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Ah_Go_On t1_isca431 wrote

Absolutely. Placebo in Latin means "I will please". The medical sense was recorded in writing by 1785, "a medicine given more to please than to benefit the patient." Nocebo in Latin means "I will not please". This refers to, say, hearing that a drug has a certain side effect and experiencing that side-effect psychosomatically when you take it. There is an element of priming since your mind is expectant, so even if this side effect is indeed due to the drug the subjective experience of it can be enhanced. It can also extend, as you say, to people being mistrustful of medicine in general experiencing far greater adverse effects than people more open to medical treatment. The causality here and the physiological vs psychological effects are obviously very difficult to determine. Anyways, it's called the Nocebo effect:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804316/

Even the wiki on this is pretty good:

https://en.m.wikipedia.org/wiki/Nocebo

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Liamlah t1_isdqee8 wrote

>Nocebo in Latin means "I will not please"

"I will harm" is a more accurate translation.

though the phrase "Primum non nocere" translating to "First, don't not please" would be kind of funny.

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dogquote t1_iscjqxo wrote

This is crazy amazing, and I learned something today. I wonder how much of this is related to vaccine apprehension. Is nocebo studied in trials along with placebo?

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Ah_Go_On t1_iscmfz5 wrote

In trials not really since all participants in trials must sign an informed consent form and in that process are informed of the details of the trial's objectives and possible outcomes, including the fact that they may receive a placebo, assuming a placebo is used in the trial. Nocebo is more often investigated retrospectively for ethical reasons.

I don't doubt that some people who didn't want (e.g.) a COVID-19 vaccine but who had to get it to keep their job (or for whatever reason) may well have experienced more side-effects than others. But this is where it gets complicated, cos some people who didn't want the vaccine, say, because they heard other people became ill after getting it - then they get it and are psychologically determined to not feel ill, cos they're "not a pussy" or whatever. But such people may still get destroyed (temporarily) by post-vaccine flu-like symptoms because ultimately individual genetic/metabolic variation is a stronger determinant of treatment response than psychological disposition (but it's not always as simple as that!)

Edit: this is a very interesting paper on side-effects in vaccine placebo arms:

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2788172#:~:text=The%20ratio%20between%20placebo%20and,51.8%25%20after%20the%20second%20dose.

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grandmabc t1_iscqsq3 wrote

Before I had my first covid jab, I was convinced it would give me flu like symptoms. I fully expected to be under the weather for several days... but nothing, no side effects at all. Now I'm wondering why I didn't get a nocebo effect.

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Ah_Go_On t1_iscvoqj wrote

Because psychological phenomena are at least as inconsistent as they are powerful :) Every imaginable factor/circumstance affects patient responses to drugs/devices/therapies. Clinical researchers can not and do not ignore placebo/nocebo effects, but their operating principles have to rely on genetic/metabolic/pharmacodynamic/pharmacokinetic data, since those are clinically measurable. Unlike thoughts and (to some extent) feelings. The disconnect between the two is the basis of mandating PROs (Patient Reported Outcomes) and HRQoL (Health-Related Quality of Life) reports to be regularly gathered from clinical trial participants:

https://en.m.wikipedia.org/wiki/Patient-reported_outcome

https://en.m.wikipedia.org/wiki/Quality_of_life_(healthcare)

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slouchingtoepiphany t1_isd34co wrote

You're absolutely correct, I work in clinical research and studies are often double-blinded, so we don't know who receives active treatment and who receives placebo. If any adverse events (AEs) occur, we record the information and later, when the study is unblinded and the data are analyzed, that's when we know if the study drug causes any AEs more than placebo.

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Ganymede25 t1_isd7j0z wrote

That is interesting. I was in the Pfizer trial. When they unblinded us, the nurse that was giving us the results asked if we thought we had received the real thing or saline. At the time, she said that the participants were 100% correct. I don't know if that was an official question for the trial, but I think she just wanted to know if the guesses were correct.

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slouchingtoepiphany t1_isd8rzm wrote

I don't see how participants could have guessed correctly, unless everybody thought that they received the actual vaccine. In that case, the people who received active treatment were 100% correct and the people who received placebo were 100% wrong. Hmmm.

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Ganymede25 t1_isdwn2m wrote

Maybe it was because we were all paying a lot of attention to any details associated with the vaccine. For instance, both the experimental and control people would have pain at the injection site, but only people receiving the vaccine would have the injection pain go away and a new pain show up 6-12 hours later that would last for a day. That is the result of an immune reaction. Saline would not do this. When you combine the delayed pain with a slightly elevated body temperature and a slight headache, it is pretty easy to tell when you are sort of focused on whether you got the vaccine or not.

