The placebo response might be important in clinical practice, but it is certainly difficult to study and the findings of such investigations can be confusing. This seems to be exemplified by two new trials.

The first study examined the possibility of using theatrical performance tools, including stage directions and scripting, to reproducibly manipulate the style and content of a simulated doctor-patient encounter and influence the placebo response (defined as improvement of clinical outcome in individuals receiving inactive treatment) in experimental pain.

A total of 122 healthy volunteers were exposed to experimental pain using the cold pressor test and assessed for pain threshold and tolerance before and after receiving a placebo cream from a “doctor” impersonated by a trained actor. The actor alternated between two distinct scripts and stage directions. One script emulated a standard doctor-patient encounter (scenario A), while the other emphasized elements present in ritual healing such as attentiveness and strong suggestion (scenario B).

The placebo response size was calculated as the % difference in pain threshold and tolerance after exposure relative to baseline. Subjects demonstrating a ≥30% increase in pain threshold or tolerance relative to baseline were defined as responders. Each encounter was videotaped in its entirety.

Inspection of the videotapes confirmed the reproducibility and consistency of the distinct scenarios enacted by the “doctor”-performer. Furthermore, scenario B resulted in a significant increase in pain threshold relative to scenario A. This increase derived from the placebo responder subgroup; as shown by two-way analysis of variance (performance style, F = 4.30; p = 0.040; η(2) = 0.035; style × responder status interaction term, F = 5.21; p = 0.024) followed by post hoc analysis showing a ∼60% increase in pain threshold in responders exposed to scenario B (p = 0.020).


Performance style and response size in placebo responders and non-responders. Bars represent mean ± SE of % change in CPT threshold of 60 subjects in scenario A: 53 non-responders vs. 7 responders and 62 subjects in scenario B: 51 non-responders and 11 responders. Two-way ANOVA by performance style and responsiveness revealed significant effects of doctor’s performance (F = 4.30; p = 0.040; η2 = 0.035) and responsiveness (F = 134.71; p < 0.001) as well as a significant interaction term (F = 5.21; p = 0.024). p = 0.020, Fisher’s least significant difference post hoc test.

The authors concluded that these results support the hypothesis that structured manipulation of physician’s verbal and non-verbal performance, designed to build rapport and increase faith in treatment, is feasible and may have a significant beneficial effect on the size of the response to placebo analgesia. They also demonstrate that subjects, who are not susceptible to placebo, are also not susceptible to performance style.

In the second study, the authors investigated if an implicit priming procedure, where participants were unaware of the intended priming influence, affected placebo analgesia.

In a double-blind experiment, healthy participants (n = 36) were randomized to different implicit priming types; one aimed at increasing positive expectations and one neutral control condition. First, pain calibration (thermal) and a credibility demonstration of the placebo analgesic device were performed. In a second step, an independent experimenter administered the priming task; Scrambled Sentence Test. Then, pain sensitivity was assessed while telling participants that the analgesic device was either turned on (placebo) or turned off (baseline). Pain responses were recorded on a 0-100 Numeric Response Scale.

Overall, there was a significant placebo effect (p < 0.001), however, the priming conditions (positive/neutral) did not lead to differences in placebo outcome. Prior experience of pain relief (during initial pain testing) correlated significantly with placebo analgesia (p < 0.001) and explained 34% of placebo variance. Trait neuroticism correlated positively with placebo analgesia (p < 0.05) and explained 21% of placebo variance.

The authors concluded that priming is one of many ways to influence behaviour, and non-conscious activation of positive expectations could theoretically affect placebo analgesia. Yet, we found no SST priming effect on placebo analgesia. Instead, our data point to the significance of prior experience of pain relief, trait neuroticism and social interaction with the treating clinician.

The two studies are similar but generate somewhat contradictory results. In the discussion section, the authors of the first paper stress that “replication of our findings in clinical populations; employing professional physicians of both sexes, are necessary in order to establish their generality and possible application in medical training, with the aim of improving patient outcome across diseases and treatment modalities.” This is certainly true. They continue by stating that  “future studies using performance tools in clinical trial settings could demonstrate the potential of borrowing performance principles and techniques from traditional healing and applying them to physician–patient encounters in Western medicine, following certain necessary modifications. Performance tools could thus eventually be incorporated into the systematic training of physicians and medical students, possibly to complement programs in Narrative Medicine and Relational Medicine.”

