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The Placebo Myth

King Arthur: Now stand aside, worthy adversary.
Black Knight: ‘Tis but a scratch.
King Arthur: A scratch? Your arm’s off.
Black Knight: No it isn’t.
King Arthur: What’s that, then?
Black Knight: [after a pause] I’ve had worse.
King Arthur: You liar.
Black Knight: Come on ya pansy.King Arthur: [after Arthur's cut off both of the Black Knight's arms] Look, you stupid Bastard. You’ve got no arms left.
Black Knight: Yes I have.
King Arthur: Look!
Black Knight: It’s just a flesh wound.Monty Python and the Holy Grail

—————
I am, I think, in a minority on this blog, in that I do not think there is a placebo effect. Period. None. Zip. Zero. Nada. Zilch.

For analysis purposes, I divide the lack of placebo effect into outcomes that do not occur with objective measurement and those that do not occur with subjective measurement.

Why the dichotomy? Those studies where there have been an active treatment, a placebo treatment and an observation group, have demonstrated no difference between observation and placebo (1). To summarize from the conclusion of the compelling NEJM review:

“We found little evidence in general that placebos had powerful clinical effects. Although placebos had no significant effects on objective or binary outcomes, they had possible small benefits in studies with continuous subjective outcomes and for the treatment of pain. Outside the setting of clinical trials, there is no justification for the use of placebos.”

Which makes sense to my reductionist materialistic way of thinking: why would actively doing nothing have any measurable physiologic effect? It shouldn’t and it doesn’t. Mind over matter? Bah, humbug.

How about subjective endpoints like pain? Isn’t there good data to support a placebo effect for pain? I saw the MASH episode where they ran out of morphine and relieved the post operative pain with placebo and the healing powers of caring and compassionate nurses and doctors (9).

Stick a knife in your finger. Pain receptors fire. Nerve impulses travel to the spinal cord for a quick withdrawal of your hand before you know you are hurt. The pain impulse travels up the spinal cord to the brain where you go ouch. Then you decide whether it hurts and if so how much (15). Ever watch a child injure themselves and look around to see if a parent is watching before deciding, at some level, that since Mom is watching, the injury is worth a good cry, some sympathy and a kiss?

There are several levels where pain can be blocked. Having had a crown this week, I am always grateful that a peripheral nerve can be blocked with some novocaine. Pain can be blocked with various medications that work at various levels in the CNS.

And then there is the appreciation of pain. How you react to the pain is different from the pain itself. Attitude can make the same amount of pain better or worse (6)

I had a herniated disc for about 9 months with chronic nerve root pain that was surgically repaired when all conservative therapies had failed (10). When I woke from the surgery my nerve pain was completely gone, and it was such a relief that in comparison the incision pain was nothing. I never bothered to take pain medications for the incision pain; I was so giddy to be pain free that the incision was nothing. Someone may argue that I was flooded with endorphins and that is why I had so little pain, but I have had enough other surgeries to wonder, if so, where were the endorphins during those other incisions where I was glad for the invention of the PCA pump.

I think that the placebo effect with pain is a mild example of cognitive behavioral therapy; the pain stays the same, it is the emotional response that is altered.

There was a recent study that sheds some light into the placebo myth.

“Sham device v inert pill: randomised controlled trial of two placebo treatments ” from the BMJ (11)

This was part of a larger study that demonstrated that sham acupuncture is better than real acupuncture (12). They took 270 patients with arm pain due to repetitive use injury of at least 3 months duration and pain rated as >= 3 on a 10 point scale.

“Participants could have any of a range of clinical diagnoses involving the tendons, soft tissues, and nerves of the arm or non-specific symptoms related to repetitive movement or overuse. We excluded people with systemic connective tissue or muscular diseases, neurological disorders, or acute trauma to the arm…This condition is the modern equivalent of “weaver’s hand,” “sprout picker’s thumb,” and “scrivener’s palsy.” Most patients had pain due to computer keyboard and mouse use.

The patients were randomized to sham acupuncture 2x per week with a blunt device that felt like acupuncture but did not penetrate the skin. They had 5 to 10 sham needles in the arm and one in the foot. The other group received a placebo pill one time a day, which they were told to take at night as they were warned it may cause drowsiness and dry mouth.

At first they were randomized to sham acupuncture or placebo as part of a run up to the study where they were then further randomized to real or sham acupuncture and amitriptyline or placebo, and they were followed after the second randomization.

Result? The pain scores (subjective findings) decreased more in the sham acupuncture than the placebo group. The magnitude of the pain relief was not impressive as admitted in the discussion: “In this trial, the magnitude of this effect was small.” Objective findings, no surprise, did not change in either group (grip strength or arm function).

More patients in the sham acupuncture (75%) thought they were receiving active therapy than placebo (48%) and the believers had the better subjective, but not objective scores.

Two different placebos decreased pain, one placebo was better than the other. Why?

The answer may be in another interesting result of the study: side effects. Patients were told in the informed consent what the side effects of the active therapies were, even though initially they all were getting placebo. And the informed consent worked to ‘cause’ side effects: three of the placebo subjects dropped out from dry mouth and fatigue and 10% of the sham had increased pain after the needle was ‘removed’.

Also, the sham acupuncture group had more interaction with their providers. So more chance of developing expectations, important in placebo effects

My take: Aint no such thing as a placebo effect, only a change in perception.

Take a different example of how expectation can alter the perception of a complex sensory experience. The example is taste.

I know that the same bottle of Bordeaux tastes far better in a 2 star restaurant on a summers day in the south of France with friends than it does on a January day alone with a bowl of top raman.

The wine will taste better if the bottle has a higher price tag. There was a recent study where people were given the same wine, but were told it cost 10 dollars or 90 dollars. They thought the 90 dollar wine tasted better (2). They did functional MRI’s on the participants as well and when they had the 90 dollar wine the part of the brain that deals with pleasure lit up but the same area did not light up with the 10 dollar bottle of wine.

I would argue the molecules in the wine did not change, the same receptors were activated in the mouth and nose, and information conveyed to the brain did not change, but the perception of the wine did. The wine became better, even as it stayed the same.

Same thing happens, I wager, with the so called placebo effect. No physical change. Pain is unchanged but the perception of the pain is changed. People have the result they expect to have and the side effects they are told they will have.

Outside of alt med, perception does not alter reality (13). People can talk themselves into believing anything. You may think that is nonsense, but in medicine you get to see the extremes of human experience. People will see things that are not there and not see things that are (16).

I remember the first time I saw a patient with this issue. I was a 3rd year medical student in the ER and a patient came in feeling lightheaded. I went through the extensive review of systems med students do, and found nothing, so I moved on to the exam. He had a blood saturated bandage under his gown, and beneath the bandage was a bleeding melanoma the size and shape of large mushroom that had oozed blood to the point where his red cell counts were 25% of normal. When asked about the tumor, he said it was nothing. He denied the huge bleeding tumor was a problem.

