Slightly more than a decade ago scientists mapped the human genome — the complete set of human DNA organized into 20,000 to 25,000 genes — and today scientists work on maps of the proteome (proteins), the gut microbiome (bacteria and other microbes found in our digestive tract), the transcriptome (human RNA), and perhaps most surprisingly of all, the placebome — genes related to the placebo effect.

A new study from Beth Israel Deaconess Medical Center explores what is known about the placebome so far. Genetic variations in specific brain signaling pathways influence our ability to experience the placebo effect, the researchers say.

Could the placebo response be harnessed to offer each of us greater benefits from precision medicine? This is one of many questions raised by the new study.

What is the Placebo Effect?

In most medical experiments, a control group of patients is given a placebo in the form of a sugar pill (or some other non-pharmaceutical substance) and told that the pill is real. Some people will actually respond to this fake pill and experience physical improvements in their symptoms due to the power of suggestion — due to the power of their own beliefs. This symptom change is called the placebo response.

“The estimate of one-third of all people being placebo responders was first made by Henry Beecher in 1955,” Dr. Kathryn Hall, a member of Beth Israel Deaconess Medical Center's Program in Placebo Studies, told Medical Daily in an email. “Although scientists argue about his derivation of this number, estimates have hovered around 20 to 35 percent, but there is so much variability by condition, treatment, and experimental paradigm.”

Scientific experiments include a placebo control group so that researchers can compare the true effectiveness of a new medicine to a baseline that includes such random effects caused by patient expectations. Even if it lasts only a short time, placebo effect is real. Strikingly, some patients also experience nocebo effects, when, because they have been warned of side effects, a fake pill causes them unpleasant symptoms, such as headache or nausea.

For the current study, Hall and her colleagues reviewed past research of the placebo effect.

“Although there are no formal start dates for the study of the placebome, you could say that the pace of research in this field has increased over the last three years,” Hall told Medical Daily.

In the brain, specific signaling pathways — a group of molecules in a cell that work together to control one or more cell functions — mediate the placebo effect. These include the dopamine, opioid, endocannabinoid, and serotonin pathways, with the first two pathways having greater effect on the placebo response. Even more, the evidence suggests that the individual genetic variations that shape these brain pathways ultimately alter the placebo effect. And, if genetic differences influence placebo effect, they also may determine each patient's physiological response.

The power of any drug’s effect, which includes a placebo response for some patients, could depend in part on your genotype.

If it is possible to create genetic profiles of placebo responders, the researchers note, a number of practical and ethical issues need to be considered and addressed. First, they propose including no-treatment controls in addition to placebo controls in future clinical trials for new drugs in order to get more accurate results. Should your doctor test your placebo-response? The researchers wonder whether knowing our individual placebo response might affect its magnitude. They also ask whether physicians should use this information and, if so, how?

Speculating somewhat wildly, Medical Daily asked: If patients with incurable disease received pills targeting their placebo signaling pathways (instead of the untreatable disease itself), would they feel some benefit and maybe even find their lives extended?

“We have absolutely no data to support placebo being a treatment that can prolong life in the face of a life-threatening disease,” Hall told Medical Daily. Once again, stark reality intrudes. Thank goodness for the down-to-earth practicality of scientists.

Source: Hall KT, Loscalzo J, Kaptchuk TJ. Genetics and the placebo effect: the placebome. CellPress. 2015.