Warning labels can act as nocebos

Remember the nocebo effect? It's the flip side of placebos. Placebos can make people feel better or even relieve pain (to a certain extent). Nocebo happens when a placebo causes negative side-effects—nausea, racing heart, dizziness, etc. And here's one more weird thing to add to this veritable bonfire of weirdness: When we tell people about the possible negative side-effects of a real drug, that might make them more likely to experience those side-effects.

In one study, 50 patients with chronic back pain were randomly divided into two groups before a leg flexion test. One group was informed that the test could lead to a slight increase in pain, while the other group was instructed that the test would have no effect. Guess which group reported more pain and was able to perform significantly fewer leg flexions?

Another example from the report: Patients undergoing chemotherapy for cancer treatment who expect these drugs to trigger intense nausea and vomiting suffer far more after receiving the drugs than patients who don’t.

And, like placebos and classic nocebos, this isn't just "all in their head"—at least, not in the sense that they're making it up or deluding themselves. There are measurable physical effects to this stuff.

As science writer Steve Silberman says in the article I've quoted from above, what we're learning here is that the feedback we get from other people ("That might make you feel yucky" or "You look tired today") has a physical effect on us. It's a little insane. It's also worth thinking about when we talk about medical ethics. Full disclosure of what treatments you're getting and what the risks and benefits are is generally regarded as the ethically right way to practice medicine. And that's probably correct. But how do you balance that with what we know about placebo/nocebo? What happens when transparency keeps you from using a harmless placebo as a treatment? What happens when transparency makes you more likely to experience negative health outcomes? It's a strange, strange world and it's not always easy to make the right ethical choices.

Read Steve Silberman's full story on the nocebo effect



  1. True story, if my mom was telling the truth.

    When she was young, gorgeous, and just starting in an office job (during WWII, she rebuilt aircraft generators…but that’s another story), one of the mid-level managers made a crude, physical, and distinctly unwelcome pass at her first thing one morning.  She was pissed.

    She got together with all the ladies in the office and had a quick meeting.  They’d all been groped by this guy at one time or another and were happy to help.  The plan: they all, individually and randomly that morning, would walk by his desk.  Then stop and look at him with a look of concern.  Then move on.  If he asked (and he did, to almost every one of them), they’d ask him if he was OK and mention that he didn’t look well.  According to mom, when they got a chance they really poured on the sympathy.

    He took it all to heart and left on sick leave before lunch.  They had so completely convinced him that he was sick that he stayed gone for an extra day.

    Costing the guy a day and a half of sick time was a small price for his forwardness but, given management attitudes back then, it was considered by all the ladies in the office to be a major win.

    Yes, “…the feedback we get from other people…has a physical effect on us.”  Definitely.  But I never thought it was “…a little insane.”  I thought this was just something that everyone sorta instinctively knew.

    1. Makes one rethink the “innocence” of schoolyard verbal bullying. Tho perhaps experiencing such, directly or indirectly, have a mental inoculation effect (if it does not kill the “patient”, that is).

  2. Maybe it makes sense to not read the list of side effects when taking a drug.  If you experience new symptoms, that’s useful information to have around when trying to determine if those are likely to be drug side-effects, but reading the list in advance might be counter-productive.

    1. Unless you’re considering not taking the drug, or choosing a different one.

      For instance, I get nosebleeds very easily – if two drugs are both indicated for some condition I have, I’ll favour the one that isn’t likely to lead to nosebleeds (I even get nosebleeds from the recommended dose of dextromethorphan – nosebleeds from DXM are sufficiently rare not to make it onto the list in the package; I only confirmed it by googling and finding references to it on forums for people who drink ridiculous amounts of the stuff to get high).

      1. Yeah, that’s a good point, it makes a big difference if the drug is one where you have a lot of options (cold medicine) or one that you’re basically stuck with (chemotherapy).  And if there are specific things you’re looking out for, a chance to avoid those can outweigh the chance of psychosomatic side-effects.

