Placebo Effect: What is it and how does it work?

 

The medical and scientific community has recognized the placebo effect for many years. For a person that is not involved with science, the phrase might be somewhat familiar too. Regular people, however, might not believe in the true power of what is the placebo effect. Until they experience it themselves. It doesn’t have to be some sort of groundbreaking cure of cancer or dementia. The placebo effect has many examples in everyday life. Of course, nobody documents them but they do happen quite regularly.

 

The Placebo Effect

The Placebo Effect
by Pixel Flicker

What is the placebo effect?

Imagine you have dinner with your partner. A lovely oven-baked salmon and lemon juice, roasted potatoes and a side of asparagus. You wash it all down with a glass or two of your favorite red wine. For dessert, you have vanilla and chocolate ice cream with a dollop of fresh fruit and mint on top. The mood is perfect, the dinner is perfect and the night itself is perfect.

That is until the next day when your partner is not able to leave the bathroom. He or she are suffering from clear food poisoning symptoms. Your partner needs to call in sick. In the morning you are fine and you just worry about your partner. You go to the pharmacy and get some relief medicine. Then you make a quick run to the supermarket to stock up on plain chicken and vegetable broth in case your partner gets hungry during the day. You are preoccupied with the thoughts and worries for your partner.

As you leave for work, you put your phone on loud in case he or she needs anything from you. As the day progresses, however, you start feeling a little bit of a stomach ache. Not enough pain to actually bother you, but worrisome when you think of your partner’s fate at home. His or her food poisoning is on your mind constantly and you check on them throughout the day.

When you get home from work you see your partner fast asleep with quite a high fever. Suddenly, your head starts hurting a little bit too, in addition to the growing pain in your stomach. You start worrying even more. You run to the kitchen and check every product for their expiry date. Your stomach ache and headache are getting even bigger.

Of course, you might be really experiencing the symptoms of food poisoning since both of you had the same exact dinner. The chances are quite high, you think. But what if someone was to tell you that the food poisoning came from the work lunch that day. In fact, 2 or 3 other people caught the same thing. Your stomach ache and headache seem pointless now, but for some reason, it won’t go away.

This might be quite a naïve example of the way the placebo effect can manifest itself. It is quite a common one, however. You don’t need to get food poisoning to experience the placebo effect but there are many other regular things that might bring it on that we face in our everyday lives.

Of course, science explains the placebo effect a little bit differently. We have to remember, though, that the placebo effect does not only work with medicine. That being said, it is the most widespread definition of it. In the medical and scientific field, the placebo effect is the response that people (patients) can get when they are administered something that is actually nothing. In fact, it is one of the most common experimental methods in good scientific studies and clinical trials.

When testing for a new drug, scientists will often create a control group to whom they will give the placebo (e.g. a pill that does not give any treatment.) They do so in order to show that the effects of the drug on whatever it is they are testing, are genuine.  After the administration of the placebo to a control group, researchers will compare the results from the experimental group to the control group. Of course, they hope that the control group will not show any type of changes because that would undermine the effective results that the experimental group might have achieved.

Scientists make placebos of substances that do not have any effect. The most common ingredients include starch or sugar.

How does the placebo effect work?

The Placebo Effect

The Placebo Effect

Certain people, however, might experience a response to an administered treatment of any kind. Scientists have documented this type of response for years now and it is quite well-known. The response that the person might experience could be positive. This person might feel the effects of the treatment and their condition and symptoms might subside. The placebo effect can go in the opposite direction as well, making the person feel the side effects of the administered treatment – headache, nausea, dizziness. The list can go on. What is astonishing in regards with the placebo effect is that sometimes it can have results that are equally as successful as the treatment itself. Buddha is believed to have said that “What you think, you become. What you feel, you attract. What you imagine, you create.” In the concept of the placebo effect, the quote becomes quite real?

How can we explain the placebo effect, then? What is the reason behind it? Many scientists have spent a considerable amount of time trying to understand how a mind can do such an enormous thing? Imagine the possibilities! Getting rid of all of the pain symptoms in a cancer patient without any chemotherapy! Of course, researchers want to find the origin of the placebo effect and make full use of it.

Placebo effect and conditioning

Certain scientists believe that conditioning can play a role in the formation of the placebo effect. Classical conditioning works by introducing neutral stimuli to unconditioned stimuli. The association between the two often leads to the formation of a conditioned response that is similar to the unconditioned response that happened as a result of the unconditioned stimuli. The placebo effect usually happens in clinical trials with the introduction of a pill/treatment through a syringe etc. Because of that people can form associations between the treatment and the response – the decrease in symptoms.

Why does the placebo effect work?

As mentioned before, a lot of research generated after discovering the placebo effect and how common it actually is. In fact, mentions of the placebo effect go into the beginning of 1900’s and continue on throughout World War 2 with soldiers refusing treatment due to what doctors believed was a feeling of euphoria.

Scientists have been hard at work trying to find the origin of the placebo effect. According to many scientific publications, researchers believe that the placebo effect has a lot to do with expectation. When a patient believes that the treatment will work, then their body produces certain reaction as if they really took the drug. Quite interestingly, researchers found that the body’s reaction is very similar to the one that the treatment might have caused.

Where can we localize the placebo effect in the brain?

The Placebo Effect

The Placebo Effect

If it’s happening on a regular basis, there is a reason for it. There must be a region in the brain that is active when the placebo effect occurs. In 2016, scientists in a journal of PLOS Biology published a study that explored the effects of the placebo effect in a human brain. “Brain Connectivity Predicts Placebo Response across Chronic Pain Clinical Trials” study used a functional magnetic-resonance-imaging (fMRI) in order to find their results.

