Meet the Ethical Placebo: A Story that Heals

Irving Kirsch, photo by Bo Tenberg

Irving Kirsch at the University of Hull, photo by Bo Tenberg

A provocative new study called “Placebos Without Deception,” published on PLoS One today, threatens to make humble sugar pills something they’ve rarely had a chance to be in the history of medicine: a respectable, ethically sound treatment for disease that has been vetted in controlled trials.

The word placebo is ancient, coming to us from the Latin for “I shall please.” As far back as the 14th Century, the term already had connotations of fakery, sleaze, and deception. For well-to-do Catholic families in Geoffrey Chaucer’s day, the custom at funerals was to offer a feast to the congregation after the mourners sang the Office for the Dead (which contains the phrase placebo Domino in regione vivorum, “I shall please the Lord in the land of the living”). The unintended effect of this largesse was to inspire distant relatives and former acquaintances of the departed to crawl out of the woodwork, weeping copiously while praising the deceased, then hastening to the buffet. By the time Chaucer wrote his Canterbury Tales, these macabre freeloaders had been christened “placebo singers.”

In modern medicine, placebos are associated with another form of deception — a kind that has long been thought essential for conducting randomized clinical trials of new drugs, the statistical rock upon which the global pharmaceutical industry was built. One group of volunteers in an RCT gets the novel medication; another group (the “control” group) gets pills or capsules that look identical to the allegedly active drug, but contain only an inert substance like milk sugar. These faux drugs are called placebos.

Inevitably, the health of some people in both groups improves, while the health of others grows worse. Symptoms of illness fluctuate for all sorts of reasons, including regression to the mean. Since the goal of an RCT, from Big Pharma’s perspective, is to demonstrate the effectiveness of a new drug, the return to robust health of a volunteer in the control group is considered a statistical distraction. If too many people in the trial get better after downing sugar pills, the real drug will look worse by comparison — sometimes fatally so for the purpose of earning approval from the Food and Drug Adminstration.

For a complex and somewhat mysterious set of reasons, it is becoming increasingly difficult for experimental drugs to prove their superiority to sugar pills in RCTs, which was the subject of an in-depth article I published in Wired called “The Placebo Problem,” recipient of this year’s Kavli/AAAS Science Journalism of the Year award for a magazine feature.

Only in recent years, however, has it become obvious that the abatement of symptoms in control-group volunteers — the so-called placebo effect — is worthy of study outside the context of drug trials, and is in fact profoundly good news to anyone but investors in Pfizer, Roche, and GlaxoSmithKline. The emerging field of placebo research has revealed that the body’s repertoire of resilience contains a powerful self-healing network that can help reduce pain and inflammation, lower the production of stress chemicals like cortisol, and even tame high blood pressure and the tremors of Parkinson’s disease.

Jumpstarting this network requires nothing more or less than a belief that one is receiving effective treatment — in the form of a pill, a capsule, talk therapy, injection, IV, or acupuncture needle. The activation of this self-healing network is what we really mean when we talk about the placebo effect. Though inert in themselves, placebos act as passwords between the domain of the mind and the domain of the body, enabling the expectation of healing to be translated into cascades of neurotransmitters and altered patterns of brain activity that engender health.

That’s all well and good, but what does it mean in the real world of people getting sick? You can hardly expect the American Medical Association to issue a wink and a nod to doctors, encouraging them to prescribe sugar pills for seriously disabling conditions like chronic depression and Parkinson’s disease. Meanwhile, more and more studies each year — by researchers like Fabrizio Benedetti at the University of Turin, author of a superb new book called The Patient’s Brain, and neuroscientist Tor Wager at the University of Colorado — demonstrate that the placebo effect might be potentially useful in treating a wide range of ills. Then why aren’t doctors supposed to use it?

The medical establishment’s ethical problem with placebo treatment boils down to the notion that for fake drugs to be effective, doctors must lie to their patients. It has been widely assumed that if a patient discovers that he or she is taking a placebo, the mind/body password will no longer unlock the network, and the magic pills will cease to do their job.

