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The Placebo Effect

Placebo pills can make you happy

Thursday June 16, 2005
The Guardian

Just as placebos can bring relief from pain, researchers have found that they can affect our emotions too. Predrag Petrovic of the Karolinska Institute in Sweden, reporting in this week's Neuron, has shown that if placebos are used to relieve anxiety, they affect the same brain circuitry as when relieving pain.

Previous research has shown that people's expectation of relief plays a big role in the effectiveness of placebos. In his experiment, Petrovic induced this expectation by giving his volunteers an anti-anxiety drug to reduce their unpleasant perception of pictures including mutilated bodies. The volunteers were then given an antidote, and told that it would restore the unpleasant perception.

The next day, the volunteers were told that they would receive the same drugs. But instead, they received a saline solution as a placebo. Their brains were also scanned during these experiments using functional magnetic resonance imaging (fMRI).

Petrovic found that the placebo reduced the volunteers' ratings of the pictures by 29% as well as reducing the activity in the brain's emotional areas. In addiction, the placebo increased brain activity in the part where activity increases when placebos have been used to relieve pain.

Those people who expected the largest effect showed the largest changes in activity in the emotional and modulatory areas of the brain.

www.guardian.co.uk/life/dispatch/story/ ... 44,00.html
Placebos activate your home-grown painkillers

Nothing magic, just physiology, but at least it'll help us to design better placebos

Placebo sparks brain painkillers
US researchers say they have evidence of why some people get pain relief from sham treatment.
They looked at the so-called placebo effect - when a person is successfully treated by a dummy drug just because they believe it works.

Using brain scans the University of Michigan Health System scientists found placebo treatment triggers the brains natural painkillers, called endorphins.

Their work on 14 volunteers appears in the Journal of Neuroscience.

Physical phenomenon

Researchers have already shown that some people given a placebo experience reduced pain sensation and have lower activity in brain regions that process pain as a result.

Dr Jon-Kar Zubieta and his team set out to see precisely what was happening in the brain. They injected a salt water solution into the jaw muscles of the volunteers to cause pain.

At the same time, the volunteers had their brains scanned by a positron emission tomography (PET) scanner that would show up any endorphin activity.

During one of the scans, the volunteers were told they would also receive a medicine that might relieve the pain. This medicine was actually a dummy drug.

Throughout the experiments the volunteers were asked to score their level of pain and what they were experiencing.

After they received the placebo, nine of the volunteers reported much less pain and were able to tolerate higher doses of the pain-inducing salt water injections.

"Natural" painkillers

Their brain scans also showed that they had more endorphin activity after simply being told they were about to get the "medicine".

The most pronounced effects were seen in four parts of the brain known to be involved in processing and responding to pain, namely the left dorsolateral prefrontal cortex, the pregenual rostral right anterior cingulate, the right anterior insular cortex and the left nucleus accumbens.

Furthermore, activity in the dorsolateral prefrontal cortex was associated with the expectation of pain relief.

Activation of the other brain areas was associated with relief of the intensity of pain, how unpleasant it was and how the individuals felt emotionally during the pain.

Dr Zubieta said the findings show that the placebo effect is not purely psychological and has, at least partly, a physical explanation.

"The endorphin system was activated in pain-related areas of the brain, and that activity increased when someone was told they were receiving a medicine to ease their pain."

Dr George Lewith from Southampton University, who has studied the placebo effect and acupuncture, said: "I'm not at all surprised by the findings.

"They are consistent with what we know and have suspected. There is a physical side to the placebo response. You get a physiological change induced by expectancy."

He said that research so far suggested that 80-90% of people who benefit from analgesic drugs would probably get relief from a placebo too.

Story from BBC NEWS:
http://news.bbc.co.uk/go/pr/fr/-/1/hi/h ... 176078.stm

Published: 2005/08/24 09:22:58 GMT

You get a physiological change induced by expectancy

So whats the next step, training your brain to release endorphins without a placebo? would this be possible?
apparently, placebo's work -at least for some- even when the individual knows that he or she is taking a placebo...

Never worked out why that would work, myself...

Brains are such Nice things... :p
Pain Research Using Electronic Diaries & 'Placebo Effect

Source: University of Michigan Health System
Date: 2005-11-23
http://www.sciencedaily.com/releases/20 ... 211846.htm


Pain Research Using Electronic Diaries Helps Identify Who Responds To 'Placebo Effect'
Studies involving people who suffer from chronic pain often give some of them placebos, "sugar pills" with no medicinal value, to show whether the treatment has real value. Little is known, however, about the types of people who tend to respond positively to placebos, a mystery that places a hurdle before researchers who want to learn the best way to treat people's pain.

