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The Complex Interplay Of Genetics And The Placebo Response

Why do some people respond to placebos while others don’t?

One possible answer: genetics.

A provocative new paper introducing the concept of a “placebome” — that is, the complex interplay between genetics and an individual’s response to placebos — raises questions that might ultimately lead to changes in how clinical studies of drugs are evaluated.

Indeed, researchers from Harvard Medical School suggest that genes, and genetic variation, might play a far bigger role in the placebo response than previously thought.

That the placebo effect is an actual physiological response is well established. But the new report, a research review, looks specifically at the placebo response in the context of drug studies, where some participants get the active medication while others get a placebo, or non-active version of the drug.

The new findings, “call into question whether or not the outcomes in a drug treatment arm of a clinical trial are limited to the effect of the drug on the condition,” says Kathryn Hall, an integrative medicine fellow in the Division of General Medicine and Primary Care at Beth Israel Deaconess Medical Center, and one of the study authors.

Instant Vantage/flickr

Instant Vantage/flickr

Several neurotransmitters, such as dopamine, appear to be involved in the placebo response, Hall said, and variation in the genes in these pathways appears to change our response to placebo. So different people with different genotypes respond differently to placebos.

But Hall takes it one step further. “When you are in a trial you don’t know if you are getting the drug or the placebo, so not just the people in the placebo arm can have placebo responses. We are curious about the drugs’ effect on the placebo response.”

It’s all a bit tough to wrap your brain around, so I asked Hall to give me an example. Here’s what she said:

In the literature we see several studies in which in the placebo arm one group of people with a certain genotype have a strong placebo response and the other group has a weak placebo response. And when we look at the drug treatment arm, we see the outcomes are reversed, the people who had the strong response in the placebo arm now have a low response and the people who didn’t have a response in the placebo arm now have a strong response. The historical interpretation of these results has been that only one group of people responds to the drug and we’re pointing out that it’s more complicated than that. It’s that one group responded to the placebo and that response is eliminated in the drug treatment arm.

What all this means in the real world is still hard to know. But in their paper published this week in the journal, Trends in Molecular Medicine, the researchers offer these three key takeaways in the abstract:

•The predisposition to respond to placebo treatment may be in part a stable heritable trait.

•Candidate placebo response pathways may interact with drugs to modify outcomes in the drug treatment arms of clinical trials.

•Genomic analysis of randomized placebo and no-treatment controlled trials are needed to fully realize the potential of the placebome.

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