Now, however, a group of leading placebo researchers — including Irving Kirsch at the University of Hull in England (who I interview at length below) and Ted Kaptchuk at Harvard — has produced a little bombshell of a study that makes these assumptions obsolete. For “Placebos Without Deception,” the researchers tracked the health of 80 volunteers with irritable bowel syndrome for three weeks as half of them took placebos and the other half didn’t. A painful, chronic gastrointestinal condition, IBS is serious business. It’s one of the top ten reasons why people seek medical care worldwide, accounting for millions of dollars a year in health care expenditures and lost work-hours.

In a previous study published in the British Medical Journal in 2008, Kaptchuk and Kirsch demonstrated that placebo treatment can be highly effective for alleviating the symptoms of IBS. This time, however, instead of the trial being “blinded,” it was “open.” That is, the volunteers in the placebo group knew that they were getting only inert pills — which they were instructed to take religiously, twice a day. They were also informed that, just as Ivan Pavlov trained his dogs to drool at the sound of a bell, the body could be trained to activate its own built-in healing network by the act of swallowing a pill.

In other words, in addition to the bogus medication, the volunteers were given a true story — the story of the placebo effect. They also received the care and attention of clinicians, which have been found in many other studies to be crucial for eliciting placebo effects. The combination of the story and a supportive clinical environment were enough to prevail over the knowledge that there was really nothing in the pills. People in the placebo arm of the trial got better — clinically, measurably, significantly better — on standard scales of symptom severity and overall quality of life. In fact, the volunteers in the placebo group experienced improvement comparable to patients taking a drug called alosetron, the standard of care for IBS.

Meet the ethical placebo: a powerfully effective faux medication that meets all the standards of informed consent.

The study is hardly the last word on the subject, but more like one of the first. Its modest sample size and brief duration leave plenty of room for followup research. (What if “ethical” placebos wear off more quickly than deceptive ones? Does the fact that most of the volunteers in this study were women have any bearing on the outcome? Were any of the volunteers skeptical that the placebo effect is real, and did that affect their response to treatment?) Before some eager editor out there composes a tweet-baiting headline suggesting that placebos are about to drive Big Pharma out of business, he or she should appreciate the fact that the advent of AMA-approved placebo treatments would open numerous cans of fascinatingly tangled worms. For example, since the precise nature of placebo effects is shaped largely by patients’ expectations, would the advertised potency and side effects of theoretical products like Placebex and Therastim be subject to change by Internet rumors, requiring perpetual updating?


100% pure placebo

Even at this preliminary stage in the research, however, it’s clear that it’s time to flip our ideas about fake pills upside down. It’s common to use the word “placebo” as a synonym for “scam.” Economists talk about placebo solutions to our economic catastrophe (tax cuts for the rich, anyone?). Online skeptics mock the billion-dollar herbal-medicine industry by calling it Big Placebo. The fact that our brains and bodies respond vigorously to placebos given in warm and supportive clinical environments, however, turns out to be very real.

We’re also discovering that the power of narrative is embedded deeply in our physiology. Perhaps that’s not surprising. In the long centuries before doctors discovered antibiotics, they often had little else but an observant eye, a listening ear, and a bag of nostrums with names like decoction of barley and compound infusion of roses to offer their desperately ill patients.

In an age of computerized diagnostics, talking about the power of storytelling in health care seems like a throwback to those medical Dark Ages. After reading the new study, however, one of the pioneers of placebo research, anthropologist Dan Moerman at the University of Michigan, noted how much even the volunteers who didn’t get placebos benefited from the support and attention of clinicians.

“I was really surprised at how well the non-placebo group did,” Moerman says in email. “Note I don’t call them a ‘no treatment group’ because they, and everyone else, received exemplary treatment here: they were listened to, examined, encouraged, supported. They were able to talk with, and be taken seriously by, people who understood their issues, things they probably had serious difficulty discussing with their own families. I think it likely that the effectiveness of the placebos above and beyond all the other treatment would have been diminished without the whole system of compassionate care.”

