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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A Pediatrician’s Take On The Power Of Placebo

Dr. Carolyn Roy-Bornstein

Dr. Carolyn Roy-Bornstein is a Haverhill-based pediatrician who writes about health care. In her piece, “Take Two of Anything and Call Me in the Morning,” she considers the non-pharmaceutical aspects of healing:

We all know about the placebo effect. Patients often report improvement in their symptoms if they think they are taking an approved treatment for them, even if that treatment turns out be no more than a sugar pill. In typical studies comparing real drugs to placebo, patients are not told which kind of pill they are taking. By design, placebo studies involve a certain amount of deception. Indeed the terms “placebo” and “sham” are often used interchangeably.

But two recent fascinating studies have challenged the notion that a patient needs to be tricked to benefit from the placebo effect. In a study performed at Beth Israel Deaconess Hospital and reported in The Boston Globe, nearly 60% of patients with Irritable Bowel Syndrome (IBS) reported improved abdominal pain and bowel symptoms even though they knew their pill contained no active ingredients. In another study published in Developmental and Behavioral Pediatrics, children with Attention Deficit Hyperactivity Disorder (ADHD) on optimal doses of appropriate stimulant medication were able to have their doses cut in half by using placebo instead of half of their daily medication. Surprisingly, parents did not report any increase in the severity of their kids’ ADHD symptoms, even though they knew their children were taking the placebo, also referred to in this study as a “dose-extender.”

What I find interesting about both of these studies is that placebo can work even when patients are fully aware that they are ingesting the “sham” product. Why might that be? Is the power of the pill that strong in our American culture that there doesn’t have to be anything in it for it to work?

The authors in the Beth Israel study hypothesized that the taking of a pill “triggers a sort of unconscious conditioning in our body to begin the healing process.” Maybe folks feel empowered. Maybe they feel like they are doing something active to help themselves feel better when they take something for symptom relief. If that’s the case, maybe the “something” doesn’t have to be a pill. Continue reading

The Healing Wig — And The Power Of Cherished Objects

Can certain special objects, like wigs, actually have healing power?

This story is not about politics. It’s about a wig. A wig passed from one woman with breast cancer to another, and another, until it became a cherished gift, seemingly imbued with the power to heal.

Jeff Zaslow, writing in The Wall Street Journal, nicely explores the “talisman placebo effect,” that is, the power of physical objects to embody hope, and the notion that if something worked for someone else, it can possibly work for you.

Why do human beings attach such great power to objects that are given to them, especially in times of crisis? For thousands of years, civilizations have embraced the mystical possibilities in amulets and talismans. Now science is explaining how these items actually work, and why, in today’s digital age, they often take on even more significance.

“It’s not voodoo,” says Barbara Stoberock, a researcher at the University of Cologne in Germany. “It can be explained. If you have a lucky charm, and believe it helps you, there’s a psychological mechanism. It lifts your beliefs in your own capabilities, and gives you a boost.”

In a study released this year, Ms. Stoberock and a team of social psychologists found that people are more likely to attach superstitions to items during moments of uncertainty—when they’re under high stress and low levels of perceived control.

The researchers conducted several experiments in which subjects performed better on memory and dexterity tests if they had personal talismans with them, whether stuffed animals, childhood blankets or inherited jewelry.

He also gave a nice plug to my blogging partner, Carey Goldberg, and her book, “Three Wishes,” about some extraordinary (or so it seems) vials of donor sperm that she passed to another woman, who then passed it along again, until the three pushing-40 women were all happily married, and with children they’d been dreaming of for years. “The unused vials of sperm,” writes Zaslow, “became talismans for romance, luck and motherhood.”