Placebo Effect Question

[Graham Jackman]

The other aspect of the placebo effect is in apparent side effects. If you conduct a clinical trial comparing an inactive treatment (placebo) against your test drug, it is advisable to monitor both groups for apparent side effects such as aches, nausea, fainting etc.. If you find no difference between the groups you are reasonably confident that the side-effects are due to normal occurrences or the imagined effect of treatment rather than truly drug-related. If homeopathy is thought to be unsuited to testing by double blind procedures, I wonder if they ever record such side-effects. of course it may be minimised by the practitioner implying that this treatment will do nothing but good, whereas in normal clinical practice we would ask the patient to report any side-effect, which may lead to more being reported.

 

[Kumar]

The Biochemical and Neuroendocrine Bases of the Hyperalgesic Nocebo Effect

. These data indicate a close relationship between anxiety and nocebo hyperalgesia, in which the CCKergic systems play a key role in anxiety-induced hyperalgesia. These results, together with previous findings showing that placebo analgesia is mediated by endogenous opioids, suggest that the analgesic placebo/hyperalgesic nocebo phenomenon may involve the opposite activation of endogenous opioidergic and CCKergic systems.
http://www.jneurosci.org/cgi/content/abstract/26/46/12014

The Biochemical Bases for Reward
Implications for the Placebo Effect
Raúl de la Fuentefernández
A. Jon Stoessl

Pacific Parkinson’s Research Centre, University of British Columbia

The authors propose that the placebo effect is mediated by reward-related mechanisms. Recent evidence suggests that it is the expectation of reward (in this case, the expectation of clinical benefit) that triggers the placebo response. In Parkinson’s disease, the placebo effect is mediated by the release of dopamine in the striatum. The authors argue that placebo-induced dopamine release in limbic structures, particularly in the nucleus accumbens, could also be a major biochemical substrate for the placebo effect encountered in other medical disorders. Other neuroactive substances involved in the reward circuitry (e.g., opioids) are also likely to contribute to the placebo response, and such contribution may be disorder specific (e.g., opioid release in placebo analgesia; serotonin regulation in response to placebo antidepressants). In addition, placebos may have a role in substitution programs for the treatment of drug addiction.
http://ehp.sagepub.com/cgi/content/abstract/25/4/387

Few people can be devited other benefited by above basis.

 

[Kumar]

The other aspect of the placebo effect is in apparent side effects. If you conduct a clinical trial comparing an inactive treatment (placebo) against your test drug, it is advisable to monitor both groups for apparent side effects such as aches, nausea, fainting etc.. If you find no difference between the groups you are reasonably confident that the side-effects are due to normal occurrences or the imagined effect of treatment rather than truly drug-related. If homeopathy is thought to be unsuited to testing by double blind procedures, I wonder if they ever record such side-effects. of course it may be minimised by the practitioner implying that this treatment will do nothing but good, whereas in normal clinical practice we would ask the patient to report any side-effect, which may lead to more being reported.

They note aggravations in right and wrong directiond, proving effects and improvements.

 

[Mashuna]

They note aggravations in right and wrong directiond, proving effects and improvements.

But they don't compare them against a control group, they just claim everything is caused by the treatment.

 

[Kumar]

But they don't compare them against a control group, they just claim everything is caused by the treatment.

They do try but can get inconsistent outcomes dye to many factors specific to these, as I indicated previously. However, if few out of a group can get placebo others not, this itself shows variations.

 

[drkitten]

That will be just experimenting stage by staking our body.

Given that you can't even prove that you have a body or that other people exist, how do you expect to prove that any substance will have a beneficial effect on other people's bodies?

 

[Kumar]

Given that you can't even prove that you have a body or that other people exist, how do you expect to prove that any substance will have a beneficial effect on other people's bodies?

Energetic effects, prime force and/or secondary force/s based.

 

[fagin]

Energetic effects, prime force and/or secondary force/s based.

Primary force= Batman
Secondary force=Robin
??

 

[Unalienable]

A large portion of warts go away without any treatment, just like headaches, regardless of your state of mind.

That's absolutely true, but it's very well understood (if not proven) by people in this industry that a salve containing nothing will make a wart go away in a larger percentage of the population than warts untreated. So it's not just a matter of some salves being applied needlessly to a wart that was about to vanish anyhow. The "state of mind" obviously has some very real measurable impact in a way that, to my knowledge, science doesn't have a very deep understand of.

