Placebos Work Even When You Know They’re Placebos—Here’s Why

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Mind Over Meds

“Here they are,” John Kelley said, taking a paper bag off his desk and pulling out a big amber pill bottle. Inside were the capsules we’d designed: a magical concoction to treat my chronic writer’s block and the panic attacks and insomnia that always come along with it.

I’ve known Kelley since we were undergrads at Harvard in the early 1980s. Now he’s a psychology professor at Endicott College in Massachusetts and the deputy director of PiPS, Harvard’s Program in Placebo Studies & Therapeutic Encounter. Launched in 2011, 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 2008 survey of 679 American 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—fakes explicitly prescribed as such.

So in 2015, 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 it for maximum effectiveness, colour, shape, size, dosage and time before working. What colour 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 discussed my treatment in greater detail. Kelley 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 composed a set of instructions that covered not only how to take them but also what they were going to do. Finally, we ordered 100 capsules, which cost a hefty $405, though they contained nothing but cellulose. Placebos are not covered by insurance.

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.”

“That’s true.”

“But do you think there’s a chance I could get addicted?”

“Ah, well, now that’s a really 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 they perform 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 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’d written together, which he read to me out loud. Then he asked me 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, about his gentle manner. As it turns out, that’s another key element of the placebo effect: an empathetic caregiver. The healing force, or whatever you want to call it, passes into you from the placebo, but it helps if it starts with 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 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 meant 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, per the instructions, closed my eyes and tried to imagine the pills doing what I wanted them to do. But still, I 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 10, where zero is no anxiety and 10 is the worst anxiety you have ever experienced, please rate how you felt during the session today,” one section read. I was giving myself eights out of a misplaced sense of restraint, though I wanted to give 10s.

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 made me feel a little better, but I didn’t actually get to writing. 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 travelled an eccentric path. He became embroiled in radical politics in the 1960s and studied Chinese medicine in Macau. After returning to the United States, he practised acupuncture in Cambridge, Mass., and ran a pain clinic before being hired at Harvard Medical School. But he’s not a doctor, and the degree he earned in Macau 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?”

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 post-operative patients, for example, prescription pain medications lost up to half their effectiveness when the patient did not know they had just been given a painkiller. A study of the migraine drug rizatriptan found no statistical difference between a placebo labelled rizatriptan and actual rizatriptan labelled 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’s found that the placebo effect is not a single phenomenon but rather a group of interrelated mechanisms. It’s triggered not just by fake drugs 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 aren’t 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 gain a greater understanding of the physiology, PiPS has begun sponsoring research into the genetics of placebo response. After meeting with Kaptchuk, I visited the Division of Preventive Medicine at Brigham and Women’s Hospital to see Kathryn Tayo Hall, a geneticist. She studies the gene for catechol-O-methyltransferase (also called COMT), an enzyme that metabolizes dopamine. In one study, Hall 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’s another layer: worriers—people who have 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 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 used to take to help with pain in her arm from an old injury. “My placebo. The only thing that helped.”

What might the future of placebos look like? Kaptchuk imagines doctors one day prescribing open-labels 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 posits 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 also hopes to refocus our attention on the relationship between patient and caregiver, reminding us all of the healing power of kindness and compassion.

I’d been taking my writing capsules for two weeks when I began to feel an effect. My sentences were awkward and slow, and I disliked them as much as ever, but I didn’t throw them out: I didn’t 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 swallow a couple of extra capsules (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 a situation 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 seemed interested. “Like the ones 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. “Placebos help many people. It helped me, and it will help you.” She took two of the shiny yellow capsules and within minutes was deeply asleep.

Standing in the doorway, I shook a couple more capsules into the palm of my hand. I popped them into my mouth and went back to work.

Next, find out the real reason why women’s pain is often dismissed.