Who’s Afraid of the Placebo Effect?

Jeremy Howick admits that there was a time when he thought that it was all “gobbledygook.” A professor of empathic healthcare at the University of Leicester, Howick used to be a competitive rower, but suffered debilitating bouts of anxiety before every race. A coach suggested he try yoga as a means of calming his mind. Despite his skepticism, he felt immediately better at the end of just one session. “That got my academic mind whirring,” he says. “I needed to investigate just how the mind and body are not so separate.”

Over the subsequent years, Howick became, despite all the raised eyebrows, a leading researcher into the placebo effect — that’s when a substance leads to positive health results even if it’s devoid of any pharmaceutical content. It works to make you better when, scientifically speaking, it shouldn’t.

Most of us are familiar with placebo’s modern role in drug testing. In order for a new drug to be approved, it typically has to be proven superior to that of a dummy drug, which is administered unbeknownst to members of a control group.

“Placebo studies were fringe just a couple of decades ago. It was considered wacky by the mainstream,” says Howick, whose book The Power of Placebos came out last year. “But studies have gradually taken it into the mainstream. It can’t be dismissed as ‘not real’ anymore. In fact, we’re building sufficient knowledge about it now that, I’d argue, it’s time for a revolution in the placebo effect that sees entrepreneurs rather than academics take its potential forward into implementation.”

Is a Placebo Revolution on the Horizon?

Howick’s wish is already in motion. The Society for Interdisciplinary Placebo Studies was established five years ago, with its annual conference wrangling together new thinking on the topic. But according to Kathryn Hall, assistant professor of medicine at Harvard Medical School and author of Placebos, her “strong sense” is that placebo research is still pretty fringe. “I remember my mentor saying that when he would talk about placebos there would be nervous laughter,” she says. “And still not enough people take the idea seriously.”

“The ‘placebo effect’ still gets used by some people in a derogatory way,” Howick adds, “because medicine has this undue focus on the bio-mechanical idea of the body — that it’s just a very complicated machine. But the fact [of the placebo effect] calls into question a lot of our drug-oriented medical training.”

Think of the body more as integrating the physiological and the mental; these elements interact in ways we don’t yet fully grasp, somewhere at the intersection of epigenetics, neurobiology and psychology. The placebo effect involves the release of feel-good neurotransmitters, plus increased activity in parts of the brain related to mood and emotions. It appears to be the product of our positive expectations and some Pavlovian conditioning.

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We Respect the White Coat

Put another way, it’s a response to the culture of rituals we in the developed world have placed around medicine, from the processes we follow in seeking medical attention (making an appointment, traveling for consultation, undressing for examination, being given a prescription, and so on) to the imagery that’s all imbued with (white-coat authority, stethoscopes, clipboards, the Muzak).

As Hall asks, is the fact that so many of us start to feel better as soon as we make an appointment just regression to the mean? That’s to say, many of us seek medical help when an illness is at its zenith, so subsequent recovery might be expected? Or, as some studies suggest, is that the placebo effect in action? “The idea that all we take from that whole process is chemicals from pills is myopic,” she asserts. The rituals of “healthy living” — focusing on diet, exercise, relaxation, mental wellness and so on — may provide a placebo effect above and beyond those behaviors’ measurable effects, too.

Howick points out that prescribed drugs often have minimal pharmaceutical effect in treatment, anyway. Nonetheless, taking a pill does have a placebo effect. And having an injection — which is more invasive, more “medical” — has a greater placebo effect than a pill. As for taking those drugs that do work, it’s been found that these can in some cases be quietly replaced with a placebo with no change in health outcomes. Thus, pharmaceutical and placebo effects start to look more intertwined, bedfellows rather than rivals, collaborators rather than competitors.

“After all, most of our thoughts are subconscious, so no matter what we consciously think, even if we’ve just had a good experience with our doctor on the last occasion then the body will respond to that the next time,” Howick argues. “And it responds even if the doctor tells the patient that they’re giving them a placebo treatment.”

The Power of Placebo

Yes, as if the placebo effect wasn’t strange enough, it can work even when you know, categorically, that there’s no active drug in your treatment; that is, if you take what’s called an “open label non-deceptive” drug, the body can nonetheless be tricked into thinking it’s getting some healing effect.

And even when there isn’t any real surgery in your surgery, as with so-called “sham surgery” (put the patient under, wait a while, then bring wake them up) such “physical” interventions have been shown in some specific instances to be as effective as the messier, more dangerous kind. Sham keyhole surgery for shoulder impingement or knee osteoarthritis are two cases in which it has seemed to work — just because we’re convinced something has been done to help.

Fabrizio Benedetti, professor of neurophysiology at the University of Turin Medical School, explains that, given pause to think about it, we all know from our daily lives that the placebo effect is a real thing. He draws an entertaining parallel: watching movies.

“Movies are powerful triggers of strong emotional responses, ranging from love and tears to heartache and fear,” he says. “These reactions take place despite the fact that the viewer is aware that everything is a fiction. Considering human evolution and biology, this is quite surprising, as these reactions are supposed to have evolved for social interaction and survival. The fact that they take place during movie viewing even though neither social interaction nor survival is at stake indicates that emotional and behavioral responses can be elicited unconsciously — automatically — by merely simulating situations of real life.”