At the same time, as Kirsch explains in our interview, the volunteers who took placebos felt significantly better than those who didn’t. The act of taking the pills made a difference.

Placebo expert Amir Raz at McGill University observes that the new study follows up on a groundbreaking experiment conducted in 1964 by Lee Park and Uno Covi, who administered “open” placebos to 15 patients from a psychiatric clinic and tracked similar levels of improvement in their anxiety. In a paper slated to be published in the April 2011 issue of the Canadian Journal of Psychiatry, Raz will talk to many physicians who doubt that one has to lie to patients for placebos to be effective. In fact, in the real world of doctoring, many physicians prescribe medications at dosages too low to have an effect on their own, hoping to tap into the body’s own healing resources — though this is mostly acknowledged only in whispers, as a kind of trade secret.

Kirsch’s 2010 book The Emperor’s New Drugs caused a huge stir by claiming that the effectiveness of antidepressants — one of the top-selling classes of drugs in the world — may be entirely dependent on the placebo effect. Before spending time with him at a placebo workshop hosted at McGill in July, I was frankly expecting to meet a fiery anti-pharma avenger  — albeit one with a compelling argument backed up by data.

Instead, Kirsch is a soft-spoken, modest, diligent, boyishly handsome 67-year-old psychologist who thoroughly understands why his notions are so upsetting to people who insist that their lives have been turned around by Paxil or Lexapro. He also has an intriguing personal history that includes organizing against the Vietnam War with Bertrand Russell, producing a Grammy-nominated comedy album in 1973 with the editors of National Lampoon, and playing violin in the Toledo Symphony behind Aretha Franklin. Kirsch is currently working on a new book about the potential of placebo therapy.

Silberman: What’s the most subversive aspect of this new study?

Kirsch:  Simply that placebos work even when you tell people that they’re placebos. To me that’s fascinating. As is the fact that patients can experience substantial and clinically meaningful improvement of the symptoms of irritable bowel syndrome when given placebos.

One of the assumptions that we made in this study, however, is that you have to offer the patients a convincing rationale to use placebos as well as giving them a pill. That’s the next thing we have to test.

Silberman:  What kinds of ailments are amenable to placebo treatment?

Kirsch:  Depression, anxiety disorders, and pain; pain in particular is highly responsive to placebo therapy. Irritable bowel syndrome — we’ve shown that not only in this study, but in one published in the British Medical Journal a couple of years ago. Parkinson’s Disease, ulcers, and asthma too. There’s a long list of conditions treatable with placebos that have some subjective component and can be intensified by conditions like stress.

Silberman: If all of these ailments have a subjective component, does that mean they share a set of neurological mechanisms?

Kirsch:  I’m afraid that’s outside my area of expertise. But I know what these conditions don’t share in common. The kinds of effects you see in the brain when people respond to a placebo depends on the condition you’re supposed to be treating. So if you take a placebo analgesic, you get reductions in activity in the brain’s pain matrix. If you take a placebo antidepressant, you get changes in brain activity in areas related to depression.

Silberman: Does the placebo response tell us anything about how active medicines work?

Kirsch: For any condition susceptible to placebos, the placebo effect is a component of the response to active medication. In most cases, placebo effects and drug effects are additive — the net response to the medication is larger because of placebo effects than it would be on its own.

Silberman: You’ve done a lot of work analyzing placebo effects in antidepressant therapy, which you write about in your book The Emperor’s New Drugs. Has your opinion of antidepressants evolved at all?

Kirsch: The more I learn, the more convinced I become that the benefits of drugs for depression are not biologically driven, but driven by the placebo effect. The thing that convinces me most is that nearly all drugs for depression — despite having very different chemical compositions — are of equal benefit. In other words, you have drugs that are completely different in what they do chemically — even drugs that operate by opposing mechanisms — creating the same level of effect.