A new study by researchers at the University of Michigan Health System sheds some light on one group of people that seems to experience the "placebo effect." The researchers found that people with one type of chronic pain who have greater swings in their pain fluctuations tend to be more likely to respond to placebos.

The study of people with fibromyalgia -- a type of chronic pain affecting several million people that typically involves tenderness, stiffness and fatigue -- appears in the current edition of the journal Arthritis & Rheumatism.

"There is substantial evidence that the placebo effect has strong biological underpinnings, and that some individuals are more likely than others to demonstrate this effect," says Daniel J. Clauw, M.D., director of the U-M Chronic Pain and Fatigue Research Center and professor of rheumatology at the U-M Medical School.

"This study suggests that individuals with greater hour-to-hour and day-to-day variability in their pain may be more likely to be placebo responders," says Clauw, senior author of the paper. "When such individuals are placed in clinical trials of new interventions, the strong placebo effect they experience can make it difficult to determine if there is a superimposed effect of the treatment being tested."

"This finding is important because so far, nobody has been able to fingerprint placebo responders," adds Richard A. Harris, Ph.D., lead author of the paper, research investigator in the Division of Rheumatology at the U-M Medical School's Department of Internal Medicine and a researcher at the Chronic Pain and Fatigue Research Center. "The research is helping us gain a better understanding of who responds to placebos. That's especially important to the research community as we design clinical trials."

It is not clear if these findings are only present in fibromyalgia, or may also be seen in other chronic pain conditions, the researchers said.

Each of the 125 participants in the study carried a Palm-based electronic diary and was prompted at random intervals to record his or her pain level. Participants were prompted on average about three and a half times per day.

The patients who were enrolled in a multicenter drug trial of the anti-depressant milnacipran versus a placebo. Some of the participants experienced a large range of pain variability, while others experienced pain at fairly constant levels.

Those whose pain levels varied widely were more likely to respond to the placebo. They were not, the researchers found, necessarily more likely to respond to milnacipran, which suggests that high pain variability may be a predictor of a placebo response.

"These results have direct implications for drug trials in fibromyalgia and perhaps broader implications for other pain syndromes," the researchers note.

The researchers also found that the electronic recording of pain levels was much more accurate than earlier pencil-and-paper recordings. The electronic system contained a time stamp when the participants recorded the data, removing some of the uncertainty and inaccuracy that often accompanied pencil-and-paper diaries.

Fibromyalgia is a common condition that affects 2 to 4 percent of the U.S. population and is more commonly diagnosed in women. Clauw and his colleagues at the Chronic Pain and Fatigue Research Center are conducting extensive research into the causes and treatments of fibromyalgia.

For more about the U-M Chronic Pain and Fatigue Research Center, go to www.med.umich.edu/painresearch. For more about other recent research at U-M related to pain and the placebo effect, go to www.med.umich.edu/opm/newspage/2005/placebo.htm.

In addition to Clauw and Harris, other authors of the study were David A. Williams, Ph.D., associate professor of psychiatry at the U-M Medical School, director of research development within the Center for the Advancement of Clinical Research at U-M and co-director of the Chronic Pain and Fatigue Research Center; Samuel A. McLean, M.D., lecturer in the Department of Emergency Medicine at the U-M Medical School; Ananda Sen, Ph.D., associate research scientist at the U-M Center for Statistical Consultation and Research; Richard H. Gracely, Ph.D., professor of internal medicine and neurology at the U-M Medical School and co-director of the Chronic Pain and Fatigue Research Center; Michael Hufford, Ph.D., of Amylin Pharmaceuticals, San Diego, Calif.; and R. Michael Gendreau, M.D., of Cypress Bioscience, San Diego, Calif.

The research was supported by Cypress Bioscience. Grants from the National Institutes of Health supported Harris's and McLean's work.

Hufford has received consulting fees or honoraria of more than $10,000 a year from invivodata and owns stock in invivodata, creator of the Palm-based electronic diary. Clauw is chairman of the FMS Scientific Advisory Board at Cypress.

Citation: Arthritis & Rheumatism, Vol. 52, No. 11, Nov. 2005, pages 3670-3674.
Is the sample group big enough to really make such claims?

Scientists present first genetic evidence for why placebos work

July 20th, 2009 in Medicine & Health / Research

usually mere sugar pills designed to represent "no treatment" in a clinical treatment study. The effectiveness of the actual medication is compared with the placebo to determine if the medication works.