There Are Limits to What Placebos Can Do

This is not to suggest that the placebo effect is some underappreciated mystical force, capable of healing anything if a patient can just master it.

The placebo effect has positively aided the treatment of many illnesses, particularly those requiring pain management or with a heavy element of stress to them: depression, PTSD, hypertension, fatigue, IBS, asthma, diabetes and other inflammatory diseases. But it cannot mend a broken leg, fight a bacterial infection or drive cancer into remission. Therein lies the danger of blaming patients for not having a sufficiently positive mindset (as cancer victims are sometimes encouraged to have). You can’t “mentally” cure yourself of physical problems.

Potential Applications of Placebo

How might the placebo effect be better recruited and deployed throughout the medical field? Howick points out that for generations we’ve spoken of doctors with a good “bedside manner.” It’s accepted (and proven) that empathy improves health outcomes. Likewise, a lack of such empathy may be a root cause of medical errors; a doctor brushing off a patient’s concerns could prompt for what’s been called the “nocebo” effect — in which there’s a negative outcome due to the belief that some intervention has caused harm.

“We have in play this false dichotomy between being a good doctor and a kind doctor,” says Howick, adding that modern healthcare systems — even those that tend to think of patients more as customers — put in place all sorts of barriers to actively implementing the placebo effect through simple kindness. For instance, there’s immense pressure on the time doctors can spend with patients, plus an overwhelming focus on paperwork and bureaucracy over actual doctoring.

By minimizing the placebo effect, we’re privileging the pharmaceutical industry and the medical establishment — we’re justifying all the money that goes into it. But nobody wants to rock the boat.
– Kathryn Hall, assistant professor of medicine at Harvard Medical School

We might need to make a less dismissive assessment of alternative medicines, too. For all the evidence that they might not stand up to scientific analysis — the liquids used in homeopathy, for example, are so dilute as to have no active ingredient at all — could they actually be effective in the way traditional medicines are not because they simply make better use of the placebo effect? Might those people who use alternative medicines be better primed for this effect to work precisely because they start out with a belief in their efficacy?

“I don’t like the term ‘alternative medicine’,” says Howick. “For me, medicine is evidence-based or it’s not. Of course there are quacks. But perhaps the fact is that alternative medicine practitioners are just better at evoking the placebo effect. Their philosophy aligns more with the science of placebos. It’s not that they’ve used crystals. It’s that they have given more time, attention and consideration to their patients, and that has a positive effect. All this calls into question a lot of the fundamental tenets of modern medicine.”

“Sure, alternative medicine can be insidious,” agrees Hall. “But to say acupuncture works for some people and not others is also true of aspirin. Why take away something that helps people? One person’s placebo may be another person’s ‘You’re wasting your money’ but I’m not sure where the equipoise [between those positions] lies.”

Big Pharma Isn’t a Fan

Fresh consideration of the placebo effect is highlighting other challenges to the medical establishment, too. Naturally enough, pharmaceutical companies don’t tend to want the preeminence of drug-based treatment questioned. “It’s hard to build interest in the placebo effect in part because you can’t patent it,” Howick points out. “There’s no money to be made from it.”

And yet, a more conscious and constructive use of the placebo effect could allow for a reduction in drug use. As he notes, “Modern medicine may be the closest thing we have to a miracle, but we tend to use too many drugs and forget that [unlike placebos] they also have deleterious side effects.”

“By minimizing the placebo effect, we’re privileging the pharmaceutical industry and the medical establishment — we’re justifying all the money that goes into it,” argues Hall. “But nobody wants to rock the boat. By definition, with the current system, we’re setting up Phase 3 [advanced testing on a massive scale] clinical trials to fail by setting up expectations that drive a placebo response. We have drugs that people have done amazing testing on, demonstrated how they work, shown them to be safe to go into humans and yet which turn out to be no better than placebo. We have to ask why. What is it that we’re missing?”

The use of placebo “dummy pills” in the clinical trials of new drugs may long have been the gold standard, but Howick contends that placebos should not be used, if only because it can keep potentially useful drugs out of the doctor’s armory. He cites, by way of example, that it’s been known for decades that certain steroids reduce the effect of alcohol-induced liver disease; but these steroids cannot beat the placebo effect in trials and so can’t be prescribed to this end. Placebos are in many ways the bane of pharmaceutical companies, which is why some have stopped looking for drugs to treat depression and chronic pain. It’s just too hard and expensive to beat the placebo effect.

We’re Left With Many Questions

It’s a messy, politically-charged situation improved not just by the advance of knowledge, but — perhaps trickier still — by a profound change of values, too. There is much yet to discover.

“What we need to know today is where, in which medical condition, in which circumstance, and with which mechanisms placebos work,” says Benedetti. “We need to map the placebo effect across different medical conditions and therapeutic interventions.”

This would help answer some key questions: Is it actually a biological phenomena? Why is it a response for one symptom but not another? Why in one person but less so another? Is it their personality, brain anatomy, genetics, something else?

“We’ve come a long way in our understanding of the placebo effect over the last 20 years and could well be in a place now where we will know a lot more in the next 10,” says Hall. “How much [the medical establishment] will listen to that is a different question. People get giggly and awkward about the placebo effect. But it’s not helping not to talk about it.”