Incidentally, I also read about a procedure that dermatologists use on children. They take a red magic marker and make a spot on the wart and instruct the child to do the same thing every day. Of course, the chemicals in the marker are mostly harmless and inert, but the doctor is trying to kill the wart strictly through invoking a placebo reaction. Because children are so gullible by nature, they are likely to believe the "red magic marker" method, and therefore it works for them. Very few doctors would try this on an adult, because if the patient realizes it's a scam, the placebo effect vanishes.

It could also be that a positive outlook boosts the immune system, which will help combat the virus...

That's exactly what I mean. How "positive outlook" can translate into "more effective viral fighting agents in your foot cells" is the part that I am hazy about. In college I was friends with a guy who, for lack of a better word, let's call him a "mystic." He used to explain how he could fight off a cold or some other infection by going into a medidative state and imaginging a shark swimming through his blood, the shark a symbol of the most ferocious fighter, and this shark would kill the enemies of his blood. Yeah I know, it sounds like a bunch of "woo", but when you think about the wart-reaction there might be something to his mumbo jumbo. Positive thinking = effective immune system response.

 

[fls]

That's absolutely true, but it's very well understood (if not proven) by people in this industry that a salve containing nothing will make a wart go away in a larger percentage of the population than warts untreated. So it's not just a matter of some salves being applied needlessly to a wart that was about to vanish anyhow.

How would you know that?

You may or may not be aware that there are some biases (e.g. lead-time, selection, length time, regression to the mean) associated with collecting a group of people to study that make it more likely that you will see results - i.e. it's the bias in the way that we collect people to study that produces the results, not anything specific to the study including the taking of a placebo treatment. Some people have ignored this and tried to compare the results in the placebo treated group to what we see in everyday life. Yes, the placebo treated group often does better than what we'd expect. But it's not because they received placebo, but because they were placed in a group.

For example, prostate cancer roughly follows two different courses - a fairly indolent course that may be present for years without spread, or a more agressive course that progresses steadily and spreads throughout the body. If you go looking for prostate cancer, you are more likely to find the slow-growing kind, just because it is around for much longer. And if you collect men with prostate cancer for a study, it is likely that a higher portion of them will have the slow growing kind than would be found in the general population. So your study group, because it is biased towards collecting men who are going to do better anyway, is going to show a placebo group that does better than expected from the general population of men with prostate cancer. This is a length time bias. It doesn't mean that the placebo had some sort of mind-body effect though. If you actually compare groups given placebo vs. groups given nothing, there is no difference except on some subjective perceptions.

The "state of mind" obviously has some very real measurable impact in a way that, to my knowledge, science doesn't have a very deep understand of.

Can you give an example of some research where the impact from this state of mind has been measured?

Incidentally, I also read about a procedure that dermatologists use on children. They take a red magic marker and make a spot on the wart and instruct the child to do the same thing every day. Of course, the chemicals in the marker are mostly harmless and inert, but the doctor is trying to kill the wart strictly through invoking a placebo reaction. Because children are so gullible by nature, they are likely to believe the "red magic marker" method, and therefore it works for them. Very few doctors would try this on an adult, because if the patient realizes it's a scam, the placebo effect vanishes.

Do we really know what was going to happen? That the wart wasn't going to go away? All the marker ensures is that when the wart does go away, it will be noticed, instead of forgotten.

That's exactly what I mean. How "positive outlook" can translate into "more effective viral fighting agents in your foot cells" is the part that I am hazy about. In college I was friends with a guy who, for lack of a better word, let's call him a "mystic." He used to explain how he could fight off a cold or some other infection by going into a medidative state and imaginging a shark swimming through his blood, the shark a symbol of the most ferocious fighter, and this shark would kill the enemies of his blood. Yeah I know, it sounds like a bunch of "woo", but when you think about the wart-reaction there might be something to his mumbo jumbo. Positive thinking = effective immune system response.

Cuz his cold wouldn't have gone away otherwise?

There has been some interesting research on some measurable physiologic changes with placebo. And acute stress can have a small suppressive effect on the immune system (so methods of reducing stress can help remove this suppression). But it hasn't been shown to produce changes in disease outcomes. I'm not saying that we shouldn't continue to study this, or that something useful won't come out of it, but whether or not there is anything there has been way overblown by the woo crowd. And, if present, must be very small.

Linda

 

[Unalienable]

fls:

You asked "How would I know that [it's well understood that a salve containing nothing will make a wart go away in a larger percentage of the population than warts untreated.]"

