Category: placebo/nocebo

Say No to Nocebo: How Doctors Can Keep Patients’ Minds from Making Them Sicker

By Elizabeth Preston | July 9, 2014 10:19 am


“First, do no harm,” the saying goes, but that might be close to impossible. Just as our expectations can make us feel better, they can also make us feel much worse. This means that how doctors phrase their instructions or introduce new drugs may have a real impact on our health. But some doctors are trying to figure out how they can do less harm by harnessing the surprising power of their words.

“In the classical view that is still taught at medical school and in textbooks, drug actions are purely determined by the drug,” says Ulrike Bingel, a neurologist at the University of Duisburg-Essen in Germany. “But that is not true.” Read More

How to Convince People WiFi Is Making Them Sick

By Elizabeth Preston | May 13, 2013 3:05 pm

All it takes is an antenna on a headband. If you’ve got a breathless video report on the dangers of wireless internet connections, that will help your case. It doesn’t take much, though, to turn an ominous hint into a real headache.

Some people consider themselves sensitive to electromagnetic fields. They report symptoms such as burning skin, tingling, nausea, dizziness, or chest pain, and they blame their malaise on nearby power lines, cell phones, or WiFi networks. A recent Slate article described such people moving to a remote West Virginia town where radio-frequency signals are banned. (The town is within the U.S. National Radio Quiet Zone, an area that’s enforced to keep signals from interfering with radio telescopes there—telescopes that work because they receive the radio-frequency signals constantly hitting our planet from space.)

There’s no known scientific reason why a wireless signal might cause physical harm. And studies have found that even people who claim to be sensitive to electromagnetic fields can’t actually sense them. Their symptoms are more likely due to nocebo, the evil twin of the placebo effect. The power of our expectation can cause real physical illness. In clinical drug trials, for example, subjects who take sugar pills report side effects ranging from an upset stomach to sexual dysfunction.

Psychologists Michael Witthöft and G. James Rubin of King’s College London explored whether frightening TV reports can encourage a nocebo effect. They recruited a group of subjects and showed half of them a clip from a BBC documentary about the potential dangers of wireless internet. (The BBC later acknowledged that the 2007 program was “misleading.”) The remaining subjects watched a video about the security of data transmissions over mobile phones.

After watching the videos, subjects put on headband-mounted antennas. They were told that the researchers were testing a “new kind of WiFi,” and that once the signal started they should carefully monitor any symptoms in their bodies. Then the researchers left the room. For 15 minutes, the subjects watched a WiFi symbol flash on a laptop screen.

In reality, there was no WiFi switched on during the experiment, and the headband antenna was a sham. Yet 82 of the 147 subjects—more than half—reported symptoms. Two even asked for the experiment to be stopped early because the effects were too severe to stand.

Witthöft says he expected to see a greater effect in people who had watched the frightening documentary. This wasn’t the case overall. Instead, the movie mainly increased symptoms in subjects who described themselves beforehand as more anxious.

“It suggests that sensational media reports especially in combination with personality factors (in this case anxiety) increase the likelihood for symptom reports,” Witthöft says.

Plenty of symptoms were reported without the sensationalist TV show, though. The antenna on the head, the researchers’ allusion to a “new kind of WiFi,” and the instructions to monitor their bodies closely were enough to trigger symptoms in many people who watched the other video.

Witthöft points out that his study would have been stronger if there were a third group of subjects who didn’t wear the “WiFi” headband at all, but were simply told to pay attention to their bodies for 15 minutes. This kind of attentiveness might trigger symptoms on its own.

Still, Witthöft says, “I think the high percentage of symptom reports nicely shows how powerful nocebo effects are.”

Though the researchers set out to show how irresponsible reports in the media can trigger a nocebo effect, they ended up showing how easy it is to make a person feel sick with just a a prop and a few choice words. Even a National Radio Quiet Zone can’t protect against that.

