Genes & the Placebo Effect: Are You Easily Pleased?


Lionel RitchieThe effectiveness of placebo may depend on someone’s DNA, so writes The Economist.

Give someone who is sick a sugar pill that you have told him is a powerful drug, and it will often make him feel better. Even if you tell him what it really is, he may still feel better.

The placebo effect, as this is phenomenon is known – from the Latin for “I shall please” – is one of the strangest things in medical science. It is a boon to doctors and a bane to those running clinical trials, who must take account of it in their designs. But how it works is obscure.

Knowing that would open up a new field of medicine. If placebos could be exploited rationally, perhaps in conjunction with functional drugs, better treatments might be effected. Drug testing, too, would be simplified, as trial designers were able select those more and less susceptible to the effect as the needs of the trial dictated. That would save effort, time and money.

One thing that is known about the placebo effect is that it involves several brain systems, each under the control of a particular type of messenger molecule, called a neurotransmitter. These systems, like everything else in the body, are regulated by genes. This has led some researchers to ask whether different versions of the genes in question might modulate a person’s susceptibility to placebos.

A review of these researchers’ studies, published in Trends in Molecular Medicine by one of them, Kathryn Hall of Harvard Medical School, and her colleagues, suggests genes do indeed seem to matter. Dr Hall looked for links between the placebo effect’s strength and certain mutations, known as single nucleotide polymorphisms (SNPS), in which a single DNA ‘letter’ in a gene changed. Altogether she found 11 genes, in four neurotransmitter systems, where SNPS made a difference. Five were in the system mediated by dopamine, which includes the brain’s reward centres. Four were in the system mediated by serotonin, which regulates mood. And the opioid and endocannabinoid systems had one each.

As their names suggest, these two systems are affected respectively by opium and its derivatives, and by cannabis and its. The other two are affected by cocaine, which blocks the retrieval of dopamine into nerve cells, thus increasing its power as a messenger; and Prozac, which has the same effect on serotonin, and is used as an antidepressant. It is not hard to imagine a similarity between the workings of these drugs and what happens in the brain when the placebo effect is operating.

The genes for which most placebo-related SNP evidence exists encodes enzymes called catechol-o-methyltransferase and monoamine oxidase. Bot hof these are parts of the dopamine system, and both are responsible for metabolising dopamine, and thus regulating the amount of it around. (Indeed, monoamine oxidase is the target of a second type of antidepressant, which has a different mechanism from Prozac.) People with different versions of either of these genes experience the placebo effect to different degrees. These various versions. moreover, are all commonplace, suggesting differences in placebo perception may be widespread.

The studies Dr Hall drew on are all preliminary, so they are better regarded as pointers for further investigation than as prescriptions for action. But if such investigations confirm these results, it may be possible to predict, on the basis of a genetic test, whether someone will experience a strong placebo effect or not. That could allow a doctor to lower the prescribed dose of a drug, if a strong placebo effect is expected. It could also permit drug companies conducting trials to exclude the placebo-susceptible, and thus to get a better sense of the underlying efficiency of what is being tested.

Reference

The Economist. (2015) Genes and the Placebo Effect: Are You Easily Pleased? The Economist. May 2nd to 8th 2015. pp.74-75.

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