The wonderful, mysterious placebo
I think one of the most curious phenomena we know about is the placebo – also known as “meaning response” (Moerman, 2002). A seemingly innocent and inactive “thing” is administered, and they miraculously get an effect. It can’t be an active substance, because often the “thing” is a sugar pill or pretend treatment, yet the effects include pain reduction, improved movement (Parkinsons), reduced nausea, and better mood, amongst others. Mysterious effects don’t just include positive ones, because people can also experience negative effects such as nausea, fatigue, headache, rashes and so on. This is the “nocebo” effect.

Some people argue that there is no such thing as a meaning response/placebo, that it’s a temporary phenomenon that quickly fades and that people who experience placebo are imagining it, or are saying what they think is wanted, but imaging studies, particularly fMRI, show that there are distinct changes of activity in areas of the brain – and some of these changes can be reversed after an opioid antagonist is administered.

What is it then? How does it work? What are the implications?

One hypothesis is that placebo is a “learned” phenomenon, based on the expectation an individual holds for “something” to happen. We develop expectations because we’re human, and these have cultural and individual origins. For example, the colour of a pill can influence its effect – but this differs depending on the country in which it’s administered. In another example, people who receive fake acupuncture can respond – but only if they are familiar with acupuncture as a treatment.

Why is this? Well, it could be that all the trappings of treatment – the ritual of seeing a special person in a special place, with special certificates on the wall, getting a special piece of paper to take to another special place, to be given a special bottle with special pills in it – can set our brains up to expect a special effect. And this is enhanced when the person giving us the special piece of paper says it’s going to have a significant effect on us.

Something that can enhance this effect is if a real effect occurs. For example, if a person is given real sedatives they will become sedated. If they do this for a week or so, they will have learned that this pill leads to sedation. If they’re then given a pill that looks exactly like the real one, they can experience the same level of sedation.

We know that intermittent reinforcement, that is, occasionally getting the result we want, is the most powerful learning schedule we have. Just think of the gambler’s high – occasionally winning a lottery leads to always buying a ticket because “I’m lucky”. It can lead to always choosing the same lottery numbers, wearing a lucky lottery hat, buying from a lucky lottery store and so on.

In treatment, it means that if, on occasion, the treatment provides a “real” effect, the likelihood will be for the learning effect to be incredibly powerful. This is what Au Yueng, Colagiuri, Lovibond and Colloca (2014) did in a recent experiment.

Partial reinforcement, extinction and placebo analgesia

Au Yeung and colleagues decided to use TENS, or transcutaneous nerve stimulation as their treatment. All 69 participants (undergraduate students) were told that TENS involves “passing an electrical current through the skin”, with no mention of how this might affect their pain. Two groups were chosen for the experimental condition, while a third were the control group who received no more information and told that the TENS was a machine to measure skin conductance by passing a current through the skin, and that they would feel a “slight sensation”.

The two experimental groups were given more information about TENS, including a handout saying how good TENS is, and included references to articles about TENS. They were also told by the researchers that TENS “can reduce pain by inhibiting the pain signals that travel up your arm and into your brain.”

Now the trick was that no TENS was actually given to the participants, instead an electrical stimulation device was used to give a very slight pulse that was only just felt by the participants.

The pain stimulus was given by an electric shock calibrated for each individual to the point that the individual reported a level that was “definitely painful but tolerable”.

All participants were given a shock, then asked to rate the pain intensity.  On placebo trials, the “TENS” was given during the stimulation (but actually was a mild electrical stimulation).

Now comes the fun part – participants in the experimental groups either had a hidden reduction in painful stimulation during the ALL placebo trials (when the “TENS” was administered along with the shocks), or SOME of the placebo trials.

Finally, at the end of the experimental, all the participants were asked if they knew the real nature of the study, and how much they knew about the placebo used in the experiment.

  1. The findings showed that the control group didn’t experience any placebo responding – so the fake TENS has no intrinsic effect.
  2. The group with “TENS” administered with every shock reported pain reduction with the “TENS” administration.
  3. The group with intermittent “TENS” also showed pain reduction – placebo analgesia was maintained even when the “TENS” wasn’t given.

What this means

Well, this study shows that placebo analgesia can be achieved with only intermittent placebo administration, but that the effect wasn’t as strong as when the placebo was given every time. BUT the placebo analgesia lasted longer when it was given intermittently.

And what THIS means is that clinically, if a “true” effect is achieved every now and then, the likelihood is that people who are supported to believe in its effectiveness will experience a long-lived placebo analgesia. Longer-lived than for those who always get a good “real” result. And this is something worth thinking about.

Pain reduction treatments are not very effective for many people with chronic pain. Some of the effects can be quite hit and miss. If we can learn how to harness this effect, we might be able to help people extend the effects of treatment while not having to have quite as much of the “active ingredient”. This could be useful especially in medication management.

On the other hand, it also suggests that for some people, the effect of “every now and then” getting a good result might lead to their ongoing belief in the usefulness of a treatment that is largely a hit and miss affair. That’s great for the clinician getting paid to give the treatment, but not so good if the aim is to help the person live well without depending on getting treatment from someone else.

Au Yeung ST, Colagiuri B, Lovibond PF, & Colloca L (2014). Partial reinforcement, extinction, and placebo analgesia. Pain PMID: 24602997

Moerman, D. (2002). Meaning, Medicine, and the “Placebo Effect”. Cambridge University Press: Cambridge.

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