Youāve got a splitting migraine. If you were offered a sugar pill, would you bother taking it? What if you were told your genetic make-up means it is very likely to make you feel better?
This is one of the questions raised by the burgeoning effort to understand which genes influence the placebo effect, and how these genes ā collectively known as the placebome ā determine a personās susceptibility to the phenomenon.
There are tremendous differences in the placebo effect between individuals, says of Harvard Medical School. āIt can vary from no measurable response to someone getting significantly better.ā Having drawn together all the studies carried out so far, Hall says there is reasonable evidence for at least 11 genes that influence a personās susceptibility.
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This is enough to warrant discussing the use of genetic screening to assess how likely a person is to respond to a placebo treatment, such as a sugar pill or saline injection. The idea is that this could lead to more personalised treatments for conditions like pain syndromes, migraines, depression, irritable bowel syndrome and even Parkinsonās disease, symptoms of which seem to be relieved by placebo in some individuals. It could also lead to the design of more balanced clinical trials.
Are you a responder?
Your personality can help you guess whether youāre among the estimated third of the population who are placebo responders. . Although brain imaging techniques can also indicate a personās likely susceptibility, a genetic read-out would offer a convenient, easily applicable and clearly codified measure.
So far, the 11 genes implicated in placebo response are all involved in known neurotransmitter pathways. One example is a common mutation in the COMT gene, which encodes an enzyme that breaks down the hormone dopamine. As many as a quarter of Caucasians carry two copies of the mutated gene, which results in higher levels of dopamine. In 2012, Hall and her colleagues showed that having in people suffering from irritable bowel syndrome.
One application for this sort of knowledge could be to guide clinicians in personalising therapeutic treatments for their patients, says at the University of Maryland in Baltimore.
An obvious start would be painkillers, where such personalisation is already unwittingly happening. When people in hospitals are given a pump that allows them to administer their own morphine, individuals with COMT mutations . Using genetic screening to identify other groups that respond well to placebo could mean these people could see effective results with lower doses of drugs, and consequently experience fewer side effects.
How you sell it
But to use placebos clinically, doctors would be ethically required to explain such treatments to their patients. This may not scupper the effect ā thereās some evidence that placebos work even if you know you are taking one (see ā4 weird things about the placebo effectā, below).
It might also come down to the words used. āIf a doctor says āweāre going to give you a drug that has very little active ingredients, but itās going to be effective,ā itās going to solicit a whole series of responses in your brain,ā says Hall.
Sugar pills could be just the start ā alternative medicines may be another way of administering a helpful dose of placebo power. Hall believes the placebo effect could help explain why alternative medicines are so popular, and a genetic understanding of it could open the door to safely and ethically administering such treatments in controlled circumstances. āSo many trials of these treatments show no benefit, yet so many people continue to use them.ā
āGenetic screening may be more useful in research than in clinical routine settings,ā says at Uppsala University in Sweden. Furmark made the first discovery of a placebo-associated gene in 2008. He suggests that research trials could use genetic information to spread placebo-responders evenly between drug and control groups, making it easier to detect whether a treatment is effective.
But Furmark warns that in general, progress in using genetic screening techniques to inform clinical treatments has been slow. āThere is still a long way to go before screening for placebo responsive gene variants becomes meaningful, especially considering the complexity of the placebo phenomenonā
Journal reference: Trends in Molecular Medicine, DOI:
4 weird things about the placebo effect
1. It doesnāt have to be a secret. Some believe that a placebo can only work if the recipient is unaware they are taking one. But thereās evidence that than those who are left untreated.
2. It works better if itās expensive. The , compared to those told that the pill is on sale for a discounted price.
3. Itās not just us, animals can get it too. A 2012 study found that between 30 and 40 per cent of rats .
4. It has an evil twin. The makes people undergoing treatment more likely to suffer from side-effects if they are warned about them by their doctor.