These ideas are not dissimilar to what we have been discussing on this blog repeatedly. For instance, I have previously tried to explain that “the science and the art of medicine are essential elements of good medicine. In other words, if one is missing, medicine is by definition  not optimal. In vast areas of alternative medicine, the science-element is woefully neglected or even totally absent. It follows, that these areas cannot be good medicine. In some areas of conventional medicine, the art-element is weak or neglected. It follows that, in these areas, medicine is not good either.”

The fact that the two studies above show contradictory findings is not easy to interpret. Possibly, this shows how fragile the placebo response can be. It can be influenced by a multitude of factors related to an experiment or the clinical setting. If that is so, and placebo effects are truly unreliable, it would be yet another argument for not relying on them in clinical routine. In my view, clinicians should try to maximize them where they can. Yet placebo effects are not normally a justification for employing placebo therapies in clinical practice. In other words, the fact that a bogus treatment can generate a placebo response is not a good reason for using it on patients who need help.

Good clinicians have probably always been good ‘performers’. Alternative practitioners tend to be excellent ‘performers’, and I am sure their success is mainly due to this ability. I see little reason why conventional practitioners should not (re-)learn the skills that once upon a time were called ‘good bed-side manners’. Maximizing the placebo effect in this way might maximize the benefit patients experience – and for that we do not require the placebo-therapies of alternative medicine.

A new study tested the efficacy of chiropractic spinal manipulative therapy (CSMT) for migraine. It was designed as a three-armed, single-blinded, placebo -controlled RCT of 17 months duration including 104 migraineurs with at least one migraine attack per month. Active treatment consisted of CSMT (group 1) and the placebo was a sham push manoeuvre of the lateral edge of the scapula and/or the gluteal region (group 2). The control group continued their usual pharmacological management (group 3).

The RCT began with a one-month run-in followed by three months intervention. The outcome measures were quantified at the end of the intervention and at 3, 6 and 12 months of follow-up. The primary end-point was the number of migraine days per month. Secondary end-points were migraine duration, migraine intensity and headache index, and medicine consumption.

The results show that migraine days were significantly reduced within all three groups from baseline to post-treatment (P < 0.001). The effect continued in the CSMT and placebo groups at all follow-up time points (groups 1 and 2), whereas the control group (group 3) returned to baseline. The reduction in migraine days was not significantly different between the groups. Migraine duration and headache index were reduced significantly more in the CSMT than in group 3 towards the end of follow-up. Adverse events were few, mild and transient. Blinding was strongly sustained throughout the RCT.

The authors concluded that it is possible to conduct a manual-therapy RCT with concealed placebo. The effect of CSMT observed in our study is probably due to a placebo response.

Chiropractors often cite clinical trials which suggest that CSMT might be effective. The effects sizes are rarely impressive, and it is tempting to suspect that the outcomes are mostly due to bias. Chiropractors, of course, deny such an explanation. Yet, to me, it seems fairly obvious: trials of CSMT are not blind, and therefore the expectation of the patient is likely to have major influence on the outcome.

Because of this phenomenon (and several others, of course), sceptics are usually unconvinced of the value of chiropractic. Chiropractors often respond by claiming that blind studies of physical intervention such as CSMT are not possible. This, however, is clearly not true; there have been several trials that employed sham treatments which adequately mimic CSMT. As these frequently fail to show what chiropractors had hoped, the methodology is intensely disliked by chiropractors.

The above study is yet another trial that adequately controls for patients’ expectation, and it shows that the apparent efficacy of CSMT disappears when this source of bias is properly accounted for. To me, such findings make a lot of sense, and I suspect that most, if not all the ‘positive’ studies of CSMT would turn out to be false positive, once such residual bias is eliminated.

Over on ‘SPECTATOR HEALTH’, we have an interesting discussion (again) about homeopathy. The comments so far were not short of personal attacks but this one by someone who called himself (courageously) ‘Larry M’ took the biscuit. It is so characteristic of deluded homeopathy apologists that I simply have to share it with you:

Ernst grew up with homeopathy [1], saw how well it worked [2], and chose to become a so-called expert in alternative medicine [3]. To his surprise, he met with professional disapproval [4]. Being the weak ego-driven person that he is [5], he saw an opportunity to still come out on top. He sold his soul in exchange for the notoriety that he now receives for being the crotchety old homeopathy hater that he has become [6]. As with all homeopathy haters, his fundamentalist zeal [7] is evidence of his secret self-loathing [8] and fear that his true beliefs will be found out [9]. It’s no different than the evangelical preacher who rails against gays only to be eventually found out to be a closeted gay [10].