And yet, for some people, the placebo works nearly as well as the medication. How well placebos work varies widely among individuals. Why that is so, and why they work at all, remains a mystery, thought to be based on some combination of biological and psychological factors.

Now, researchers at UCLA have found a new explanation: genetics. Dr. Andrew Leuchter, a professor of psychiatry at the UCLA Semel Institute for Neuroscience and Human Behavior, and colleagues report that in people suffering from major depressive disorder, or MDD, genes that influence the brain's reward pathways may modulate the response to placebos. The research appears in the August edition of the Journal of Clinical Psychopharmacology (currently available online by subscription).

Placebos are thought to act by stimulating the brain's central reward pathways by releasing a class of neurotransmitters called monoamines, specifically dopamine and norepinephrine. These are the brain chemicals that make us "feel good." Because the chemical signaling done by monoamines is under strong genetic control, the scientists reasoned that common genetic variations between individuals — called genetic polymorphisms — could influence the placebo response.

Researchers took blood samples from 84 people diagnosed with MDD; 32 were given medication and 52 a placebo. The researchers looked at the polymorphisms in genes that coded for two enzymes that regulate monoamine levels: catechol-O-methyltransferase (COMT) and monoamine oxidase A (MAO-A). Subjects with the highest enzyme activity within the MAO-A polymorphism had a significantly lower placebo response than those with other genotypes. With respect to COMT, those with lower enzyme activity within this polymorphism had a lower placebo response.

"Our findings suggest that patients with MDD who have specific MAO-A and COMT genotypes may be biologically advantaged or disadvantaged in mounting a placebo response, because of the activity of these two enzymes," said Leuchter, who directs the Laboratory of Brain, Behavior and Pharmacology at the UCLA Semel Institute.

"To our knowledge, this is the first study to examine the association between MAO-A and COMT polymorphisms and a response to placebo in people who suffer from major depressive disorder," he said.

Leuchter noted that this is not the sole explanation for a response to a placebo, which is likely to be caused by many factors, both biological and psychosocial. "But the data suggests that individual differences in response to placebo are significantly influenced by individual genotypes," he said.

Including the influence of genotype in the design of clinical trials could facilitate more powerful testing of future treatments, Leuchter said.

Source: University of California - Los Angeles
Placebo treatments stronger than doctors thought
February 18th, 2010 in Medicine & Health / Medications

(AP) -- When it comes to the placebo effect, it really may be mind over matter, a new analysis suggests.

In a review of recent research, international experts say there is increasing evidence that fake treatments, or placebos, have an actual biological effect in the body.

The doctor-patient relationship, plus the expectation of recovery, may sometimes be enough to change a patient's brain, body and behavior, experts write. The review of previous research on placebos was published online Friday in Lancet, the British medical journal.

"It's not that placebos or inert substances help," said Linda Blair, a Bath-based psychologist and spokeswoman for the British Psychological Society. Blair was not linked to the research. "It's that people's belief in inert substances help."

While doctors have long recognized that placebos can help patients feel better, they weren't sure if the treatments sparked any physical changes.

In the Lancet review, researchers cite studies where patients with Parkinson's disease were given dummy pills. That led their brains to release dopamine, a feel-good chemical, and also resulted in other changes in brain activity.

"When you think you're going to get a drug that helps, your brain reacts as if it's getting relief," said Walter Brown, a clinical professor of psychiatry at Brown and Tufts University. "But we don't know how that thought that you're going to get better actually translates into something happening in the brain."

With growing proof that placebos work, some doctors are trying to figure out how to capitalize on their effects, without being unethical.

Blair said that to be completely honest with patients - to tell them they were receiving a fake treatment - would sabotage their belief in the drug, and thus, undermine any potential benefit.

But Brown didn't agree. For certain patients, like those with mild depression or anxiety, he said placebos were likely to work just as well as established therapies.

He said that even if doctors acknowledge they are giving such patients a placebo medication, but say it could be beneficial, "it might just actually work."

More information: http://www.lancet.com
Half of Germany's doctors prescribe placebos
http://www.newscientist.com/article/mg2 ... cebos.html
* 13 March 2011

PRESCRIPTIONS of placebos are booming in Germany and Switzerland, reveals a report released last week by the German Medical Association (GMA).

For example, 53 per cent of the doctors from the Medical University of Hannover said they would prescribe placebos such as vitamin pills and homeopathic remedies. Half the doctors in a national Swiss survey agreed.