My answer, although perhaps misguided, is that in all the studies involving topical creams that I examined the test was to compare an inert cream with one containing the medicine. If the placebo effect was impossible when it comes to viral-immune responses then the application of the placebo cream could be eliminated, and doctors should feel comfortable comparing their proposed medicine with untreated warts. However, it could be argued that this practice is just done out of convention rather than necessity, and furthermore you presented another interesting argument about bias of study groups.

What you said about the natural bias due to the timing of prostate cancer is very interesting, and I had never thought of that. It strikes me as particularly relevant because warts have a characteristic life cycle: they either quickly show up and vanish, or they stick around stubbornly resisting treatment and often start to multiply.

I'm going to skip your question regarding the red-marker anecdote just because I'm short on time and it's not particularly important; my point was just that the doctors behave as if the placebo-immune effect is real, but in any case, the methods that doctors ues to treat their patients doesn't prove anything.

Your most important question was Can you give an example of some research where the impact from this state of mind has been measured? and my answer is "Not off hand but if I can locate it I will certainly share it." Your tone indicates to me that you are skeptical that any such legitimate research exists--and if you're right then what can I say, other than that I was wrong? However I boldly predict that I'll be able to come back with something that surprises you. Placebos have a role in nearly every single medical experiment--there should be more data on this subject than just about any other in medicine!

Anyhow, in conclusion you admit acute stress can have a small suppressive effect on the immune system (so methods of reducing stress can help remove this suppression) so taking that into account, I can imagine a variety of "non woo" possibilities which might seem, on the face of it, almost mystical, but could be entirely scientifically validated. Just for instance, perhaps "normal stress levels" (which in the modern day are probably very high by historical standards) create a large supressive effect that most people suffer under, and if one could learn to create a state of mind so utterly stress free, it would unleash powerful benefits to the immune system. Which brings us right back to the shark.

 

[fls]

fls:

You asked "How would I know that [it's well understood that a salve containing nothing will make a wart go away in a larger percentage of the population than warts untreated.]"

My answer, although perhaps misguided, is that in all the studies involving topical creams that I examined the test was to compare an inert cream with one containing the medicine. If the placebo effect was impossible when it comes to viral-immune responses then the application of the placebo cream could be eliminated, and doctors should feel comfortable comparing their proposed medicine with untreated warts.

I see. It turns out that we continue to be surprised at just how much our subjective perceptions influence what would appear to be something that is measured objectively, such as the presence or absence of a wart. Continued use of placebos helps guard against that.

Your most important question was Can you give an example of some research where the impact from this state of mind has been measured? and my answer is "Not off hand but if I can locate it I will certainly share it." Your tone indicates to me that you are skeptical that any such legitimate research exists--and if you're right then what can I say, other than that I was wrong? However I boldly predict that I'll be able to come back with something that surprises you. Placebos have a role in nearly every single medical experiment--there should be more data on this subject than just about any other in medicine!

Not skeptical, but wanting to get a clearer idea of what you think illustrates the state-of-mind effect.

Anyhow, in conclusion you admit acute stress can have a small suppressive effect on the immune system (so methods of reducing stress can help remove this suppression) so taking that into account, I can imagine a variety of "non woo" possibilities which might seem, on the face of it, almost mystical, but could be entirely scientifically validated. Just for instance, perhaps "normal stress levels" (which in the modern day are probably very high by historical standards) create a large supressive effect that most people suffer under, and if one could learn to create a state of mind so utterly stress free, it would unleash powerful benefits to the immune system. Which brings us right back to the shark.

Sorry, that one doesn't fly. The system doesn't really work that way.

Linda

 

[Jeff Corey]

... I can imagine a variety of "non woo" possibilities which might seem, on the face of it, almost mystical, but could be entirely scientifically validated. Just for instance, perhaps "normal stress levels" (which in the modern day are probably very high by historical standards) ...

Can't you see that that is not ever possible of being scientifically validated (whatever that means)?
I wonder what the stress level of an European peasant dying of the Black Death, while trying to save her babies was, maybe less than the victims of the Spanish Inquisition or the Rape of Nanking. Or are you talking about the stress of Tiffany Soccermom when there are so many SUVs on the road that she can't get to her psychotherapist on time?

 

[blutoski]

Can't you see that that is not ever possible of being scientifically validated (whatever that means)?
I wonder what the stress level of an European peasant dying of the Black Death, while trying to save her babies was, maybe less than the victims of the Spanish Inquisition or the Rape of Nanking. Or are you talking about the stress of Tiffany Soccermom when there are so many SUVs on the road that she can't get to her psychotherapist on time?