There is not much that makes me speechless these days, but this comment almost did. There is someone who clearly does not even know me and he takes it upon himself to interpret and re-invent my past, my motives and my actions at will. How deluded is that?

After re-reading the comment, I began to see the funny side of it, had a giggle and decided to add a few elements of truth in the form of this blog-post. So I took the liberty to insert some reference numbers into Larry’s text which refer to my brief points below.

  1. This is at least partly true; our family doctor was a prominent homeopath. Whenever one of us was truly ill, he employed conventional treatments.
  2. I was impressed as a young physician working in a homeopathic hospital to see that patients improved on homeopathy – even though, at medical school, I had been told that the remedies were pure placebos. This contradiction fascinated me, and I began to do some own research into the subject.
  3. I did not ‘choose’, I had a genuine interest; and I don’t think that I am a ‘so called’ expert – after 2 decades of research and hundreds of papers, this attribute seems a trifle unfitting.
  4. The disapproval came from the homeopathy fans who were irritated that someone had the audacity to undertake a truly CRITICAL assessment of their treatments and actions.
  5. The amateur psychology here speaks for itself, I think.
  6. Yes, I am no spring chicken! But I am not a ‘hater’ of anything – I try to create progress by convincing people that it is prudent to go for treatments that are evidence-based and avoid those that do not generate more good than harm.
  7. This attitude is not a ‘fundamental zeal’, it is the only responsible way forward.
  8. This made me laugh out loud! Nothing could be further from the truth.
  9. My ‘true belief’ is that patients deserve the best treatments available. I have no fear of being ‘found out’; on the contrary, during my career I stood up to several challenges of influential people who tried to trip me up.
  10. This is hilarious – does Larry not feel how pompously ridiculous and ridiculously pompous he truly is?

This might be all too trivial, if such personal attacks were not an almost daily event. The best I can do with them, I have concluded, is to expose them for what they are and demonstrate how dangerously deluded the advocates of quackery really are. In this way, I can perhaps minimize the harm these people do to public health and medical progress.

The ‘Deutsche Apotheker Zeitung’, a paper for German pharmacists, rarely is the most humorous of publications. However, recently they reported on a battle between the EU and the European producers of homeopathic remedies – a battle over mercury which has, I think, hints of Monty Python and the Flying Circus.

The EU already has strict regulations on the use of mercury, for obvious reasons, they apply particularly to medicines. The law in this area is now 8 years old and is about to be replaced by a new one which is even stricter. A draft has been recently published here.

The new law would prohibit all mercury in medicinal products, except for some used in dentistry. For the homeopathic and anthroposophic manufacturers, this is not good news because they have many remedies on the market that have the word ‘mercury’ on the label. Consequently, they fear that the sale of these products might be impeded or even become impossible in the EU.

„Quecksilber und Quecksilberverbindungen stellen für manche homöopathische und andere traditionelle Arzneimittel einen unverzichtbaren Bestandteil dar“ (Mercury and mercury compounds are an essential ingredient of some homeopathic and other traditional medicines) .. “Es steht keine Quecksilber-freie Alternative zur Verfügung, die als aktiver Bestandteil in der Therapie mit homöopathischen oder anderen traditionellen Arzneimitteln verwendet werden könnte“ (There is no mercury-free alternative that could be used in these medications”) wrote the Dachverband der Arzneimittelhersteller im Bereich der Selbstmedikation (AESGP) (a lobby group of the homeopathic manufacturers) in a comment adding that „Diese Produkte sind seit Dekaden auf dem europäischen Markt und gehören zum Arzneimittel-Werkzeugkoffer” (these products are on the market since decades and belong to the medical tool-kit)… and that these products contain merely tiny amounts of mercury – even the largest manufacturers of these remedies only require a few milligrams for their production.

The plea of the manufacturers therefore is for an exemption from the new law which would allow the trade of mercury-containing remedies in future. They even have the support of some health politicians; for instance Peter Liese CDU favours an exemption for homeopathic medicines. The next meeting of the EU committee on public health will vote on the matter.

Personally, I can imagine the following dialogue between the EU officials (EU) and the lobbyists of the homeopathic industry (LOHI):

EU: We are very sorry but, because of the toxicity of mercury, we will not allow any of it in medicines.