Their use of such treatments contrasts with the UK, where homeopathic treatments have been rejected by scientists. However, "physicians should be made aware of the value of the placebo effect in the daily treatment of patients", says Christoph Fuchs, chief executive of the GMA. "Their use is of enormous importance for medical practice." The report cautions that placebos should be prescribed only for very minor conditions or where traditional therapies are not available.
Placebo As Good As Asthma Drug, Say Patients

13 Jul 2011

Who is right when patients say they get the same relief from placebos for their asthma symptoms as their prescription drug, while clinical tests find that only the medication has any significant effect? These surprising findings were reported by Harvard University researchers in the latest issue of NEJM (New England Journal of Medicine).

Symptoms of wheezing and coughing, according to participating stable asthma patients, improved with placebo inhalers (inhalers with dummy drugs in them) and fake acupuncture, to the same extent as with an albuterol inhaler, the patients reported.

In this double-blind, crossover pilot study, 46 patients were randomly selected into four groups:
Albuterol inhaler group
Placebo inhaler group
Sham acupuncture group
No intervention group
The degree of symptoms relief listed below surprised the researchers:
Inhalation of albuterol - 50%
A placebo inhaler - 45%
Sham acupuncture - 46%
No intervention - 20%
The authors wrote:

"Placebo effects can be clinically meaningful and can rival the effects of active medication in patients with asthma."

However, when testing lung function, the researchers only detected a significant improvement among those given albuterol - it had a strong objective effect on airflow - a mean 20% improvement in forced expiratory volume in 1 second, compared to the 7% boost in the placebo and sham acupuncture groups.

However, the scientists warned:

"The patients could not reliably detect the difference between this robust effect of the active drug and the effects of inhaled placebo and sham acupuncture."

Subsequent studies should focus on this mind-body interaction so that doctors and researchers can determine what exactly goes on during a placebo effect.

What should a doctor do? Should they ignore the patients' subjective feedback and rely entirely on the objective clinical test results? The authors advise doctors to interpret patient feedback with caution and still rely more on objective results. However, they add that a patient's subjective description of his/her experience should not be seen simply as wrong because they clash with the test results.

The human mind obviously plays an important part in how an asthma patient responds to various types of treatments. Doctors should become more aware of this and understand that showing that you are really trying to help the patient may go a long way to making them feel better.

"Active Albuterol or Placebo, Sham Acupuncture, or No Intervention in Asthma"

Michael E. Wechsler, M.D., John M. Kelley, Ph.D., Ingrid O.E. Boyd, M.P.H., Stefanie Dutile, B.S., Gautham Marigowda, M.B., Irving Kirsch, Ph.D., Elliot Israel, M.D., and Ted J. Kaptchuk
N Engl J Med 2011; 365:119-126July 14, 2011

Article URL: http://www.medicalnewstoday.com/articles/231039.php
ramonmercado said:
Half of Germany's doctors prescribe placebos
http://www.newscientist.com/article/mg2 ... cebos.html
* 13 March 2011

PRESCRIPTIONS of placebos are booming in Germany and Switzerland, reveals a report released last week by the German Medical Association (GMA).

For example, 53 per cent of the doctors from the Medical University of Hannover said they would prescribe placebos such as vitamin pills and homeopathic remedies. Half the doctors in a national Swiss survey agreed.

Their use of such treatments contrasts with the UK, where homeopathic treatments have been rejected by scientists. However, "physicians should be made aware of the value of the placebo effect in the daily treatment of patients", says Christoph Fuchs, chief executive of the GMA. "Their use is of enormous importance for medical practice." The report cautions that placebos should be prescribed only for very minor conditions or where traditional therapies are not available.

That's it, I wanna go work in Germany. :) It's been an ongoing bugbear for me that so much western medicine prides itself on being rational and yet is just ...NOT. Like I always end up saying, we are happy to prescribe drugs that work at best 30% of the time, and happy to accept these same drugs will end up killing a certain number of patients, and making a fair number of others worse not better, because for us this is 'real' medicine. We regard the placebo effect as if it was some annoying intrusion into our nice orderly, mechanistic reality, and we try our best to marginalise and minimize it, when it's one of the most extraordinary and revelatory things we have ever discovered about the human mind and body. I mean - hey - we can heal ourselves by just thinking ourselves well! The attitude is that somehow it's cheating, or that somehow the patients aren't really better. As if the criterion isn't cure any more, but method. Just have to hope things will change slowly. But it will need a few other things to change too, principally the too-cosy relationship between physicians and pharmaceutical companies that have no interest in promoting free or cheap alternative cures.

