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# 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: | |
Can Placebos Work If You Know They're Placebos? | |
Chapter 10 about placebos from Manufacturing Depression | |
tags: article,health,science | |
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