LOHI: But we have always used it and nobody has come to harm.

EU: We don’t know that, and we have to be strict.

LOHI: We appreciate your concern, but we use only very, very tiny amounts; they cannot cause harm.

EU: The law is the law!

LOHI: Actually, the vast majority of our products are so dilute that they do not contain a single molecule of the ingredient on the bottle.

EU: That’s interesting! In this case, they are not medicines and we will have to ban them.

LOHI: NO, no, no – you don’t understand. We potentise our medicines; this means that the ingredient that they no longer contain gets more and more powerful.

EU: Are you sure?

LOHI: Absolutely!

EU: In this case, we will ban not just your mercury products but all your phony remedies. Because either science is right and they are fraudulent, or you are correct and they are dangerous.

No, I don’t want to put you off your breakfast… but you probably have seen so many pictures of attractive athletes with cupping marks and read articles about the virtues of this ancient therapy, that I feel I have to put this into perspective:

Cupping burnsI am sure you agree that this is slightly less attractive. But, undeniably, these are also cupping marks. So, if you read somewhere that this treatment is entirely harmless, take it with a pinch of salt.

Cupping has existed for centuries in most cultures, and there are several variations of the theme. We differentiate between wet and dry cupping. The above picture is of wet cupping gone wrong. What the US Olympic athletes currently seem to be so fond of is dry cupping.

The principles of both forms are similar. In dry cupping, a vacuum cup is placed over the skin which provides enough suction to create a circular bruise. Eventually the vacuum diminishes, and the cup falls off; what is left is the mark. In wet cupping, the procedure is much the same, except that the skin is injured before the cup is placed. The suction then pulls out a small amount of blood. Obviously the superficial injury can get infected, and that is what we see on the above picture.

In the homeopathic hospital where I worked ~40 years ago, we did a lot of both types of cupping. We used it mostly for musculoskeletal pain. Our patients responded well.

But why? How does cupping work?

The answer is probably more complex than you expect. It clearly has a significant placebo effect. Athletes are obviously very focussed on their body, and they are therefore the ideal placebo-responders. Evidently, my patients 40 years ago also responded to all types of placebos, even to the homeopathic placebos which they received ‘en masse’.

But there might be other mechanisms as well. A TCM practitioner will probably tell you that cupping unblocks the energy flow in our body. This might sound very attractive to athletes or consumers, and therefore could even enhance the placebo response, but it is nevertheless nonsense.

The most plausible mode of action is ‘counter-irritation’: if you have a pain somewhere, a second pain elsewhere in your body can erase the original pain. You might have a headache, for instance, and if you accidentally hit your thumb with a hammer, the headache is gone, at least for a while. Cupping too would cause mild to moderate pain, and this is a distraction from the muscular pain the athletes aim to alleviate.

When I employed cupping 40 years ago, there was no scientific evidence testing its effects. Since a few years, however, clinical trials have started appearing. Many are from China, and I should mention that TCM studies from China almost never report a negative result. According to the Chinese, TCM (including cupping) works for everything. More recently,also some trials from other parts of the world have emerged. They have in common with the Chinese studies that they tend to report positive findings and that they are of very poor quality. (One such trial has been discussed previously on this blog.) In essence, this means that we should not rely on their conclusions.

A further problem with clinical trails of cupping is that it is difficult, if not impossible, to control for the significant placebo effects that this treatment undoubtedly generates. There is no placebo that could mimic all the features of real cupping in clinical trials; and there is no easy way to blind either the patient or the therapist.

So, we are left with an ancient treatment backed by a host of recent but flimsy studies and a growing craze for cupping fuelled by the Olympic games. What can one conclude in such a situation?

Personally, I would, whenever possible, recommend treatments that work beyond a placebo effect, because the placebo response tends to be unreliable and is usually of short duration – and I am not at all sure that cupping belongs into this category. I would also avoid wet cupping, because it can cause substantial harm. Finally, I would try to keep healthcare costs down; cupping itself is cheap but the therapist’s time might be expensive.

In a nutshell: would I recommend cupping? No, not any more than using a hammer for counter irritation! Will the Olympic athletes care a hoot about my recommendations? No, probably not!


The aim of a new meta-analysis was to estimate the clinical effectiveness and safety of acupuncture for amnestic mild cognitive impairment (AMCI), the transitional stage between the normal memory loss of aging and dementia. Randomised controlled trials (RCTs) of acupuncture versus medical treatment for AMCI were identified using six electronic databases.

