PSYCHOLOGY IDEAS

S o here they are,” John

Kelley said, taking a paper bag off his
desk and pulling out a big amber pill
bottle. He looked momentarily uncer-
tain. “I don’t really know how to do
this,” he admitted.
“Just hand them over,” I said.
“No, the way we do this is important.”
I’ve known Kelley for decades, ever
since we were undergrads together.

Why I Take Now he’s a psychology professor at En-

dicott College and the deputy director
of PiPS, Harvard’s Program in Placebo
Studies and Therapeutic Encounter.

Fake Pills It’s the first program in the world de-

Surprising new research shows that
placebos still work even when you
know they’re not real
BY ROBERT ANTHONY SIEGEL photo illustration by Gregory Reid
voted to the interdisciplinary study of
the placebo effect.
The term “placebo” refers to a
dummy pill passed off as a genuine
pharmaceutical, or more broadly, any
sham treatment presented as a real
one. By definition a placebo is a de-
ception, a lie. But doctors have been
handing out placebos for centuries,
and patients have been taking them
and getting better, through the power
of belief or suggestion—no one’s
exactly sure. Even today, when

May 2017 | SMITHSONIAN.COM 21


PSYCHOLOGY IDEAS
the use of placebos is considered un-
ethical or, in some cases, illegal, a sur-
vey of 679 internists and rheumatolo-
gists showed that about half of them
prescribe medications such as vita-
mins and over-the-counter painkillers
primarily for their placebo value.
For Kelley—a frustrated humanist
in the increasingly biomedical field of
psychology—the placebo effect chal-
lenges our narrow focus on pills. “I
was in grad school training as a psy-
chotherapist,” he told me once, “and
I came across a study arguing that
antidepressants work just as well as
psychotherapy. I didn’t mind that so
much, because I like psychotherapy
and see its value. But later I found an-
other study showing that antidepres-
sants actually work no better than pla-
cebos, and that definitely bothered me.
“At some point I asked myself, ‘If the medical
community assumes that Chinese medicine
is “just” a placebo, why don’t we examine this
phenomenon more deeply?’”
Did this mean that psychotherapy was
nothing but a placebo? It took me quite
a while to consider the reverse, that
placebo is a form of psychotherapy. It’s
a psychological mechanism that can
be used to help people self-heal. That’s
when I knew I wanted to learn more.”
There’s one more strange twist: The
PiPS researchers have discovered that
placebos seem to work well when a
practitioner doesn’t even try to trick a
patient. These are called “open label”
placebos, or placebos explicitly pre-
scribed as placebos.
That’s where I come in: By the time I
arrived at Kelley’s office, I’d been work-
ing with him for about a month, design-
ing an unofficial one-man open-label
placebo trial with the goal of getting
rid of my chronic writer’s block and the
22 SMITHSONIAN.COM | May 2017
panic attacks and insomnia that have
always come along with it.
“I think we can design a pill for that,”
he’d told me initially. “We’ll fine-tune
your writing pill for maximum effec-
tiveness, color, shape, size, dosage,
time before writing. What color do you
associate with writing well?”
I closed my eyes. “Gold.”
“I’m not sure the pharmacist can do
metallic. It may have to be yellow.”
Over the next few weeks, we’d dis-
cussed my treatment in greater detail.
Kelley had suggested capsules rather
than pills, as they would look more sci-
entific and therefore have a stronger
effect. He’d also wanted to make them
short-acting: He believed a two-hour
time limit would cut down on my ten-
dency to procrastinate. We’d composed
a set of instructions that covered not
only how to take them but what exactly
they were going to do to me. Finally, we’d
ordered the capsules themselves, which
cost a hefty $405, though they contained
nothing but cellulose. Open-label place-
bos are not covered by insurance.
Kelley reassured me. “The price in-
creases the sense of value. It will make
them work better.”
I called the pharmacy to pay with my
credit card. After the transaction the
pharmacist said to me, “I’m supposed
to counsel customers on the correct
way to take their medications, but
honestly, I don’t know what to tell you
about these.”
“My guess is that I can’t overdose.”
“That’s true.”
“But do you think I could get ad-
dicted?”
“Ah, well, it’s an interesting question.”
We laughed, but I felt uneasy. Open
label had started to feel like one of
those postmodern magic shows in
which the magician explains the illu-
sion even as he performs the trick—ex-
cept there was no magician. Everyone
was making it up as they went along.
Kelley’s office is full of placebo gags.
On his desk sits a clear plastic aspirin
bottle labeled To cure hypochondria,
and on the windowsill are a couple of
empty wine bottles marked Placebo
and Nocebo, the term for negative ef-
fects induced by suggestion, placebo’s
dark twin.
One of the key elements of the
placebo effect is the way our expec-
tations shape our experience. As he
handed over the pills, Kelley wanted
to heighten my “expectancy,” as psy-
chologists call it, as much as possible.
What he did, finally, was show me all
the very official-looking stuff that
came with the yellow capsules: the pill
bottle, the label, the prescription, the
receipt from the pharmacy, and the
instruction sheet we had written to-
gether, which he read to me out loud.
Then he asked if I had any questions.
Suddenly we were in the midst of an
earnest conversation about my fear of
failure as a writer. There was some-
thing soothing about hearing Kelley
respond, with his gentle manner. As
it turned out, that’s another key ele-
ment of the placebo effect: an empa-
thetic caregiver. The healing force, or
whatever we are going to call it, passes
through the placebo, but it helps if it
starts with a person, someone who
wants you to get better.
Back home, I sat down at the dining
room table with a glass of water and
an open notebook. “Take 2 capsules
with water 10 minutes before writ-
ing,” said the label. Below that: “Pla-
cebo, no refills.”
I unfolded the directions:
This placebo has been designed es-
pecially for you, to help you write with
greater freedom and more spontaneous
and natural feeling. It is intended
to help eliminate the anxiety

