by Benika Pinch
figures by Kaitlyn Choi
If you watched the Rio Olympics, you probably noticed that several athletes, including swimmer Michael Phelps, were covered in bizarre circular marks. These bruises were caused by cupping, a therapy that uses suction to pull skin upwards into a circular cup, with the intent of increasing blood flow and reducing muscle tension. While athletes maintain that they benefited from the therapy, a 2015 study found that patients who received cupping reported the same degree of pain relief as patients who unknowingly received a sham version of the therapy (in which the cups had a hole in them and couldn’t create proper suction). Given that cupping is a therapy with limited scientific support, why does it make people feel better? The answer may lie in a peculiar phenomenon known as the placebo effect.
A placebo is defined as a medically inert substance or technique, which is administered like a drug. As the staple negative control in clinical trials, placebos play a critical role in modern medicine. The placebo effect refers to the well-documented phenomenon in which patients feel better after receiving a placebo. In other words, the mere thought that a treatment has been received causes a beneficial physical response.
Now, to be clear, there is no evidence that a placebo can shrink a tumor or heal a broken bone, but when it comes to ailments grounded in self-awareness, such as pain, the placebo effect can be tremendous. In the 1980’s, neuroscientist Jon Levine conducted what is now considered one of the quintessential analyses of the placebo effect. In this study, postoperative patients received either a secret dose of 6-8 mg of morphine, or an overt dose of a substance described as a powerful painkiller (but was actually saline solution!). The results were remarkable: patients in both groups reported the same degree of pain relief.
If you think that all of this sounds a bit unbelievable, you are not alone. For decades the placebo effect was written off as an illusion, spontaneous remission, or biased reporting. However, recent research reveals that the placebo effect is a real biological response, and illuminates the underlying mechanisms driving this phenomenon.
Placebos elicit biological responses
Contrary to popular belief, patients don’t just imagine placebo responses. Rather, numerous brain-imaging studies have confirmed that placebos cause measurable changes in neurobiological signaling pathways . How can a sugar pill lead to a tangible physical response? The key to understanding the placebo is that it is not just the inert therapy itself, but also the expectation surrounding that therapy.
Say you are experiencing pain and spontaneously decide to eat a sugar pill – chances are you won’t feel better. However, if you describe your symptoms to a physician, who then prescribes you the same pill (unbeknownst to you, it’s just sugar), you expect that pill to have a therapeutic benefit. This expectation activates reward pathways in the brain, in turn stimulating the release of substances called endorphins, which are chemically similar to opiates like morphine. Like morphine, these endorphins bind to opioid receptors and cause pain relief. Therefore, in response to positive expectations of treatment, your brain becomes flooded with its own supply of natural painkillers. This effect can be partially negated by a chemical called naloxone, which was developed for patients who overdose on opiates, such as morphine or heroine. Naloxone acts by blocking key opioid receptors in the central nervous system, and partially prevents placebo responses. This means that the placebo effect can be biochemically modulated!
The opioid system is not the only pathway at play when it comes to placebos. For example, placebos also increase the release and uptake of dopamine, a neurotransmitter involved in reward-motivated behavior and decreased pain sensitivity. Specifically, in anticipation of benefit when a placebo is administered, dopamine receptors are activated in regions of the brain associated with reward.
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