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Placebo vs Nocebo: A Powerful Mind Game

What is Nocebo and how it is different from Placebo?

To better understand the difference between Placebo vs Nocebo, Let’s start with a familiar scenario. You visited your doctor, and she was concerned about your blood pressure. You knew that you had a horrible day and probably was a one-off occasion, and believe if you rest, your blood pressure will normalise.

You have read a lot about the side effects of the medications and have been trying to avoid them. The doctor eventually twists your arm and prescribes the medicine for you. You go home and read the pamphlet, which has listed numerous “likely” side effects. 

After a few days, you feel like you are experiencing many of these side effects, to the point that you stop the medication. Another person who doesn’t worry about side effects will take the same medicine with virtually no problems. Here a complex mental game is in play that stops you from adhering to lifesaving treatment. Before diving further into the topic, let’s define some essential terms.


A placebo is any medication or treatment taken, which you believe will help you, but has no therapeutic benefits. They are mostly weakened sugars, with no biologic effect.


A nocebo is any medication or treatment taken, which you believe will harm you, but is actually not harmful or painful. This could be a medication, procedure or vaccine.

Placebo Effect:

The placebo effect is when you take the placebo, and you actually feel better. Simply because you believe it will help you, it does.

Nocebo Effect:

The nocebo effect is when you take the nocebo and you experience side effects. You have convinced yourself that it will cause harm. Simply because you believe it will harm you, it does. Think sick, be sick.

Where the evidence stands?

Statins have proven to be vital medications in reducing the risk of Heart attack and ischemic heart disease, both in people with (secondary prevention) or without (primary prevention) known heart disease. Numerous studies over the past three decades have proven this fact. With the advancement of new imaging techniques like Coronary Calcium Scoring (CAC), the preventive role of statin therapy in people with elevated CAC scores has been proven in multiple trials. Nonetheless, many patients hesitate to take these medications for various reasons, including muscle pain. However, contemporary evidence has shed more light on this complex issue. In a recent, well-done study, SAMSON Trial, it’s shown that most patients who could not tolerate statin therapy were experiencing the Nocebo effect. After a 6-months pause in treatment, most of the participants could re-start statins with no further complaints. 

Another study that shows the power of the Placebo effect is, the ORBITA trial. This was a trial in patients with significant coronary artery disease who were divided into two groups. One group had coronary angiogram or angioplasty and the other group had a sham (fake) procedure. The patients in the second group were thinking that they had a real procedure. Those who underwent a sham coronary angiogram, had remarkable improvement in their symptoms, despite not having the real procedure! They felt better because their mind BELIEVED they had an effective procedure and treatment, the Placebo effect.

We come across many other examples in daily practice. A very interesting observation is when patients have an echocardiogram or stress echocardiogram. These tests are only diagnostic; however, many individuals feel relieved as they are satisfied that something has been done, and their minds start the healing process. However, I should emphasize that these investigations should not be used for this purpose.

How the mind can control the body and symptoms?

Despite years of investigation, there is no clear answer about how the mind controls the body in this fashion. What is known is that these phenomena are real and extremely powerful. They can make a considerable change in patients’ lives, for good or bad.

While the Placebo effect can be quite positive and helpful, the Nocebo effect can endanger your life by refusing life-saving treatments. You have convinced yourself that some specific therapy will harm you and should be avoided, at all costs. This idea stems from deep beliefs you have formed during life and maybe negative past experiences, certainly going back to childhood. Changing a “cemented belief”, right or wrong, is a highly challenging task. for example, If you strongly believe eating pork is not acceptable, for religious, medical or eco-conscious reasons, getting you to try pork would be highly unsuccessful.

If you believe COVID-19 is a hoax and vaccines are manufactured to decimate humans from the face of the earth, you will avoid vaccination. If with that mindset, you get vaccinated for whatever reason, you will probably experience more side effects! Your mind is “set” to experience side effects and without them, it won’t be satisfied. You were expecting them.

How can Nocebo effect plays a role in patient outcomes?

The nocebo effect is a crucial player for better communication in healthcare settings. As an example, before prescribing a medication, you might say, “This tablet may cause a headache.” With this comment, the patient’s likelihood of returning with a headache is much higher. However, if you rephrase the sentence as such: “with this tablet, most people feel no pain at all but an absolute minority (only one percent) might have a headache”, will reduce the patient’s expectation of having a headache.

The mind-body connection is a complex and fascinating inter-relationship. Being aware of this intricate connection, patients realize how their beliefs and thoughts can positively or negatively impact their physical health. As this is a mutual relationship, the reverse is also true. How we treat our physical health (by what we eat or how physically active we are) can also affect our mental well-being. In short, our mind is an extraordinary and powerful machine that can affect our health immensely!

Accepting a medication or treatment depends on many factors, including patients’ trust in their doctor, past experiences with the same therapy, and how the doctor presents information regarding the therapy. Due to ethical obligations and full-disclosure laws, a doctor has to provide the data. However, the way this information is presented can make a significant difference to the outcomes.

Placebo vs Nocebo Dr Moazzeni
Placebo vs Nocebo - SAMSON Trial


Our thoughts are so powerful that they constantly push us towards our goals even when we don’t realize what those goals are. Whether they are good or bad, as long as they are “goals”. Our brain is wired to win. This dynamic doesn’t just apply to our health. It plays out in our relationship, career, fitness and everything else we do. We are hard-wired to win.

In the case of Nocebo, our goal is to prove we were right, and some treatment or medication isn’t good for us. Our brain plays any trick to win the argument, even at the expense of our health. On the contrary, if our brain decides something is good for us, we feel good even though there is no objective proof of that. That’s what Placebo is.

Placebo and nocebo effects are powerful and very common in daily medical practice. Neurobiological mechanisms, information about treatment, patient expectations, and previous encounters with a drug or procedure can all generate these effects. 

Increased awareness about Placebo and Nocebo helps to adopt strategies to promote the placebo effects and minimize the nocebo effects. This simple fact can improve outcomes and minimize unwanted symptoms in daily clinical practice.

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