That is not all that an unusual experience: patients with horrible pathology that they deny exists. Patients present with huge tumors or endstage AIDS and completley deny they have anything wrong. At the other end of the spectrum are the patients who have nothing wrong with them but are convinced that every bump or twinge is a manifestation of some horrible, soon to be fatal, illness. After seeing these extreme examples, someone thinking their pain is decreased, when in fact it isn’t, requires no stretch of the imagination.

In humans there is no ‘real’ effect from placebo.

It was also mentioned in this blog that animals experience a placebo effect. As is so often the case, opinions go unreferenced, but my first response was disbelief. How could a dog have a non existent experience?

So I went looking.

It would be critical in determining if there is a true placebo response in animals that there was an observation group, a placebo group and a treatment group. Even more important would be that those collecting the data have to be blinded to the intervention. It keeps coming back to N Rays. People see what they want to see, what they expect to see, not necessarily what is there (3).

I admit up front that I do not read the veterinary literature and am limited in my access to this information compared to human medicine. So I may have missed some important literature.

That said, my start was a 1999 review of placebo in animals (4). It is a good discussion as to why it is difficult to assess the placebo effect in animals and its potential mechanisms. Then it moves on to clinical studies.

“Identifying placebo effects in veterinary medical studies is problematic. To the authors knowledge, studies specificly examining the placebo effect in therapeutic trials have not been reported. Placebo data for treatment trials is available only for control group results in studies investigating specific treatments. Most importantly, in trials in which placebo is selected as the control method, untreated groups serve as second controls to distinguish placebo effects other causes of disease resolution are not used. Even if a beneficial response is detected in the placebo group, such improvement cannot be conclusively attributed to the placebo, because non treated individuals are not included in the study. Accordingly, specific placebo data in studies of therapeutic effects is sparse.”

He then discusses a double blind study of carprofen in dogs (5). While the drug was better than the placebo, 56% of the dogs objectively improved on placebo (as judged by force plate measurement), better than the subjective improvement as judged by the owner or the vet. I do not know, as I cannot yet access the article, what the activity of the animals was during the study. If I had a dog that was diagnosed with hip problems, I would exercise it less, which would also lead to improvement that could be attributed to placebo.

A Pubmed search using “animals and pain” yielded 277 references that were clinical trials and had abstracts. I found few studies with objective end points that demonstrated an improvement attributed to placebo (7).

One study, which had a 60% placebo effect for gold wires injected for hip dysplasia, makes no mention of animal activity, so making judgements as to response to placebo is problematic (8).

I tried other combinations of search terms using placebo and animals and could not find well done blinded studies that demonstrate any placebo effect in animals. If there is compelling data that demonstrates placebo effects in animals where confounding issues are controlled (14), I cannot find it. I am sure the readers will send me the references to let me know I am wrong.

I conclude placebo effect is a myth: for humans and for animals.

References and Snotty Comments

(1) IS THE PLACEBO POWERLESS? An randomized of Clinical Trials Comparing Placebo with No Treatment N Engl J Med, Vol. 344, No. 21 • May 24, 2001

(2) (http://news.cnet.com/8301-13580_3-9849949-39.html).

(3) This is a huge issue in clinical medicine. If you think you have the right diagnosis, you may not see the information that contradicts your diagnosis or suggests an alternative. Good docs are aware of this.

(4) J Am Vet Med Assoc. 1999 Oct 1;215(7):992-9.
The placebo effect in animals. McMillan FD. PMID: 10511866

(5) Randomized, controlled trial of the efficacy of carprofen, a nonsteroidal anti-inflammatory drug, in the treatment of osteoarthritis in dogs.
J Am Vet Med Assoc. 1995 Mar 15;206(6):807-11.
PMID: 7759332

(6) Curr Opin Anaesthesiol. 2007 Oct;20(5):435-9.
Nocebo hyperalgesia: how anxiety is turned into pain.

(7) J Vet Intern Med. 2007 May-Jun;21(3):410-6.
Evaluation of client-specific outcome measures and activity monitoring to measure pain relief in cats with osteoarthritis.

(8) Acta Vet Scand. 2005; 46(2): 57–68. Stratification, Blinding and Placebo Effect in a Randomized, Double Blind Placebo-controlled Clinical Trial of Gold Bead Implantation in Dogs with Hip Dysplasia

(9) Season 6, episode 24. It’s on TV, it must be so.

(10) No, I did not use acupuncture.

(11) Sham device v inert pill: randomised controlled trial of two placebo
treatments. 2006;332;391-397. BMJ

(12) Not their intent, I am sure. As if there is a difference between real and sham acupuncture. Like the difference between real and sham ghosts.

(13) And the reality of WMD’s. And don’t give me the “What the Bleep Do We Know?” bs.

(14) Thanks to Dr Hall:
“animals ought not to have a placebo effect”
Maybe they “ought not” but they clearly DO. The veterinary literature recognizes that.
“I wonder how this can be explained.” Here’s how:
(1) They can develop a learned physiologic response to a drug and then respond similarly when a placebo is substituted.
(2) They respond to attention and care from humans.
(3) Human owners can experience the placebo effect for their pets by perceiving a response where there really is none.
(4) Since animals can’t talk, we have to interpret an animal’s behavior as indicating relief of pain; this may not always be accurate.

(15) Yes, I know, simplistic. Dr. Novella is probably squirming.

(16) Sometimes like essays in blogs, which are like Rorschach tests. Or maybe Horshack tests. Welcome back.

Posted in: Science and Medicine

Leave a Comment (37) ↓

37 thoughts on “The Placebo Myth

  1. Gib says:

    I think it is Richard Wiseman (possibly Ben Goldacre…) who I’ve heard say a couple of times that studies have been done and “we know that two pills are better than one” when it comes to placebos.

    I can do some more research on who and why he says this if you don’t know of it.

    What’s your opinion on such claims Mark ?

  2. Stu says:

    bowel of top raman

    And the Gross Typo Of The Week Award goes to…

  3. vinny says:

    Nice use of anecdotes. Here is another anecdote: A fool decided to speak and instantly proved his foolishness to those around him. Sometimes it is better not to post a dumb story and tarnish an otherwise excellent blog.

  4. Stu says:

    He directly cites 7 studies. What the hell are you talking about?

  5. Andy C says:

    The placebo effect always used to bother me, but several months ago I came across an article that tipped the scales in favour of my accepting that the placebo effect is a real, physiological effect. Specifically the Amanzio et al paper

    “Response variability to analgesics: a role for non-specific activation of endogenous opioids” Pain 90 (2001);205-215.

    As I understand it (as a layperson), the study authors attempted to chemically block the placebo effect, and in short, the objective measures of pain relief showed a reduction in relief given by an announced analgesic, in the presence of an (hidden) opioid blocker, compared with the announced analgesic and no opioid blocker.