But that's another story. ;)
However, when testing lung function, the researchers only detected a significant improvement among those given albuterol - it had a strong objective effect on airflow - a mean 20% improvement in forced expiratory volume in 1 second, compared to the 7% boost in the placebo and sham acupuncture groups.

Hmmm..interesting, but possibly also a little misleading, I can't be sure without looking at the actual data. See, some people, including chronic asthma sufferers, can report asthma-like symptoms without having any appreciable reduction in airflow, or sats. Also albuterol or similar are what's known as short-acting bronchodilators. Their effect is intentionally very fast, but also very temporary. Comparing them to whatever effect the placebo may be having could be like comparing apples to oranges.
brianellwood said:
I have watched dental extractions performed under hypnosis, and not only was there no pain, there was hardly any bleeding and nothing but a slight 'soreness' afterwards.
When you hypnotise someone, they, in fact, hypnotise themselves, and having convinced themselves that it works go on to convince themselves that any further suggestions such as pain suppression will work too. Consequently, you can hypnotise yourself, and act on autosuggestions. Surely this is the same mechanism as the placebo effect?
And to carry it further, maybe that effect can influence cell growth and replacement, facilitating 'miracle' cures. Sadly, hypnosis will not work on everyone, just as faith type cures do not work on every induvidual. I'd would suggest that in cases where placebo effect , and miracle cures are most effective then the subjects are likety to be be 'good' hypnotic subjects.

I've experienced this. I don't put forward any idea as to how it works, but I've had teeth extracted under hypnosis and it doesn't hurt. It was done by a qualified dentist, a Dr Radin, now long since retired. There is the normal soreness afterwards, when you are 'dehypnotised' or whatever.

On a tangent, I imagine its difficult to analyse the effectives of asthma drugs, because asthma has a strong psychological component. As a former asthma sufferer (until I gave up smoking - doh!) I can recall occasions where the discovery that I'd forgotten or emptied my inhaler would immediatly bring on symptoms. A full blown asthma attack is very frightening, both to the victim and anyone who hasn't previously witnessed it, and no doubt the apprehension can provoke the symptoms. For years after I stopped getting attacks I had to have an inhaler around 'just in case'. In fact thinking about it now the old chest is getting a little tight - no just kidding. But 10 years ago it might have done.
Placebos Use Pot Receptor
http://the-scientist.com/2011/10/05/pla ... -receptor/

Some pain-relief placebos work in part by activating a cannabinoid receptor, stimulating the same pathway as marijuana.
By Tia Ghose | October 5, 2011

It’s well known that a placebo can relieve pain, but how such non-active ingredients can have such a positive effect has long stumped scientists. Now, new researchers suggests that placebos may help ease a patient’s pain by activating cannabinoid receptors, which are also targeted by marijuana, according to a study published October 2(Sunday) in Nature Medicine.

Researchers can give subjects an opioid prior to wrapping their arm with a painfully tight tourniquet. Thereafter, volunteers can tolerate pain longer when given a placebo instead of drugs on follow-up days, presumably because they’ve been primed to expect pain relief from the drug. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as iburprofen can also be used as a primer to induce this placebo-pain relief effect.

In the new study, researchers gave volunteers an NSAID prior to a painful stimulus, followed by rimbonant, which blocks the activation of a cannabinoid receptor, on subsequent days. Volunteers who received rimbonant on the placebo days experienced no pain relief, suggesting that part of the placebo effect was working via the cannabinoid pathway, and that blocking the pathway abolished the effect, Wired Science reported. When researchers combined rimbonant with an opioid, the placebo still quieted pain, suggesting that the opioid placebo effect works through a different mechanism.
Our mind is the clue to everything. I often feel the placebo effect on myself. An d also I often feel the opposite thing: when anyone is talking about some maladies and symptoms, I start feeling these symptoms on myself. Sometimes I can't get rid of them for quite a bit of time. But since I know it's all about my mind, I'm applying psychological methods and convince myself that I'm OK.
That's some quite sophisticated thinking, if you, er, think about it. :D

Reminds me a bit of that imaginary illness people have where their skin itches and they think they're exuding little strands of thread. Can't remember the name of it but apparently even reading about it can make you start scratching and looking for the threads.
Drug Trial Participants Not Fully Informed About Placebos

29 Jun 2012

Participants in drug trials are often not fully informed about the effect of placebos, thereby undermining the process of "informed consent", concludes a new study published this week in the open access journal PLoS ONE.

Placebos are used in randomized drug trials as to act as a yardstick or constant against which to compare the effect of the drug being tested, the "target".

