Today I found out about the “nocebo effect” which is more or less the evil twin of the placebo effect. The nocebo effect is an effect where a patient is given or told something that should make no difference whatsoever to their health, but ends up causing negative side effects because of what they believe about the thing they are taking or is done to them. Similar to the “placebo” effect where patients are given a similar such agent that ends up positively affecting their health.

The name ‘nocebo’ was chosen by Walter Kennedy in 1961 to describe these results caused by negative suggestion as it is specifically Latin for “I will harm”, whereas ‘Placebo’ is Latin for “I will please”. So if given some fake medication that should do nothing and it produces a positive result, it is to be called a placebo result; if negative side effects are reported than a nocebo result; both being caused only by the patient’s expectations and not from any other outside factor.

Despite Kennedy suggesting this all the way back in the 1960s, it wasn’t until the 1990s that distinguishing between a placebo and a nocebo became popular. Prior to that, they were just all called placebo effects or placebos. Indeed, even today it is somewhat controversial to have a separate name for these two things as it is entirely possible to have a fake drug given that could be accurately described as both a placebo and a nocebo. Such as the case where a person is given a sugar pill and told this “drug” will take away their headache, but may cause dry skin. If the patient reports that it takes away their headache, but they now have dry skin, then it is both a placebo and a nocebo, which can obviously be confusing. Though the benefit to this terminology is that the specific effects can now be more accurately distinguished; referring to the placebo effect for the positive result of taking away the headache and the nocebo effect being the negative result of dry skin; both as a result of this fake agent combined with the patient’s belief about what they are taking.

Because of the potentially negative side effects caused by the patients own beliefs, which can even be lethal at times, research on nocebos has been very scarce, though there are some well documented cases such as a study where 34 college students were hooked up to a machine and told that a small amount of electric current would be passing through their heads and it should cause them to have a headache. In fact, the machine did nothing, but over 2/3 of the students reported developing a headache while hooked up to the machine.

Another interesting one that demonstrates both the placebo and nocebo effect in one study is a study done by Japanese researches on 57 high school aged boys. They selected these boys based on the fact that when exposed to Lacquer trees, these boys would get a severe rash, much like is common with poison ivy. They then blindfolded the boys and proceeded to brush one of their arms with the Lacquer tree leaves and the other with an innocuous leaf that would have no effect. They told them however that the arm brushed with the laquer tree was brushed by the harmless leaf and the one brushed by the harmless leaf they were told was brushed by the Lacquer tree leaf. What followed was a rash developed on most of the boys arms that were brushed by the harmless leaf and the other arm that was actually brushed by the Lacquer leaf that should have caused a rash was completely fine in nearly every case.

Another such study where both the placebo and nocebo effects were observed was an experiment with asthmatic patients. They first were made to breath in a vapor that they were told was an irritant or allergen, but in fact was harmless. About 50% of the patients proceeded to experience breathing problems, with several experiencing full blown asthma attacks. All the patients who had trouble were then treated with “medicine” and all recovered immediately. In fact, both the irritant and supposed medicine were the exact same solution, nebulized saltwater.

This effect has also been observed very commonly in patients who fixate on supposed side effects of real medication. Even when given a nocebo, many will report having the negative side effects that can be associated with the real drug. Indeed, both the placebo and nocebo effects have been observed recently to be becoming “more effective” in that placebos are suddenly working better and likewise more people given fake drugs are reporting the side effects associated with the actual medicine. It’s theorized, though nobody really knows why, that this could well be because people are now much better informed about the drugs they take and the side effects, both through more drug advertisements and the readily available information on the internet.

In some cases, this nocebo effect has actually been lethal to patients. For instance, in the 1970s doctors diagnosed a man with liver cancer and told him he had just a few months to live. This was not some sick trick, they really thought he had liver cancer. He died within a few months of apparent liver cancer like effects. Upon doing his autopsy though, they found the doctors had been mistaken and he did not in fact have liver cancer at all and other than being dead, had a healthy enough body.

This effect is also why doctors will often not tell patients when a procedure may be particularly painful. It has been found that in doing so they drastically increase the amount of pain the patients report feeling throughout the procedure. Likewise, doctor’s warning about all possible side effects of a particular drug seems to drastically increase the number of side effects patients experience, even when given nocebos. By neglecting to be 100% honest with the patients about negative side effects, it generally seems to work out better for the patients because of this mysterious nocebo effect. Likewise, being overly optimistic about the positive effects of some drug seems to drastically increase the effectiveness of the drug because of the equally mysterious placebo effect.

Exactly why either of these things should be the case is not yet understood.

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