Placebo1Diabetes, mental illness, and musculoskeletal disorders account for an estimated 86% of deaths and 77% of the disease burden in the World Health Organization European region. One hundred million EU citizens have musculoskeletal pain alone, causing almost 50% work absences and costing the EU €240 billion each year. Meanwhile at least 21 million EU citizens were affected by depression, costing an estimated €118 billion in 2004. In spite of well-planned treatment regimes, interventions for musculoskeletal pain (such as opioids and intra-articular corticosteroids) have small-moderate effect sizes while patients are concerned about adverse effects. Likewise, drugs for mild to moderate depression show (at best) small benefit over ‘placebos’.Placebos often have negative associations because of the need to control for placebo effects (often considered as ‘noise’) in clinical trials. Yet doctors and patients have always recognized the benefits of the less tangible aspects of medical care including empathy, communication, and expectations. These factors are often lumped together and called ‘placebos’. We are developing a group of placebo researchers within the University of Oxford who address problems surrounding placebos and how they work. The research we conduct is interdisciplinary and spans philosophy, epidemiology and we are building collaborations with neuroscientists and surgeons.

Philosophy: what are placebos and how can the mind heal the body?There is near universal consensus within medicine that ‘gold standard’ evidence for the existence of therapeutic effects is provided by placebo controlled trials. In sharp contrast, many believe that attempts to characterise what a ‘placebo’ is have foundered, there is no agreement on what effect–if any!–placebos (whatever they exactly are) have, and there is on-going controversy regarding what counts as an adequate placebo control for complex treatments such as acupuncture. The failure to characterize the placebo has created confusion concerning questions of whether placebos are ethical in clinical practice [1] and clinical trials [2]. Our research group is working on a definition of placebos that will help resolve some of the ethical debates and debates about placebo effects.

The success of placebo surgery also raises questions about the mind/body problem in philosophy. How can placebo surgery (a psychological intervention) cure a biomechanical problem? Before Descartes almost all philosophers and scientists before Descartes believed that ‘mind’ (or ‘soul’ or ‘vital force’) was an inherent part of all matter, so to change the mind was (by definition) to change matter. Until Descartes, therefore, the idea that something just affected the mind just didn’t make sense. Descartes separated the mind from the body and turned the body into a machine. If you believe Descartes, then it is literally difficult to see how changing your mind can change your body. Your body produces its own endorphins (pretty much the same as morphine), dopamine, adrenaline, growth hormones, and many other powerful drugs. These healing processes can be suppressed under chronic stress (and most of us are chronically stressed). Nice empathetic doctors can help your body activate these inner healers simply by reducing anxiety and deactivating the stress response. Summing it all up in the New England Journal of Medicine, Dan Moerman states:

“Does this [belief effects and doctor effects] mean that we might double our gas mileage if we wished for it hard enough? Well, no. But people are not machines, and we shouldn’t treat them as such.”

Medical research: how powerful are placebos and how do they work?
Our recent systematic review revealed found that placebo effect sizes are sometimes as large as ‘real’ treatment effect sizes. [3] The mechanisms explaining how placebos work are becoming well understood: [4] empathetically inducing positive expectations reduces anxiety and activates the neuronal reward mechanisms including increased dopamine activity in the nucleus accumbens. Placebo effects are one of the main attractions for the widespread use of complementary and alternative medicine (CAM) by patients according to the House of Lords select committee Report on CAM. [5] Unfortunately the methodological advances in Evidence-Based Medicine (EBM) have not been used to investigate placebo effects (empathy and positive expectations) in a way that doctors can use to help patients. For example systematic reviews [6] and randomized trials [7] of the effects of positive expectations do not report what verbal and non-verbal instructions must be used to produce these effects. This leaves many doctors wondering how to implement the results of these studies.

Ethics: are placebos ethical in clinical practice and clinical trials?Placebos are sometimes considered unethical in clinical practice because they require deception, yet the extent to which deception is required is currently unknown. [1]

Our research is also revealing an increasing number of problems with World Medical Association (WMA) Declaration of Helsinki policy on the ethics of placebo controls in clinical trials. [8,9] The WMA allows for placebo controls even when there is an established therapy for “methodological” reasons yet they did not consult patients, and the reasons given are questionable. [2]

Dr. Howick’s article ‘Questioning the Methodologic Superiority of “Placebo” Over “Active” Controlled Trials’ was followed by invited responses from policy makers – including Franklin Miller, National Institutes of Health and advisor to the United States Food and Drug Administration and Ronald Dworkin, founder of the Calvert Institute for Policy Research in Maryland. As a result, the ethical concerns expressed in the article about the use of placebos have had effects on clinical tests and clinical practice. In response to a draft of the survey results of placebo use by UK primary care practitioners the General Medical Council (GMC) issued a revised guide to Good practice in prescribing and managing medicines and devices in clarification of their stance on ‘placebos’.


  1. Foddy B (2009) A duty to deceive: placebos in clinical practice. The American journal of bioethics : AJOB 9: 4-12.
  2. Howick J (2009) Questioning the methodologic superiority of ‘placebo’ over ‘active’ controlled trials. Am J Bioeth 9: 34-48.
  3. Howick J, Friedemann C, Tsakok M, Watson R, Tsakok T, et al. (2013) Are treatments more effective than placebos? A systematic review and meta-analysis. PLoS One 8: e62599.
  4. Benedetti F (2009) Placebo effects : understanding the mechanisms in health and disease. Oxford: Oxford University Press. 295 p.
  5. Select Committee on Science and Technology (2000) Sixth Report. In: Lords Ho, editor: Science and Technology Committee Publications.
  6. Di Blasi Z, Harkness E, Ernst E, Georgiou A, Kleijnen J (2001) Influence of context effects on health outcomes: a systematic review. Lancet 357: 757-762.
  7. Verheul W, Sanders A, Bensing J (2010) The effects of physicians’ affect-oriented communication style and raising expectations on analogue patients’ anxiety, affect and expectancies. Patient education and counseling 80: 300-306.
  8. Howick J (2009) Questioning the Methodologic Superiority of ‘Placebo’ Over ‘Active’ Controlled Trials American Journal of Bioethics 9: 34-48.
  9. Howick J (2011) The Philosophy of Evidence-Based Medicine. Oxford: Wiley-Blackwell.


Associated media
 PLOS ONE – A list of media articles ensuing from PLOS ONE survey article:
Reuters – So, what’s in Placebo, any way?