Although often thought as "inert" pills, placebos can cause significant health changes, say researchers from the University of Southampton in the UK, and Harvard Medical School and Northern Arizona University, in the US.

Lead investigator, Dr Felicity Bishop, who lectures in psychology at Southampton, told the press:

"We believe the health changes associated with placebos should be better represented in the literature given to patients before they take part in a clinical trial. At the moment these effects are largely being ignored in the participant information leaflets."

Before taking part in a drug trial, participants give "informed consent" to show they have been given full information about the currently known changes to health that may occur.

But it appears that in some cases, the information falls short where placebos are concerned, said the researchers.

"There is an important issue of consent here - patients should be fully aware of possible health changes from all treatments in a trial before agreeing to take part," said Bishop.

For their study, Bishop and colleagues analyzed the content of 45 participant information leaflets from recent high quality clinical trials that used placebos. The trials are listed in the UK Clinical Research Network Database.

They noticed that target treatments were given priority over placebos. This was noticeable from the words used in the titles, through the description of the trial process, to explanations of what happens at the end of the trial. The researchers also observed that:
Placebos were referred to significantly less often than target treatments.

Placebos were often described in negative terms, using words like "dummy" or "fake", while target drugs were often described in relation to a class, such as statins (cholesterol lowering) or antibiotics (infection fighting), thus implying they had a particular effect.

Placebos were rarely described in their own right: in most cases they were referred to in comparison to the target treatment.

On the other hand, target drugs were often described as "genuine", or "real", and the focus of the trial.

The information emphasized the potential benefits and side effects of the target drug but largely ignored what might result from taking the placebo.

The leaflets emphasized the target treatment as being more desirable than the placebo.

Eight of the leaflets (18%) explicitly stated that the placebo treatment was either undesirable or ineffective.
Bishop and colleagues conclude that participant information leaflets "provide incomplete and at times inaccurate information about placebos."

"Trial participants should be more fully informed about the health changes that they might experience from a placebo. To do otherwise jeopardises informed consent and is inconsistent with not only the science of placebos but also the fundamental rationale underpinning placebo controlled trials," they add.

Professor of Health Research at the University of Southampton, George Lewith, comments on the potential implications of the study:

"The leaflets largely ignored the overwhelming evidence that placebos can actually have significant and sustained effects on people. This could affect the treatment beliefs and expectations of those volunteering for studies and in turn the results."

He said from their own studies at Southampton they have seen that placebos can help about half the people they treat for chronic pain, and the effect can last a long time afterwards.

In those trials, the placebo effect works by releasing patients' own natural painkillers into their nervous system, he added.

If volunteers taking part in clinical trials are not given full information about the health changes that might occur as a result of taking placebos, then their "informed consent", a crucial part of the trial process, is questionable, argue the researchers.

They recommend that different ways of describing placebos and their potential effects should now be tested, not only where such information appears in leaflets, but also in how it is communicated by researchers and administrators who have personal contact with participants in drug trials.

Southampton University's Faculty of Medicine funded the study.

"Informed Consent and Placebo Effects: A Content Analysis of Information Leaflets to Identify What Clinical Trial Participants Are Told about Placebos"; Bishop FL, Adams AEM, Kaptchuk TJ, Lewith GT; PLoS ONE 7(6): e39661, published online 27 June 2012; DOI:10.1371/journal.pone.0039661; Link to Article.

Additional source: Universityof Southampton.
More on nocebos.

Placebo Or Nocebo
16 Jul 2012

Negative suggestion can induce symptoms of illness. Nocebo effects are the adverse events that occur during sham treatment and/or as a result of negative expectations. While the positive counterpart - the placebo effect - has been intensively studied in recent years, the scientific literature contains few studies on nocebo phenomena. In the latest issue of Deutsches Arzteblatt International, Winfried Hauser of the Technical University of Munich and his co-authors present the underlying neurobiological mechanisms and highlight the relevance of the nocebo effect in everyday clinical practice (Dtsch Arztebl Int 2012; 109(26) 459).

Nocebo responses can, for instance, be brought about by unintended negative suggestion on the part of doctors or nurses, e.g., when informing the patient about the possible complications of a proposed treatment. It is also assumed that a certain proportion of the undesired effects of drugs can be attributed to nocebo effects. The mechanisms behind this phenomenon are - as with placebo effects - learning by Pavlovian conditioning and reaction to induced expectations.