        Maybe lists of side-effects should be divided in some way into those likely to cause nocebo symptoms (headache, nausea) and those unlikely to (including nosebleeds?).  Don’t know.

  3. I’m a radiologist. We give contrast media (iodine containing drugs) for CT scans many times a day. Some years ago there was a discussion about whether informed consent should be obtained. Many people feel warm (big deal), some feel a little queasy (big deal). Some get hives, they go away in a few hours. But some, a very few, have an anaphylactic reaction which can be life threatening. There was research 20 years ago or so that demonstrated a sharp increase in  reactions, including moderate and severe reactions,  if the patients were told it might happen. Therefore, by giving information, you are putting the patient’s life at risk. My judgement is that it is unethical to risk the patient’s life in that way.
    It is also interesting that, while it is somewhat understandable that saying “you might feel nauseous” could promote nausea, the anaphylactic reaction is basically an immune reaction, which you wouldn’t really think would have much input from the brain. But it does happen. 

    1.  That’s bizarre. I believe you – but the body is very weird.

      There are more things in heaven and earth, Horatio,

      Than are dreamt of in your philosophy.

    2. I work in high-field MRI research. If you move too quickly in a strong magnetic field (as produced by the machine), it’ll make you feel dizzy and possibly nauseous. We used to warn volunteers about the nausea. But then we realised far more people reported feeling nauseous after we started warning them. Now we warn about the dizziness and make sure nobody moves too quickly. Reports of nausea have all but disappeared.

      For the record, nether effect is harmful, it just feels a bit unpleasant at the time.

    3. You forgot to add females also feel like they are urinating. Peeing and feeling a rushing warmth is the most common reaction I’ve always got. Ladies actually feel better that they are told to expect that sometimes.

      -The peson who does the consenting, starts the IV, fills out the forms, takes the history, talks to Radiologist/MDs to protocol the exam , and also inserts the enema for the rectal contrast. (Can you tell it was a tough day today? Lol)

  4. I never read pill labels.  In fact, I draw pills at random from a large barrel like they use for Lotto, and swallow them eyes closed.  Maybe it’s aspirin, maybe it’s Adderol,  maybe it’s Viagra!

    The mystery is half the fun!

  5.  Interesting. I tweeted back in April: “I just figured out how to double the effectiveness of a placebo: introduce side effects.” Glad I didn’t wait.

    1. It’s done, and refered to as “active placebo” – using a drug with similar side-effects to the drug under study, but (hopefully) none of the effects you’re testing for (e.g. atropine as the placebo for tested drugs that cause dry mouth, or pins poked in non-acupuncture points as the placebo for acupuncture treatments)

  6. Are you all friggin’ crazy!?  There’s a damn good reason why you do not tell the general public that nocebos even exist, much less that they have measurable impact.  

  7. We had chemo patients who would throw up in the parking garage before they even made it into the hospital for their first dose.  And they had the worst problem with chemo once they started the course.

    1. Interesting. Atul Gawande talks about this sort of phenomenon in Complications, but as something that happens over time, not as nausea that precedes the treatment.

  8. I’ve been saying for years there’s probably a nocebo basis to a class-action lawsuit against those responsible for plastering horrific imagery on tobacco…

    And before anyone attempts to counter with some crap about choice, they might care to look up the meaning of addiction. The fact is, many smokers don’t die of a horrible smoking-related illness, but presumably reminding them that they’re likely to will increase the proportion who do.

    Then there’s the simple principle that it’s just dumb to bring even more yuck into the world…

  9. Karl Pilkington once asked “Does the brain control you or are you controlling the brain?” and of course Steve Merchant and Ricky Gervais laughed hysterically at him. But seriously… SERIOUSLY! Our brains are up to all sorts of @#$! we know nothing about!

    1. “The mind commands the body and it obeys. The mind orders itself and meets resistance.”
      — Augustine of Hippo (354 – 430CE)

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