    Given that Mark’s hypothesis is that the placebo is perceptual, and not physiological (ignoring any arguments about the physiological basis of perception ;-) – although perhaps we can’t do that?.. my brain hurts), how would this explain the role of the opioid blocker in this experiment?

    I hope that makes some sense. And to Gib, I’ve definitely heard Ben Goldacre talk about “2 pills are better than 1″.

  6. durvit says:

    Hróbjartsson and Gøtzsche updated the NEJM review in their Cochrane Review of Placebo Interventions [1], however, their conclusions remain unaltered.

    Preamble
    Dr Ben Goldacre posted some interesting references relating to back pain and acupuncture.

    back pain is incredibly interesting: in 90% no cause is found, and we know that things like psychosocial stressors, work problems, bed rest and depressive symptoms are significant risk factors for moving from a twinge to chronic enduring pain…

    Back pain is clearly a problem which requires more than simply pharmaceutical pills. The question is whether an elaborate, expensive, gimmicky and theatrical placebo ritual is an effective use of money, or whether other, cheaper, more pragmatic, honest psychosocial interventions might be more appropriate and cost effective.

    If I characterise his argument correctly, he is intrigued by the notion that the theatricality and cultural significance of an intervention may influence the placebo response in something that approximates to a dose-response relationship.

    [T]here’s nothing wrong with the idea of homeopaths giving out sugar pills. The placebo effect can be very powerful, because it’s not just about the pill, it’s about the cultural meaning of the treatment: so we know from research that four placebo sugar pills a day are more effective than two for eradicating gastric ulcers…we know that salt water injections are a more effective treatment for pain than sugar pills, not because salt water injections are medically active, but because injections are a more dramatic intervention; we know that green sugar pills are a more effective anxiety treatment than red ones, not because of any biomechanical effect of the dyes, but because of the cultural meanings of the colours green and red. We even know that packaging can be beneficial.

    Meat of comment
    All of the above was a way of introducing the fact that in his lectures (and possibly his soon-to-be-published book) Goldacre frequently refers to the placebo response meta-analyses/assessments of gastric ulcer medication and healing by de Craen and Moerman [2, 3, 4]. Understandably, these meta-analyses were not appropriate for inclusion in the Cochrane Review of placebo response that focused on randomised placebo trials with a no-treatment control group.

    Crudely, de Craen and Moerman demonstrate that the gastric ulcer healing rate not only has a dose response to placebo (the more pills, the better the response) but the assessment of that healing is objectively assessed by gastrocopic examination.

    However, the Cochrane conclusion, and Dr Crislip’s statement that he concludes that the placebo response is a myth, does not seem to offer a satisfactory account to explain the outcomes of the work reported by de Craen, Moerman and others.

    References
    [1] Hróbjartsson A, Gøtzsche PC. Placebo interventions for all clinical conditions. Cochrane Database of Systematic Reviews 2004, Issue 2. Art. No.: CD003974. DOI: 10.1002/14651858.CD003974.pub2. (pdf for those with access)
    [2] de Craen AJ, Moerman DE, Heisterkamp SH, Tytgat GN, Tijssen JG, Kleijnen J. Placebo effect in the treatment of duodenal ulcer. Br J Clin Pharmacol. 1999 Dec;48(6):853-60.
    [3] Moerman DE. General Medical Effectiveness and Human Biology: Placebo Effects in the Treatment of Ulcer Disease Medical Anthropology Quarterly, Vol. 14, No. 4 (Aug., 1983), pp. 3-16
    [4] Moerman DE. Cultural variations in the placebo effect: ulcers, anxiety, and blood pressure. Med Anthropol Q 14:1-22, 2000

    (The reference links aren’t live because I didn’t want to be banished to the spam filter where this will probably end up anyway.)

  7. Harriet Hall says:

    Mark,

    Have you read R. Barker Bausell’s “Snake Oil Science”? It includes a fascinating discussion on the question of placebos. I’d be very interested to hear your reaction to what he wrote. He describes an experiment where dogs were given morphine injections, inducing salivation as a side effect, and they developed a learned response so that when placebo injections were substituted they also salivated. The physiologic response to placebos is less than to the original drug, but it is documented. There are also experiments where placebos appear to induce endorphin production in the brain, and the response can be blocked with narcotic antagonists. The experimental evidence isn’t conclusive, but it is intriguiing.

    Even if you conclude that placebos have no objective effects, aren’t subjective effects “real”? There is a difference between pain and suffering. If taking a placebo can psychologically alter the perception of pain and reduce suffering, I consider that a “real” effect. Maybe we’re just quibbling about terminology.

    I’ve noticed a “placebo” response when I take an effective drug. If I have a headache, I will debate with myself for a while, wondering if I should bother getting up and finding an aspirin. When I finally take the aspirin the debate is over. I stop thinking about it and I realize later that my headache seemed to “go away” before the drug had time to be absorbed. I “really” stopped noticing my headache.

  8. Joe says:

    This seems rather philosophical, and I dislike philosophy.

    If there were no placebo effect, then placebo controls would be pointless.

  9. vinny says:

    I take issue with the liberal use of anecdotes and some likely poor studies to make the case. Placebo effect is well documented, especially when dealing with subjective end points. But primarily for the endless use of anecdotes I thought the whole essay was dumb, and was surprised to see it appear on this site. I guess I became used to seeing consecutive excellent essays at this blog.

  10. Dr. Scifi says:

    I first learned about placebos from Star Trek. Three plain women are transformed into beauties when they take a placebo (Mudd’s Women). Is the placebo effect only real in science fiction?
    If the changes seen on functional MRI in the cited wine study are real then isn’t this “caused” by the placebo effect?
    Another example is the placebo effect in Parkinson’s disease that is related to the release of dopamine (http://www.ncbi.nlm.nih.gov/pubmed/17017561).
    Now, should I take the red pill or should I take the blue pill? (http://en.wikipedia.org/wiki/Redpill)

  11. daedalus2u says:

    Mark, I thought this was supposed to be Science Based Medicine.

    Is death a sufficiently “objective” measure, when brought about by non-pharmacologic means to constitute a placebo effect? (or its negative equivalent the nocebo effect?)

    http://www.psychosomaticmedicine.org/cgi/reprint/19/3/182

    So what is your explanation of the so called “voodoo death”?

    My explanation of why sham acupuncture works better than “real” acupuncture is that the only positive effects of either sham or “real” acupuncture are via the placebo effect. Actually sticking needles in someone causes actual activation of actual pain transmitting nerves and that actual pain neutralizes a portion of the placebo effect. No actual pain with sham acupuncture, the net therapeutic effect of sham acupuncture is greater than that of “real” acupuncture.