Witthöft, M., & Rubin, G. (2013). Are media warnings about the adverse health effects of modern life self-fulfilling? An experimental study on idiopathic environmental intolerance attributed to electromagnetic fields (IEI-EMF) Journal of Psychosomatic Research, 74 (3), 206-212 DOI: 10.1016/j.jpsychores.2012.12.002

Image: Scott Beale/Laughing Squid (via Flickr)

12 Days of Inkfish, Day 4: Help Desk

By Elizabeth Preston | December 28, 2012 3:27 pm

When you use website analytics, you quickly learn that there are a lot of people out there Googling things like “how do i make robot” and “which is best medicine for make baby.” This year I’ve seen many visitors whose search queries were probably not answered here. To make things up to them, I’ll try to address a few of those questions now.

orangutan stop following me
Unless you live in Borneo or Sumatra and spend a lot of time in rainforest trees, it’s very unlikely that you’re being followed by an orangutan. Are you sure it isn’t a very hairy human or a large orange dog? If an orangutan is, in fact, following you, don’t worry—they mostly eat plants.

can you use ab toning belt on butt for bigger muscles

Ab toning belts will not make your muscles stronger (they only stimulate the surface of the muscle) or more toned (because the contractions are involuntary). But if you’re really attached to the idea, don’t bother strapping the belt around your rear: they sell toning shorts too.

what pills can make a man’s hair fall out in clumps
I don’t know the answer to that but it sounds like you’re working on a super hilarious prank.

toilet training pigeon
Here’s a website with some advice on potty-training pet birds. Consistency is key! But if I had a pigeon I’d skip the toilet training and teach it to carry messages, or to find its home from hundreds of miles away. Or to take pictures, like those cool pigeons in World War I.

is science harmful or useful

Did you not just see that pigeon with a camera strapped its chest?

giant barbies on the loose
Please send a picture so I can better assess the problem. Maybe you and the person with the orangutan problem should coordinate.

that story about the monkeys in the room

Your faith in organic search is touching. I don’t know what you’re looking for, but here’s a story about rhesus macaques raised by water bottles instead of mothers.

if you swap brains will you still have the knowledge inside?
Even if this question is only research for a science-fiction story, I really think you should reconsider.

unnecessary otter
sex robot sperm go?
Since you clearly know search terms don’t have to be in the form of a coherent sentence, I’m confused about why you think they still need a question mark at the end. On the off-chance you’re wondering what the similarities are between a sperm cell and a Roomba, here are some.
why is sperm brown
Wow, please see a doctor. Why are all the sperm people coming here?

i have to pee
No one is stopping you. 

what company makes placebo
Okay, I quit.

Images: Help desk by Aryc Ogre; war pigeon via Wikimedia Commons 

Subliminal Placebo: You Didn’t See It, but It’s Working

By Elizabeth Preston | September 10, 2012 7:01 pm

The latest additions to the placebo effect family might be the rudest. First there was placebo, which uses your body’s own tools to make you feel better after you try a treatment you imagine will help you. Then there was nocebo, placebo’s evil twin: it makes you feel worse only because you think you will. Now researchers have discovered that placebo and nocebo effects can be triggered subliminally, which is like finding out that the good and evil twins have both been living in your basement without you knowing it.

Usually, placebo and nocebo look like cases of our own expectations manipulating us. Someone swallows his favorite headache remedy or visits a doctor, and his body, expecting to feel better, ramps up production of its own pain-relief molecules. Someone else steps onboard a plane and begins to feel nauseous, simply because her body has learned that airplanes mean queasiness. If we were more ignorant of our circumstances, the effects wouldn’t be there.

But there seem to be some cues we can take in subliminally, without noticing them. So researchers led by Karin Jensen at Harvard Medical School wondered whether visual signals that are too brief to reach our consciousness—but perhaps not too brief for certain areas of our brains to snag as they pass—can trigger placebo and nocebo effects too.

For their visual signals, the team chose photos of male faces. “We know from previous studies that faces can be detected and processed very quickly in the brain,” Jensen says. Their models came from a set of photos created for use in psychology experiments.

The researchers carried out two experiments, the first of which was a classic test of placebo and nocebo. Subjects were shown pictures of two expressionless male faces over and over. Each time they saw face A, they felt a painfully hot sensation on the forearm. Face B was paired with heat that was milder, but still uncomfortable. (The A and B models alternated between different subjects—just in case one man’s face really was more painful to look at.) During the conditioning part of the experiment, subjects saw each face 25 times. This taught them to expect higher pain with face A and lower pain with face B.

Then came a second series where subjects saw the same two faces as before, with a few new ones mixed in as controls. With each face they saw, subjects rated the pain they felt from the heat instrument on a 100-point scale. The twist was that in this part of the experiment, the heat level was exactly the same every time. But subjects consistently reported high pain for face A and low pain for face B. When they saw a new face, subjects reported an intermediate level of pain (which corresponded to what they were actually feeling).

