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Diseases the placebo effect works for, and ones it doesn't work for (it's to do with dopamine)

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3,263
The article linked to in the first post of this thread is about which diseases respond well to the placebo effect, and which respond poorly. To quote the article:
Parkinson’s, chronic pain, irritable bowel syndrome, depression, anxiety, certain types of asthma, and autoimmune deficiencies are all very placebo-responsive. But cancer is not.
Yea, this is because the processes that underlie the placebo effect operate to bias the way we perceive and recall symptoms in a fluctuating context. So it will only work if your outcome measure involves reporting symptoms in a fluctuating context.

So, not cancer.

If I could do one thing to improve the psychological education of doctors, it would be to disabuse them of their firmly held preconceptions about the 'power of the placebo'. Its the gateway drug to psychobabble.
 

Mithriel

Senior Member
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It is also misused. There was an article in the papers that said that placebo pills were just as effective in depression as antidepressants, but it turns out that the actual paper showed that while that was technically true it was a false impression. The highest responders to placebo did have the same outcome as the lowest responders to antidepressants but most of the patients treated with traditional medicine had a far better response.
 

Hip

Senior Member
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If by the placebo effect you mean expectancy effects (higher chance of reporting success if one believes one has had a potentially helpful treatment than if one doesn't), then they are a human universal.

MECFS people are likely to be just like other mere mortals, they will be vulnerable to confirmation bias, recall bias, and all the other things that may contribute to expectancy effects.

I agree that much of the placebo effect may be due to expectancy effects, which create a bias in the way patients view and report their symptoms. The following nicely captures what you are saying:
Another study in 2011 on asthma patients found that placebo inhalers had no effect on increasing lung function. But asthma patients nevertheless reported that they felt significantly better after using a “useless” inhaler – a baffling result to say the least.

Source: The placebo effect: is there something in it after all? | Science | The Guardian



But I am partial to the idea that in addition to expectancy effects, in diseases involving abnormalities in brain dopamine, a placebo may have a direct physiological action in the brain, based on the fact that positive expectancy raises brain dopamine (which it does: see the PET study below).

This could be why the placebo response in depressed patients is particularly strong: because dopamine itself has antidepressant effects (many antidepressant drugs work on the dopaminergic system), so in the case of depression, placebos may be directly and physiologically modifying the illness (but to complicate things, there may also be expectancy effects going on as well, which introduces bias in reporting one's symptoms).

In clinical trials, the placebo response rates in depression are 30% to 40%. Ref: 1

In terms of evidence for the dopamine-raising effects of placebos, this paper says:
The activation of dopaminergic system when giving placebo has been documented by using PET with the D2/D3 receptor–labeling radiotracer 11Craclopride. One study performed on healthy subjects proved that intravenous placebo induced dopamine release at the basal ganglia level. In patients with Parkinson's disease, placebo administration produces dopamine release in both dorsal and ventral striatum, as well as in the limbic system. By providing dopamine at the dorsal striatum level, the alleviation of motor symptoms in Parkinson's disease appears as a logical consequence.

So administration of placebos causes dopamine release in the brain, which logically may lead to improvements in diseases like Parkinson's, where there is dopaminergic dysfunction.



I am however certainly against any "mind over matter" interpretation of the placebo effect, the idea that the mind can somehow magically affect disease outcome. I think this idea is nonsense. If the placebo effect can directly improve some diseases, it will be via tangible physiological mechanisms in the brain, such as the dopaminergic activation that positive expectancy creates.
 
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A.B.

Senior Member
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3,780
But I am partial to the idea that in addition to expectancy effects, in diseases involving abnormalities in brain dopamine, a placebo may have a direct physiological action in the brain, based on the fact that positive expectancy raises brain dopamine (which it does: see the PET study below).

That sounds like the reward system in action. Giving a person something they want will produce a feeling of satisfaction and dopamine is involved in that.

It's one thing to observe such a reaction and another to conclude that placebos are good for treating any illness.
 

Hip

Senior Member
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17,824
One study mentioned in the Guardian article had a very interesting finding: in MRI scans they found physical differences in the mid-frontal gyrus in the brains of placebo responders, compared to placebo non-responders. So people who are susceptible to the placebo effect tended to have a different brain architecture:
Baliki used an MRI scanner to observe in real time how the brain of patients responded to a placebo – in this case a sugar pill instead of a painkiller. In short, he found that an area within the mid-frontal gyrus lit up or, in his own words, “showed a higher functional connectivity” in patients who responded to the placebo, compared with non-responders.

He concluded that this brain region seemed to be quite separate from another region of the brain known to be involved in responding to the effects of real painkilling drugs. In other words, Baliki appeared to have found the “seat” of the placebo effect within the brain.


The utility of this finding is the following:
The findings suggest a biological basis for the placebo effect and raise the prospect of tests to see if individuals are going to be good placebo responders or not. For those who are responders, it could mean targeting them with placebo pain treatments that might work specifically for them. Or it could result in identifying placebo responders so that they don’t get included in clinical trials, which have long been thought to be compromised by them.

So maybe in future, if placebo responders can be reliably excluded from clinical trials, such that the trials only use placebo non-responders, conceivably it might be possible to do away with the control group, which would make conducting trials much easier and cheaper.
 