  12. Harriet Hall says:

    I hate to be a Devil’s Advocate, but I’m not sure voodoo death isn’t a myth. All we have are historical reports, which can be unreliable. Even when the cases were reported by reliable physicians, other explanations were not entirely ruled out. The paper you cite was a historical review written in 1957, and it only concluded that the phenomenon “may” be real.

    Ray Hyman’s Categorical Imperative applies here: don’t bother trying to explain a phenomenon until you can verify that the phenomenon exists.

  13. durvit says:

    I’m spam-shy about posting more references (they are mostly available in Ben Goldacre’s posts that I linked to above). However, Rob Walker’s book Buying In: The Secret Dialogue Between What We Buy and Who We Are (reviewed by Mind Hacks which links to other good reviews) might offer some interesting ideas about why branding and packaging influences the impact of some placebo preparations more than others. In some ways, his book is an extensive elaboration of cultural differences and relevance.

    I am sympathetic to the suggestion that you are both what you consume and what you don’t consume. It is perhaps feasible to consider that some of us would be irritated if our back pain yielded to an aspirin and would feel that the pain had received more validation if the appropriate intervention had to be delivered by IV pain-relief. As discussed by Orac, one study reported that the perception of price as a proxy for quality affected the perception of pain relief [1].

    However, given the subjective nature of pain and pain relief, it doesn’t explain the de Craen and Moerman reports nor Daedalus’ comment about voodoo deaths.

    [1] Waber, R.L., Shiv, B., Ariely, D. (2008). Commercial Features of Placebo and Therapeutic Efficacy. Journal of the American Medical Association, 299(9), 1016-1017.

  14. Mark Crislip says:

    My lack of clarity comes back to haunt me again.

    When I discuss about placebo effect in my mind I have a specific notion.
    I think of placebo effect in the context of treating disease.

    For there to be a placebo effect, there needs be three groups: a treatment, a placebo and no therapy. The placebo should have more effect than doing nothing.

    I do not think of the dog and morphine study as a placebo effect; I do not think of any of the classic pavlovian conditioning as a placebo effect. I would not call voodoo death a placebo effect either. Perhaps I should. If so, then when one of our troops comes home from the war and throws himself to the ground when he hears a car backfire, I can tell him its a placebo effect, not PTSD.

    We have placebo controlled studies not because placebo has effects, but all too often the treatment has none.

    I have yet to read the Snake Oil medicine, you are one of many to suggest it, I’ll get it from Amazon this week.

    Anecdotes? I thought they were uncontrolled clinical observations ☺.
    Anecdotes can serve two purposes: proponents of quackery use them as proof.

    In medicine we have a long history of teaching by using anecdotes, or in the language of the medicine, case reports, as illustrative of broader well established concepts. If I talk about, say, meningitis, I start with a case of meningitis. In teaching medical concepts we always try to tie them to real cases to make it memorable. It is the way I am used to teaching, and evidently it is another example of my inexperience as a writer that it did not translate well into the blog.

    I will get back to an illustrative example of what you may consider a philosophical problem: the annals study on saw palmetto and bph.

    at the start everyone had placebo.
    Some thought they had improved urine flow that when measured was not improved. They had subjective but not objective improvement.

    In the studies mentioned in the blog post, there was a decrease in pain but not in function. One would think that if pain were decreased, since it is the limiting issue with repetitive strain injury, the function would improve,

    So here is the question.

    Was there a placebo effect and if so what what it.

    I say in both cases placebo did nothing. There was no effect from the placebo. Since the subjective change did not have an objective effect, it was all self delusion and no effect.

    As to voodoo death, while not placebo effect in my mind, probably has a real physiologic reason, there is a thing called stress cardiomyopathy, I wrote or talked about it somewhere before. http://www.sciencebasedmedicine.org/?p=79.

    But it is not (I am a splitter not a lumper) part of placebo effect. I think.

    pain is tricky. I have had a lot of it, I have treated a lot of it, and I have inflicted a lot of it. I remain conflicted about how to judge the subjective effects of pain treatment. If you say pain is decreased, it is. Even if it isn’t.
    If the nerves are firing the same all the way to the brain, the pain is the same. If the brain ‘decides’ it is decreased, then the pain is less, even if it isn’t. Like the wine is better, even if it isn’t. I really don’t know if that is the right interpretation of pain. I think it is. Seems a little woo-y, but it is the best I can do.

    We have a long tradition in my family of serving top ramen in sausage casings, so no typo :). MMMMMMMmmmmmmm sausage.

  15. daedalus2u says:

    Could you give us your specific definition of what you mean by “placebo effect”?

  16. Harriet Hall says:

    Mark,

    you said “We have placebo controlled studies not because placebo has effects, but all too often the treatment has none.”

    If the treatment had no effect, it would be enough to compare it to no treatment. Even effective treatments have a placebo effect. Studies consistently show that almost “any” treatment will appear superior to no treatment. That’s why we have to compare the real treatment to a placebo treatment.

  17. vinny says:

    I think the problem here is clear terminology and this post really reminds me off a Life of Obrian scene where the prophet said “there will come a time of confusion and someone will be very confused about this,….” We are working too hard trying to figure out what you mean by placebo effect, and these anecdotes you are using are not making the task any easier.

  18. vinny says:

    I actually have great respect for the ID crowd and almost joined that branch of IM, but this is a very confusing post.

  19. Mark Crislip says:

    the placebo effect occurs in the treatment of a disease.

    It is where actively doing nothing has an effect on the disease. this effect if present, needs to be more than passively doing nothing.

    I treat disease X

    the treatment has 40% inmprovement
    the placebo has 10% improvement
    doing nothing has 10% improvment

    No placebo effect.

    treatment has 40% improvement
    placebo has 40% improvement
    doing nothing has 10 % improvment

    An effect from the placebo.

    you never consistantly see the latter

    If there is just a treatment and a placebo, you do not know if the alleged effects of placebo are because the placebo is doing something or it is natural history of disease/regression towards the mean phenomena. Most placebo control studies do not show an effect from placebo, as there is no non treatment wing.

  20. durvit says:

    Dr Crislip wrote:

    Most placebo control studies do not show an effect from placebo, as there is no non treatment wing.

    Doesn’t that pesky Helsinki Declaration mean that the chances of you getting a human subjects trial in which one group is left untreated through an IRB are slim to non-existent? For clinical conditions don’t the spoilsports strongly recommend that you should compare your innovative intervention to the current standard best-practice for that condition?

    As I mentioned above, the lack of a no-treatment group for the gastric ulcer studies seems to have made them ineligible for inclusion in the Cochrane Review for Placebo Interventions.

    However, despite the observed differences between the groups, are you suggesting that the results in the gastric healing studies are mostly explicable by regression to the mean or similar mechanisms?

  21. daedalus2u says:

    What about this?