The most commonly employed antidepressants are supposed to increase the amount of serotonin in synapses in the brain, but there are also antidepressants that decrease the level of serotonin in the brain, and they both have the same effect therapeutically. The effects of these drugs seem to be completely independent of their chemical composition.

Silberman: Dan Moerman mentioned to me in an email that he was surprised by how well the non-placebo group did in your study.

Kirsch: That’s true. We said that we compared open label placebo to a no-treatment control group, but actually, the “no-treatment” description is not entirely accurate in this case.  The patients in the control group met with the clinician before being given the pills and midway between the beginning and end of the study. Both visits were in the context of a warm, supportive, patient-practitioner relationship. Like many other researchers, we assume that the therapeutic relationship is an important component of the placebo effect.

But many people — including doctors — think that the therapeutic relationship entirely accounts for the placebo effect.  Our data show that this is not true. If the placebo effect was entirely due to the therapeutic relationship — the time, attention, warmth, and enthusiasm communicated by the doctor — then our placebo pill would not have produced any effect beyond that seen in our “no-treatment” control condition, because the no-treatment control patients received the same level of therapeutic relationship as that received by patients in the placebo pill condition. That tells us two things –one, that giving patients the placebo pill improved their condition, and two, that the difference in improvement was due to getting the pill. It was not due to the therapeutic relationship.

Silberman:  One of the ways that you prepped the volunteers in this trial was that you informed them that placebo effects work via conditioning, like Pavlov’s dogs being trained to salivate at the sound of a bell. What trains people all over the world to respond to act of taking a pill?

Kirsch: The existence of successful treatments. People come to expect and believe that they’re going to get better if they take medication. The whole process of going to a physician and being treated reinforces this belief. That constitutes the basic aspects of classical conditioning. Eventually, the pill alone is enough to produce a placebo effect, whether it contains an active drug or not.

Silberman:  Does direct-to-consumer advertising also play a role? In America, when you open a magazine, the good-looking jock playing with puppies in the sun is the formerly depressed patient on Zoloft.

Navigating the road ahead with Abilify

Advertisement for Abilify, used to treat depression, schizophrenia, bipolar disorder, and autism-related irritability

Kirsch: No doubt about it. One thing that’s clear is that the placebo effect of antidepressants has gotten stronger over the years as these drugs have been more widely accepted, touted, and advertised. The response to them in general has increased because of the additivity I was talking about before.

Silberman:  What would a world in which placebos were given openly by doctors look like?

Kirsch:  Our study points to something that a number of people have suspected, but has been hard to demonstrate under controlled conditions: We have the capacity for healing physical conditions through psychological means. First, we have to accept that. Studies of placebo effects are great demonstrations of it.

You might think of this healing capacity as a self-regulatory mechanism. Then the question then becomes how best to unlock it. This kind of research shows the potential of our being able to treat certain conditions without drugs — particularly in cases where we don’t have effective drugs, and/or where the drugs we have are not much more effective than what we can accomplish with placebos. And especially in cases where the drugs carry serious risks.

Silberman: A lot of very smart people dismiss homeopathy, acupuncture, and other alternate treatments as nothing more than quackery for dullards — “woo,” as P.Z. Myers or Ben Goldacre might put it. But couldn’t the placebo response play the role of being, in a sense, the “active principle” of woo? For example, I recently saw a controlled trial of homeopathic therapy for rheumatoid arthritis that concluded that the effectiveness of the therapy was due to the homeopathic consultation process, not the little pills themselves. Your colleague Ted Kaptchuk spoke to me for my Wired article about the importance of “therapeutic ritual” in eliciting the placebo response, and homeopathic consultation — even if the notion that pills containing a few molecules at most of an active ingredient seems obviously ridiculous — is a good example of an elaborate therapeutic ritual. I think the door is still open on whether acupuncture does more than jump-start the placebo response…

Map of Acupuncture Meridians

Traditional map of 经络, the acupuncture meridians

Kirsch:  That door is closing. I think the effects of acupuncture are largely placebo effects, if not entirely. It’s a very good placebo effect; a really healthy and large placebo effect. The last study we did on IBS was with placebo acupuncture — sham acupuncture. Sham acupuncture does as much good as real acupuncture. You can do it without needles and still get the same effect. Practitioners of acupuncture, homeopathy, and other alternative and complimentary medicines do an excellent job of eliciting and bolstering placebo effects.

