
Researchers have been examining placebos for centuries.
In 1784, Benjamin Franklin tested whether magnetic force
fields could cure illnesses, a notion that Austrian physician
Franz Anton Mesmer had profitably introduced and used
in his practice. In Franklin’s experiments, participants
responded dramatically to plain water they were told had been
“mesmerized.” These days, researchers use neuroimaging to
see how our brains respond to placebos and have found that
placebos mimic symptom relief for a number of ills.
For example, a meta-analysis of 25 neuroimaging studies of
pain and placebos conducted by Wager and Lauren Atlas, PhD,
of the National Center for Complementary and Integrative
Health (NCCIH), found that people who took placebos
and expected to have reduced pain had less activity in brain
regions often associated with pain processing, including the
dorsal anterior cingulate, thalamus and insula (Handbook of
Experimental Pharmacology, 2014).
Though placebos may work through various mechanisms,
University of Colorado at Boulder psychology student and neuroscience researcher Scott Schafer
research suggests that they have the greatest effect in neural
systems involved with processing reward seeking, motivation
and emotion. Placebos seem to be particularly effective in
patients with depression, Parkinson’s disease and pain. All three
conditions, Atlas says, involve the neurotransmitter dopamine.
“They’re also all areas where people can consciously monitor
their own treatment results: ‘I know how much pain I’m
feeling’ or ‘I know how slow my movements are.’ That’s why
neuroimaging markers of placebo response are so important
when paired with subjective reports. We can now show that
when people say they’re getting better, they really are.”
In one study of patients with Parkinson’s disease, Wager and
colleagues found that simply expecting medication altered brain
activity in the striatum and ventromedial prefrontal cortices —
brain areas associated with reward learning — in ways similar
to actual dopaminergic medication (Nature Neuroscience, 2014).
And in a recent study of patients with depression, Andrew
Leuchter, MD, and colleagues at the University of California,
Los Angeles, found that participants who received placebo
pills and supportive care did better than those who had only
ast year, 40 people participated in a study that tested, essentially, the power of their beliefs.
and colleagues asked participants to apply a “powerful analgesic” on their hands and arms. The
researchers then administered small bursts of heat where the cream had been applied. The cream
was really petroleum jelly, but as expected, participants reported that the so-called powerful