    I treat disease X

    the treatment has 40% improvement
    the placebo has 20% improvement
    doing nothing has 10% improvment

    Is that an instance of a postive placebo effect?

  22. Harriet Hall says:

    Examples from Bausell’s book:

    Patients who were given a firm diagnosis and told confidently that they would be better in a few days reported recovery from minor illnesses much faster than patients who were told “I cannot be certain just what is wrong with you.”

    Patients with post-op pain were given an IV containing nothing but saline. Those who were told it was a powerful analgesic required 34% less analgesia than patients who weren’t told anything about what the IV was for.

    Pain tolerance in minutes for patients with:

    No treatment 12.0 minutes
    No analgesic, but a hidden opioid blocker 11.8 minutes
    Hidden analgesic, no opioid blocker 17.0
    Hidden analgesic, hidden opioid blocker 17.2
    Announced analgesic, no opioid blocker 20.4
    Announced analgesic, opioid blocker 17.3

  23. David Gorski says:

    Bausell’s book lays out evidence for the placebo effect (and that the vast majority of “alternative medicine” is nothing more than an exercise in the placebo effect) in the clearest, most compelling way I’ve seen.

  24. kgrimes says:

    daedalus2u,

    Depends on whether the difference is significant or not! For all we know, there could be no significant difference between the treatment and no treatment arm either.

    However, I’m sure that’s not the point you are making here…just posting for the first time.

  25. Kimbo Jones says:

    I wonder if part of the reason there is a difficulty in grasping what Mark is trying to say in this post comes from a difference in definitions (as other people have evidently picked up, seeing as how a definition has already been requested). Mark seems to be defining “objective” pain as the rate at which the pain nerve is firing, whereas it appears from the comments that many of us are thinking of “objective” pain in other ways, such as the brain state. (Correct me if I’m wrong.)

    Questions:

    If the brain is “interpreting” the pain signal differently it is doing so by firing or not firing this or that neuron in the brain. How is neuron firing any less objective than the initial axon (nerve) firing rate? They’re all neurons, so why is one more objective a measure than the others? What I mean is, I’m interpreting here from the original post that the psychological state is not evidence that there is a placebo effect because there is no change in objective measures. But: 1) What if we did not measure the “right” objective measures? and 2) If our psychological state is determined by our brain state and our brain state can be altered (ignoring or accepting certain signals and then interpreting them via neuron firing), isn’t the psychological state integral to the placebo effect?

    If anyone could clarify, I’d be very appreciative of the response.

    I am also confused by the notion that the placebo effect would have to equal the treatment effect for the placebo effect to be “real”. What if the placebo effect is a portion of the real effect; i.e., that which can be altered by brain state? Again, why is the brain state not a “real” effect?

  26. Harriet Hall says:

    Bob Carrol has responded to Dr. Crislip in the latest edition of the Skeptic’s Dictionary Newsletter at http://www.skepdic.com/news/newsletter93.html#8

  27. IBY says:

    Huh, I thought placebos depended all on the attitude. Maybe I didn’t understand what placebos were, then.

  28. pmoran says:

    It is natural that we critics of alternative medicine should be uneasy about mankind’s capacity to respond in various ways to sham treatments. It lends an unwanted credibility to some of the claims of alternative practitioners and their supporters.

    It even allows of a “Grand Unified Theory of Medicine”.

    The Grand Unified Theory of Medicine states the bleeding obvious, once you can bring yourself to see it. It says that anything at all can serve as medicine under the right conditions, meaning that it can satisfy at least some of the complex needs that persons bring into medical interactions, and thereby favourably influence symptoms, sense of well-being, and illness behaviour.

    I think nearly everyone perceives that this is so on some level, from Mark Crislip’s mother’s kiss (mentioned by him in a previous post), on. Yet it is a repellent concept for the medical skeptic. We habitually work from a model of medical practice wherein everything hangs upon having a correct diagnosis, and treatments having INTRINSIC efficacy. We have never considered that there might be huge fringe of medical activity wherein neither of these things matter very much. The idea smacks to us of New Age airy-fairiness, or the undoubtedly exaggerated imaginings of the mind-body crowd. Or, we compartmentalize it out of consideration with demeaning language as “only placebo effects”, ignoring the probability that 99.99% of all the medical interactions in history. and close to that even today, are based upon or include some such phenomena and that sometimes nothing much else is on offer for suffering people.

    The GUT is a powerful concept that is entirely consistent with the evolving evidence, even if some are not yet prepared to accept where it is heading. This blog should be looking at such matters if it is interested in the fullest understanding of medicine in its infinite convolutions. In fact, conditions that wholly fit into the “biomedical” model of medical practice (for want of a desperately needed better term for it) may be a tiny exception rather than the rule. Even the symptoms of cancer patients will respond, at least temporarily, to placebo treatments.

    That’s not even the bad news, I am afraid. An awful consequence of the idea for the skeptic is that all of medicine, even its fraud and quackery, can be looked upon as one to some extent, and susceptible to evaluation along the usual lines of cost and potential for harm in relation to benefits. . Medicine is a special case so far as the evils of fraud and delusional ideas are concerned, because the supposed victims are often their staunchest defenders. .The place of caveat emptor is more complex than in other settings and dependent upon the precise claim rather any inherent medical properties of the methods being promoted. .

    Nevertheless, there are many advantages to such an approach in healthfraud discussions, perhaps because it incorporates an important aspect of truth that everyone can relate to. The most important advantage is a possible shift in debate from the “it can’t work”/”yes, it does” impasse onto the more constructive “why?”, the absolutely crucial “for what?” and the as yet not fully resolved “how much, really?”. Equally importantly it allows us to treat the views and experiences of other fallible human beings with a touch more respect and understanding, which cannot be all bad — uncompromising confrontation has definitely not achieved much.

    Observe that concern as to the possible adverse effects of any tolerance of TT or homoepathy on the public’s understanding of science or on scientific progress can be easily factored in under “harm”. It too, will be dependent upon the precise claim being addressed. The framework is established for a proper evidence-based weighing-up process in which everyone understands the rules.

  29. bonedoc says:

    I don’t agree that the “placebo effect” is an effect caused by the placebo. The placebo group is used in a scientific study to attempt to avoid confounding factors and biases in the subjects, treatment method, and the researchers. The placebo does not cause these placebo group outcomes, however. The comments and the postings here are a good illustration of these confounding factors, including conditioned responses, expectations of the patient and the researchers, and the natural history and variation of the condition being studied. I conclude that the term “placebo effect” is semantic shorthand for the sum of the effects of the environment of treatment and natural history of disease in the absence of an intervention being studied. It has meaning in the context of a scientific investigation.

    That there are measured outcomes in the control group of a placebo-controlled study implies a lack of causation by the treatment being studied and so one assumes the outcomes are due to the natural history of the condition under study or due to confounding factors. The outcomes in the group not given the studied treatment (sham treatment or placebo) are the true baseline; they are the outcomes that can be expected in the absence of treatment.