This first experiment showed the researchers that pairing faces with painful heat stimuli could create both a placebo effect (when subjects rated moderate heat as less painful because they saw face B) and a nocebo effect (when subjects found moderate heat more painful, thanks to face A). So they moved on to the second experiment. In this round, the visual signals would be “nonconscious,”or subliminal.

A new group of subjects went through the same conditioning sequence as before. Then they were given a testing sequence using face A, face B, and the new (control) faces, all paired with the same moderate heat on the arm. But the faces in this sequence flashed on the screen for just 12 milliseconds, compared to 100 milliseconds in the earlier experiment.

12 milliseconds is fast. Too fast, in fact, for subjects to consciously process the faces zipping by. They reported that they couldn’t tell who was who (and a separate experiment confirmed that people can’t recognize faces shown this quickly).

But, as the researchers report this week in PNAS, the pain scores still matched the faces subjects said they couldn’t see. Face A got significantly higher pain scores than face B, with the control faces scoring in the middle—and don’t forget that, once again, subjects were actually feeling the same degree of heat every time.

Even though the pictures flashed too briefly to enter conscious awareness, they seem to have snuck in through the brain’s back door. These visual cues made subjects experience more or less pain than they should have, even though they had no idea what they’d seen.

There were only 20 subjects in each experiment; it would take further studies to show how consistent or how powerful the subliminal placebo and nocebo effects are. But the fact that they found an effect at all is exciting news to the researchers. “To the best of my knowledge, there has not been an experiment [previously] where placebo/nocebo effects have been activated by nonconscious cues,” Jensen says.

The common assumption, Jensen says, is that placebo and nocebo rely on the signals we’re paying attention to (pills, needles, drug commercials) and the results we expect (relief, discomfort, alarming side effects). But this study “proves that we don’t need to be aware of the cue to elicit a conditioned response,” Jensen says.

Don’t expect to start seeing mysterious images flashing at you in the doctor’s office. The subjects in Jensen’s study had to be trained to associate photos of faces with high or low pain. And even if there were another kind of image that automatically produced a placebo effect in a wide audience (teddy bears? puppies?), our brains might not be able to recognize it as quickly as a human face.

But the idea that placebo and nocebo effects can be triggered by cues patients don’t even notice could be important for healthcare, Jensen says. Certain conditions such as asthma, depression, and irritable bowel syndrome are known to respond well to placebos. Maybe doctors’ offices and hospitals in the future will tailor everything patients see—from the posters on the wall to the instruments on the counter to the fish swimming in the lobby aquarium—to encourage placebo and avoid nocebo. Or maybe we’ll be able to use the same tricks at home to keep ourselves feeling our best. Let’s kick those weird placebo relatives out of the basement and put them to work.

Karin B. Jensen, Ted J. Kaptchuk, Irving Kirsch, Jacqueline Raicek, Kara M. Lindstrom, Chantal Berna, Randy L. Gollub, Martin Ingvar, & and Jian Kong (2012). Nonconscious activation of placebo and nocebo pain responses PNAS : 10.1073/pnas.1202056109

Image: freya.gefn/Flickr
CATEGORIZED UNDER: brains, disease, magic, medicine, placebo/nocebo

How Placebo’s Evil Twin Makes You Sicker

By Elizabeth Preston | July 16, 2012 3:15 pm

Whenever a pharmaceutical company tests a new migraine prevention drug, nearly 1 in 20 subjects will drop out because they can’t stand the drug’s side effects. They’d rather deal with the headaches than keep receiving treatment. But those suffering patients might be surprised to learn that the drug they’ve quit is only a sugar pill: the 5 percent dropout rate is from the placebo side.

Lurking in the shadows around any discussion of the placebo effect is its nefarious and lesser-known twin, the nocebo effect. Placebo is Latin for “I will please”; nocebo means “I will do harm.” Just as the expectation of feeling better can make our symptoms ease, the expectation of feeling worse can make it a reality.

In a review paper published last week in the German journal Deutsches Ärzteblatt International, researchers say doctors and drug companies are unwittingly introducing patients to the demon of nocebo. Led by Winfried Häuser of the Technical University of Munich, the authors say that nocebo in the doctor’s office can add unnecessary pain and distress to ordinary procedures. In clinical drug trials, it can create side effects that shouldn’t be there—and perpetuate them in the patients who will take that drug in the future.