There are stress indexes used in psychology that are somewhat standardized for this purpose. The one I've seen used most frequently is the Elder Life Stress Index (ELSI). It scores premature death of spouse as the most stressful event, for example. There is also the important distinction between egocentric vs nonegocentric (external) stress.

Using this and simiarl indices, it has been proposed that we are in the lowest-stress era of human history.

(I sort of wear two hats: not only do I have a degree in immunology, I also have a degree in family psychology, and stress levels are relevant to treatment planning in both fields.)

 

[blutoski]

A few years ago I had a common wart on my foot, I did a little research and found that it was the virus called papilloma, and that it's very common, not particularly harmful, and curable using a brute-force method of killing millions of skin cells, both healthy and infected, until you force it into remission.

But here's what made my jaw hit the floor... I was reading up on a variety of experimental cures for papilloma virus, and what I discovered is that in all of the experiments they would compare the effects of a salve (containing the experimental medicine) against a salve that contains only inert ingrediants. "Why don't they simply compare a wart treated with the salve, to a wart not treated whatsoever?" I thought to myself. The answer was simple: because even a salve containing inert ingrediants will kill the papilloma virus if the patient believes that the salve might help.

Or that your assumption about an 'inert' salve is unfounded.

Or that you're forgetting that some untreated warts see improvement.

The only way to see if the application of inert salve is actually making a difference is to compare against a non-treatment group. Until you have that extra control group, there are too many variables to conclude that belief is the only mechanism of action.

Now I can easily see why a headache medicine might show positive benefits even if it is inert. The person's mind might fool itself into relieving pain, because of the expectation of pain relief. But a virus, on one's foot? What 'state of mind' enables our feet to fight off a virus more effectively? It's positively mind-blowing.

Headache is different than wart progress: only the latter is objectively verifiable.

 

[blutoski]

My answer, although perhaps misguided, is that in all the studies involving topical creams that I examined the test was to compare an inert cream with one containing the medicine. If the placebo effect was impossible when it comes to viral-immune responses then the application of the placebo cream could be eliminated, and doctors should feel comfortable comparing their proposed medicine with untreated warts. However, it could be argued that this practice is just done out of convention rather than necessity, and furthermore you presented another interesting argument about bias of study groups.

I think you have it backwards: the point of a placebo control is that it should differ in only one way from the test substance. If the test substance needs to be embedded in a starch-matrix tablet or salve, then it is appropriate to assure that the placebo is as closely matched as possible, so the measured difference between the two groups' results can be attributed to the one different ingredient only.

In the background, there are a zillion unknowns that influence outcomes: the timing of the condition's cycle, the chemical effects of the additional ingredients, &c.

It's not just a convention to match placebo as closely as possible - it's the culmination of all the mistakes we've had to make through millennias of sloppy procedures.

 

[blutoski]

Hi everybody,

In regards to the placebo effect, I'm curious to know how often the response occurs. Do we have a lot of documented information on how often the placebo effect occurs for every condition? I'm guessing that for one illness it may be 30%, for another it may be 35%.. are there illnesses where the placebo effect could be really low, like less than 5%, like for cancer? I'm guessing we have a ton of information in regards to this since all the pharmaceutical drug testing is placebo-controlled. Which also makes me wonder how much stronger does a drug have to be than a placebo to be determined effective? If 50% of depressed people aren't depressed anymore after 3 months, and 55% of depressed people aren't depressed anymore after 3 months of taking drug XYZ, is that enough to prove it is effective? Anyway, it's just a topic that really intrigues me, any interesting facts or tidbits would be appreciated. Thanks.

In your example above, I would say that it depends just as much on the study design and statistical power. For example, if the sample size is too small to drop below p<.05, then we can't say it 'works' even if the control group had 0% improvement compared to 55% experimental group improvement.

Assuming a p<.05, then the 55% vs 50% is suggests efficacy. You would want more than one study to increase confidence in the efficacy claim before changing prescribing patterns. You would also want to compare it against existing antidepressants' efficacy to see if a 50 vs 55% improvement is better than what's currently being offered.


As to overall pattern, there is no 'knowledge' about this, since the same experiment run twice will probably have different baseline results. The effect is not predictable, and is almost always considered an artefact of the experiment, rather than a reflection of any actual clinically-relevant effect on the illness caused by treatement.