Mapping the human placebome? Genetics may hold key to placebo effect

placeboCould the reason why the placebo effect works for some people and not others lie in their DNA?

The authors of a new scientific review article make the case that, just as an individual’s response to medications is dependent upon their unique genetics, so too could their response to placebos. In the article, authors Hall, Loscalzo and Kaptchuk delve into research on the topic and discuss possible impacts a “placebome,”—a term coined by the authors to describe genomic effects on placebo response—could have on patient care.

Once something thought to be simply in a person’s imagination, the placebo effect is emerging as a legitimate series of biological reactions thanks to recent research on the topic. Recent neuroimaging and physiological experiments have supported the position that “placebo effects are biological responses to psychosocial environmental cues surrounding the administration of inactive (or active) treatments,” the authors write.

From the Latin for “I shall please,” a “placebo” is an inactive treatment designed to simulate a real one, most often used in scientific clinical trials to determine the efficacy of an actual medication or treatment. The placebo response, or effect, describes the positive health benefits—perceived or actual—patients can receive in response to a placebo.

In the review article, published online in the journal Trends in Molecular Medicine, the authors identified 11 candidate genes, variations in which could contribute to individually varied placebo response. Many of these genes are involved in moving neurotransmitters in the brain, processes well-understood to be dependent upon individual genetics.

“We’re finding that the placebo response seems to be modified by several of these pathways, leading people to think that there’s more than one type of placebo response,” study lead author Kathryn Hall told The Atlantic in a recent article.

The review article calls out the gene COMT one of those candidates. Hall and colleagues in 2012 found that irritable bowel syndrome patients with a specific COMT variation that increased the brain’s levels of dopamine also experienced improved response to placebo treatment.

“This potential intersection of disease, drug, and placebo effects suggests that COMT is an excellent model for the sophisticated network analyses that may be necessary to fully appreciate the potential complexity of the placebome,” the article authors write.

Overall, Hall and her coauthors make clear the placebo response picture is far from straightforward, with many genetic pathways interacting in complex ways likely contributing to individually varied response. Understanding these complexities warrants further research, Hall and colleagues write, as knowledge of the placebome’s effect and how it varies in the context of specific diseases and treatments could be an important consideration in personalized medicine and drug development through design of randomized controlled trials (RCT).  RCTs are often considered the “gold standard” for clinical trials used to determine the efficacy of drugs.

“In general, the placebo arm is considered to be an adequate control for outcomes in the active treatment arm of RCTs,” the authors write. “However, if the placebo response does, indeed, vary by genotype, we might expect challenges with confounding, potential gene–drug–placebo effect modification and disease-specific effects.”

Want to learn more about placebo research? Check out the Program in Placebo Studies, a joint venture of Harvard Medical School and Beth Israel Deaconess Medical Center.