Five RCTs involving a total of 568 subjects were included. The methodological quality of the RCTs was generally poor. Participants receiving acupuncture had better outcomes than those receiving nimodipine with greater clinical efficacy rates (odds ratio (OR) 1.78, 95% CI 1.19 to 2.65; p<0.01), mini-mental state examination (MMSE) scores (mean difference (MD) 0.99, 95% CI 0.71 to 1.28; p<0.01), and picture recognition score (MD 2.12, 95% CI 1.48 to 2.75; p<0.01). Acupuncture used in conjunction with nimodipine significantly improved MMSE scores (MD 1.09, 95% CI 0.29 to 1.89; p<0.01) compared to nimodipine alone. Three trials reported adverse events.

The authors concluded that acupuncture appears effective for AMCI when used as an alternative or adjunctive treatment; however, caution must be exercised given the low methodological quality of included trials. Further, more rigorously designed studies are needed.

Meta-analyses like this one are, in my view, perfect examples for the ‘rubbish in, rubbish out’ principle of systematic reviews. This may seem like an unfair statement, so let me justify it by explaining the shortfalls of this specific paper.

The authors try to tell us that their aim was “to estimate the clinical effectiveness and safety of acupuncture…” While it might be possible to estimate the effectiveness of a therapy by pooling the data of a few RCTs, it is never possible to estimate its safety on such a basis. To conduct an assessment of therapeutic safety, one would need sample sizes that go two or three dimensions beyond those of RCTs. Thus safety assessments are best done by evaluating the evidence from all the available evidence, including case-reports, epidemiological investigations and observational studies.

The authors tell us that “two studies did not report whether any adverse events or side effects had occurred in the experimental or control groups.” This is a common and serious flaw of many acupuncture trials, and another important reason why RCTs cannot be used for evaluating the risks of acupuncture. Too many such studies simply don’t mention adverse effects at all. If they are then submitted to systematic reviews, they must generate a false positive picture about the safety of acupuncture. The absence of adverse effects reporting is a serious breach of research ethics. In the realm of acupuncture, it is so common, that many reviewers do not even bother to discuss this violation of medical ethics as a major issue.

The authors conclude that acupuncture is more effective than nimodipine. This sounds impressive – unless you happen to know that nimodipine is not supported by good evidence either. A Cochrane review provided no convincing evidence that nimodipine is a useful treatment for the symptoms of dementia, either unclassified or according to the major subtypes – Alzheimer’s disease, vascular, or mixed Alzheimer’s and vascular dementia.

The authors also conclude that acupuncture used in conjunction with nimodipine is better than nimodipine alone. This too might sound impressive – unless you realise that all the RCTs in question failed to control for the effects of placebo and the added attention given to the patients. This means that the findings reported here are consistent with acupuncture itself being totally devoid of therapeutic effects.

The authors are quite open about the paucity of RCTs and their mostly dismal methodological quality. Yet they arrive at fairly definitive conclusions regarding the therapeutic value of acupuncture. This is, in my view, a serious mistake: on the basis of a few poorly designed and poorly reported RCTs, one should never arrive at even tentatively positive conclusion. Any decent journal would not have published such misleading phraseology, and it is noteworthy that the paper in question appeared in a journal that has a long history of being hopelessly biased in favour of acupuncture.

Any of the above-mentioned flaws could already be fatal, but I have kept the most serious one for last. All the 5 RCTs that were included in the analyses were conducted in China by Chinese researchers and published in Chinese journals. It has been shown repeatedly that such studies hardly ever report anything other than positive results; no matter what conditions is being investigated, acupuncture turns out to be effective in the hands of Chinese trialists. This means that the result of such a study is clear even before the first patient has been recruited. Little wonder then that virtually all reviews of such trials – and there are dozens of then – arrive at conclusions similar to those formulated in the paper before us.

As I already said: rubbish in, rubbish out!

What a silly question! At least this is what most sceptics would say: if we are not sure that it works, we do not need to spend any thoughts on a potential mechanism!

However, in the realm of acupuncture, the potential mode of action remains a hotly debated and fundamentally relevant issue.

The TCM folks, of course, ‘knew’ all along how acupuncture works: it re-balances the life-forces yin and yang. This is a nice theory – it has but one disadvantage: it has no bearing whatsoever on reality. Vitalistic ideas such as this one have long been proven to be nothing but fantasy.

