Open-label placebos are like a magician explaining the illusion even as he performs the trick.
Matthew Cohen for Reader's Digest
“Here they are,” John Kelley said, taking a paper bag off his desk and pulling out a big amber pill bottle. Inside were the pills we’d designed: a magical concoction put together to treat my chronic writer’s block and the panic attacks and insomnia that have always come along with it.
I’ve known Kelley since we were undergrads together. Now he’s a psychology professor at Endicott College in Massachusetts 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 them out for centuries, and patients have been getting better, whether through the power of belief or suggestion—no one’s exactly sure. Even today, when the use of placebos is considered unethical by many medical professionals, a survey of 679 doctors showed that about half of them prescribe medications such as vitamins and over-the-counter painkillers primarily for their placebo value.
Interestingly, the PiPS researchers have discovered that placebos seem to work well even when a practitioner doesn’t try to trick a patient. These are called open-label placebos, or placebos explicitly prescribed as placebos.
So I had turned to my old friend for help with my writer’s block. “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 also made 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 also what they were going to do. Finally, we’d ordered the capsules, which cost a hefty $405, though they contained nothing but cellulose. Placebos are not covered by insurance. Find out the 49 secrets your pharmacist isn’t telling you.
Kelley 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.”
“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.
One of the key elements of the placebo effect is the way our expectations shape our experience. As Kelley handed over the pills, he wanted to heighten my expectancy, as psychologists call it, as much as possible. He showed me 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 whether 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 a notebook. Take two capsules with water ten 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 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. I became worried that my anxieties about their not working might prevent them from working.
Over the next few days, I felt my anxiety level soar while at work and when filling out the self-report sheets. On a scale of zero to ten, where zero is no anxiety and ten 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 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. Learn how placebos may be almost as effective as antidepressants in teens.
Ted Kaptchuk, Kelley’s boss and the founder and director of PiPS, has traveled an eccentric path. He became embroiled in radical politics in the 1960s and studied Chinese medicine in Macao. After returning to the United States, he practiced acupuncture in Cambridge, Massachusetts, and ran a pain clinic before being hired at Harvard Medical School. But he’s not a doctor, and the degree he earned in Macao isn’t recognized here.
Kaptchuk’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,” he told me. His interests shifted 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?’ ”Matthew Cohen for Reader's DigestLike real pharmaceuticals, placebos actually trigger neurochemicals in the brain.
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 the sham treatment group 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.”
Working with Kelley and other colleagues, he has found that the placebo effect is not a single phenomenon but rather a group of interrelated 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 magnetic resonance imaging, which maps brain activity by detecting small changes in blood flow, shows 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.
“Nobody would believe my research without the neuroscience,” Kaptchuk told me. “People ask, ‘How does a placebo work?’ I want to say by rituals and symbols, but they say, ‘No, how does it really work?’ and I say, ‘Oh, you know, dopamine’—and then they feel better.”
To better understand the physiology, PiPS has begun sponsoring research into the genetics of placebo response. After meeting with Kaptchuk, I went across town to the Division of Preventive 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 one study, she found that the type of COMT enzyme patients possessed seemed to determine whether a placebo would work for them.
Is the COMT gene “the placebo gene”? Hall was quick to put her findings into 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 personality types as one might expect: Worriers tend to be more sensitive to placebos; warriors tend to be less sensitive.
I told Hall, 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 placebos look like? Kaptchuk talks about doctors one day prescribing open-label placebos to their patients as a way of treating certain symptoms without the costs and side effects that can come with real pharmaceuticals. Other researchers are focusing on placebos’ ability to help patients with hard-to-treat symptoms such as nausea and chronic pain. Still others talk about making conventional medical treatments even more effective by using the symbols and rituals of health care (such as getting an injection from someone in a white lab coat) to add a placebo effect.
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. Citing the research showing that an empathetic caregiver is key, Kelley hopes to refocus our attention on the relationship between patient and caregiver, reminding us all of the healing power of kindness and compassion.
After I took my magic pills for two weeks, the writing capsules seemed to kick in. I found my sentences were awkward and slow, and I disliked 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 such as “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 was 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 Kelley had done for me in his office, 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.
Next, find out some of the most amazing medical breakthroughs of the last year.
Smithsonian (May 2017), Copyright © 2017 by Smithsonian Institution. Reprinted with permission from Smithsonian Enterprises. All rights reserved. Reproduction in any medium is strictly prohibited without permission from Smithsonian Institution.