    There are a variety of known and well studied causes of this apparent placebo effect. Conditioned responses, such as salivating in Pavlov’s dogs, noted in some of the comments above, are not caused by the inciting factor (the bell ringing) but rather, are caused by the conditioning of the dog. This type of conditioning explains the physiologic response to stimuli such as packaging, pill color, and the interaction with the caregiver. Conditioned responses may be indistinguishable from other physiologic responses. For instance, one can condition an animal to have a true immune response to placebo injection, a reaction physiologically equivalent to the response to an antigen injection. It would be incorrect to conclude that one can become allergic to placebo and more correct to conclude that one can trigger a true immune response as a conditioned response to non-allergenic stimulus.

    It is exactly this bias and confounding effect that a placebo is designed to control for, and it is the reason that a placebo-controlled study is less bias prone than a no treatment control group study.

    Steven Zeitzew
    - This document has been prepared with voice recognition software. Please excuse unusual errors. -

  30. pmoran says:

    Steve: “The outcomes in the group not given the studied treatment (sham treatment or placebo) are the true baseline; they are the outcomes that can be expected in the absence of treatment.”

    No. The question being asked here is a different one to the usual — whether patients respond beneficially to sham treatment. The true baseline would be outcomes in patients with no medical contact whatsoever. which is unmeasurable. The closest we can get to it is patients allotted to a “waiting list” for treatment.

  31. bonedoc says:

    I disagree, the point of using a placebo is that patients are not responding to the placebo per se, but rather they are responding to the characteristics and environment of the interaction. By understanding the actual mechanisms of these interactions, whether it is conditioning or a psychological response to the nature of the personal interaction, we can improve the delivery and efficacy of science based healthcare.

    If the green pills are more effective than red ones, then we should also color them green in addition to studying their biochemistry.

    If the personal interaction with a misguided quack satisfies a patient and relieves his suffering, we should not emulate the quackery, we should learn more about how to better interact with our patients while providing legitimate science based medical care.

    If patients report satisfactory relief after the administration of a placebo it is incumbent upon us to study the interaction since by definition we know that there is no objective response to the placebo itself.

    Sometimes patients report to us that they feel they have improved after ineffective quack treatment although we cannot measure an objective change in their underlying condition (saw palmetto comes to mind). This relief of their suffering has some value, but is insufficient to justify quack treatment recommendations. We can learn from this interaction so that in the future our treatments that effectively relieve the underlying condition will do a better job at also relieving the patient’s suffering. It seems clear that our patients desire not only a cure of their problem but relief from the suffering the problem has caused them, and that relief is sometimes not provided by the resolution of the problem alone (analogous to the way one might feel about a previously flawless automobile after body damage with subsequent apparently satisfactory needed body work).

    Steven Zeitzew
    - This document has been prepared with voice recognition software. Please excuse unusual errors. -

  32. Mark Crislip says:

    I am slow to respond, slow to think, and slow to write, esp when its summer time in the Pacific Northwest. Write a blog reply or golf with the kids and eat the worlds best strawberries? No contest. So by the time this gets posted, the original post will be in the blog netherworld. I also wanted to read Snake Oil Science by Baussel before writing this, and I would definitely call it a must read, even if I disagree that the effects of alt med is due to placebo effects.

    I am going to focus on pain; ulcer studies not withstanding I think the preponderance of data suggests no placebo effect for objective outcomes.

    Pain is usually a mostly subjective endpoint, but there is a surrogate marker for pain and that is function. In my world of acute care medicine, the better the pain control, the more function improves.

    Pain is a limiting response for activity. The more you hurt, the less you do. And as a rule, pain stops you from functioning (if it can) a fraction of a second before you are aware of it. The purpose of pain is to prevent further trauma. People who cannot feel pain in their feet, like those with diabetic neuropathy, end up trashing their feet.

    The sham acupuncture vrs placebo pill is interesting in that while patients reported they were better, they did not function as if they had decreased pain. Functional assessment of their repetitive strain injury suggested that they were not better.

    Although they reported improvement, they FUNCTIONED as if the pain was the same. This outcome is often seen in other pain studies in alt med: pain improved, function not. It is why I think the pain is not better, but the perception is better. Semantics I know, but.

    With the placebo, the pain receptor is firing at the same rate at the site of injury. The body stops at the same threshold level that prevents further pain/injury. Even if the patient says there is less pain, there isn’t as far as function goes.

    If the wine is unchanged chemically, but you think it is better because it costs more, is there a placebo effect?
    If the urinary obstruction is unchanged by urodydmanics studies but the patient thinks symptoms are better, is there a placebo effect?

    How do these examples differ from pain? If the body acts like the pain is not changed, the pain being the response to a given level of trauma that prevents further damage, then there is no change in pain if there is no change in function.

    In his book Baussel uses studies where patients had a very short course of pain inflicted upon them and demonstrated that the response to pain could be blocked by placebo, presumably by endogenous opioids. It would be nice in these studies of endogenous opioid levels were measured instead of the surrogate of a blocking medication, since these medications are not ‘clean’ in their response.

    These are interesting studies about placebo and pain but to my mind little clinical correlate with disease. Short course of minor pain inflicted on normal volunteers. The models are interesting and informative, but I don’t appear to have much to do with the pain I see clinically.

    Most patients I see or who seek quack care have chronic pain or, in the acute medical care, we treat (trauma) or inflict serious pain that lasts a long time.

    Once, to add another what I hope is an illustrative example, I was listening to a lecture on the pathophysiology of inner ear infections in the chinchilla model of disease. The study focused on what happens in the first hour after infection started with nice graphs of cytokines and bacterial growth. Towards the end of the lecture an older, wiser head leaned over to me and said something to the effect that anything that happens in the first hour of an infection is probably not clinically relevant.

    I would think, but I do not know, and do not know of any data one way or the other, that the the endogenous opioid system in both cases in acute severe pain and in chronic pain would be turned on and functioning fully.

    I speak from the bias of acute care medicine, but all the diseases I see have a ‘maxed out’ physiologic response. The only way one can augment the normal response is by either adding more (levophed for septic shock) or interfering with the system to get more or less of a desired effect. I can’t think of another instance where we can augment a physiologic effect by doing nothing.

    Perhaps it can be explained to me why we have evolved a pain control system that does not respond maximally to the pain at hand but can be augmented by suggestion? Most of human existence the main threats to life and limb were infection and trauma. Why do we have a system, pain control, that only works at its best if you suggest there is a therapy. It is the only physiologic response to disease I know of that has that characteristic. It would be like the cardiovascular system only functioning at its best when you were told you could run farther and faster if you take this here sugar pill.

    Where is the survival advantage in that? Why have we evolved a placebo effect? I can’t find anything substantive on why we evolved so inept a response to trauma.