Meanwhile, several more plausible hypotheses have been developed, and hundreds of papers have been published on the subject. One recent article, for instance, suggests a range of mechanisms including microinjury, increased local blood flow, facilitated healing, and analgesia. Acupuncture may trigger a somatic autonomic reflex, thereby affecting the gastric and cardiovascular functions. Acupuncture may also change the levels of neurotransmitters such as serotonin and dopamine, thereby affecting the emotional state and craving… By affecting other pain-modulating neurotransmitters such as met-enkephalin and substance P along the nociceptive pathway, acupuncture may relieve headache. Acupuncture may affect the hypothalamus pituitary axis and reduce the release of the luteinizing hormone…

Another article states that the Western explanation for acupuncture effectiveness is based upon more than half a century of basic and clinical research, which identified the activation of sensory system and the subsequent activity-dependent regulation of neurotransmitters, neurohormones, and several classes of neuromodulators as plausible mechanism for the acupuncture‘s therapeutic properties. The regulation of neurotrophins’ expression and activity is one of the possible neurophysiological mechanisms underlying acupuncture‘s effects on neuropathic pain, nerve injury, neurodegeneration, and even in the regulation of gonadal functions…

Recently Burnstock proposed that mechanical deformation of the skin by needles and application of heat or electrical current leads to release of large amounts of ATP from keratinocytes, fibroblasts and other cells in skin; the ATP then occupies specific receptor subtypes expressed on sensory nerve endings in the skin and tongue; the sensory nerves send impulses through ganglia to the spinal cord, the brain stem, hypothalamus and higher centres; the brain stem and hypothalamus contain neurons that control autonomic functions, including cardiovascular, gastrointestinal, respiratory, urinogenital and musculo-skeletal activity. Impulses generated in sensory fibres in the skin connect with interneurons to modulate (either inhibition or facilitation) the activities of the motoneurons in the brain stem and hypothalamus to change autonomic functions; specifically activated sensory nerves, via interneurons, also inhibit the neural pathways to the pain centres in the cortex.

A brand-new article in the journal SCIENTIFIC AMERICAN puts the hypothesis in perspective:

…scientists have been studying a roster of potential biological pathways by which needling might relieve pain. The most successful of these efforts has centered on adenosine, a chemical believed to ease pain by reducing inflammation. A 2010 mouse study found that acupuncture needles triggered a release of adenosine from the surrounding cells into the extracellular fluid that diminished the amount of pain the rodents experienced. The mice had been injected with a chemical that made them especially sensitive to heat and touch. The researchers reported a 24-fold increase in adenosine concentration in the blood of the animals after acupuncture, which corresponded to a two-thirds reduction in discomfort, as revealed by how quickly they recoiled from heat and touch. Injecting the mice with compounds similar to adenosine had the same effect as acupuncture needling. And injecting compounds that slowed the removal of adenosine from the body boosted the effects of acupuncture by making more adenosine available to the surrounding tissue for longer periods. Two years later a different group of researchers went on to show that an injection of PAP, an enzyme that breaks other compounds in the body down into adenosine, could relieve pain for an extended chunk of time by increasing the amount of adenosine in the surrounding tissue. They dubbed that experimental procedure “PAPupuncture.”

Both sets of findings have excited researchers—and for good reason. The current options for treating pain are limited and rely mostly on manipulating the body’s natural pain-management system, known as the opioid system. Opioid-based painkillers are problematic for several reasons. Not only does their efficacy tend to wane over time, but they have been linked to an epidemic of addiction and overdose deaths across the U.S.—so much so that the Centers for Disease Control and Prevention has recently advised doctors to seriously restrict their use. The available nonopioid pain treatments are few; many of them require multiple injections or catheterization to work; and they often come with side effects, such as impaired movement. Adenosine offers an entirely new mechanism to exploit for potential treatments—one that may come with fewer side effects and less potential for addiction. What is more, adenosine can be made to circulate in the body for prolonged stretches. Pharmaceutical companies are actively investigating adenosine-related compounds as potential drugs.

