Professor Lohse, at the GDNÄ meeting in Potsdam, you recently gave a lecture on placebos or therapy with nothing. But your profession as a pharmacologist is more about therapy with something. How does that fit together?
At first glance, one might see a contradiction here. But placebo effects also accompany every drug therapy and other medical measures, and that is why they are part of it.

The audience was enthusiastic about your lecture, applauded extensively and had many questions. Why is there so much interest in placebos?
I think that many people are affected by it because they have experienced it themselves or seen it in others and have thought about it. The topic also brings together most diverse schools of thought – from scientific drug therapy to shamanism.

How did you come across the topic?
I have been covering it in my introductory pharmacology lectures for more than twenty years because I think that doctors and pharmacists should know about it. They all work, consciously or unconsciously, with placebo effects. These also include harmful effects, so-called nocebo effects. Over the years, I then delved deeper into the subject because I wanted to know what was actually proven in this field and what was just speculation. Just recently, I have come across many new results and some amazing things.

What has amazed you the most?
That the same brain centers are activated in the mind of the doctor as in the mind of the patient when it comes to placebo effects. This has been studied primarily in the treatment of pain. It seems that the doctor must first empathize with the patient's pain. Then, with this idea, he can activate his own pain-suppressing systems, and that in turn is transferred to the patient. This ability of the doctor correlates closely with his ability to empathize, as can be measured in psychological tests. In my lecture, I went into more detail about the corresponding research results.

Placebo effects in pain suppression result from the interaction between patients and doctors. Pain activates so-called pain centers in the brain (yellow star), as shown by functional magnetic resonance imaging. When empathic doctors come together with such patients, they in turn activate the same centers in the brain. However, they can also activate their own pain-suppressing centers in their brain (blue symbol). This is transferred to patients and leads to the activation of pain-suppressing nerves in them, which release endogenous opioids and other transmitters in the body and thus produce the pain-suppressing placebo effect. This effect occurs regardless of whether the drug administered to the patient contains an analgesic active ingredient or whether it is a pure placebo.

What does this mean for medical practice?
Doctors who are able to put themselves in their patients' shoes can achieve a great deal with empathy in the reciprocal relationship. It would be good if we could use such placebo effects more systematically and on a reasoned basis, not just intuitively and based on personal experience. That's why we should increase knowledge in this field and incorporate it more into the training of doctors and pharmacists. 

Can empathy, which obviously plays a major role, be taught and learned at all?
Some things are a matter of talent, but others can be learned. Since empathy is a core skill for therapists, it should be incorporated into the entire training program. The current courses in medical psychology for prospective doctors are a start. 

How far has placebo research come?
Compared to many other areas of medicine, it is still in its infancy. We have only been able to speak of serious, scientifically based placebo research for about three decades. It is an area where medicine, psychology and the new imaging techniques come together. Functional magnetic resonance imaging, in particular, gives us an idea of what is happening in the minds of patients and therapists. So, placebo research is making progress and Germany is playing an important role in it. Four years ago, for example, a national special research area was set up that has already led to a number of interesting results.

© MIKA-fotografie | Berlin

Great interest from the audience: After the lecture, there were many questions and comments on the placebo effect.  

So far, placebos have mainly been used in drug studies to find out whether drugs work compared to them. Do we also learn something from this about how placebos work?
Not really, because in such studies, the placebo arm only serves as a background against which the effect of a drug is to be shown. But treatment with placebos is not neutral. This is shown by studies with open placebos, in which patients know that they are receiving a placebo but still feel a healing effect. There are probably many types of placebo effects – just as there are countless drugs. In the future, we should characterize these in detail and examine their interactions.

A few more words about drug trials: it is rare for a verum to be tested against a placebo alone. If an effective drug already exists, giving a dummy drug is prohibited on ethical grounds. In these cases, the standard treatment plus a placebo is tested against the standard treatment plus a new drug. This makes it more difficult for new drugs to gain market approval: they not only have to work themselves, but also have to provide an additional benefit to standard therapy. 

Let's take a closer look at the placebo effect: what do we know about its psychological and biological basis?
Psychologically, the expectations of patients are important. Both positive and negative expectations have a strong influence on the success of treatment – therapy with nothing, so to speak, is based on our expectations. We still know very little about the biological processes involved. What we do know is that placebos increase the activity of certain brain regions. For example, when it comes to pain suppression, placebos activate precisely those regions and neural pathways in the brain that are responsible for controlling pain perception. 

Do you need pills for the placebo effect or is positive expectation enough?
Pills, with or without active ingredients, or other specific measures such as acupuncture have a placebo effect. The best approach is a good medicine combined with positive expectations. Most studies show that a medicine plus placebo works twice as well as a placebo alone. 

For which illnesses is the placebo effect greatest?
The effect has been well studied for pain, especially for migraine, for functional disorders of the gastrointestinal tract, and in general for disorders with a strong psychosomatic component. Even depression can often be alleviated with placebos. This effect has been convincingly demonstrated and it is what makes studies on antidepressants so difficult. 

For which diseases should the placebo effect not be relied upon?
Whenever you know that there are drugs with a good verum effect, whose ingredients have been shown to help against a specific disease. In this case, you have to use the verum – knowing that its effect will be supplemented by placebo effects. If you don't do that as a doctor, for example in cancer therapy, it becomes dangerous. This is also the strongest criticism of controversial forms of therapy such as homeopathy. 

More than a few patients report amazing healing successes with homeopathic remedies. What is your opinion on this?
Good homeopaths know how to use placebo effects efficiently. The effect of homeopathy is based on this, and not on the almost infinitely diluted medicines that are used. I think it is nonsense to ascribe verum effects to these remedies. 

What is the future of the placebo effect?
I expect to see a lot of new findings soon. And I hope that we will identify and understand very different placebo effects and mechanisms, and that we will be able to draw practical conclusions for training and therapeutic practice.