How does the placebo effect work?

07 October 2012

Interview with

Karen Jensen, Harvard University; John Forrester, Cambridge University; Shane Glacken, University of Exeter

Martha::  The placebo effect is a reported improvement in a patient's condition in response to their own expectation that a drug or treatment will make them better.  Prescription placebos used in research and practiceEven giving a person a pill containing sugar and nothing else can still produce powerful painkilling effects if the person believes it's an analgesic.  So, what's going on in the brain to make this happen?  I began by speaking with Harvard based research fellow in psychiatry Karen Jensen.

Karen::  The first study that provided the biological evidence for the placebo effect was done in the 70s by a researcher called Levine and he was able to show that he could block the placebo effect by giving people an antagonist for opioids.

Martha::  Opioid antagonists prevent opioid chemicals -  for example, painkilling drugs like codeine and morphine - from binding to their receptors in the brain.  This acts to lower the sensation of pain in the body.  Levine showed that the placebo effect was also reduced when these opioid receptors were blocked, meaning that the analgesic placebo effect involves these chemical receptors just as much as chemical painkillers do.  There are, however, some interesting differences in the brain during placebo and active analgesia treatments.  Brain imaging studies by Jensen and her colleagues showed that the prefrontal cortex, the outermost layer of the front part of the brain, seems to play a stronger role in placebo treatments...

Karen::  When you compare a real drug to placebo, very similar networks in the brain are activated, but the prefrontal cortex is uniquely activated during placebo analgesia as compared to morphine for example.  This might represent "expectancy" effects.  So, if there's an expectancy for pain relief, that expectation might be processed there in the lateral prefrontal cortex.

Martha::  But even knowing this, the first cause of the placebo effect, the thing that initially gives rise to the stimulation of those brain regions, still isn't clear.  The full mechanism of the placebo effect between the first expectation of getting better and actually getting better isn't scientifically understood.  I spoke to John Forrester at the History and Philosophy of Science Department at the University of Cambridge about other factors involved in the placebo effect.

John::  One of the peculiar things about this is physical evidence about placebo effect it's in an extraordinary range of variation - between 18% to 75% - partly dependent on condition, but it seems to be dependent on geographical location.  Now, this complicates the study of the placebo effect, but, in a sense, it's what you might expect, if it's not just neurochemical, it's not just psychological, but in some sense it's a "social" condition.  There's a complicated social production of a placebo effect, which is the next obvious thing to say: that placebo effect really has to be the relationship, not only of the patient to the doctor or the patient to the doctor's coat, to the kind of equipment the doctor has in the office, to the kind of hospital that they're entering into, to the reputation of the hospital.  That is going to be part of what we call the placebo effect; it's going to be bound up in it.  You don't want to restrict yourself immediately to saying it's neuroscientific, or psychological, or sociological, because it's a very complicated creature.

Martha::  So, social and cultural factors, for example, public attitudes towards the medical profession in a certain geographical area influence the patient's expectations of what will happen to them.  In turn, this expectation translates into a real change in symptoms.  This means people's values, beliefs, and prejudices can partly determine the outcome of their condition.  If the placebo effect is so prevalent and so powerful, is this something doctors can exploit to benefit their patients?  If a sugar pill is much cheaper than an active painkiller and just as effective, and may also avoid some nasty side effects, what's stopping the doctor using the placebo?  One of the main problems is the element of deception.  Lying to patients is obviously a bad thing and leads to endless legal battles in public mistrust in the medical profession.  But can the power of the placebo effect be used in an honest and non-deceptive way?  Medical philosopher Shane Glacken at the University of Exeter believes so.

Shane::  So, usually, the formulation a doctor would use in recommending a placebo treatment is something like, "Well, I'm going to give you these pills, I'm going to give you this shot.  We don't really know how exactly it works, but it's been very effective in relieving pain, or for people in your situation, and I'm confident that it's going to be effective in your case."  Now, it doesn't seem to me that anything relevant is being left out there.

Martha::  And, to add one last twist to the story, placebo treatments can even have an effect when the patient knows all about them.

Shane::  Interestingly enough, there are at least 2 studies that show placebos tend to work even when the patient knows that there's a placebo.  I think there's a Parc and Covi study from the '60s, there's a more recent one done at the Harvard Medical School, you can tell people, "This has no pharmacological effects.  It's just a sugar pill, but it will make you feel better," and it does tend to work!

Martha::  So, a doctor can be completely open about placebos and they'll still do the trick, although they tend to be less effective if given this way.  With an increasing knowledge of the neuroscience behind the placebo effect to back up subjective reports, and with an appreciation of the social and cultural influences on this phenomenon, perhaps an ethically sound way of using placebo treatments more widely in clinical practice isn't such a stretch of the imagination.

Add a comment