What are the consequences for clinical practice? Doctors find themselves in an ethical dilemma between their obligation to tell the patient about the possible side effects of a treatment and their duty to minimize the risk of a medical intervention and thus to avoid triggering nocebo effects. As one possible strategy to solve this dilemma, Häuser et al. suggest emphasizing the tolerability of therapeutic measures. Another option, with the patient's permission, would be to desist from discussing undesired effects during the patient briefing.

Deutsches Aerzteblatt International
This idea is suggested by a computer model.

Evolution could explain the placebo effect
http://www.newscientist.com/article/mg2 ... ffect.html
06 September 2012 by Colin Barras
Magazine issue 2881.

For similar stories, visit the The Human Brain and Evolution Topic Guides
ON THE face of it, the placebo effect makes no sense. Someone suffering from a low-level infection will recover just as nicely whether they take an active drug or a simple sugar pill. This suggests people are able to heal themselves unaided - so why wait for a sugar pill to prompt recovery?

New evidence from a computer model offers a possible evolutionary explanation, and suggests that the immune system has an on-off switch controlled by the mind.

It all starts with the observation that something similar to the placebo effect occurs in many animals, says Peter Trimmer, a biologist at the University of Bristol, UK. For instance, Siberian hamsters do little to fight an infection if the lights above their lab cage mimic the short days and long nights of winter. But changing the lighting pattern to give the impression of summer causes them to mount a full immune response.

Likewise, those people who think they are taking a drug but are really receiving a placebo can have a response which is twice that of those who receive no pills (Annals of Family Medicine, doi.org/cckm8b). In Siberian hamsters and people, intervention creates a mental cue that kick-starts the immune response.

There is a simple explanation, says Trimmer: the immune system is costly to run - so costly that a strong and sustained response could dangerously drain an animal's energy reserves. In other words, as long as the infection is not lethal, it pays to wait for a sign that fighting it will not endanger the animal in other ways.

Nicholas Humphrey, a retired psychologist formerly at the London School of Economics, first proposed this idea a decade ago, but only now has evidence to support it emerged from a computer model designed by Trimmer and his colleagues.

According to Humphrey's picture, the Siberian hamster subconsciously acts on a cue that it is summer because food supplies to sustain an immune response are plentiful at that time of year. We subconsciously respond to treatment - even a sham one - because it comes with assurances that it will weaken the infection, allowing our immune response to succeed rapidly without straining the body's resources.

Trimmer's simulation is built on this assumption - that animals need to spend vital resources on fighting low-level infections. The model revealed that, in challenging environments, animals lived longer and sired more offspring if they endured infections without mounting an immune response. In more favourable environments, it was best for animals to mount an immune response and return to health as quickly as possible (Evolution and Human Behavior, doi.org/h8p). The results show a clear evolutionary benefit to switching the immune system on and off depending on environmental conditions.

"I'm pleased to see that my theory stands up to computational modelling," says Humphrey. If the idea is right, he adds, it means we have misunderstood the nature of placebos. Farming and other innovations in the past 10,000 years mean that many people have a stable food supply and can safely mount a full immune response at any time - but our subconscious switch has not yet adapted to this. A placebo tricks the mind into thinking it is an ideal time to switch on an immune response, says Humphrey.

Paul Enck at the University of Tübingen in Germany says it is an intriguing idea, but points out that there are many different placebo responses, depending on the disease. It is unlikely that a single mechanism explains them all, he says.
How on earth - speaking as a programmer and systems designer of nearly 40 years standing - could a computer model do any such thing? What parameters would you feed it with to cover _all_ the variables in a body's response to an infection, human or otherwise? What assumptions do youi make regarding those parameters?

When you think of the cumulative number of human judgements (guesses) involved in creating such a model, you may share with me the view that regarding something so complex, a computer model can be no different to reading tea-leaves. What we have here is what I call the 'Star Trek' effect, where because something comes out of a computer, people forget that fallible humans put it in.

Computer modelling works fine where all the variables except one or two are known and independently measurable, for example for predicting the life of electrical components. When many of the variables (except the ones you are interested in manipulating) have to rely on 'educated guesses', then the reliability of the result is diminished by a cumulative calculation of the confidence factors of each individual guess or assumption. If there are a lot of guesses, this number will approach zero.
Cochise said:
How on earth - speaking as a programmer and systems designer of nearly 40 years standing - could a computer model do any such thing? What parameters would you feed it with to cover _all_ the variables in a body's response to an infection, human or otherwise? What assumptions do youi make regarding those parameters? ...


I'm a bit dubious as well.
I didn't go through the links, but there was an interesting story regarding placebos.