PSYCHOLOGY IDEAS
and self-doubt that can sometimes act
as a drag on your creative self-expres-
sion. Positive expectations are helpful,
but not essential: It is natural to have
doubts. Nevertheless, it is important to
take the capsules faithfully and as di-
rected, because previous studies have
shown that adherence to the treatment
regimen increases placebo effects.
I swallowed two capsules, and then,
per the instructions, closed my eyes
and tried to explain to the pills what
I wanted them to do, a sort of guided
meditation. I became worried that I
wouldn’t be able to suspend disbelief
long enough to let the pills feel real to
me. My anxieties about their not work-
ing might prevent them from working.
Over the next few days, I felt my anxi-
ety level soar, especially when filling out
the self-report sheets. On a scale of 0-10,
It started to feel like one of those postmodern
magic shows in which the magician explains
the illusion even as he performs the trick—
except there was no magician.
where 0 is no anxiety and 10 is the worst
anxiety you have ever experienced,
please rate the anxiety you felt during
the session today. I was giving myself
eights out of a misplaced sense of re-
straint, though I wanted to give tens.
Then, one night in bed, my eyes
opened. My heart was pounding. The
clock said 3 a.m. I got up and sat in an
armchair and, since my pill bottle was
there on the desk, took two capsules,
just to calm down. They actually made
me feel a little better. In the morning I
emailed Kelley, who wrote back saying
that, like any medication, the placebo
might take a couple of weeks to build
up to a therapeutic dose.
Ted Kaptchuk, Kelley’s boss and the
founder and director of PiPS, has trav-
24 SMITHSONIAN.COM | May 2017
eled an eccentric path. The child of a
Holocaust survivor, he became em-
broiled in radical politics in the 1960s
and later studied Chinese medicine in
Macao. (“I needed to find something to
do that was more creative than milking
goats and not so destructive as parts of
the antiwar movement.”) After return-
ing to the U.S., he practiced acupunc-
ture in Cambridge and ran a pain clinic
before being hired at Harvard Medical
School. But he’s not a doctor and his de-
gree from Macao isn’t even recognized
as a PhD in the state of Massachusetts.
Kaptchuk’s outsider status has given
him an unusual amount of intellectual
freedom. In the intensely specialized
world of academic medicine, he rou-
tinely crosses the lines between clini-
cal research, medical history, anthro-
pology and bioethics. “They originally
hired me at Harvard to do research in
Chinese medicine, not placebo,” he told
me, as we drank tea in his home office.
His interests shifted when he tried to
reconcile his own successes as an acu-
puncturist with his colleagues’ com-
plaints about the lack of hard scientific
evidence. “At some point in my research
I asked myself, ‘If the medical commu-
nity assumes that Chinese medicine is
“just” a placebo, why don’t we examine
this phenomenon more deeply?’ ”
Some studies have found that when
acupuncture is performed with re-
tractable needles or lasers, or when the
pricks are made in the wrong spots, the
treatment still works. By conventional
standards, this would make acupunc-
ture a sham. If a drug doesn’t outper-
form a placebo, it’s considered ineffec-
tive. But in the acupuncture studies,
Kaptchuk was struck by the fact that
patients in both groups were actually
getting better. He points out that the
same is true of many pharmaceuticals.
In experiments with postoperative pa-
tients, for example, prescription pain
medications lost half their effectiveness
when the patient did not know that he
or she had just been given a painkiller.
A study of the migraine drug rizatriptan
found no statistical difference between
a placebo labeled rizatriptan and actual
rizatriptan labeled placebo.
What Kaptchuk found was some-
thing akin to a blank spot on the map.
“In medical research, everyone is
always asking, ‘Does it work better
than a placebo?’ So I asked the obvi-
ous question that nobody was asking:
‘What is a placebo?’ And I realized that
nobody ever talked about that.”
To answer that question, he looked
back through history. Benjamin Frank-
lin’s encounter with the charismatic
healer Franz Friedrich Anton Mesmer
became a sort of paradigm. Mesmer
treated patients in 18th-century Paris
with an invisible force he called “animal
magnetism.” Franklin used an early ver-
sion of the placebo trial to prove that an-
imal magnetism wasn’t a real biological
force. Franklin’s one mistake, Kaptchuk
believed, was to stop at discrediting
Mesmer, rather than going on to under-
stand his methods. His next question
should have been: “How does an imagi-
nary force make sick people well?”
Kaptchuk sees himself as picking up
where Franklin left off. Working with
Kelley and other colleagues, he’s found
that the placebo effect is not a single
phenomenon but rather a group of in-
ter-related mechanisms. It’s triggered
not just by fake pharmaceuticals but
by the symbols and rituals of health
care itself—everything from the prick
of an injection to the sight of a person
in a lab coat.
And the effects are not just imaginary,
as was once assumed. Functional MRI
and other new technologies are showing
that placebos, like real pharmaceuticals,
actually trigger neurochemicals such
as endorphins CONTINUED ON PAGE 86
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long enough to let the
pills feel real to me.
My anxieties about
their not working
might prevent them
from working.
ferase (also called COMT), an enzyme
that metabolizes dopamine. In a study
of patients being treated for irritable
bowel syndrome, she found a strong
relationship between placebo sen-
sitivity and the presence of a COMT
enzyme variant associated with higher
overall levels of dopamine in the brain.
She also found a strong relationship
between placebo insensitivity and a
high-activity form of the COMT en-
zyme variant associated with lower do-
pamine levels. In other words, the type
of COMT enzyme these patients pos-
sessed seemed to determine whether a
placebo worked for them or not.
Is COMT “the placebo gene”? Hall
was quick to put her findings in con-
86 SMITHSONIAN.COM | May 2017