But however promising adenosine may be as a treatment, the findings from this research do not prove that acupuncture itself “works.” For one thing, the researchers did not show that the release of adenosine was specific to acupuncture. Acupuncture needles might cause adenosine to flood the surrounding tissue, but so might a hard pinch, or applied pressure, or any number of other physical insults. In fact, both of the studies found that when adenosine was turned on in mouse tissue by other mechanisms, the pain response was equal to or better than the response generated by acupuncture. For another thing, the study results offered no support for the use of acupuncture to treat any of the other conditions for which the procedure is often advertised. A localized adenosine response may mitigate localized pain. That does not mean it can also cure insomnia or infertility.

It may well be that the reams of research scientists have done on acupuncture have lit the path toward improved understanding of—and eventually better treatments for—intractable pain. But it may also be time to take whatever bread crumbs have been laid out by that work and move on.


As we see, there is no shortage of potential explanations as to HOW acupuncture works. The most plausible theory still is that it works largely or even exclusively via a placebo effect.

Due to this type of mechanistic research, acupuncture has gained much credibility. The question is, does it deserve it? In my view, it would be much more fruitful to first make sure THAT acupuncture works (beyond a placebo response) and, if so, for what conditions. The question HOW it works is unquestionably interesting but in the final analysis it probably is secondary.

On Sunday 21 February, Andrew Herxheimer died at the age of 90. He was a clinical pharmacologist, founding editor of the Drugs & Therapeutics Bulletin from 1963 to 1992, Emeritus Fellow of the UK Cochrane Centre, convenor of the Cochrane Collaboration on Adverse Effects Methods Group and a co-founder of the DIPEx charity, which owns and runs .

Andrew has contributed a significant amount of papers on a large variety of subjects to the medical literature. His most recent articles were published only a few months ago. Andrew’s energy, wit and enthusiasm seemed infectious, and he has inspired many.

The official CV of Andrew is most impressive but, in my view, it can never do justice to the man himself. He was kind, witty and bright – a true gentleman through and through. His interests ranged wide, and his comments on so many different issues were as incisive as they were inspiring. His knowledge was vast and his vision clear. With everything he did, he seemed guided by a never-failing moral compass. He was a rational and critical thinker like few else, yet his warmth and kindness always dominated.

I had the pleasure to meet Andrew soon after I took up my post in Exeter. We became friends almost instantly and, many times, he supported me with his kindness. In 1996, we published an article together in the BMJ entitled THE POWER OF PLACEBO. Here is its concluding paragraph:

“…all doctors should be encouraged to look at their own practice to examine the nonspecific ingredients that they use daily and those that they do not use. Giving greater attention in daily practice to ‘adjuvants’ (specific as well as non-specific) could considerably increase effectiveness and efficacy – for example, by saying more useful things to patients in better ways. Methods will be needed for implementing such approaches. Until they are available, good common sense and old-fashioned bedside manners might already take us far – as they say, when all else fails, talk to your patient.”

Andrew Herxheimer was a great man, a kind friend, a brilliant scientist and a compassionate doctor. Without him, medicine seems far less inspired, amusing and joyful.

Germany is, as we all know, the home of homeopathy. Here it has an unbroken popularity, plenty of high level support and embarrassingly little opposition. The argument that homeopathy has repeatedly been shown to merely rely on placebo effects seems to count for nothing in Germany.

Perhaps this is going to change now. On January 30, a group of experts from all walks of life have met in Freiburg to discuss ways of informing the public responsibly and countering the plethora of misinformation that Germans are regularly exposed to on the subject of homeopathy. They founded the ‘Information Network Homeopathy’ and decided on a range of actions.

No doubt, some will ask where does their financial support come from? And no doubt, some will claim that we are on the payroll of ‘Big Pharma’. The truth is that we have no funding; everyone gives his/her own time free of charge and pays for his/her own expenses etc. And why? Because we believe in progress and feel strongly that it is time to improve healthcare by relegating homeopathy to the history books.

One of the first fruits of the network’s endeavours is the Freiburger Erklärung zur Homöopathie’, the ‘Freiburg Declaration on Homeopathy’. I have the permission to reproduce the document here in full (the translation is mine):


Despite the support of politicians and the silence of those who should know better, homeopathy has remained a method which is in clear opposition to the proven basics of science. The members and supporter of the ‘Information Network Homeopathy’ view homeopathy as a stubbornly surviving belief system, which cannot be accepted as part of naturopathy nor medicine. The information network is an association of physicians, pharmacists, veterinarians, biologists, scientists and other critics of homeopathy who are united in their aim to disclose this fact more openly and make the public more aware of it.


