New research is zeroing in on a biochemical basis for the placebo effect

New research is zeroing in on a biochemical basis for the placebo effect, by Gary Greenberg.

Give people a sugar pill, [researchers] have shown, and those patients — especially if they have one of the chronic, stress-related conditions that register the strongest placebo effects and if the treatment is delivered by someone in whom they have confidence — will improve. Tell someone a normal milkshake is a diet beverage, and his gut will respond as if the drink were low fat. Take athletes to the top of the Alps, put them on exercise machines and hook them to an oxygen tank, and they will perform better than when they are breathing room air — even if room air is all that’s in the tank. Wake a patient from surgery and tell him you’ve done an arthroscopic repair, and his knee gets better even if all you did was knock him out and put a couple of incisions in his skin. Give a drug a fancy name, and it works better than if you don’t.

You don’t even have to deceive the patients. You can hand a patient with irritable bowel syndrome a sugar pill, identify it as such and tell her that sugar pills are known to be effective when used as placebos, and she will get better, especially if you take the time to deliver that message with warmth and close attention. Depression, back pain, chemotherapy-related malaise, migraine, post-traumatic stress disorder: The list of conditions that respond to placebos — as well as they do to drugs, with some patients — is long and growing. …

Why do placebos work? Is it “just” psychological?

Aided by functional magnetic resonance imaging (f.M.R.I.) and other precise surveillance techniques, [Ted Kaptchuk, head of Harvard Medical School’s Program in Placebo Studies and the Therapeutic Encounter] and his colleagues have begun to elucidate an ensemble of biochemical processes that may finally account for how placebos work and why they are more effective for some people, and some disorders, than others. …

The findings of the I.B.S. study were in keeping with a hypothesis Kaptchuk had formed over the years: that the placebo effect is a biological response to an act of caring; that somehow the encounter itself calls forth healing and that the more intense and focused it is, the more healing it evokes. … Kaptchuk suggested that the ritual itself is part of what makes the procedure effective, as if the combined experiences of the healer and the patient, reinforced by the special-but-familiar surroundings, evoke a healing response that operates independently of the treatment’s specifics. …

[Kathryn Hall] and Kaptchuk attended a talk in which a colleague presented evidence that an enzyme called COMT affected people’s response to pain and painkillers. Levels of that enzyme, Hall already knew, were also correlated with Parkinson’s disease, depression and schizophrenia, and in clinical trials people with those conditions had shown a strong placebo response. When they heard that COMT was also correlated with pain response — another area with significant placebo effects — Hall recalls, “Ted and I looked at each other and were like: ‘That’s it! That’s it!’ ” …

Genetic correlation to placebo response:

It is not possible to assay levels of COMT directly in a living brain, but there is a snippet of the genome called rs4680 that governs the production of the enzyme, and that varies from one person to another: One variant predicts low levels of COMT, while another predicts high levels. When Hall analyzed the I.B.S. patients’ DNA, she found a distinct trend. Those with the high-COMT variant had the weakest placebo responses, and those with the opposite variant had the strongest. …

Hall found that the women with the low-COMT gene variant had significantly higher rates of heart disease than women with the high-COMT variant, and that the risk was reduced for those low-COMT women who received the active treatments but not in those given placebos. Among high-COMT people, the results were the inverse: Women taking placebos had the lowest rates of disease; people in the treatment arms had an increased risk. …

Where now?

But Kaptchuk also has a deeper unease about Hall’s discovery. … “Once you start measuring the placebo effect in a quantitative way,” he says, “you’re transforming it to be something other than what it is. You suck out what was previously there and turn it into science.” Reduced to its molecules, he fears, the placebo effect may become “yet another thing on the conveyor belt of routinized care.” …

After all, if Hall is right that clinician warmth is especially effective with a certain genotype, then, as she wrote in the paper presenting her findings from the I.B.S./sham-acupuncture study, it is also true that a different group will “derive minimum benefit” from “empathic attentions.” Should medical rituals be doled out according to genotype, with warmth and caring withheld in order to clear the way for the drugs?