Groggy Doggy

Guest
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One study mentioned in the Guardian article had a very interesting finding: in MRI scans they found physical differences in the mid-frontal gyrus in the brains of placebo responders, compared to placebo non-responders. So people who are susceptible to the placebo effect tended to have a different brain architecture:



The utility of this finding is the following:


So maybe in future, if placebo responders can be reliably excluded from clinical trials, such that the trials only use placebo non-responders, conceivably it might be possible to do away with the control group, which would make conducting trials much easier and cheaper.
Not to derail your thread.. but wonder if placebo responders (dopamine starved) are more prone to addiction or addictive habits? And if so, like the chicken and the egg... was it the addiction that started the brain dysfunction or was it the brain dysfunction that started the addiction.
http://www.npr.org/sections/health-...brain-differently-depending-on-what-you-play?
 
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3,263
So @Hip, you're saying that depressed people feel more hopeful on their dummy pills, and this in turn produces dopamine that helps treat their illness? Its certainly an interesting idea.

BUT: depression has a lot of other features that could explain the high responsiveness to placebo:
- fluctuating symptoms (some days are better than others)
- relatively high rates of spontaneous remission
- severity is measured entirely through self-report
- time to diagnosis is relatively short, on average (a lot shorter than MECFS).

Also, human contact and having a regular daily schedule of activity might actually be effective interventions for depression too, so you would want to be sure your control group was the same in all respects except for the dummy pill.

I also worry about any treatments based on offering false hope, because the withdrawal effects can include despair and mistrust. Eventually, people will come to the realisation that despite the 'treatment', things are still really bad, and they may feel even more hopeless than before (ever tried a drug you thought might really help your ME that did nothing? Sometimes I have felt really despairing an disheartened when I finally came to the realisation it wasn't working). I think giving anyone false hope in anything is harmful, not to mention disrespectful.
 

Hip

Senior Member
Messages
17,824
So @Hip, you're saying that depressed people feel more hopeful on their dummy pills, and this in turn produces dopamine that helps treat their illness? Its certainly an interesting idea.

That's the general idea proposed by the article I linked to in the first post, by Erik Vance, who says that the placebo effect involves a dopaminergic mechanism, and so stands a good chance of working for diseases where dopamine is low, or for diseases where increasing dopamine may be helpful.

Perhaps the best illness to test his theory on would be epilepsy, since it is easy to get objective evidence of improvement (improvement would translate to a reduced frequency of seizures, which can be objectively measured). Epilepsy is an illness which responds to increased dopamine, as dopamine agonists are known to improve epilepsy.


I am not suggesting that using placebos is a good way to treat illnesses; but in terms of understanding the placebo effect and the way it can confound clinical trials, this dopamine theory looks interesting.
 

lauluce

as long as you manage to stay alive, there's hope
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the article says: "The latest research in biochemistry reveals that your brain can actually self-medicate.", it's like saying "that's why you shoudn't bother your doctor, the medical system, or the goverment about your disease, yo can heal it with positive thinking! stop being so negative! it's your fault you're sick, don't you see?"
 

Mary Poppins

75% Smurf
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560
Just watched my FIL die of Parkinson's

It's a slow, cruel disease. Slowly dying over a period of years. Took 2 weeks without food at the end to finally find peace. No amount of therapies or pills brought any kind of placebo relief to him.

I am cynical.

My deepest sympathies; I'm in the same situation with a close family member. I'm not sure if you're still around on PR but I couldn't read your post and not offer emphatic condolences.
 

Mithriel

Senior Member
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690
Location
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There were headlines about placebo pills working as well as medication for depression which surprised me until I read an article about the study. What they actually found was that the highest responders to placebo did just as well as the lowest responders to SSRIs so it was technically true. But the results for the active medication were much better.
 

TenuousGrip

Senior Member
Messages
297
I haven't read the entire thread so please forgive any repetition.

I'm wondering if ME/CFS might represent a unique phenotype vis-a-vis the Placebo Effect.

Most of us have probably been led down the path of There Is No Hope for years and years -- primarily by the medical community. While I can't swear that we're the only group that Medicine treats just this way, I do believe we're notorious for the invalidation, dismissal, and psychologizing of our illness (even if only among ourselves <grin>).

In other words: we may not stand alone in this regard but this is how we tend to be treated.

By definition, doesn't the Placebo Effect require some measure/a certain kind of faith ? What happens to your susceptibility to placebos if you no longer have that faith ?

I sometimes wonder if I'm jinxing myself (ie, eliminating the possibility of any placebo effect) when I order a new supplement ... 'quite sure that it isn't going to work' ;-)

TL;DR: can pessimists have a true Placebo Effect ?
 
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Yes, I've noticed a similar experience through the years - feeling better when researching or preparing for a new treatment. I'm a big fan of the placebos of Hope, Optimism, and Magical Thinking, and have tried to modify my thinking to include more of them. For me at least, they give me a guaranteed boost when imagining a positive outcome, with a possible second boost if that outcome ever comes to pass. Earlier in this thread, a poster mentioned that placebos are a mental "distraction" from a measurable medical condition, and effects from placebos have been criticized as being subjective rather than objective. I am very open to mental distractions that improve my subjective reality!
Mr.cat please i found your post when you talked about bemer that it didnt do you well that you felt horrible energy and so on couldnt sleep i got the same problem please im so desperate im now on antidepressant can you tell me how you solve this problem please