We know from our research the things that make a difference: how much time you spend with a patient, how supportive and empathic you are, how well you listen, and how confident you are in being able to help.  Complimentary and alternative medicine practitioners are particularly good at these things. These are obviously things that physicians can do as well, and some are very good at eliciting placebo effects.

But those qualities are becoming more rare in conventional medical practice. Certainly here in the UK, it’s very uncommon to have a good placebo intervention in primary care, because the standard visit with the doctor is ten minutes at most.

Silberman: Ten minutes sounds long to me. If I see my doctor for three minutes as she rushes around, it’s a good day.

Kirsch:  In the IBS study we did in 2008, we maximized the amount of time spent in the initial interview, and other qualities of listening and empathy, and got much more substantial placebo effects.

Silberman: These days, however, the emphasis is increasingly on data-driven medicine — blood tests, genome and proteome scans, and the search for biomarkers. Studies like this suggest that narrative medicine as it was practiced in the 19th century — the doctor listening to the patient, hearing the story of the symptoms, and reframing it as a story of how the patient will get better — also plays a crucial role in healing.

Kirsch:  We’re breaking the boundary between the two approaches.  The reason we do studies like this is to make placebo research data-driven. We’re starting to build up a database on the effects of enhancing patient-physician contact, and on the administration of placebos openly and honestly, without deception.

Silberman: Have you had any hostile responses to your book from people who worry that by telling depressed people that antidepressants are really placebos, the pills will stop working?

Photo of Irving Kirsch by Bo Tenberg

Photo of Irving Kirsch by Bo Tenberg

Kirsch: Definitely. People have suggested that I take a line comparable to “don’t ask, don’t tell.” They say, “OK, so the placebo effect is doing most or all of the work. We don’t want to ruin that. We have nothing else to give our patients!” Well, now we know that the placebo effect still works even when people know they’re taking placebos. That’s one of the nice things we’ve learned from this study. Plus, there’s an ethical problem when you keep secret the fact that you’re giving someone a drug that barely works — especially when the drug has harmful effects as well.

Silberman:  Has your research changed the way you think about taking medicine?

Kirsch: Interesting question. It has made me more wary. It certainly makes me less likely to talk to my doctor about getting an antidepressant if I’m feeling down or sad.

Silberman: What kinds of follow-up studies are needed now?

Kirsch: We know that open placebo treatment works for IBS. Does it also work for depression? How crucial is telling patients about the placebo effect? Might placebo therapy work even without giving patients a convincing rationale? My guess would be that it wouldn’t, but I don’t really know for sure.

Silberman:  One interesting aspect of this study is that it suggests that are two layers of belief in the brain — one that knows there’s nothing in this pill, and another that knows that a placebo can be an effective treatment. It’s as if the brain can entertain two different notions of the effectiveness of a pill at once.

Kirsch:  Yes, but they’re not contradictory notions. I believe in both. I know that this pill does not contain a physically active ingredient, and I also understand the conditioning process. I know that the placebo effect is real, so I understand that this inert pill might help trigger that healing response within me. We need to recognize and understand that patients are active agents in their treatment, not passive. The placebo effect does not come from the pill. It comes from the patient.

A prescription from Amir Raz

A placebo prescription from Amir Raz at McGill University

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58 Responses to Meet the Ethical Placebo: A Story that Heals

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  7. Leigh Jackson says:

    Kirsch: We know that open placebo treatment works for IBS.

    We most certainly do not know that. This study was fundamentally flawed and could never have demonstrated that; not without a second placebo control group being told that they would be given an inert sugar pill, not considered to have any possible beneficial or harmful effect whatsoever.