Many scientists notice the placebo effect in patients with neurological diseases and painful conditions, this is the type of population that the researchers for this study chose as well. Knowing the origin and the neuro marker for the placebo effect can be quite beneficial in creating individualized treatment plans and, also, help researchers with clinical trials. The study found that the right mid frontal gyrus, posterior cingulate cortex, anterior cingulate cortex and the right secondary somatosensory and primary motor cortices showed an effect according to their measurement of functional connectivity with the resting state fMRI.

After running the entirety of their study they speculate that it is exactly the right mid frontal gyrus that is the neuro marker for the place effect in the population that they used. The result is quite significant due to the fact that the researchers of this study specified this particular region to be the origin of the placebo effect that happens in clinical settings. This could lead to future investigations to see whether some people really do possess the necessary biological makeup for the production of the placebo effect.

Many of the studies found increases in neural activity in areas of emotional regulation and decreases in areas responsible for pain and anxiety. These scientists propose that placebo effect works as a reward or aversion.

Opioid network explanation

Scientists found a connection between the placebo effect and the opioid mechanisms in the brain. We know that opioid network works by producing endorphins – hormones responsible for the analgesic effect. Researchers found that the analgesia, often associated with the placebo effect, can have an origin in the opioid neuronal network.

Parkinson’s disease and the placebo effect

Scientists also found an association between Parkinson’s disease and the placebo effect. Patients diagnosed with the disease show a placebo effect quite often. Studies found that Parkinsonian patients show this placebo expectation and activate dopamine pathway in the striatum. This has a therapeutic effect on patients with Parkinson’s disease in regards to their motor performance.

The placebo effect: individual differences

Many scientists see a link between the placebo effect and the genetic make-up. As mentioned before, the dopamine pathway showed to be important in the relationship between Parkinson’s disease and the placebo effect. Because of that, scientists studied the dopamine metabolism and pathway genes as potential biomarkers for the placebo effect. They found that one of the metabolic dopamine polymorphisms can change results in clinical trials.

Apart from genetic differences, there are, of course, psychosocial and environmental differences. These are mentioned beforehand including conditioning and expectations. Many of these can depend upon the clinical trials that the patients undergo, the health practitioners, suggestions during the study etc.

Negative outcomes of the placebo effect: nocebo

The placebo effect has a big association with expectancy. It comes as no surprise that sometimes the expectation can be negative. Due to the fact that some people might expect a negative outcome, nocebo happens. Nocebo means that the result becomes more negative than it was originally thought to be.

This is the reason why clinical studies need to be careful with using control groups. The negative effect is real and they can happen due to this negative expectancy of the outcome. That’s why clinical trials need to be as objective as possible with minimal interaction with the patients.

The Placebo Effect and Disorders

As mentioned before, the placebo effect plays quite a big role in the pain pathways in the brain. In fact, many studies showed a decrease in neural circuitry associated with pain as a result of placebo administration. Similar results were obtained for studies with anxiety.

Scientists found that patients who were part of the control groups for clinical trials in depression showed metabolic and electrical changes in the brain. Those who experienced the placebo effect showed faster cognitive processing time during neuropsychological testing.

Clinical Significance: Ramifications

First of all, it is worthy of noting that the administration of a placebo itself can be considered unethical. It is due to the fact that with the presence of treatment, subjects and patients are not given the treatment, but instead a sugar pill. Medically, it shouldn’t help them with the disease, therefore, can potentially hinder their treatment progress.

Of course, the main problem with the placebo effect is the significance of the studies with active treatment compounds. How can the results be accurate if there is a control group showing similar outcome without any administered treatment? It’s always better to opt for a non-pharmacological treatment and the placebo effect can sometimes hinder the results of medication related clinical trials. And if then the placebo is removed after the termination of a clinical trial, the patients could go back to experiencing the symptoms which is detrimental to their cause.

All of this needs to be considered in regards to the placebo effect and the use of it in clinical trials.

The Placebo Effect: future directions

It comes as no surprise that the placebo effect is such a hot topic for scientists around the world. The possibilities to exploit the placebo effect are endless. Just to think of the opportunity to be able to stimulate certain brain parts and activate the placebo effect, is exciting! If we were to do that, we could maybe diminish certain symptoms. These painful symptoms are most common in patients who suffer from neurological conditions and chronic pain conditions. Even the slightest decrease in their painful symptoms could be of quite high value and a big relief for them and for the medical community in itself. That is why it’s important to investigate the placebo effect and find out everything there is to know about it!

The placebo effect is, of course, quite beneficial as scientists have found out. It is important to note, however, that the placebo effect is not a cure for all. It does seem to relieve people of certain patients but no studies have found its effect on curing diseases. If you are experiencing painful symptoms, please consult your physician for help. However, do not forget to hope and expect the best. No matter what, the positive thinking seems to be quite a powerful tool that many people should try to utilize to their benefit.

 

References

Gross L. Putting placebos to the test. PLoS Biol. 2017;15(2).

Tétreault P, Mansour A, Vachon-Presseau E, Schnitzer TJ, Apkarian AV, Baliki MN. Brain Connectivity Predicts Placebo Response across Chronic Pain Clinical Trials. PLoS Biol. 2016;14(10).

Price DD, Finniss DG, Benedetti F. A Comprehensive Review of the Placebo Effect: Recent Advances and Current Thought. Annu Rev Psychol [Internet]. 2008;59:565–90. Available from: http://psych.annualreviews.org

Hall KT, Loscalzo J, Kaptchuk TJ. Genetics and the placebo effect: The placebo. Vol. 21, Trends in Molecular Medicine. 2015. p. 285–94.

Valerie is a psychology student who is trying to pursue a career in Cognitive Neuroscience. She is passionate about the brain and finds it fascinating. She loves learning about new discoveries and research that is going on in the world of psychology and neuroscience. One day she hopes to contribute to the scientific community!