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The placebo effect can be good medicine, for pain and other problems

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“The placebo effect is not magic, but real,” one researcher says.

(Petra Péterffy for The Washington Post)

Catarina Craveiro, a biomedical research technician from Lisbon, had been hobbled by lower back pain from scoliosis since childhood, unable to do much physically and dependent on ibuprofen for relief.

“It really interfered with my life,” she says. “I had bad pain. I wanted to do the same things as my friends, and I was not able to.”

In 2013, she signed up for a clinical trial, “expecting they had some magical drug that would take my pain away,” and was disappointed — and skeptical — to learn that the research would be studying the effects of a medically inert placebo, which looks like a real drug, and is taken like one, but lacks active ingredients. “I didn’t believe it was going to work but gave it a try,” she recalls. “It couldn’t be any worse than my actual situation at that point.”

Today, at 33, she’s pain-free, a competitive kickboxer who now coaches the sport, and mother of two sons, convinced none of this would have been possible earlier. And she’s a believer.

“Our mind is a powerful thing, and that in my subconscious I wanted so badly to feel better, that the basic mechanic action of taking a pill” — even though she knew it was medically inert — “did the job,” she says. “I have no doubt that the willingness to get rid of the pain combined with the taking a pill took my pain away.”

The “placebo effect” is a phenomenon that occurs when a person’s physical or mental health improves after taking what is essentially a sham treatment with no clear therapeutic benefits.

“The placebo effect is not magic, but real,” according to a growing body of research in recent years, says Luana Colloca, director of the Placebo Beyond Opinions Center at the University of Maryland’s school of nursing in Baltimore. “Years ago this sounded futuristic. Now it is part of science.”

Historically, the placebo effect typically was seen in the context of deception — patients didn’t know they were receiving an inert substance but still got better because they believed that they would.

Bioethicist Arthur Caplan, for example, recalls one of the first cases he consulted on decades ago when a physician sought his advice about giving low-dose aspirin — essentially a placebo in this instance — to an otherwise healthy woman suffering from exhaustion. The doctor feared if he did nothing the single mother of four, who worked two jobs — bus driver and office cleaner — might go elsewhere seeking amphetamines, stimulants that can be addictive. Abusing them can potentially cause dangerous physical symptoms and psychotic effects.

Caplan approved of the idea, and, while the dishonesty probably was questionable, the sham treatment worked, restoring the woman’s energy and relieving her fatigue.

“I didn’t like the lack of transparency, but I think using a no-risk placebo to avoid an addictive drug was right,” says Caplan, professor of bioethics at the NYU Grossman School of Medicine. “She came back happy on follow-up two months later.”

Researchers now believe that the placebo effect can happen even when patients know they are getting a placebo, as Craveiro did, a process known as “open-label use.” For this reason, experts believe clinicians should include them in mainstream medical practice, but be entirely truthful with patients.

“You never tell a patient it’s going to work,” says Ted Kaptchuk, professor of medicine at Harvard Medical School and director of the program in placebo studies and the therapeutic encounter at the Beth Israel Deaconess Medical Center. “Honesty is critical. We make it crystal clear: ‘This is a placebo, no active ingredient, [it’s ] like a sugar pill. It might work, it might not work. Improvement can be quick or gradual.’ It’s a crazy idea, but we have evidence that it works some of the time.”

Research has found that placebos can alleviate many complaints modulated by the brain, for example, pain, anxiety and depression, and fatigue, among others. “Placebos don’t shrink tumors or lower cholesterol. They don’t cure the common cold,” Kaptchuk says. “But they do relieve symptoms for things such as chronic pain, cancer-related fatigue, osteoarthritis pain. It doesn’t get rid of the arthritis, but it can get rid of the pain,’’ which is controlled by the brain.

Experts stress, however, that placebos only seem to work in the context of a supportive and trusting patient-doctor relationship. This is critical as to why patients feel better, they say.

“It’s the empathy, attention, emotional support, thoughtfulness, acts of decency, laying on of hands that goes on between a patient and doctor,” Kaptchuk says. “You can’t just take a Tic Tac, a sugar pill. It doesn’t work without a doctor.”

Cláudia Ferreira de Carvalho, the clinical and health psychologist who conducted the study that helped Craveiro, agrees. “Open-label placebo is much more than prescribing inert pills or treatments,” she says.

While scientists have identified conditions that are more likely than others to respond to the placebo effect, they still can’t explain why it works in some patients but not others.

