The placebo effect: Rarely dramatic, but surprisingly consistent and adjustable

I remember the soft wisp of smoke that would follow my mother around the house. An earthy aroma that lingered for a few moments. She would be holding a small metal sieve with smouldering seeds inside called esfand. A staple of many Iranian homes. The plant – wild rue – has claimed some medicinal use historically, but the practice is mystical: The burning seeds are said to ward off omens and illness.

I’ve burned esfand in my home as well. I don’t personally believe in omens or illness-preventing smoke, but there’s a calming aspect to the ritual. It’s most likely a placebo, but something about the practice has allowed it to survive beyond its Zoroastrian roots, beyond the Islamic expansion, and into the modern age.

The placebo effect is typically viewed as the miraculous healing power of the mind or brushed off as gullible folks imagining a benefit. But the clinical data doesn’t validate either of these descriptions. When the placebo effect is studied in trials, what manifests is rarely fantastical or fantasized. Rather, a small, consistent and tractable response is seen. A placebo can paint someone’s overall experience and nudge it in a direction. How much depends on what and whom you’re studying, and some placebos are better than others.

For example, colour has affected response in several studies: blue and green tablets being more sedating; red and yellow more stimulating. In one trial of a sleeping aid, participants who received the study drug as a blue tablet slept longer than the same drug as a white tablet – a change that was small (around 10 per cent longer sleep duration) but statistically significant.

Capsules also appear more potent than tablets, and placebo injections can be more effective than both. The packaging placebos come in can also boost response, and in one study on chronic headache, placebos were almost 10 per cent more effective in fancy branded packaging than plain.

Aesthetics aren’t the only factor either: In a meta-analysis of peptic ulcer treatment, patients in the control arm (i.e., those who received placebos instead of actual medicine) were eight per cent more likely to have endoscopy proven resolution of their ulcer if they received their placebo four times a day versus two. Like our other results, this was a small but statistically significant difference.

Our emotional state is part of our overall health.

Sleep and headache are one thing, but stomach ulcers? You might be able to explain away some of the difference through trial structure or patient characteristics, but it’s also reasonable to acknowledge that stress response has many physiological consequences, and people receiving a medication regimen four times a day are more likely to feel they’re receiving intensive treatment. Stress response can affect blood pressure, heart rate, neurological activity and a wealth of other processes depending on its intensity and duration. Our emotional state is part of our overall health.

Placebos are also not limited to medicines. Both setting and practitioner are important factors. Many famous placebos and their peddlers started with individual appointments that were emotionally intense and ritualistic. Elisha Perkins would hold his metal tractors against a patient’s body for 20 minutes per spot to “draw out” inflammation and disease. Franz Mezmer’s hypnotic sessions using “animal magnetism” could last hours and were so emotionally taxing that patients were known to exhibit convulsions without even being touched. Interestingly enough, the analyses that exposed both these practices as fraud (in 1799 and 1784, respectively) were milestones in the scientific use of placebo control and blinding.

These examples are not a call to deceive patients or an endorsement of false hope from some “alternative” treatment. The effects were ultimately too small to be meaningful to people truly suffering from a pathology. But they should serve as a warning of how easily we might be misled by hollow treatments with good marketing. They’re also a warning that placebo use in controlled trials should be scrutinized almost as much as the treatment.

But more than anything, this data provides lessons on how to make modern medicine better. People like to understand their care – even if it’s through a cursory explanation or a matching-coloured pill. They respond to patterns and rituals. They benefit from feeling heard and having some control in their care.

We view these acts as niceties that are the first to fall when the system is under duress, but there is a real clinical benefit to them. Using the placebo effect to improve care in these ways is not deception, it’s evidence-based medicine.

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Amir Imani 


Amir Imani PharmD, RPh, is a Hospital Pharmacist and Instructor at the University of Toronto’s Leslie Dan Faculty of Pharmacy.

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