During the more than 200 years of its existence, homeopathy has not managed to demonstrate its specific effectiveness. Homeopathy only survives because it has been granted special status in the German healthcare system which is, in the opinion of the experts of the network, unjustified. Drugs have to prove their effectiveness according to objective criteria, but homeopathics are exempt from this obligation. We oppose such double standards in medicine.

Homeopathy has also not managed to demonstrate a plausible mode of action. Instead its proponents pretend that there are uncertainties which need to be clarified. We oppose such notions vehemently. Homeopathy is not an unconventional method that requires further scientific study. Its basis consists of long disproven theories such as the ‘law of similars’, ‘vital force’ or ‘potentisation by dilution’.


We do not dispute the therapeutic effects of a homeopathic treatment. But they are unrelated to the specific homeopathic remedy. The perceived effectiveness of homeopathics is due to suggestion and auto-suggestion of the patient and the therapist. The mechanisms of such (self-) deceit are multi-fold but well-known and researched. Symptomatic improvements caused by context-effects must not be causally associated with the homeopathic remedy. We assume that many physicians and alternative practitioners using homeopathy are unaware of the existence and multitude of such mechanisms and are acting in good faith. This, however, does not alter the fact that their conclusions are wrong and thus potentially harmful.


We do not claim that the scientific method which we uphold can currently research and explain everything. However, it enables us to explain that homeopathy cannot explain itself. The scientific method shows the best way we have for differentiating effective from ineffective treatments. A popular belief in therapeutic claims nourished by politicians and journalists can never be a guide for medical activities.


Our criticism is not aimed at needy patients or practising homeopathic clinicians; it is aimed at the school of homeopathy and the healthcare institutions which could have long recognised the nonsensical nature of homeopathy, but have chosen not to interfere. We ask the players within our science-based healthcare system to finally reject homeopathy and other pseudoscientific methods and to return to what should be self-evident: scientifically validated, fair and generally reproducible rules promoting top-quality medicine for he benefit of the patient.


Dr.-Ing. Norbert Aust, Initiator Informationsnetzwerk Homöopathie

Dr. med. Natalie Grams, Leiterin Informationsnetzwerk Homöopathie

Amardeo Sarma, GWUP Vorsitzender und Fellow von CSI (Committee for Skeptical Inquiry)


Edzard Ernst, Emeritus Professor, Universität Exeter, UK

Prof. Dr. Rudolf Happle, Verfasser der Marburger Erklärung zur Homöopathie

Prof. Dr. Wolfgang Hell, Vorsitzender des Wissenschaftsrates der GWUP

Prof. Norbert Schmacke, Institut für Public Health und Pflegeforschung, Universität Bremen

Dr. rer. nat. Christian Weymayr, freier Medizinjournalist

Chronic pain is a common and serious problem for many patients. Treatment often includes non-pharmacological approaches despite the mostly flimsy evidence to support them. The objective of this study was to measure the feasibility and efficacy of hypnosis (including self-hypnosis) in the management of chronic pain in older hospitalized patients.

A single center randomized controlled trial using a two arm parallel group design (hypnosis versus massage). Inclusion criteria were chronic pain for more than 3 months with impact on daily life activities, intensity of > 4; adapted analgesic treatment; no cognitive impairment. Fifty-three patients were included. Pain intensity decreased significantly in both groups after each session. Average pain measured by the brief pain index sustained a greater decrease in the hypnosis group compared to the massage group during the hospitalization. This was confirmed by the measure of intensity of the pain before each session that decreased only in the hypnosis group over time. Depression scores improved significantly over the time only in the hypnosis group. There was no effect in either group 3 months post hospitals discharge.

The authors concluded that hypnosis represents a safe and valuable tool in chronic pain management of hospitalized older patients. In hospital interventions did not provide long-term post discharge relief.

So, hypnotherapy is better than massage therapy when administered as an adjunct to conventional pain management. As it is difficult to control for placebo effects, which might be substantial in this case, we cannot be sure whether hypnotherapy per se was effective or not.

Who cares? The main thing is to make life easier for these poor patients!

There are situations where I tend to agree with this slightly unscientific but compassionate point of view. Yes, the evidence is flimsy, but we need to help these patients. Hypnotherapy has very few risks, is relatively inexpensive and might help badly suffering individuals. In this case, does it really matter whether the benefit was mediated by a specific or a non-specific mechanism?

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