A patient was suffering from brain tumors. He heard that there was a new medicine called Krebiozen, which was effective on horses. He asked his doctor for it, but the doctor didn't have any krebiozen. The doctor instead, injected him with water.

Within a couple days, the tumors had melted away.

A couple days later, the guy read that Krebiozen was a failure.

Next day, the tumors were back.

A bit of a classic tale this:

Many doctors know the story of ''Mr. Wright,'' who was found to have cancer and in 1957 was given only days to live. Hospitalized in Long Beach, Calif., with tumors the size of oranges, he heard that scientists had discovered a horse serum, Krebiozen, that appeared to be effective against cancer. He begged to receive it.

His physician, Dr. Philip West, finally agreed and gave Mr. Wright an injection on a Friday afternoon. The following Monday, the astonished doctor found his patient out of his ''death bed,'' joking with the nurses. The tumors, the doctor wrote later, ''had melted like snowballs on a hot stove.''

Two months later, Mr. Wright read medical reports that the horse serum was a quack remedy. He suffered an immediate relapse. ''Don't believe what you read in the papers,'' the doctor told Mr. Wright. Then he injected him with what he said was ''a new super-refined double strength'' version of the drug. Actually, it was water, but again, the tumor masses melted.

Mr. Wright was ''the picture of health'' for another two months -- until he read a definitive report stating that Krebiozen was worthless. He died two days later.

Remainder of a far longer article on the power of placebo:
There's a letter in the current FT that says paracetamol works because of the placebo effect: it's 20% the medication and 80% the power of suggestion. This could explain why I never feel any benefits from it on the occasional times I take it. Anyone know anymore?
This new article from Australia argues that placebos are overrated and their reputation doesn't stand up to close scrutiny. The full report is accessible at the link below.
The Placebo Effect Is an Amazing Illusion, But That Doesn't Mean It's Medicine

The placebo is one of science's greatest mysteries. The pill that isn't a pill. The medical illusion that somehow becomes real.

The mind-boggling weirdness of the placebo effect is certainly a strange thing, nobody doubts that.

But just because the placebo effect occasionally delivers unexpected outcomes doesn't mean we should overestimate how powerful it is – nor try to find a place for it in the medical care of patients, scientists are now warning.

In a new perspective article, researchers from the University of Sydney argue that recent suggestions placebos could play a role in clinical care are unfounded, and are based on flawed evidence. ...

"Much of the current discourse on placebo seems to focus more on enshrining placebos as mysterious and highly effective and less on making a practical difference to patient care and outcomes" ...

Observations of the placebo effect can be traced back to the 18th century, and the reputation of the placebo has grown ever since: the idea that an inert, sham treatment, taken unknowingly by a patient, can sometimes deliver therapeutic effects like the real thing.

That reputation is mostly [undeserved] ... if you look closely at much of the evidence, placebos tend to only offer very modest effects, and even then only in a small minority. ...

Placebos in clinical care: a suggestion beyond the evidence
Christopher G Maher, Adrian C Traeger, Christina Abdel Shaheed, Mary O'Keeffe,
The Medical Journal of Australia.
Volume215, Issue 6. September 2021 Pages 252-253.e1

There's a letter in the current FT that says paracetamol works because of the placebo effect: it's 20% the medication and 80% the power of suggestion. This could explain why I never feel any benefits from it on the occasional times I take it. Anyone know anymore?
If it's 20% medication, than is it truly the placebo effect? Some people are more susceptible to medication than others, so maybe 20% medication is a sufficient dose to be effective for a high proportion of the population.
If it's 20% medication, than is it truly the placebo effect? Some people are more susceptible to medication than others, so maybe 20% medication is a sufficient dose to be effective for a high proportion of the population.
And not all people react the same. I'm disproportionately sensitive to some drugs and virtually unaffected by others. Which is why AI will never be able to replace a quality medical practitioner. Again, see above - too many variables.

Funnily enough both AI and modelling have had their roots in the analysis of electrical systems. There is a brilliant paradox there in that we still don't fully understand electricity itself but it behaves in such predictable ways that without that fundamental understanding we can still successfully use modelling and AI to work with it. Humans, alas, are anything but predictable.
If it's 20% medication, than is it truly the placebo effect? Some people are more susceptible to medication than others, so maybe 20% medication is a sufficient dose to be effective for a high proportion of the population.

If paracetamol was only 20% effective then why would anyone buy it in the 1 in 5 chance it might work on you? You'd try aspirin or codeine instead, wouldn't you? Sounds like a conspiracy to keep sales up and prevent the truth coming out! (Note to self: try those tinfoil hats)