    While Mr Carrol has a great and thoughtful response to my blog, his one error is assuming I know more than I do (http://www.skepdic.com/news/newsletter93.html#8).

    I was unaware of the thoracomy study when I wrote the post. Interesting study. I would be happy to eat my words with a coating of BBQ sauce if there was a functional correlate in the placebo group.

    So if pain was decreased, then function should have decreased. If only the perception of pain was altered, then their function would not have decreased.

    They had decreased pain and thoracotomies hurt. A lot. With every breath you take. Did the patients have more rapid extubation? Shorter length of stay? Better peak flow on pulmonary function? Were there changes in the vital signs; patients with less pain should have a lower pulse and respiratory rate. Taking a deep breath after thoracic surgery is no easy task. Did placebo group could take in a deeper breath sooner? I would concede your point.

    If there was a real placebo effect on the pain ie the quantity of pain receptors firing and those signals reaching both the spinal cord and the brain, then those with effects from placebo/deceptive treatment would have the same functional response to being asked to take in a deep breath as those with real pain control

    It is interesting that they excluded two groups from the data: those that received a basal amount of narcotic and were told they might get narcotic or placebo and those that received a basal amount of narcotic and were told they were getting a strong medication.

    If those getting narcotics at a basal level were have a placebo effect as well, one would expect that they too would have had decreased need for narcs as well. While only 4 patients in those groups (as opposed to 10 in the others), it would have been interesting to report that data.

    The problem as a clinician I bet I could tell if a patient was getting a narc or not. It alters mental status, it slows speech, it decreases vitals, the patient is less agitated. I have had a pca pump, all be it with Demerol, and I knew I was not getting placebo as it went in and I knew it when it ran out. Not because of how it altered my pain (as I remember it, the pain didn’t so much get lessened, but I didn’t really care that I had it) but the other changes in my mental functioning. It makes true blinding questionable.

    And was it clinically relevant improved pain control? In terms of doses of narcotic, it was not that impressive. The saline group had 6.7 doses of narcotic over 3 days, the randomized group had 5.1 doses over three days and the deceptive group had 4.1 doses over three days. The deceptive group had 2.5 less doses over a three day hospitalization. In those terms, not so impressive a difference. If someone gets better a few hours faster over a week long clinical course, it may be statistically significant, but it is clinically unimportant. If they functioned the same despite better perceived analgesia, then I would not be so impressed. If the body is acting like it is experiencing the same amount of pain, then the pain is not changed. Just the perception. If the placebo group functioned worse than other groups, I would take it as a hint that my interpretation of pain/placebo is closer to the mark.

    It would also be interesting if somehow the endorphin levels could be measured in each group. I still cannot understand why the endogenous opioid system is not already maxed out in a thoracotomy patient and why the belief in a placebo would augment it. A much wiser head than mine will have to explain the physiologic and evolutionary rational behind this response to pain. If placebo does indeed to this, it makes the pain control system unique.

    Patents respond to placebo and to their interaction with me. I aggressively use that fact everyday. I do not think I make the patient better faster. Everyone seems to get better at more or less the same rate from a given illness. But I think they do better emotionally. Good attitude and hopeful attitude do not make my patients better faster. But it makes it easier to tolerate their pain and suffering. That is the best that placebo can do.

    I am sure the study will come, and soon if the thoracotomy study is any indication, that will make me eat my words. Not yet. The data doesn’t convince me that treatment of pain in clinical disease is decreased by placebo just the perception of the pain. The amount of pain reaching the brain is not changed, just the interpretation of the pain. To my mind this makes more sense give how small the placebo effect is.

    This spring we had a couple of weeks of 40 degree weather and then it jumped to 70. It seemed hot. This summer we had a string of 100 degree days, then if fell to 70. It seemed chilly. Both times it was 70 degrees. The perception of the temperature was drastically different. The patients think of 70 degrees as cool rather than hot. It is a small and probably unimportant point, but it is how I read the literature. It may be quibbling, but if there is a placebo effect, I want to know where and why it works.

    Mr Carrol, in his reasoned critique of my post, then mentions an irritable bowel syndrome study where patients had some subjective improvement when they had a caring physician. It was short term study, and I get back to the NEJM article on saw palmetto where everyone thought their urinary obstruction was improved on placebo even when their urinary dynamics were not. It took a year before the subjective symptoms on placebo returned to baseline while objective findings remained unchanged. It would have been nice to have extended the study to see if the patients ‘relapsed’. It would been a simple matter to put a counter on the toilet handle to count the number of flushes to see if they did indeed have a functional correlate with the perceived improvement.

    There may be some diseases that respond to placebo if they alter parasympathetic response. IBS may be one of these, as might a disease like Parkensons, that may be amenable to placebo. But I am not so certain that the occasional exception proves a generalizable phenomena.

    As I ponder the placebo myth and why we have it, I wonder if I am thinking about placebo in the wrong context. A minor effect for pain where it makes little sense to have evolved as a response to disease.

    My problem may be that I think of the effect in a medical context because that is where it is usually evaluated. Perhaps, and this is obviously wild speculation, the placebo effect has nothing to do with the response to pain and disease. Just because people have been using a quart of ice cream to hammer a nail doesn’t mean that is the reason for the quart of ice cream. In Infectious Diseases, I wonder what the real reason for bacterial toxins are. Tetanus toxin doesn’t seem to have a benefit in perpetuating the organism. I have assumed that the toxic effects are an un intended epiphenomena of its real purpose, what ever it may be.

    Perhaps, it is the same with the placebo effect. It makes no sense that we have evolved a system to deal with pain and disease that has such minor effects and is activated by suggestion. Perhaps I should not be thinking of it in medical terms.

    Certainly humans appear to be able to believe in any number of irrational things. Perhaps the placebo effect is an epiphenomena of some other system of the brain: our ability to be believe, or love, or some other emotional/psychological system. That we measure it in the medical/disease realm is a fluke.

    I tried without success to see if the placebo effect on fmri is the same seen with altered states like love or meditation or religious belief. Nothing. But my ability to find these is limited by my lack of knowledge for search terms.

    But I wonder if the study of placebo belongs in some other area of neurological study than pain. I hope to be further educated.

  33. daedalus2u says:

    Mark, you have made a long comment with a number of premises and conclusions from those premises. Some of those premises are not supported by data but have simply been assumed by you. The placebo effect hasn’t been well enough studied to make some of the statements you have made.

    You say “With the placebo, the pain receptor is firing at the same rate at the site of injury. The body stops at the same threshold level that prevents further pain/injury. Even if the patient says there is less pain, there isn’t as far as function goes.” However, there is no data to support that statement. You are simply assuming that the pain receptor is firing at the same rate.