Chemically, nocebo seems to use the same toolkit that placebo does. Say you have a headache and treat it however you normally like to—maybe with an ibuprofen, or a few drops of homeopathic whatever under your tongue. If you expect to start feeling better soon, your body will use internal molecules such as dopamine and opioids to start creating its own pain relief. (Depending on what treatment you’ve used, you may or may not get some chemical backup once it kicks in.) It’s good old-fashioned conditioning, just like Pavlov’s hungry dogs salivating before food was anywhere in sight. But in nocebo, when you expect your headache to get worse, your body turns the pain-relief machinery down instead of up.

Nocebo doesn’t need a doctor’s help to find you. But a doctor can harness it too. The standard assumption in medicine, Häuser and his coauthors write, is that patients should be warned ahead of time about anything painful (“You’re going to feel a little pinch!”). But telling a patient to expect discomfort might actually make it worse. In one study, patients getting an injection felt more anxiety and pain when their doctors used words such as “sting,” “burn,” or “bad,” even if the doctor was only trying to express sympathy.

In another study, women receiving epidural injections felt more pain when they were warned that the “big bee sting” would be the worst part of the procedure. When women were instead reminded that the injection would numb them and make them more comfortable, they experienced less pain. The authors point out that patients in emergency situations or facing major surgery are often in a “trance state” that makes them even more suggestible than usual.

Nocebo can really throw a wrench into clinical drug trials. Placebo is well accounted for; these trials always include a large placebo group in which patients are given a sugar pill or other fake treatment. To minimize the effect of suggestion, neither doctors nor patients know which group they’re in. After the trial, researchers can subtract the positive effect seen in the placebo group from that in the patients taking a real drug, and see how much good their treatment really did.

In both the real and placebo groups, subjects report any side effects they experienced. When drug companies report the results of their trials, the Food and Drug Administration asks that they only report side effects (or “adverse events”) that they have some reason to believe were caused by the drug. But the FDA acknowledges that this is “a matter of judgment.”

As we saw with the migraine patients, side effects can be common even with a sugar pill. In one study, 44 percent of lactose-intolerant people reported gastrointestinal problems after taking a fake lactose tablet. (Impressively, a quarter of people without lactose intolerance also reported digestive troubles after taking the tablet.) And in a somewhat cruel prostate drug study, one group of subjects was told that sexual dysfunction was a possible side effect, while the other group wasn’t. The better-informed group reported sexual side effects at a rate of 44 percent, compared to only 15 percent in the blissfully ignorant group.

Whatever side effects are attributed to a new drug, doctors may increase patients’ odds of feeling those effects just by mentioning them. In Germany, Häuser says, “most of the product inserts contain very many potential non-specific adverse events, raising the risks of nocebo effects.” So how can doctors avoid making their patients sicker?

Häuser and his coauthors have a couple of suggestions. Patients could consent to not be informed about mild side effects, knowing that just hearing about these effects makes them more likely. And doctors can phrase their warnings more positively, emphasizing that most patients respond well to a treatment rather than focusing on potential negatives.

“Doctors can and should be trained to positively use the power of their words,” Häuser says. If we know where nocebo is lurking, we may be able to keep it far away.

Winfried Häuser, Ernil Hansen, & Paul Enck (2012). Nocebo phenomena in medicine: Their relevance in everyday clinical practice. Deutsches Ärzteblatt International : 10.3238/arztebl.2012.0459

Image: takgoti/Flickr

The Plus Side of Eating Placenta

By Elizabeth Preston | March 30, 2012 5:54 pm

He’s not suggesting new parents pause in the delivery room to whip up a placenta sandwich. But neuroscientist Mark Kristal says human mothers might be missing out on the benefits other mammals receive from gobbling up their afterbirth. With luck, there might be a way for us to take advantage of placenta power that’s not totally disgusting.

Mark Kristal is a professor at the University of Buffalo who’s been studying the practice of placenta eating–or placentophagia, if you want to bring it up in polite company–for more than 40 years. His interest in the subject sprang from his study of maternal behaviors in mammals giving birth. “I had the field to myself,” he said in an email.

And he knows it’s gross. “Unfortunately, people often ask me what my research is on during dinner,” he says. “It always gets a laugh (and a gag).”

Humans, with the exception of some naturopaths and celebrities, don’t eat placentas. But that makes us nearly alone among mammals. From rodents to cattle to apes, new moms turn to the business of eating or licking up the afterbirth, including the liver-like placenta, as soon as the baby is out.