Regarding the 100% wrong for the placebo, maybe you got confused on my comment. In the trial, 50% of the people received the vaccine and 50% of the people received saline. The people who received the saline knew that they had no symptoms and were 100% correct that they didn't get the vaccine.

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slouchingtoepiphany t1_ise8sfe wrote

I did misunderstand your previous comment. It's conceivable that people who guess correctly had experienced delay hypersensitivity reactions at the injection site (with vaccine, but not with placebo), but it's also possible that the group of correct guessers was small, say 3-6, and with a smaller number it's easier to obtain a series of correct guesses by chance alone. It's like flipping a coin and having it come up heads 3-4 (or more) times in a row. Statistics can do that. However, I think it's more likely to be the delayed hypersensitivity reactions.

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eltrebek t1_isdsqy0 wrote

Adverse effects with placebo tend to range from 1-10% when reported in approved drug package inserts. I don't know why adverse effects to placebo are individually in the minority, but it does suggest that at baseline, this isn't an effect that guarantees a poor outcome.

Glad you had an uneventful reaction to your jab despite expectations <3

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International_Bet_91 t1_isfbzcc wrote

The majority of side effects of the Covid vaccine are thought to be nocebo.
This article in Nature says 76%

People who haven't heard that there are side effects to vaccines, don't experience side-effects. İn my opinion, that means we should stop posting on social media about how we were in bed for 2 days after the vaccine.

https://www.nature.com/articles/d41586-022-00146-y#:~:text=%27Nocebo%27%20underlies%20vaccine%20side%20effects&text=Researchers%20reviewed%2012%20randomized%20clinical,fatigue%2C%20after%20the%20first%20dose.

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Rice-Weird t1_ise2gb0 wrote

Due to varied outcomes depending on outlook, it is sometimes called the 'expectancy effect,' and doesn't have to be a chemical treatment. Listening to a tone that has been 'experimentally shown to influence/diminish/ improve performance' will show an effect. This is why personal anecdotes can't be relied upon. If I pay for a quack treatment that had done wonders to treat my complaints, you may feel and believe it works due to nothing more than expectation. The take away is that you should choose to believe your efforts & choices are mightily helpful when committing to them!

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Mjolnirsbear t1_isfcuot wrote

And there is a drug that blocks the nocebo effect, cholecystokinin antagonist proglumide.

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Boas-Malinowski t1_isc9hw9 wrote

Yes. Or diminish its efficacy. Or cause illness. It's called a nocebo effect. It's been known about for awhile, even if it wasn't called that. Walter Cannon in 1942 wrote a scientific article about VooDoo Death, explaining how belief in the curse can cause real physiological outcomes (like death).

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cupris_anax t1_ischfxd wrote

I remember reading about a case where an immigrant woman from africa went to the hospital somewhere in the US, with complaints about pain and partial paralysis "due to a curse". Doctors examined her and she was dismissed from the hospital after concluding that she was fine. She came back and this was repeated 3-4 times. First they thought she was trying some sort of insurance scam (i think she was homeless), but finally decided to call a "priest" with knowledge about her religion who performed something like an exorcism on her. She was fine after that.

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SeeMarkFly t1_iscqk5y wrote

Whatever you think has an effect.

Here is another example.

A 2014 study published in the Journal of Public Health found that people whose spouses had just died had a 66% increased chance of dying within the first three months following their spouse's death. 2 Prior studies had placed the increased chances of death for the surviving spouse even higher, at up to 90%.

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carrotstien t1_iscst9d wrote

wouldn't that be more easily attributed to stress related to a loss of a loved one..coupled with usually people lose spouses when they are both old

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Jimmy2Hertz t1_isf25e1 wrote

Seems pretty obvious that an elderly person with likely health issues and at risk of further ones would experience a fatal issue due to stress. People really underestimate how bad being stressed is for your entire physiology, suppressed immune system, hormonal imbalance, poor eating habits, blood pressure and heart rate fluctuations and many more things happen that can trigger serious issues in a short period of time.

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Significant_Sign t1_isd7hyk wrote

Aren't both nocebo & placebo seen really just in the area of pain management? Nocebo can't make you get cancer or whatever.

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KodaSmash12 t1_iscam8q wrote

Yes actually. What you're thinking of is called the nocebo effect. Distrust and other similar things can cause symptoms to worsen and cause problems health wise.

Infact Voodoo is one of the biggest causes of the nocebo effect, which can go so far as to cause death. All with just the power of belief.

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regular_modern_girl t1_iscvnc2 wrote

A lot of culture-bound syndromes are also partly based on this phenomenon, particularly those concerning some type of perceived witchcraft.

