A Staff Report from the Straight Dope Science Advisory Board

Is there an "anti-placebo" effect?

January 28, 2000

Dear Straight Dope:

I've always wondered about any anti-placebo effect. For instance, I am skeptical that zinc lozenges prevent colds, but if they do, I sure want them to prevent mine, but I am worried that my skepticism will negate any real effects. So, is there an anti-placebo effect?

In a word: Yes.

Now let's look at it in many more words, including one that is a relatively new word to the English language: "nocebo."

As most people probably know already, placebos are inert pills or other harmless therapies once prescribed for hypochondriacs who demanded that the doctor "do something."  (The Latin word placebo means "I will please.") Today placebos are given as part of medical experiments to examine how well a treatment works. The idea is that the treatment should do better than the placebo, or else there's no point. This weeds out treatments that don't actually help, but just rely on, well, the placebo effect--you think a treatment will help you get better and so you do get better, even though the treatment is worthless. The placebo effect is likely the main reason people believe in all sorts of wacky medical claims, from homeopathy to therapeutic touch.

The placebo effect can be quite powerful. Dr. Ben Krentzman, in his web page on placebos (http://www.loop.com/~bkrentzma n/meds/placebo.html), notes: "The medical literature is replete with reports on the power of the placebo to help patients with anxiety, tension, melancholia, schizophrenia, pain of all sorts, headaches, cough, insomnia, seasickness, chronic bronchitis, the common cold, arthritis, peptic ulcer, hypertension, nausea, senile dementia, etc. But the placebo is not only able to help, it has also been associated with side effects including nausea headache, dizziness, sleepiness, insomnia, fatigue, depression, numbness, hallucinations, itching, vomiting, tremor, tachycardia, diarrhea, pallor, rashes, hives, ataxia, and edema, to name a few."

While Krenztman uses the term "placebo" for both positive and negative effects, "nocebo" is finding more use these days. As you might have guessed, the nocebo effect is the opposite of the placebo effect. In Latin, nocebo, which only showed up in English usage in the last decade (and, in fact, is not even recognized as a real word by my word processor's dictionary), means "I shall cause harm or be harmful." While the medical profession recognized a while ago that they needed to take into account the placebo effect, they have only recently recognized that they need to also take into account the nocebo effect.

Like the placebo effect, the nocebo effect is usually generated by "beliefs, attitudes and cultural factors" (http://quinion.com/words/turnsofphr ase/tp-noc1.htm). This occurs when the expectation of deterioration is created. For an extreme example, the July 1997 Harvard Mental Health Letter notes that the nocebo effect has been credited with causing "so-called voodoo deaths." In other words, people who truly believe in voodoo and believe they have been cursed by a voodoo practitioner may be so affected by the nocebo effect that they actually get sick and die. The article further notes: "For surgical patients, the expectation of death on the operating table can be fatal. In one study of people with asthma, deliberate misinformation about the effects of medication reduced its effectiveness by nearly 50%. Also, allergic reactions can be induced merely by telling the patient that they are receiving a substance to which they are allergic, when in fact they are receiving salt water."

The evidence on zinc lozenges is still a bit sketchy. Some experiments make it seem they do something, others don't. The FTC stepped in recently and made the main manufacturer stop making claims they couldn't back up. Like you, I'm skeptical that they do anything.

If they do nothing and their effect is completely attributable to the placebo effect, and you don't believe they do anything but take them anyway, you probably won't see the same effect as those who believe. That said, John Dodes notes, in his Skeptical Inquirer article, "The Mysterious Placebo" (http://www.csicop.org/si/9701/placebo.html ), "Belief in the treatment only appears to explain a portion of the placebo effect. It appears that belief, operant conditioning, and suggestibility all play important roles." So it is possible that, even if you don't believe, the placebo effect may still have some impact. And, let's face it, somebody who has absolutely no doubts probably won't waste the money to take these things, which don't exactly taste great. So it's likely that even if somebody is a bit skeptical, there may be a flicker of hope that triggers the placebo effect.

If the lozenges really do have medical benefits, we still need to consider the nocebo effect. As Robert and Michele Root-Bernstein noted in Honey, Mud, Maggots and Other Medical Marvels: "Research has also shown that the nocebo effect can reverse the body's response to true medical treatment from positive to negative." So if they actually work and you don't think they do, their effect may be reduced--they may live down to your expectations.

Perhaps the most interesting thing that links it all together came from Michael Fumento, in his January 19, 1996, Chicago Tribune article, "How the Media and Lawyers Stir Up False Illness," where he noted: "For example, if someone in your office is suffering from a cold you, too, may feel your throat tightening, your bones aching a bit, your head hurting perhaps." So the nocebo effect may actually be one reason the placebo effect helps zinc lozenges seem to work! According to the label, you are supposed to "begin treatment at first sign of cold." Well, if the first sign of the cold is really a nocebo effect because you've been around sick people, then you are merely countering nocebo with placebo, and you think you've just taken a great medicine that cured your non-existent cold!

All in all, I'll wait for some nice double-blind studies to show that zinc lozenges prevent and/or cure colds. Until then, I think the following anonymous quote sums it up: "A treated cold will last a week. Left untreated, it will last seven days." Barring the placebo and nocebo effects, of course.

ABOUT THAT PLACEBO EFFECT . . .

Here's a twist. According to a new study, the placebo effect may be a myth. The idea of a placebo is that it doesn't actually do anything, you just think it does, so you get better. In other words, a placebo helps you harness the power of positive thinking. But the new study suggests it doesn't even do that. 

The study is entitled "Is the Placebo Powerless?--An Analysis of Clinical Trials Comparing Placebo with No Treatment," by Danish researchers A. Hrobjartsson and P. C. Gotzsche, New England Journal of Medicine, May 24, 2001. The New York Times summarizes it this way:

The investigators analyzed 114 published studies involving about 7,500 patients with 40 different conditions. The report found no support for the common notion that, in general, about a third of patients will improve if they are given a dummy pill and told it is real.

Instead, the researchers theorize, patients seem to improve after taking placebos because most diseases have uneven courses in which their severity waxes and wanes. In studies in which treatments are compared not just with placebos but also with no treatment at all, they said, participants given no treatment improve at about the same rate as participants given placebos.

In other words, it's not a question of mental attitude; you'll get better even if nothing is done. 

Whether or not you buy the study's conclusions, an important distinction needs to be drawn. The New York Times notwithstanding, no one disputes the "common notion" that "about a third of patients will improve if they are given a dummy pill and told it is real." What's at issue is whether the patients improve because they are given such a pill. Many proponents of the placebo effect think they do, and that we're seeing an example of mind over matter. But maybe not. Maybe improvement following placebo is just coincidence. If you think about it, believers in the placebo effect may have fallen into the same mental trap as those who swallow those useless pills.

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