    Kirsch: Does it also work for depression? How crucial is telling patients about the placebo effect? Might placebo therapy work even without giving patients a convincing rationale? My guess would be that it wouldn’t, but I don’t really know for sure.

    I have no doubt that it would not work. Why did they not have a standard placebo control? We would then know the answer.

    “Convincing rationale” is double-speak for deceiving patients.

    What patients were told wasn’t true. They were told that the placebo effect is powerful. True, but only when compared with no-treatment. That was not the case in this trial.

    They were told the body can automatically respond to taking pills like Pavlov’s dogs, and that a positive attitude was not necessary; but the placebo effect in clinical trials is generally thought to be due having a reasonable expectation of receiving an active substance – something ruled out in this trial.

    Contrary to what Kirsch believes the results of this study are entirely consistent with the therapeutic relationship accounting for all the benefits of the placebo and the non-placebo groups.

    The placebo group received a boosted therapeutic relationship; by being given pills and encouragement to think they could benefit whether or not they believed it, they also received a boosted placebo effect.

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  9. A great article!

    We need to begin to look at the benefits of placebo in the field of psychiatry…
    Where psychiatric drugs are clinically no better than placebo…
    yet extremely harmful!

    Thank you,

    Duane Sherry, M.S.

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  18. tooealry says:

    an excellent article appeared in 2002 on this subject :

  19. tooealry says:

    “You can hardly expect the American Medical Association to issue a wink and a nod to doctors, encouraging them to prescribe sugar pills for seriously disabling conditions like chronic depression and Parkinson’s disease. ”
    indeed, not unless the sugar industry decides that a profit can be made through placebo pills

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  24. Charles Lambdin says:

    So is that really a placebo effect or just classical conditioning? Sounds like the latter to me. If you poison mutton and feed it to wolves, eventually normal, non-poisoned mutton will still make wolves sick. That’s not a placebo effect; it’s just plain old conditioning.

    • Steve Silberman says:

      It’s a semantics issue. Some placebo effects are conditioning effects. That doesn’t mean they’re not placebo effects.

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  27. Not Seth Rory Or Any Twister says:

    The patients suffered from IBS. Which is quite a complex illness involving physiological and psychologial factors.

    To conclude anything general from the results of the study is not scientifically appropriate in any way.

    Which will of course not stop anyone misusing it and cramping it in their little boxes.

    • Steve Silberman says:

      That seems rather broad, Not Seth or Rory. As far as I know, IBS is fair game for scientific study, as the thousands of studies in PubMed attest.

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  33. Charlotte Price says:

    I would be very interested in knowing about research into a different aspect of the placebo: can someone direct me to information about people who resist getting well–in other words, who use the mind to turn OFF the healing mechanisms of the body?

    • Steve Silberman says:

      Interesting! I’ve never heard of a study like that, sorry.

      • People who resist getting well? These may be the same people who get sick. Think: sickness is not the normal state, being well is. When you get sick, whatever you have done has “turned off” the healing (or not-getting-sick) response. If I get sick again and again and again, we tend to identify these people like me as “chronically sick,” especially if they get the same thing over and over. The other side of this is that their self-healing is turned off over and over and over. So chronically sick people, especially with the same illness, would be the group to start with. What do they do to “turn off” their self-healing? THAT is the question. This “anti-placebo” effect is the other side of how people make themselves well. Perhaps the key lies in self-caring, in the same way perceived caring of the physician now plays a role in the placebo, even the known-placebo, effect.

  34. Leigh Jackson says:

    “The medical establishment’s ethical problem with placebo treatment boils down to the notion that for fake drugs to be effective, doctors must lie to their patients. It has been widely assumed that if a patient discovers that he or she is taking a placebo, the mind/body password will no longer unlock the network, and the magic pills will cease to do their job.”