‘This is a really important question,” Kaptchuk says. “There is no consistent and reliable picture of which patients respond. The research is full of contradictory answers. It’s not gender, age, severity of condition, and there are no personality qualities that point to who will respond or not. … This is why the placebo is so mysterious, and so difficult.”

Placebo researchers think placebo treatment could have an important role in medical practice. One way to introduce it, they say, might be to add it to a patient’s current therapy — patients would take their regular medicines while adding a placebo, a process known as “dose-extending placebos.”

The result might end up reducing the dosage of their regular medications or even wean patients from them entirely. This scenario could diminish the side effects that often accompany both long- and short-term drug use, experts say, and also could lower the addiction risk from opioids.

“The main goal would be to combine the actual effect of a drug with a proven efficacy with the actual placebo effect produced by the brain when the patient expects the drug to work,” says Grégory Scherrer, associate professor of cell biology and physiology, and researcher in the neuroscience center at the University of North Carolina School of Medicine.

“To do this, clinicians need to behave and deliver the treatment in a way that maximizes expectations. Certainly this could enable patients on drug therapy with side effects, including patients taking potentially addictive opioids, to have a safer alternative with the same positive results,” adds Scherrer, whose research recently discovered what he says is a previously unidentified circuit in the brains of mice that produces placebo effects that could accelerate understanding the response in humans. “Clinicians could tailor and fine-tune their treatment plans for many of their patients with this in mind.”

Historically, placebos have been used as “controls” in some studies to test a new drug or treatment when there was no standard treatment available. The goal is to determine the efficacy of a new therapy by comparing it to a placebo, with all participants unaware of which one they were receiving. The placebo effect kicked in if both groups got better, potentially muddying the results.

Sometimes researchers would try to avoid that confusion by including a third group that got no treatment at all and then compare all three. But bioethicist Caplan points out that “most studies don’t involve a placebo and are run against existing therapy,” and when placebos are used, “the new drug needs to do better than the placebo, but the placebo effect often is not zero,” he says.

Brain imaging suggests that the placebo effect works by prompting certain regions of the brain to secrete endorphins — neurotransmitters or chemical messengers that can relieve pain, stress and elevate mood, Colloca says.

Brain imaging suggests that the placebo effect works by harnessing the body’s natural abilities to relieve pain, which include prompting certain regions of the brain to secrete endorphins — neurotransmitters or chemical messengers that can relieve pain, stress and elevate mood, Colloca says.

“We release endorphins when we expect to feel better, and this mindset contributes to the perception of reduced pain and other symptoms, such as anxiety and fatigue,” Colloca says. “The improvement of symptoms is related to activation in the brain regions linked to cognition, including expectations.”

However, the mechanisms of action can differ among individuals “which explains why some patients benefit and others don’t,” she adds.

The placebo effect “is associated with real changes in the brain that contribute to pain relief,” says Lauren Atlas, chief of the National Institutes of Health’s National Center for Complementary and Integrative Health’s section on affective neuroscience and pain, who points out that most placebo effect research has focused on pain, including several shown to be effective for lower back pain.

Karen Knight, an interventional pain physician in Denver, for example, conducted a small study in patients with chronic lower back pain with intravenous injections of a placebo. The procedure produced significant relief after one month — which lasted for at least one year — and also improved symptoms of depression, anger and impaired sleep, which are “the overlapping symptoms of suffering,” and “what is what makes a difference in people’s lives,” Knight says.

The trial conducted by Carvalho and her colleagues found a 30 percent reduction in their usual pain and when pain was at its worst in the placebo group after three weeks of placebo pills taken twice a day along with their regular treatments, compared to reductions of 9 percent and 16 percent respectively in the group that only received its regular routine care. The relief persisted for at least five years, according to a follow-up study, which also found that the use of pain killers had decreased from 80 percent to 31 percent in the placebo group.

Unlike most scientists, who believe the placebo response depends on patient expectations, Kaptchuk places less emphasis on expectations and more on the biological processes that take place in the brain. “It’s not in your mind, but in your brain,” he says. “It’s not about what you think. Open-label placebo patients don’t have to believe it will work, yet it does.”

He thinks the brain continues to send pain signals even after the body has healed and the placebo “in some patients, some of the time, gives the brain an opportunity to adjust and turn down the [pain] signals that are reporting a fire when there no longer is one,” he says.

For patients like Craveiro, however, it matters little how it works — only that it does. With her pain now gone, she no longer needs to take ibuprofen — or a placebo. “It really worked,” she says. “The whole experience was life-changing for me.”

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(Abbey Lossing for The Washington Post)

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