The Science Behind the Placebo Effect

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Placebo – I shall please.

   The placebo effect is a widely known medical phenomenon used in modern medicine to test the effectiveness of new drugs. However, it is becoming less and less distinguishable from the actual drug in more recent years; from 27% in 1996 showing pain reduction from the drug compared to the placebo, to 9% in 2013. It must be noted that the placebo effect is essentially a family of various occurrences. These include regression to the mean, confirmation bias, expectations and learning, pharmacological conditioning, social learning and human connection. These various subgroups put the placebo effect into action as a result of different triggers – not just a sugar pill.  However, the actual placebo is defined as ‘a medically inert substance or technique, administered like a drug’ – a product that results in a beneficial response regarding illnesses that are rooted in self-awareness; for example, pain. [1]

   Despite previously being played off as misconceptions, research now shows the placebo effect as a legitimate biological response. This is proved by various brain-imaging studies that confirm measurable changes in neurobiological signalling pathways as a result of the use of placebos. One of the most significant studies regarding the placebo effect took place in the 1980’s by neuroscientist Jon Levine. The result of the study conducted on postoperative patients using either morphine or saline, showed all patients reporting the same degree of pain relief. [2]

Regression to the mean: time acting as a natural placebo to heal the patient.

Confirmation bias: the intense hope of getting better results in the patient focussing more on the signs suggesting they are getting better; blind siding the signs proving deterioration.

Expectations and learning: the idea of cause and effect.

   The memory of feeling better using an actual drug is revisited and recreated when using a placebo.

   Patients require a larger amount of the drug to experience the same pain relief when received from a hidden distributor compared to when injected by a nurse that could be seen. This presents the idea that awareness of being given something to relieve pain impacts its perceived effectiveness. 

   Positive expectation activates reward pathways to stimulate the release of endorphins. Endorphin acts in a similar manner to opioids and morphine as the chemical binds to opioid receptors to relieve pain.

   A similar idea to expectations and learning is the anticipation of benefit when the placebo is given. Due to the positive anticipation, dopamine receptors are activated to increase their release and uptake, reducing pain sensitivity.

   The extent to which the opioid and dopamine signalling pathways are both affected partially depends on a patient’s genetics. The genetic receptors control whether they experience a strong or weak placebo effect. This means that participants of the trial that have less active receptors are less likely to be respondent to placebo triggered chemicals.

Pharmacological conditioning: when a patient is unknowingly switched from the actual drug to a placebo yet continues showing improvements in health.  

   An example includes a study on Parkinson’s disease when the placebo triggered a similar response in the brain as when the actual drug was being used. However, it must be noted that this conditioning can only occur if the drug is affecting a process that can be carried out by the brain naturally. Another example is the continued decrease in interleukin production despite only the placebo being used. This was due to the placebo being taken with the same sweet tasting drink as the drink given with the pill. The flavour was associated with a decreased immune response.

Social learning: the copied response expressed by a patient after seeing another participant experience relief.

Human connection: the belief that empathy and warmth makes patients feel better. Studies have shown that a positive treatment full of empathy, communication and warmth notably affects the clinical outcome.

   This combination of effects shows an overlap between psychological and biological responses in science, with the biological aspect being proved by negates such as naloxone; counteracting the endogenous opioid release causing the placebo effect. Another test includes the increased activity in the region of the brain controlling pain management – the periaqueductal grey matter. The spinal cord regions that respond to pain also shows decreased activity; this shows that the perception of any pain is reduced when experiencing the placebo effect. Patients with Alzheimer’s disease also show dwindling responses to placebos as a result of damaged frontal lobes – the parts of our brain that effect the subjective perception of the world.

   The increased response to placebos over time has been hypothesised to be the result of increasingly positively associated perceptions of clinical trials as a result of direct advertising to general consumer. The large-scale covering of the positive effects of the drug trials have been theorized to raise the patient’s expectations of drug efficacy; increasing the expectations and ideas phenomenon. This has resulted in it becoming progressively more difficult to prove the efficacy of the drug being trialled as it shows the same effects as the placebo. Nevertheless, the drugs effect should be additive to the placebo effect – patients should experience the response produced by the drug’s biochemical effects itself, as well as from the placebo effect. However, this proves a difficulty for drugs affecting the pain field as both the placebo and drug activate the same mechanisms; strong placebo responses could mask the effects of pain-killing drugs. Subsequently, fewer new pain-affecting drugs are succeeding in placebo control trials.


References

  1. Brian Resnick, “The weird power of the placebo effect, explained”, Vox, Jul. 7, 2017 https://www.vox.com/science-and-health/2017/7/7/15792188/placebo-effect-explained
  2. Benika Pinch, “More Than Just a Sugar Pill: Why the placebo effect is real”, SITN Blog, Sep. 14, 2016 http://sitn.hms.harvard.edu/flash/2016/just-sugar-pill-placebo-effect-real/

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