The placebo effect

Sugar pills ease depression, colourful creams numb the skin and saline injections make pain melt away. The placebo effect is a powerful healer, but how does it actually work?

In the 1890s, Ivan Pavlov discovered classical conditioning. His famous experiments taught dogs to associate the sound of a bell with the arrival of food. When they heard the noise, they started to dribble in anticipation. The same thing can happen to us with medicine. We make associations based on our experiences. If people take aspirin for a headache, they start to associate the shape and taste of the tablets with pain relief. Replace the pills with a placebo and the pain will still be lessened.

Placebos, also known as ‘dummy’ or ‘inactive’ treatments, are made from inert substances like saline, starch or sugar. They look and feel like the real thing but without any of the chemical effects. The whole experience receiving treatment can help us to feel better. One study gave people a painkilling cream for two days and then replaced it with a placebo.

The participants had experienced the cream working, so they expected it to continue helping. Also, the tone of voice of medical staff and the information they give people about what to expect during treatment can change the way people respond. In this instance, if the staff reassured them that the new cream would work, it did. But if staff told them that the cream would increase their pain, it actually made things worse.


Changing the colour of placebo medication

The appearance of medicines can also shift our expectations. We associate bold colours like red, orange and yellow with a stimulant effect and blues and greens with sedation. Change the colour of a tablet and it’ll change what people expect it to do. Similarly, if a pill costs more or comes in a branded box, we expect it to outperform its cheaper or generic counterparts. Even the name of the treatment has an impact. One study found that putting the word ‘placebo’ on a migraine medicine called rizatriptan reduced its impact. Calling a placebo ‘rizatriptan’ made it work better. Not surprisingly, calling the real medicine by its proper name worked best of all.

Placebo surgery and painkillers

The placebo effect even works with surgery. The process of cutting the skin open and stitching it back together again can help people with knee pain, and fake operations can even ease heart pain caused by angina. Nothing actually needs to happen inside the body: the sights and smells of the hospital and the procedure of an operation can trick the brain. The first neurobiological evidence for how the placebo effect works came in the 1970s.

A famous study published in 1978 in the Lancet looked at what happened when people received a placebo painkiller after having a tooth removed. To find out how the placebo effect worked, half of the participants were also given a drug called naloxone, which blocks the activity of natural painkillers called endorphins. In this study, naloxone stopped the placebo tablets from working, but only when people expected the placebo to help with their pain.

When we expect a tablet to kill pain, the brain makes its own painkillers. Current evidence now suggests that this effect starts in a part of the brain called the prefrontal cortex. This region handles complex behaviours and planning. When we expect to feel better, it boosts activity in nerve pathways that extend down into the spinal cord. MRI scans have shown that the placebo effect decreases blood flow in the parts of the spinal cord that let pain signals through.

The endorphins triggered by taking placebo tablets help to stop pain signals from reaching the brain. The placebo effect works less well on people with Alzheimer’s disease, who often have damage to the nerve cells in their prefrontal cortex. The effect can also be blocked by placing magnets over the scalp, interfering with nerve signals in the front of the brain.

Anxiety can block the effect of placebo pain relief 

Anxiety can also block placebo pain relief. Studies have found that simply telling people that their pain will get worse can make it worse. It can even make non-painful touching hurt, a phenomenon known as allodynia. Reading about side-effects or looking diseases up on the internet can shape what we expect to happen, and this affects the brain. The second part of the brain’s placebo system is a chemical messenger called cholecystokinin (CCK). It is produced when we are anxious. Blocking its activity with a drug called proglumide enhances the placebo effect, as does calming anxiety with the medicine diazepam. Most of the work to understand the placebo effect has focused on pain, but dummy pills can affect other aspects of health and disease too.

People with Parkinson’s disease suffer damage to nerve cells in a part of the brain called the substantia nigra. These damaged nerve cells stop producing dopamine, and this leads to problems with movement that worsen with time. Placebo medicines can increase the amount of dopamine in the brains of people with Parkinson’s disease. If they expect to receive real treatment and think that they will improve, dopamine levels rise on their own. The immune system can also respond to a placebo. In 2002, the Goebel research group at the University of Duisburg-Essen in western Germany trained the immune system using a flavoured drink. They repeatedly dampened immune activity using an immunosuppressant called cyclosporin A.

Each time they accompanied the treatment with the drink. After the conditioning was complete, they didn’t need the drug any more. The drink was able to suppress the immune system on its own. In 2008, they repeated the experiment with allergies. This time they gave antihistamines with the flavoured drink. Incredibly, not only did the drink make people feel better even when the antihistamines had been removed, it also reduced the activity of allergy-inducing immune cells called basophils.

Understanding the placebo effect

We still don’t fully understand the placebo effect, but there’s no escaping it. Every time we receive medical treatment, part of the experience is psychological, and medical professionals are already using this knowledge to help us get better. There are two types of placebo. Pure placebos do nothing chemical to the body, like sugar pills or saline injections. Impure placebos are treatments that do have chemical effects but not for the condition for which they are being used. Antibiotics are an example; they treat bacterial infections but are often prescribed for flu even though it’s caused by a virus.

A recent survey of UK GPs found that, though few use pure placebos, three-quarters prescribe impure placebos to their patients at least once a week. Examples can include giving people nutritional supplements, probiotics, antibiotics and alternative medicines. Alternatively, it can entail booking patients in for non-essential tests. The most simple option is just using the power of positive suggestion. There is an ongoing debate about whether this is ethical, but similar studies in other countries have found that placebo use is widespread. The more we understand how it works will be able to harness its power.

 This article was originally published in How It Works issue 109, written by Laura Mears 

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