    Assuming that there is a beneficial potential placebo effect available from any treatment willingly accepted in the belief that it may be of benefit, how can that effect be legitimately utilised by medical practitioners? Obviously, by means of any treatment which has been demonstrated to be more effective than a placebo for a relevant medical condition. The placebo benefit and more is available for the patient. No problem at all.

    What of a treatment whose benefits are precisely those of the placebo effect? If there is no better option and as long as the patient has no objections then there is no problem. This implies informed consent. A simple solution would be for patients to agree with their doctor that he/she can use placebo treatments at their discretion if there is no clearly superior option.

    The problem has been that placebos in clinical trials are fake treatments, intended to be ineffective, and scientific understanding of the clinically beneficial placebo effect (CBP – sans regression, natural aetiology, etc) has been poor. For clinicians to recommend fake treatments on the basis of an effect which is poorly understood, whilst assuring a patient that it is well understood, is unethical. It is not that it has been assumed that the “mind/body” password will no longer unlock the “network” if a patient discovers that they have been given a fake treatment; it has been crystal clear that the placebo effect requires that patients believe they may be receiving a potentially beneficial treatment.

    The reason why there is a CBP effect in randomised clinical trials is because volunteers or patients know they have an equal chance of receiving a candidate treatment or a fake treatment. They are informed that the fake treatment has no effect but they know that there is a real prospect of receiving an effective treatment. Genuine informed consent applies.

    Now consider the situation where one is guaranteed a fake treatment. How can a CBP effect be generated if there is zero prospect of receiving an effective treatment? How can a positive expectation be conjured from such a situation? A CBP effect in this situation would appear to be perverse.

    After the fact of clinical trials, what was assumed to be completely ineffective has been demonstrated to be otherwise. After non-clinical, non-specific, components of the placebo effect are removed, there remains a residual clinical effect. There is no need to coach patients in Pavlovian conditioning and “mind-body” hand waving. Placebo pills work if one has a reasonable expectation of them being able to work – that’s what patients ought to be told. Then see what happens. Scientific authority was used to persuade patients in this study, by suggesting that the pills could help them in a way which verges on magic; in a way which overstates the state of scientific knowledge whilst simultaneously evoking a sense of mystery. This is not non-deception as we know it, Jim.

    The authors did not utilise the same placebo in this study as in their previous placebo study on IBS patients. That study used sham acupuncture as the placebo treatment. Would the open use of sham acupuncture (sham-needling) have given the same result? An interesting thought.

    • Steve Silberman says:

      For clinicians to recommend fake treatments on the basis of an effect which is poorly understood, whilst assuring a patient that it is well understood, is unethical.

      That’s true, but there is increasing understanding of the mechanisms of placebo response. Fabrizio Benedetti, one of the leading researchers in this area, recently published a helpful overview in Nature:

      There is no need to coach patients in Pavlovian conditioning and “mind-body” hand waving.

      I know that many people are allergic to the phrase “mind-body,” because of its overuse by New Agers, but it’s an accurate description of the placebo response. No hand waving involved.

      • Leigh Jackson says:

        Increase of understanding (science) is sorely needed and I applaud those engaged in the process.

        “Mind-body” might be consideed to be is a culturally loaded term – not a scientific term. If, as Benedetti says, words, symbols and meanings shape our brains, then researchers had better be very careful with them.

        But you are missing my main point. Whatever the state of understanding of the placebo effect and however it works, this paper is fundamentally flawed. The non-specific clinical (placebo) benefits which show up in clinical trials depend on the possibility of the trial subjects receiving a specific clinical benefit from the candidate treatment. The expectancy of such benefit is normally an inherent feature of the clinical trial situation.

        This trial offered the subjects no such prospect. Given that the trial subjects understood that the pills they were being given had no intrinsic potency, any expectancy of improvement could only be due to what subjects were told. The benefit which they were told had been scientifically proven depended upon a condition not present in this trial. Any expectation of benefit had to arise entirely from the authority and persuasiveness of clinicians – together with any pre-existing belief in trial subjects in the power of placebo. This belief could exist in normal clinical trials as well, but the manner of recruitment to this trial was a positive encouragement to such true believers.