In a new review paper (soon to be available here), Kristal and his coauthors discuss the potential benefits of placentophagia for mammals that practice it, as well as for mammals that don’t (us). There are several practical reasons why animals might ingest their placentas. Maybe they want to hide the odor of blood from predators, for example, or to keep their nests clean. Maybe mothers are famished after the ordeal of giving birth, or perhaps the placenta replaces nutrients that were depleted during pregnancy.

Though some of these explanations fit subgroups of mammals, none of them works universally. So Kristal thinks there must be a more basic evolutionary explanation for placentophagia. If almost every mammal does it, the simplest explanation is that they do it for the same reasons.

One intriguing possibility, and the strongest lead researchers have so far, has to do with pain. In the 1980s, researchers discovered that female mammals’ bodies produce pain-relieving endorphins during labor and delivery. Studying rats, Kristal found that eating the placenta increased the effect of these endorphins. The placenta didn’t dampen pain on its own. But rats that ingested placentas felt less pain, because they responded more strongly to their bodies’ own pain relievers.

The effect also works with morphine, a similar pain suppressant. Rats that ate placenta, or amniotic fluid, experienced greater pain relief from morphine. Kristal found that the pain-relief-enhancing effect of afterbirth works in male rats, too, and in animals of other species. It also worked when researchers fed rats with human placentas.

This suggests human placentas have the same health benefits as other mammals’. So why do humans, alone among land mammals, deny ourselves the pleasures of eating placenta? It’s possible, Kristal says, that evolution destroyed our appetite for afterbirth for a good reason. Maybe it has to do with toxins caught in the placenta as the organ filters them out of the fetus’s environment. Or maybe extra-painful childbirth was helpful in human evolution because it encouraged women to help each other through delivery.

Kristal thinks that with further research, scientists can identify the ingredient in placenta that enhances pain relief from morphine or endorphins. Then the compound can be made in the lab and used as a drug–for all kinds of pain in males and females, not just childbirth.

These days, a few women who have gotten wind of the potential advantages of placentophagia are experimenting with it themselves. But they’re interested in more than just pain relief. There are claims that eating one’s placenta cures conditions ranging from postpartum depression to nursing difficulties.

Though such claims aren’t backed up by any research, Kristal is interested in these same postpartum problems–which, he says, are uniquely human. Sure, other mammals sometimes go so far as to kill and eat their newborns. Rodents, for example, are tempted to ingest everything that comes out of them during delivery, baby included. But a healthy newborn will get its mother’s attention by moving around and making noise. Other mammals only eat their young after an extremely stressful pregnancy.

Kristal says none of these behaviors, though, are parallel to the human problems of postpartum depression or an inability to bond with one’s baby. If scientists could pinpoint the mechanisms that cause these issues, they could then start asking whether any element in the placenta might help treat them.

While science lags behind, eager placenta-eaters are going ahead with their own methods. Actress January Jones recently outed herself as a fan of placenta pills. After delivering her son, she had her placenta dried and made into capsules. Pill poppers are also featured in this gruesomely detailed 2011 New York Magazine article about placentophagia. (Focused on trend-conscious Brooklynites, the story contains the horrifying sentence, “I threw a chunk of placenta in the Vitamix with coconut water and a banana.”)

Mark Kristal gets emails “all the time” from women who have tried placentophagia, he says. Without exception, they all insist it helped them.

But the claims of placentophagia fans are the same regardless of how much placenta they ingested, when they took it, or how they prepared the organ (cooked? raw? encapsulated? smoothied?). And it’s unlikely that any real medicinal effect of the placenta could be so universal. For example, experiments have shown that placenta loses its pain-suppressing power when it’s heated.

It’s more likely that the benefit human women report from eating their afterbirths is the benefit of placebo. The ability to make women feel that they’re tapping into a primal force to keep themselves healthy may be the real power of placenta.

Mark B. Kristal, Jean M. DiPirro, & Alexis C. Thompson (2012). Placentophagia in Humans and Nonhuman Mammals: Causes and Consequences Ecology of Food and Nutrition

Image: avlxyz/Flickr (Note: This is a picture of someone’s French toast remains. Not placenta.)



Like the wily and many-armed cephalopod, Inkfish reaches into the far corners of science news and brings you back surprises (and the occasional sea creature). The ink is virtual but the research is real.

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