One of the more peculiar examples is Koro, aka “penis panic”, which has been reported in a number of different cultures across the world, and basically involves men becoming so paranoid that a witch is making their genitals shrink and/or not work properly that they actually become delusional and hallucinate their penises retracting into their bodies (to some extent the retraction might be quite real, considering anxiety can cause testicular/penile retraction, the thing is that in reality it’s obviously not actually permanent, though).

The funny thing about culture-bound syndromes is that not only can (fear of) witchcraft cause them, but appropriate magic charms or spells can actually be effective in treating them (via the regular placebo effect, obviously).

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KodaSmash12 t1_isd4xun wrote

Isn't the brain a neat little thing? It can be affected by so many things, big and small, and all it takes is the power of belief.

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regular_modern_girl t1_isdqlxk wrote

Another interesting (possible) example of this was the very weird “Morgellons disease” phenomenon during the ‘00s.

Basically, a bunch of people around the US (and maybe elsewhere) suddenly began going to doctors complaining of some really bizarre symptoms, such as itching and general skin irritation, lesions, sensations of “crawling” under the skin, panic (and iirc some also reported memory loss), and strangest of all, the appearance of inexplicable colorful fibers in their lesions (which were claimed by the patients to be growing out of their skin), and in some cases also supposed sightings of tiny black gnats or flies exiting the lesions.

Initially, some of the medical community took the whole thing seriously, and I believe there was even a CDC investigation to see if it was in fact some novel epidemic, but fairly quickly a lot of doctors grew a lot more skeptical when they couldn’t really find any signs of any sort of parasite or pathogen whatsoever in the patients (I think it was reported briefly that a number of them had previously suffered Lyme disease, but this may not have turned out to be a significant enough correlation), and also the fact that lab tests of the mysterious fibers revealed mundane, household sources for the most part (implying that patients were placing them in the lesions themselves, and probably creating the lesions with excessive scratching).

A lot of medical professionals dismissed the whole thing as an unusually-widespread example of Münchausen syndrome (which is p much a fancy medical way of saying “bullshitting for attention”), but there were also some more charitable assessments that it was actually an unusual epidemic of delusional parasitosis (where, again because of the nocebo effect, a person actually starts experiencing signs of parasitic infestation simply by psyching themselves into believing they have parasites) spreading as a culture-bound syndrome (partly due to the internet).

In my humble opinion, I think it was probably some mixture of both genuine psychogenic illness and Münchausen.

From what I understand, the whole thing calmed down after a few years and people stopped reporting “Morgellons” symptoms mostly, although I’ve heard it still occasionally pops up as a thing even to this day.

It just goes to show that, even though there’s a popular perception of culture-bound syndromes as a phenomenon of less enlightened past times and “primitive” cultures, something that we educated Westerners are surely above, the thing is we’re not, we’re still human and just as subject to these things as anyone else, really no matter how “rational” we think we are.

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fatWhiteGoodman t1_ism6zx1 wrote

Great response. CDC did a deep dive into it. Another hypothesis was some kind of fabric (fibers) or substance getting into human skin. But they could never identify much of anything in common between subjects. I think some kind of mental disorder like delusional parasitosis is still the most likely interpretation based on the experiences I had with patients.

But yes, there are multiple doctors like Stricker still publishing about Morgellon's to this day.

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GoldPhoenix52 t1_ise1qt9 wrote

Ngl “Nocebo” sounds like something you just made up. I know it isn’t, but the name is silly

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PvtDeth t1_isdwbd6 wrote

All these posts are citing the nocebo effect, but not in the context of the original question. Yes, nocebo is the opposite of placebo, but the question was >Can your body prevent a medicine from working because you strongly believe it doesn't work?

So, we know belief in a side effect can cause the side effect, but can disbelief in the beneficial effect of a medicine diminish that effect.

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c3fepime t1_ismsrde wrote

Yes- if you are in pain and you take a painkiller that you believe is ineffective, you will experience less pain relief.

One interesting example is to compare pain management after surgery in the U.S. versus Europe. Opioids are prescribed for post-operative pain something like 10x more commonly in the U.S. than in Europe. In Europe, often the combination of ibuprofen (or other NSAIDs) and paracetamol (acetaminophen) is the only pain medication given after surgery. In the U.S., if you just give ibuprofen and acetaminophen, most post-operative patients will report uncontrolled pain, and will require opioids to get it under control.

It has been suggested that one factor at play here is a cultural nocebo effect in the U.S. towards non-opioid pain medications, i.e., belief that they are "weak" pain killers that could not possibly be effective for post-operative pain since they are generally used for "mild" everyday aches and pains.

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PvtDeth t1_isn0jbj wrote

Thank you. This is great info. Anecdotally, it might explain why I don't seem to need much pain medication.

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pyrophilus t1_isep2aw wrote

20 years ago, I read somewhere in one of my college psyche or bio (was double-major) textbook that a study was done using milk spiked with caffeine and decaf coffee.