        What was required was a control group where subjects were simply told that they were going to be given sugar-pills. A better enrolment procedure, also.

        • Blaze Birch says:

          Leigh Jackson,

          You say that this study is flawed and unethical because participants were given no possibility of receiving an effective treatment. You are missing a critical point: the placebo response IS an effective treatment.
          Furthermore, the researchers presenting the placebo response in a positive light is not improper. You are correct that the response is due to the belief the researchers planted that taking the placebo will help the patient, not the mere act of ingesting a capsule; no one is suggesting otherwise.
          The placebo response hinges on the patient’s acceptance that the treatment can help them, that their condition can improve. This acceptance triggers a parasympathetic response, prompting a switch from fight-or-flight to rest-and-digest.
          This is in fact the same principle that underpins talk therapy. Please don’t get me wrong: I’m not saying that psychotherapy is ineffective. If the patient is an active participant, therapy can be highly effective.

          And so can placebo.

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  40. Hadrian says:

    When my doctor told me that he was going prescribe a placebo for me, I said, “That’s fine. Just make sure you give me the very best.”

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  42. fsteele says:

    And when you’re not having one to one time with any kind of sympathetic professional but just ordering a supplement or herb through the mail, still the narrative is there. The history of use of the herb, perhaps some snake oil history of a supplement — or just a name like ‘evening primrose oil.’

    Or the intriguingly unlikely narrative of the theory of homeopathy.

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  44. David Dobbs says:

    A few years ago I had a ligament reconstruction surgery in one of my knees; really painful surgery. They gave me a patient-controlled morphine drip: Every 10 minutes, but not more often, I could press a button that would cause a plunger to press a bit of morphine (“Sweet, sister morphine!”) into the IV tube that was already feeding me fluids. The plunger took a couple seconds to work, and the morphine took a few more seconds to get down the tube into my arm. I want to tell you, I was glad to have that thing. But the cool thing placebo-wise was that even though it took probably 10 seconds for the morphine to even reach my arm, I felt relief the very instant I pushed the button. Not just psychological: the pain felt better. (As if you could separate the two.)

    I didn’t like it much when they took that thing away.

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  47. Daniel Zigman says:

    Dr. Kirsch has made very valuable contributions in this field. However, many of his comments regarding depression and antidepressants are incorrect.

    In this interview he ignores the extensive literature indicating that depression is a very heterogeneous condition. Some patients, particularly those with melancholic features and psychosis respond poorly to placebo.

    His comment “The most commonly employed antidepressants are supposed to increase the amount of serotonin in synapses in the brain, but there are also antidepressants that decrease the level of serotonin in the brain, and they both have the same effect therapeutically” is incorrect. There is no antidepressant that causes a net decrease in serotonin. All currently approved antidepressants boost either serotonin, norepinepherine or dopamine. Subjects who are deprived of tyramine, leading to a decrease in serotonin, develop depression. Dopamine depleting agents, such as reserpine, also induce depression.

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  49. Orchid64 says:

    Some years ago, I developed crippling back pain and sought a variety of treatments. I investigated the effectiveness of various options – physical therapy, surgery, etc. I found out that doing absolutely nothing was equally effective to any other option and realized that it is more about what I think and do than about what the doctor does.

    Since that time, it has been my firm belief that, short of a serious injury, most people can be actively involved in promoting their own healing simply through mental processes. The placebo is simply a scientific word for “healing oneself”. Science generally plays down the fact that this is a clear mind-body connection because the concept is decidedly unscientific sounding, and there is nothing to be gained financially from telling people they can do a lot to “think themselves well”. Also, there is the inherent risk of people thinking they can do so for serious problems and deciding not to seek treatment.

    To me, this is the true frontier issue in medicine. It’s not about better drugs, but about understanding this connection between psychology and biology and helping people utilize it to the fullest.

  50. Andrew Alden says:

    Love the punch line at the end, in your prescription!

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