Do Placebos Work?

photo by Kali Nine / iStock

photo by Kali Nine / iStock


THERE IS NOTHING either good or bad, but thinking makes it so. That’s a line from Act II of “Hamlet,” but it could apply to recent research on placebos.

Among the surprising findings are that both personalities and genetic differences appear to explain individuals’ varying reactions to placebos. In addition, the effectiveness of placebos now makes it clear that our bodies do not distinguish between a chemical process and the thought of a chemical process.

Also surprising: as many as 80 percent of all doctors say they have prescribed placebos – which include saline (salt water) injections along with familiar “impure” placebos, such as prescribing an antibiotic for a viral illness.  In a Swiss study, of the doctors who admitted to using a placebo, more than half told patients they were getting “a drug or therapy.”

Nicer patients respond best to placebos.  In a multi-university study, people with traits like resiliency, straightforwardness and altruism experienced a greater reduction in pain after taking a placebo than did those with an “angry hostility personality trait.”  The brains of those with “more agreeable” personalities released more mu-opoids – the brain’s own pain-killers, according to Jon-Kar Zubieta, M.D., of the University of Michigan.

The more agreeable traits “are part of an overall capacity to be open to new experiences and integrate that information in a positive fashion,” Zubieta told Scientific American Mind magazine.  “That’s probably what drives the placebo effect.”

Ted Kaptchuk, Harvard Medical School professor who studied Chinese medicine but never got an M.D. degree, was determined to find out not if but how the body responds to placebos.  With colleagues, he founded the Program in Placebo Studies and the Therapeutic Encounter (PiPS) at several Harvard-affiliated hospitals.   A recent PiPS study found that patients with a variation of one gene linked to dopamine production were more likely to respond to sham acupuncture than those with a different variation.

Early PiPs research on patients with irritable bowel syndrome (IBS) was the first to show a dose-dependent placebo response: the more fake care patients received, including “very schmaltzy” attention from doctors for one of the study groups, the better the patients did medically.

Because deceiving patients goes against the ethics of doctoring, Kaptchuk’s next experiment compared a control group who received no treatment with a group told they were getting placebos, from bottles clearly labeled “placebo pills.”  The placebo group had twice the improvement in symptoms – in fact, as much improvement as seen with “the best real IBS drugs,” according to Kaptchuk.

Imaging studies support these findings, showing that placebos affect the same areas of the brain that modulate pain reception. According to Italian neuroscientist Fabrizio Benedetti, what “placebo neuroscientists” have learned is that therapeutic rituals move the same molecules in the brain – use the same biochemical pathways – as drugs.

Anticipation plays a role in the placebo effect. Our “forward-thinking brain” shapes our actions, personality and health, explains Chris Berdik in his book “Mind over Mind” (Current/Penguin, 2012).  For the same reason that wearing all black can make you a more aggressive competitor and striking a pose can make you act authoritative, believing that a treatment will work can cause a patient’s body to mimic the effects of medication and even of surgery.  Fulfilling expectations is what our brain does best, and most convincingly in the work of placebos, says Berdik.  And a placebo’s effects can increase with time as confidence in the treatment grows.

Placebos work via the same physical pathways as the body’s active healing mechanisms, by stimulating real physiological responses that range from changes in heart rate and blood pressure to chemical activity in the brain.  They work best for pain, allergies, insomnia, fatigue, nausea and disturbances of bowel, urinary and general functioning – and least well for broken bones.  In an analysis of 46,000 heart patients, the half taking a placebo did as well as those taking the heart drug, as long as all believed they could be getting the drug.

In the early 1970s, researchers demonstrated that brains of patients given placebos for depression show increases in dopamine as well as in electrical and chemical activity in several regions of the brain.  Conversely, they also showed that chemicals blocking the release of endorphins – the brain’s natural pain-relievers – also blocked the placebo effect.

Maybe genetic differences help explain my own skepticism.  Assigned years ago to report on homeopathy, I realized that, even after speaking to many medical doctors, patients and personal friends among its adherents, I could never believe in medication so diluted that no trace of an active ingredient could be found using existing technology.  Enthusiasts argue efficacy can be traced to the “memory of a molecule.”  Believing that a pill can remember an active but invisible ingredient was too much for me.  While the research on homeopathy doesn’t always meet the highest standards of controlled studies, the anecdotal evidence is overwhelming: homeopathy can work wonders – but perhaps only on believers.

— Mary Carpenter


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