When Linda Buonanno was invited to take part in a trial where she would knowingly be given a placebo, she wasn’t hopeful. By that stage, the 57-year-old medical assistant had suffered excruciating symptoms of irritable bowel syndrome (IBS) for 10 years. “I thought, ‘A placebo study? That’s a sugar pill – that’s not going to work.’ ”

While she scoffed at the idea, she was also “desperate” for relief. “I used to keel over in cramps,” she says. “I’d have sharp pain and … had to lay down and couldn’t leave the house.” Eating exacerbated her pain, so Linda would starve herself during the day for work and only eat in the evening. “If I wanted to go dancing on a Sunday night, I’d have to stop eating by Friday.”

Four days after taking the first placebo pill, Linda, from Massachusetts, found her symptoms resolved. “I thought to myself, ‘This is impossible, there’s no way a sugar pill could get rid of this.’ ”

When the trial ended three weeks later, Linda was distraught. She begged her doctor for more placebos, to no avail. Her symptoms returned less than a week later. Her local doctor gave her medicine to help with the cramps, which provided only short-term relief, but no further treatment. Once again, her symptoms wreaked havoc on her life.

Last year, Linda, now 71, was invited to be part of a further placebo trial, which remains ongoing. Again, it has transformed her life. She can eat what she wants, go dancing, or to the movies, and spend full days out and about, symptom-free. 

Linda’s grateful for the relief, but remains baffled as to why a placebo works. “I don’t know, I really don’t know,” she says. “I had to wait all this time to get my life back together and this is not even a medication – I can’t believe it.”

Associate Professor Damien Finniss understands it. The clinician and researcher from the University of Sydney has been studying placebos – inactive or inert substances, with no physiological qualities – for more than 15 years. He is also the chair of the International Association for the Study of Pain group on placebo.

Rather than simulating a therapeutic ritual, he says taking a placebo is therapeutic in its own right, that “something in the interaction [between patient and caregiver] triggers endogenous mechanisms and that means people feel improvement”. That “something” is known as the “placebo effect” but Finniss says that rather than constituting a singular effect, there are many.

One of the effects may be attributable to patient expectations, says Associate Professor Ben Colagiuri of the school of psychology at the University of Sydney. He says if patients are given a placebo in a “nice and empathic way and told it might help”, such positive reinforcement may account for their physical improvement.

Classical conditioning may also play a part. Patients may feel better because their issue has been “medicalised”. “It could be the case that going into these medical environments, or swallowing a pill itself, has some conditioning associated with it,” Colagiuri says. “And when we do that, even when we know it’s not an active treatment, it’s triggering certain responses within our central nervous system.”

Those responses involve various chemicals and neurotransmitters, such as endogenous opioids, endogenous cannabinoids and dopamine, Finniss says. Whenever you take a tablet for pain relief, your body releases such chemicals – dubbed the “body’s own painkillers” – in anticipation, thus naturally reducing discomfort.

That effect can be seen in everyday life, he notes, such as when you pop a pill for a headache. “Your brain starts to change the way the pain is processed before the drug’s actually absorbed into your blood.” Such effects aren’t simply psychological. Colagiuri says physiological responses, such as heart rate and skin conductance, are measurable.

Placebos have been recorded in the medical literature for about 200 years. Finniss says doctors would sometimes use them as a sham treatment in a bid to please patients. When randomised controlled trials (RCTs) began, placebos were used as a control in a trial, to compare how effective a certain active treatment was against one that was known to do nothing. Traditionally, such studies were blinded, meaning the patient knew they would receive either an active treatment or a placebo, but did not know which it would be.

In blinded studies, patients receiving placebos sometimes showed improvement. Such results were seen as “nuisance variables” or “bogus responses”, says Colagiuri. The patient was assumed to be merely claiming to feel better. And yet such effects persisted in studies.

Recently, research has found that, as experienced by Linda Buonanno, even knowingly taking a placebo can be effective. Such studies are known as “open label” trials, and though they are in their infancy, with less than a handful of such trials conducted worldwide, Finniss says the results are promising.

He credits researcher Ted Kaptchuk, professor of medicine and professor of global health and social medicine at Harvard Medical School, and his 2010 study of IBS – in which Linda took part – for igniting new interest in open label studies. That work, published in the journal of the Public Library of Science, PLOS One, concluded that taking a placebo was more effective at relieving symptoms of IBS than doing nothing.

“I didn’t think it would work,” says Anthony Lembo of the Beth Israel Deaconess Medical Center, senior author of the paper. “I felt awkward asking patients to literally take a placebo. But to my surprise, it seemed to work for many of them.”

Now a new open label study, published in Nature Scientific Reports in February, adds further weight to evidence backing placebos. The results showed cancer survivors given placebos experienced a 29 per cent improvement in fatigue severity and a 39 per cent improvement in the extent to which fatigue disrupted quality of life, compared with those who received no treatment.

Some researchers urge caution, warning that while placebos may bring symptomatic relief, there’s a risk that, in the meantime, underlying disease processes may worsen.

This was reflected in research published in The New England Journal of Medicine in 2011. It describes asthma patients being either given treatment with an active inhaler, two possible placebos, or no intervention. While patients reported similar improvements if they received either the active inhaler or the two placebos, their lung function tests improved most when using active treatment.

It is clear there are ethical considerations when considering placebos. According to a National Health and Medical Research Council (NHMRC) spokesperson, in Australia placebos are deemed ethically unacceptable when other treatment has already been clearly shown to be effective, or if there is known risk of significant harm in the absence of treatment. There have been no open label studies in Australia to date.

“As a general rule, it would compromise the objective of using a placebo in a research project if patients are aware of being given the placebo,” said the NHMRC spokesperson, who added it would be difficult to predict whether they will play a greater role in the future of clinical trials.

Finniss is hopeful of overcoming such obstacles, but says that, first, people need to better understand placebos.

He stresses that the placebo effect doesn’t require a pill changing hands to work. “Most people don’t really understand this, doctors included … that you don’t have to give a dummy tablet to turn on the placebo mechanisms.” Rather, he says, it’s the power of the overall interaction that activates the effect.

He also hopes attitudes towards the placebo effect shift, particularly in the medical community. When he started in the field he met resistance from medical professionals, both in developing understanding and garnering support for research. Over the past decade or so, he’s pleased to find medical thinking has “changed quite dramatically”.

Patients have proved much more willing to embrace placebos. In a recent blinded trial, as yet unpublished, Finniss witnessed that firsthand. The trial compared a placebo injection for lower back pain with an injection of active treatment.

Many patients told him they believed they were receiving the placebo, yet reported significant reduction in pain. He says patients are “very open” to the idea that internal processes of the mind – the placebo effect – can play an important part in feeling better.

“The challenge now is to actually get the trials done.”

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