The Placebo Effect – a Neglected Field of Treatment

Placebo treatment can have highly effective and long-lasting results, even in cases where the patient knows that the medicine or treatment isn’t real. Positive (and negative) expectations in patients and doctors, e.g. based on previous experiences with the treatment methods being implemented, or even just contact with a medical professional can all contribute to success. This is especially the case for subjective parameters, such as the perception of pain or depressed moods. This effect can also be seen in biological reactions, e.g. in immune system activity, neurotransmission processes, or the release of hormones.

Specific prior experiences support the placebo effect. Like Pavlov’s dogs, who salivated at the sound of a gong, humans also learn to react systematically to repeated stimuli. After a positive experience with a specific painkiller, the act of taking the pill can be enough to trigger a reduction in pain just seconds later, long before the medicine can actually affect the synapses. Strong reactions to mock treatments are especially common among children.

However, not all patients react to placebos in exactly the same way. Scientists have been trying to find out why for several years. Clinical researchers are especially interested in the subject, since the possibility of excluding “Placebo Responders” from future studies would reduce the number of study participants required to establish statistically relevant differences. This, in turn, would lead to significant savings.

Scientists have long debated whether genetic variants are responsible for these different reactions – a theory which is receiving more and more support from current publications. So much so, that a new term was coined: placebome (a combination of the terms placebo and genome).

The polymorphisms of the COMT gene are said to play a role in placebo reactions. The COMT gene is responsible for the development of the catechol-O-methyltransferase enzyme. This enzyme in turn builds catecholamines, including dopamine and adrenaline. Two variants of the COMT gene are known: “val” and “met”. If both DNA strands contain two of the same “val”-type alleles, dopamine is broken down faster than if the two alleles are of the “met” variant. Dopamine also plays a role in the brain’s reward system, which triggers the feeling of relief after treatment. Carriers of the “met” variant react much more strongly to mock acupuncture treatment than carriers of the “val” variant. A recent study even shows that people with two “met” variants also experience greater feelings of fear during medical treatments, which may explain their strong reactions to placebos.

It has also become known that a variation in the OPRM1 gene, which is responsible for the expression of the µ1 opioid receptor, can influence placebo reactions. The opioid system is involved both in the perception of pain and in reward processes.

Prof. Winfried Rief, a placebo researcher from the University of Marburg, is pushing for these effects to be (re-) integrated into mainstream medicine. We agree. Because a treatment can only be truly successful if it combines evidence-based measures with methods that actively make use of the placebo effect. Scientifically evaluating these effects, instead of continuing to regard them as nuisances, can lead to new approaches to treatment in which patients benefit from fast and sustainable results.