    Pain is an extremely important signal that the body uses to avoid damaging itself. An injured leg is favored because an injured leg would be injured more if it is not favored. A treatment that relieves the conscious feelings of pain, but does not extinguish the unconscious favoring of the injured leg is better pain relief because it has fewer side effects (the loss of favoring an injured leg being an undesirable side effect because it exacerbates the injury).

    You say “Towards the end of the lecture an older, wiser head leaned over to me and said something to the effect that anything that happens in the first hour of an infection is probably not clinically relevant.” But how could someone “older and wiser” know that unless it had been studied scientifically? When is the transition from “bacterial growth” to “bacterial infection”? That transition occurs when the bacteria reach a sufficient density to trigger quorum sensing. That quorum sensing causes expression of virulence factors including toxins, proteases, biofilm formation, swarming behavior and a host of other things. The lack of expression of virulence factors in response to the lack of quorum sensing is why people can be colonized with virulent strains but not have an infection. It only becomes an infection when virulence factors are expressed. If that never happens, an infection never happens.

    Pain is a signal the body uses to tell the brain that damage thresholds are being exceeded and that damage to the body needs to be weighed against what ever physical activity is being done. When one is running from a bear, increased injury due to a sprained ankle is of negligible consequence compared to being caught by the bear. The ideal damage control system would report the status of bodily functions and for those under volitional control would report when further use causes damage. When you are running from a bear, it is important to be able to use any muscle, any bone, any limb, any physiological system that is necessary to escape. But if a system is compromised, such that a limb won’t bear weight because the bone is broken, the organism needs to account for that in its escape plan. If you need to use a broken leg to escape from a bear, you need to have an accurate signal telling you what load that leg can sustain.

    The placebo effect is part of the neurogenic control of the damage control system. When you are running from a bear, you don’t have time to mend a broken bone. Spending resources on healing while running from a bear is to waste those resources and increase the likelihood that the bear catches you. Diverting those resources away from healing and into running is the evolutionary correct decision and is what our evolved damage control system does. Once the bear has been escaped from, then the emergency overload of systems involved in escape can “stand down” and the ATP production capacity that has been held in reserve for them can be diverted to other things, such as healing.

    The control signal that is used to modulate this allocation of resources is NO. Low NO is the state of stress, where resources are allocated to things under voluntary control so the voluntary control system can use those resources to run from the bear. The involuntary control system that controls things like healing has shut them all down to divert ATP to voluntary systems. When the life threatening stress has passed, NO levels come back up (usually, and in the wild, but modern life has disrupted some of the systems that do this), resources get allocated to healing and the organism can repair the damage that accumulated during the acute stress that the organism survived. If the NO level does not come back up the organism stays in the state where resources are allocated away from healing.

    A placebo tells the control system that “everything is ok”, and that ATP can be allocated to healing. A placebo only works if it generates enough NO via neurogenic mechanisms to switch physiology back to a high NO state. The low NO state has hysteresis and it takes an active generation of NO to get out of it. If the NO generation pathways are insufficient to make enough, then the organism stays in the low NO state.

  34. pmoran says:

    It is such a complicated field. Most scientific research on placebo tries to isolate the effects of supplying patients with a fake treatment, but there is much, much more to medical interactions than this. A little explanation and reassurance can make a huge difference to how patients perceive and cope with their illness, and it probably doesn’t matter whether the practitioner’s opinions are based upon science or not. All that matters is that the patient respects them.

    The placebo itself may mainly serve as a symbol of the practitioner’s desire to help, satisfying that almost insatiable human urge to “do something” about problems, and especially avoiding the negative effects of frustrated expectations should the practitioner not offer any treatment. Some patients accept that, others will interpret it as rejection.

    The test of the placebo hypothesis lies not merely in the studies that seem to require the existence of the imputed phenomenon. It is also extremely PLAUSIBLE in terms of what else we know about human behaviour and perceptions.

    It is EXPLANATORY of a great deal of medical experience. It explains much about medical history but also helps explain the very existence of alternative medicine (it is not wholly satisfactory to have to explain the extensive anecdotal material in terms of spontaneous events and other misattributions and it has also not proved easy to sell that viewpoint outside of skeptical circles).

    You wonder about the EVOLUTIONARY benefits. I see it as being extremely important for the hunter-gatherer to have some form of healing ritual that may help injured or sick members function when food is scarce.

    I agree that there are weaknesses in placebo theory such as its general inability to perform in terms of more objective outcomes and often weak apparent effects. However, we don’t yet know how “powerful” the placebo complex can be in medical practice because our clinical evidence comes mainly from the kind of studies wherein placebo benefits will be minimised.

    The other main weakness I see is uncertainty as to how much of the reported benefits are simply due to biased reporting –the patients are not “really” better. Hence the importance of the endorphin and MRI studies, if these are being interpreted properly.

    My position is not absolutist. There is much we don’t know. This is not an argument from ignorance; the mere possibility that some are deriving real benefits from this neo-folk or DIY medicine (that some like to call CAM) should have some influence on how we discuss and react to it.

  35. Harriet Hall says:

    Mark,

    When we kiss our toddlers’ boo-boos, I don’t think anyone believes we are doing it to reduce pain signals. We do it for the psychological effect, not for any physiological effect.

    The conscious mind can only pay attention to one thing at a time, and anything we can do to distract attention from the pain makes people feel better. That’s valuable in itself, even if it has no physiologic effect. Does it matter if we still “have the pain” if we’re not aware of it? Placebos may not “really” reduce pain, but they “effectively” reduce it through psychological mechanisms. That’s worth something.

    As you pointed out, even narcotics don’t so much reduce the pain as dull the pain-interpretation faculties and make you not care so much.

    I wonder if you might have the epiphenomenon thing backwards. It’s very valuable to be able to fool ourselves into ignoring symptoms so we can go about our business. Maybe as an epiphenomenon of that ability, we unfortunately are able to fool ourselves about other things where being fooled is not to our advantage.

  36. cbamity says:

    Yes, I know that I am reading this a year after it was written. Its interesting to read a seemingly logical person biased by his own belief. It is obvious that he has a problem that the placebo effect exists, and rationalizes why it doesnt exist. Even when an effect is acknowledged (salivating via conditioning or via patient expectations), he calls it something else other than a mechanism for placebo.

    How about this: Would you think differently of a study that didnt have a placebo control? If the placebo effect doesnt exist, then we would never need that control, just compare the treatment group to a do-nothing group. If you are honest, you would view such a study differently. Elsewhere you admit that a double blind randomzied placebo-controlled trial is the gold standard.

    Ever hear of sickbuilding syndrome? Vomiting is an objective measure. Sure, that is the nocebo effect, but that is just the flipside of placebo and if anything the placebo effect is even more established. Why does sham accupuncture usually outperform placebo capsules?

    Its obvious that you keep a very narrow view of what the placebo effect is so you can deny its existence.

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