By Christian Jarrett

The placebo effect usually triggers an eye-brow raise or two among even the most hard-nosed of skeptics. We may not be able to forecast the future or move physical objects with our minds, but the placebo effect is nearly as marvellous (Ben Goldacre once called it the “coolest, strangest thing in medicine”).

The term “placebo effect” is short-hand for how our mere beliefs about the effectiveness of an inert treatment or intervention can lead to demonstrable health benefits and cognitive changes – an apparently incontrovertible demonstration of the near-magical power of mind over matter. It’s not literally magic, of course. Our beliefs are the subjective echo of physical processes in the brain – and it’s this constellation of neurochemical and electrical events , and their downstream effects, that underlies the placebo phenomenon (in some cases the placebo effect can also be interpreted as a form of conditioned response, in which a learned physiological reaction occurs in the absence of the original trigger).

There is another angle to this topic. To research psychologists, the placebo effect isn’t always a phenomenon of wonder, but a methodological nuisance. Researchers must go to extreme lengths to rule out the influence of participant expectations, so as to establish which observed effects are truly attributable to an intervention.

Here, in a celebration of the mysterious and maddening placebo effect, and to help inspire future research into this most fascinating aspect of human (and animal) psychology, we digest 10 amazing placebo-related findings:

The Placebo Effect Works Even When You Know It’s A Placebo

For the placebo effect to occur, it’s usually considered that deception is required – tricking the patient into thinking that an inert treatment is actually a powerful drug or similar. It’s this need for trickery that has long meant the deliberate inducement of placebo effects in mainstream medicine is seen as unethical. Nearly ten years ago, however, researchers showed that people with irritable bowel syndrome showed greater improvement after being given a so-called “open placebo” that they were told was completely inert, as compared to receiving no treatment. Presumably some residual belief and expectation of an effect survives being told that the treatment is physically impotent (or there is a condition response to the placebo that does not require positive beliefs). More recent research has since shown benefits of open placebos for many other conditions including back pain and hay fever. Open placebos “bypass at least some of the conventional ethical barriers” to the clinical use of placebos, according to some experts. Others however have highlighted the lack of suitably robust research in this area, and it’s worth noting there have been some null findings – for instance, open placebos failed to speed up wound healing.

Branding, Colours and Medical Paraphernalia Can All Boost The Placebo Effect

Putting aside open placebos, there’s evidence that different forms of deceptive placebo vary in their effectiveness. The more powerful we imagine their effect will be, the larger the benefit. This means that four placebo pills have a larger effect than two; and placebo injections (filled with nothing other than saline solution) are more powerful than pills (in fact, in the context of osteoarthritis, a placebo injection was found to be more effective than a real drug). Also – depending on the condition being treated – pills of certain colours and descriptions are more effective than others, such as blue placebo pills making better sedatives than pink ones, and branded placebo pills being more effective than those without any labelling. The influence of the credibility of a given placebo on its subsequent effectiveness may help explain one of the most astonishing demonstrations of the placebo effect that I’ve come across. It involved “placebo brain surgery” – and what could elicit a greater hope for a treatment effect than the elaborate paraphernalia and protocols involved in experts operating on your brain? Specifically, the research showed that patients with Parkinson’s Disease who undertook a form of placebo brain surgery (supposedly, but not really, involving the injection of stem cells) showed greater symptom improvements than those patients who received the stem cell treatment, but didn’t think they had. “The placebo effect was very strong in this study,” the researchers said, “demonstrating the value of placebo-controlled surgical trials.”

Some People Are More Prone To The Placebo Effect Than Others

Certain personality traits are associated with it being more likely that a person will experience the placebo effect. This is logical since the placebo effect depends on our beliefs and expectations, which some of us may subscribe to more readily and enthusiastically than others. Among the results in this area, optimists are more responsive to analgesic placebos, as are people who score higher for emotional resilience and friendliness (this last finding may relate to the social dynamic involved in the elicitation of the placebo effect by physicians). Curiously, the traits related to placebo response vary according to the condition being treated – in the context of stress, for instance, one study found it was the more pessimistic and less empathic participants who showed a greater placebo response. Whereas personality traits appear to play an important role in the placebo effect, the evidence to date suggests that age and gender are largely irrelevant.

Some Doctors Are Better At Inducing The Placebo Effect Than Others

As placebo effects depend on the patient believing in the power of the treatment being given to them, it follows that some doctors will be better placed to reinforce this hope and expectation than others. Research backs this up: a study that involved a placebo injection for the treatment of an allergic reaction found that symptom improvement was greater when the injection was given by a doctor conveying warmth and confidence. Feelings of similarity toward one’s doctor may also be relevant: another study found that subjective pain was lower after a medical procedure when participants thought they’d been paired with a doctor who shared the same values and personal beliefs as them.

The Placebo Effect Isn’t Just About Pain Reduction – It Can Boost Creativity And Cognitive Performance Too

We usually think of the placebo effect in the context of medical interventions and especially pain relief. However, there is growing evidence that the effect can also work in other ways, including enhancing our physical and mental performance. In terms of athletic abilities, various studies have shown placebo effects on speed, strength and endurance (in a placebo-like study, researchers asked cyclists to train to complete exhaustion and found they were able to persist significantly longer when their clocks had been secretly tampered with to make them run slow).

In relation to creativity, one study found that people who smelt an odour that they were told boosts creativity went on to excel at tests of their creative performance as compared with a control group who smelled the same odour but weren’t told it had any special benefits. Another experiment involved participants receiving placebo non-invasive brain stimulation and performing a learning task. The placebo group thought their brains had been stimulated by a mild electrical current – in reality they hadn’t – and they were led to believe that this stimulation would boost their mental function. The placebo participants were subsequently more accurate in the learning task, and showed steeper reductions in their reaction times than control participants. “We conclude that experimentally induced expectancy can impact cognitive functions of healthy adult participants,” the researchers said.

