TEXT View source
# 2024-02-25 - Why I Take Fake Pills by Robert Anthony Siegel
Surprising new research shows that placebos still work even when you
know they're not real.
"So here they are," John Kelley said, taking a paper bag off his desk
and pulling out a big amber pill bottle. He looked momentarily
uncertain. "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. Now he's a psychology professor at Endicott College and
the deputy director of PiPS, Harvard's Program in Placebo Studies and
Therapeutic Encounter. It's the first program in the world devoted
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 deception, 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 the use of
placebos is considered unethical or, in some cases, illegal, a survey
of 679 internists and rheumatologists showed that about half of them
prescribe medications such as vitamins 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 challenges our narrow focus
on pills. "I was in grad school training as a psychotherapist," 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
another study showing that antidepressants actually work no better than
placebos, and that definitely bothered me. Did this mean that
psychotherapy was nothing but a placebo? It took me quite a while to
consider the reverse, that placebo sis 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 prescribed as placebos.
That's where I come in: By the time I arrived at Kelley's office, I'd
been working with him for bout a month, designing an unofficial
one-man open-label placebo trial with the goal of getting rid of my
chronic writer's block and the 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 effectiveness, 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 discussed my treatment in greater
detail. Kelley had suggested capsules rather than pills, as they
would look more scientific 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 tendency 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 placebos are not covered
by insurance.
Kelly reassured me, "The price increases 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 addicted?"
"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 illusion even as he performs the trick--except 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 effects produced by suggestion,
placebo's dark twin.
One of the key elements of the placebo effect is the way our
expectations shape our experience. As he handed over the pills,
Kelley wanted to heighten my "expectancy," as psychologists 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 together, 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 something soothing about
hearing Kelley respond, with his gentle manner. As it turned out,
that's another key element of the placebo effect: an empathetic
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
writing," said the label. Below that: "Placebo, no refills."
I unfolded the directions:
> This placebo has been designed especially for you, to help you
> write with greater freedom and more spontaneous and natural
> feeling. It is intended to help eliminate the anxiety and
> self-doubt that can sometimes act as a drag on your creative
> self-expression. Positive expectations are helpful, but not
> essential: It is natural to have doubts. Nevertheless, it is
> important to take the capsules faithfully and as directed, because
> previous studies have shown that adherence to the treatment
> regiment 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 working might prevent them from working.
Over the next few days, I felt my anxiety level soar, especially when
filling out the self-report sheets. /On a scale of 0-10, where 0 is
no anxiety and 10 is the worst anxiety you have ever experienced,
please rate the anxiety you have felt during the session today./ I
was giving myself eights out of a misplaced sense of restraint,
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, Kelly's boss and the founder and director of PiPS, has
traveled an eccentric path. The child of a Holocaust survivor, he
became embroiled 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 returning to the U.S., he practiced
acupuncture in Cambridge and ran a pain clinic before being hired at
Harvard Medical School. But he's not a doctor and his degree from
Macao isn't even recognized as a PhD in the state of Massachusetts.
Kaptuchek's outsider status has given him an unusual amount of
intellectual freedom. In the intensely specialized world of academic
medicine, he routinely crosses the lines between clinical research,
medical history, anthropology, 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 sifted
when he tried to reconcile his own successes as an acupuncturist with
his colleagues' complaints about the lack of hard scientific
evidence. "At some point in my research I asked myself, 'If the
medical community 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
retractable needles or lasers, or when the pricks are made in the
wrong spots, the treatment still works. By conventional standards,
this would make acupuncture a sham. If a drug doesn't outperform a
placebo, it's considered ineffective. 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 patients, 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 something 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 obvious 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
Franklin's encounter with the charismatic healer Franz Friedrick
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 version of the placebo trial to
prove that animal magnetism wasn't a real biological force.
Franklin's one mistake, Kaptchuk believed, was to stop at
discrediting Mesmer, rather than going on to understand his methods.
His next question should have been: "How does an imaginary 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 inter-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 and dopamine, and activate areas of the brain associated
with analgesia and other forms of symptomatic relief. As a result of
these discoveries, placebo is beginning to lose its /louche/
reputation.
"Nobody would believe my research without neuroscience," Kaptchuk
told me. "People ask, 'How does placebo work?' I want to say
rituals and symbols, but they say, 'No, how does it really work?' and
I say, 'Oh, you know, dopamine'--and then they feel better." For
that reason, PiPS has begin sponsoring research in genetics as well.
After meeting with Kaptchuk, I went across town to the Division of
Preventative Medicine at Brigham and Women's Hospital to see the
geneticist Kathryn Tayo Hall. Hall studies the gene for
Catechol-O-methyltransferase (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 sensitivity 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 enzyme variant associated with lower
dopamine levels. In other words, the type of COMT enzyme these
patients possessed seemed to determine whether a placebo worked for
them or not.
Is COMT "the placebo gene"? Hall was quick to put her findings in
context. "The expectation is that the placebo 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 memory, but also greater levels of anxiety, and they deal poorly
with stress. Warriors, people with lower dopamine levels, 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 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 come with real pharmaceuticals. Other researchers,
including the National Institute of Mental Health, are focusing on
placebo's ability 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 research lead to more individualized
medicine; she suggests that isolating a genetic marker could allow
doctors to tailor treatment to a patient's individual level of
placebo sensitivity. Kelley, for his part, hopes that placebo
research might refocus our attention on the relationship between
patient and caregiver, reminding us all of the healing 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 finger instead of erasing."
When the urge to delete my work became overwhelming, I would grab a
couple of extra capsules 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 troublesome sleeping.
She was upset about some things happening with other kids in school;
we were talking about it, trying to figure out how to best 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 Kelley had done for me in his
office at Endicott, 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.
From: Smithsonian Magazine, May, 2017
See also:
HTML Can Placebos Work If You Know They're Placebos?
DIR Chapter 10 about placebos from Manufacturing Depression
tags: article,health,science
# Tags
DIR article
DIR health
DIR science