Two groups of students cramming for exams were studied. One group was given milk with same amount of caffeine as regular cups of coffee, and other group was given decaf. Neither groups were told about the caffeine content and the decaf group thought they had regular coffee while caffinated milk group thought they had plain milk.

While decaf folks thinking that they had caffeine and being able to stay up and study wasn't surprising, the study found that a large portion of the milk drinkers reported not being able to stay awake.

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Eqvvi t1_iseqxj6 wrote

Yes, Alia Crum and Ellen Langer did a similar experiment to test whether physical exercise can actually be unhelpful if the person doesn't believe it IS exercise. They tested it on hotel housekeepers: gave some of them a presentation on how their work provides healthy exercise and the control group got nothing. The group that got the presentation improved on most of the parameters they measured. https://pubmed.ncbi.nlm.nih.gov/17425538/

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It has also been tested with painkillers. If morphine is administered by a hidden IV after thoracic surgery patients don't experience as much relief as the ones who get it from a doctor (thus aware of it when it happens). They also tested it on Parkinson's disease treatment, hypertension and anxiety.

https://psycnet.apa.org/record/2003-07872-001

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And as others have mentioned, there are also studies on nocebos, that actually generate negative effects rather than just blunting the effects of a treatment.

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sanaatani t1_ishs4ox wrote

In the field of Mental Health - aside from addicting medicines - most medicines only make some things possible- more like altering the balance of multiple mechanisms.

So it is possible to "fight" the effects of the medicine unless it is very strong. That is one of the reasons that of the old antipscyhotic and antidepressant medicines the ones that worked best were those that had a sleeping side effect. This effectively bypassed the patient fighting the effects of the medicine, as the most effect is in the first few hours.

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the6thReplicant t1_isjjrar wrote

It gets even more interesting. People have mentioned the nocebo effect.

The placebo effect can backfire. Australian science popularizer Dr Karl talks about when he was on duty in a hospital he had to give a saline solution in lieu of morphine to a patient in pain. He told the patient he was giving him something to combat the pain. When the saliva solution was injected the patient’s pain went away as though he was actually given morphine.

The nurse wasn’t surprised by this and told Dr Karl to make sure they treat this medically as a morphine injection and time the next one as such since I’d they immediately gave him a real morphine injection he would OD.

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JoshuaIsBrown t1_iugzszl wrote

The placebo effect's opponent is known as the nocebo effect. It portrays a scenario in which a bad result happens because someone thinks an intervention will be harmful. It is a phenomenon that the field of medication safety occasionally overlooks. Nocebo is a derivative of the Latin word for "to injure." Nocebo suggests that patients are more likely to encounter an unpleasant reaction to medication if they anticipate or are concerned about the adverse reaction. The negative effects are frequently clinically diagnosable and may be felt physically by the patient. The extreme negative impacts patients who were given a placebo during a clinical trial experienced are an illustration of the nocebo effect. Given that negative views are developed far more quickly than positive ones, some experts claim that the nocebo effect may have a greater impact on clinical outcomes than the placebo effect.

The nocebo effect might also have an impact on how patients react to generic drugs. When switching from an innovative "branded" product to a generic pharmaceutical, some patients may experience negative effects due to pre-existing cynicism about generic medications. It's crucial to keep in mind that nonverbal communication can sometimes cause a nocebo reaction. Nocebo effects seem to be more likely to occur in some patients. To prevent unintentionally starting the nocebo effect, women, people with anxiety or despair, people with a negative attitude, and people who are highly influenced by their environment may require extra attentive counseling. By achieving a proper balance between explaining both the beneficial and bad aspects of the treatment, as well as making sure the patient understands the treatment's logic, the danger of nocebo can be decreased.

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BeuPingu t1_isci0ds wrote

Well, I don't know if this is exactly what you're looking for but I was quite impressed by the following experiment run on Wim Hof https://www.youtube.com/watch?v=BqsvJedwUyg

I wouldn't say it's the reverse placebo, perhaps the best explanation would be a manually manifested placebo.

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brianfedirko t1_iseiis1 wrote

Mental attitude has about 1/3 of the total outcome of effect in a body's ability to heal itself. It is a factor in the feedback loop of our body working in harmony with it's cells and parts.

So yes, a negative attitude about an outcome can give a disadvantage to "success"... If you don't believe the penicillin will fight the abcess, then it will suffer an amount instead of gain. If you "believe" you are allergic to penicillin, then an even worse feedback loop of the entire system will be gained. It is possible to "believe" oneself into an overdose without actually having taken the drug/poison, and the placebo effect can produce a real heart attack. There are good numbers showing this on NIH, and it should be taken into account for Bayesian reason/logic of this subject.

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