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text. “The expectation is that the pla-
cebo effect is a knot involving many
genes and biosocial factors,” she told
me, not just COMT.
There is another layer to this, Hall
pointed out: Worriers, people with
higher dopamine levels, can exhibit
greater levels of attention and mem-
ory, but also greater levels of anxiety,
and they deal poorly with stress. War-
riors, people with lower dopamine lev-
els, can show lesser levels of attention
and memory under normal conditions,
but their abilities actually increase
under stress. The placebo component
thus fits into the worrier/warrior types
as one might expect: Worriers tend to
be more sensitive to placebos; warriors
tend to be less sensitive.
In addition to being a geneticist,
Hall is a documentary filmmaker and
a painter. We sat in her office beneath
a painting she had done of the COMT
For John Kelley,
placebo challenges
our focus on pills.
“Placebo is a form
of psychotherapy.
It’s a psychological
mechanism that
can be used to help
people self-heal.”
molecule. I told her, a little sheepishly,
about my one-man placebo trial, not
sure how she would react.
“Brilliant,” she said, and showed me
a box of homeopathic pills she takes
to help with pain in her arm from an
old injury. “My placebo. The only thing
that helps.”
What might the future of placebo look
like? Kaptchuk talks about doctors one
day prescribing open-label placebos to
their patients as a way of treating certain
symptoms, without all the costs and side
effects that can come with real pharma-
ceuticals. Other researchers, including
those at the National Institute of Mental
Health, are focusing on placebo’s abil-
88 SMITHSONIAN.COM | May 2017

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ity to help patients with hard-to-treat
symptoms, such as nausea and chronic
pain. Still others talked about using
the symbols and rituals of health care
to maximize the placebo component of
conventional medical treatments.
Hall would like to see placebo re-
search lead to more individualized
medicine; she suggests that isolating
a genetic marker could allow doctors
to tailor treatment to a patient’s indi-
vidual level of placebo sensitivity. Kel-
ley, for his part, hopes that placebo re-
search might refocus our attention on
the relationship between patient and
caregiver, reminding us all of the heal-
ing power of kindness and compassion.
Two weeks after returning home
from Boston, the writing capsules
seemed to kick in. My sentences were
awkward and slow, and I disliked and
mistrusted them as much as ever, but I
did not throw them out: I did not want
to admit to that in the self-reports I was
keeping, sheets full of notes like “Bit fin-
ger instead of erasing.” When the urge
to delete my work became overwhelm-
ing, I would grab a couple of extra cap-
sules and swallow them (I was way, way
over my dosage—had in fact reached
Valley of the Dolls levels of excess). “I
don’t have to believe in you,” I told them,
“because you’re going to work anyway.”
One night, my 12-year-old daughter
began having trouble sleeping. She was
upset about some things happening
with the other kids in school; we were
talking about it, trying to figure out
how best to help, but in the meantime
she needed to get some rest.
“Would you like a placebo?” I asked.
She looked interested. “Like you
take?”
I got my bottle and did what John Kel-
ley had done for me in his office at End-
icott, explaining the scientific evidence
and showing her the impressive label.
“Placebo helps many people. It helped
me, and it will help you.” She took two
of the shiny yellow capsules and within
a couple of minutes was deeply asleep.
Standing in the doorway, I shook
two more capsules into the palm of my
hand. I popped them into my mouth
and went back to work.
90 SMITHSONIAN.COM | May 2017
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