There’s Even Such A Thing As Placebo Sleep

There is almost no end to the ways that the placebo phenomenon can manifest. In one particularly novel instance researchers tricked participants into thinking they’d had more sleep than they actually had, and then observed how this affected their performance the next day. The researchers achieved this deception by wiring their participants up to various physiological measures and then giving some of them false feedback on how much REM sleep they’d had. After hearing that they’d had an impressive amount of sleep, participants performed better on tests of language and arithmetic. Other imaginative examples and manifestations of the placebo effect include the study that showed health gains among hotel cleaning staff who had been reminded that their work counts as exercise, including in terms of improvements to their weight, body mass index, body-fat, waist-to-hip ratio and blood pressure. Another intriguing research finding, which might be explained by a kind of placebo effect, was that people who believe they exercise more than their peers tend to live longer, regardless of how much they actually exercise.

Animals Seem To Experience The Placebo Effect Too

It is common in drug trials involving animals to compare an active treatment against a placebo, similar to the procedure in human drug trials. And when this is done, researchers have often observed that a significant number of animals in the placebo group show a treatment response, such as happened in a trial of an anti-seizure medication for dogs, and in a dietary intervention for muscle stiffness in horses. The problem with interpreting these kind of findings is that it’s possible the placebo effect really lies with the owners, who may interact with their animals differently when they believe they are receiving medial care or nutritional supplements.

However, the argument that animals can demonstrate a kind of placebo effect is irrefutable in the context of lab studies involving rodents – in this case, researchers have paired an active drug, such as morphine, with a particular taste or smell, and then shown that the analgesic effect still occurs when the same taste or smell is repeated but without the drug. In this case the placebo effect is arising from a conditioned response rather than the animals’ expectations, but this is probably part of the placebo phenomenon in humans too. As Edward Ernst told BBC Earth: “A major chunk of what we believe constitutes the placebo effect has been in fact discovered in animals.”

The Placebo Effect Has An Evil Twin

If the placebo effect occurs simply because you believe a given treatment will be beneficial, it follows that if you have negative expectations, this could result in a worsening of your symptoms. That’s exactly what researchers have found and they’ve called this the “nocebo effect”. The placebo effect’s twin is not to be sniffed at either. A meta-analysis in the context of analgesia (in which some participants are told that an inert cream or pill leads to increased pain in some people) found that the nocebo effect is roughly similar in size to positive placebo effects.

Intriguingly, nocebo effects can even occur in the presence of real pain-relieving medications, not just inert treatments – in one study, participants were told that their pain would increase after an analgesia treatment was stopped. The physiological effect of the analgesia would normally persist, however in these participants it ended abruptly, as if the negative expectations had cancelled out the genuine analgesic effect. The real-life implications of these kind of findings are obvious – if nothing else, it’s probably worth taking care when you read the side-effects leaflet that came with your latest prescription.

The Placebo Effect Is A Bit Of A Pain For Many Psychology Researchers

The placebo effect is fascinating in its own right, but for researchers interested in establishing the efficacy of psychological interventions, it can be maddening. The influence of expectations on our thoughts, feelings and behavior is so powerful and pervasive that it complicates the interpretation of many studies, unless they are very carefully designed. In their 2013 paper titled “The Pervasive Problem With Placebos In Psychology“, a team led by Walter Boot at Florida State University argued that in fact many psychology studies (on things like brain training, expressive writing and internet therapy) do not do enough to match participants’ expectations across different conditions. They explain that simply having an active control condition is not adequate if participants in the control group do not expect it to have as beneficial or powerful an effect as participants in the intervention condition expect of their experience. The way around this, Boot and his colleagues explained, is to measure participants’ expectations and take steps to try to match them across control and intervention conditions as much as possible. “‘We are hopeful that, with better designs and better checks on placebo effects, future research will provide more compelling evidence for the effectiveness of interventions,’ they concluded.

The Placebo Effect Appears To Be Getting Stronger

Curiously, it’s become apparent in recent years that the placebo effect is getting stronger – this has been shown for placebo antipsychotic medications, placebo anti-depressants, and – in the US only – for placebo analgesics. With regards to that last finding, research team leader Jeffrey Mogil told Nature News, “We were absolutely floored when we found out”. Specifically, in the 90s, they found that participants receiving an active drug reported 27 per cent greater pain relief than participants receiving placebo, but by 2013, the difference was just 9 per cent. One explanation is that drug trials have become larger and more elaborate, especially in the US, thus increasing the drama and intensity of the experience for participants only receiving placebo.

Another possibility is that the general public has become more aware of the placebo effect – and of the idea that its impact on symptoms can be real (as reflected in less pain-related brain activity, for instance) and not merely illusory. That was the argument put forward by anesthesiologist Gary Bennett in the journal Pain last year. In fact, Bennett goes so far as to suggest that, because the term placebo now elicits such a strong placebo effect, its use should be dropped from drug trials. “The word ‘placebo’ should be avoided in all information and instructions given to the patients,” he advises. “Patient instructions should have the goal of forcing the patient’s expectations to the form: ‘I may receive pain relief’ vs. ‘I will not obtain pain relief’.”

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However hard we try to control, conceal and comprehend the placebo effect, it looks certain it will continue to baffle and amaze us for a long time to come.

Christian Jarrett (@Psych_Writer) is Editor of BPS Research Digest