The opioid crisis is big news. Thousands have died either directly or indirectly from this phenomenon, whereby a surgery is performed, or an accident causes significant trauma, requiring the prescribing of a narcotic pain medication. Denying relief of a painful condition is difficult for a caring physician, dedicated to the well-being of his patients. For relief of significant pain, opioid medications continue to be the typical choice, but chronic use too often leads to addiction. Thus, it was big news when doctors noted a disturbing trend: fewer pain-relieving drugs were getting through the double-blind clinical trials required by the FDA.

Did you know that all drugs must prove more effective than a sham, a fake, a phony? The technical term for the administration of an inactive substance is a placebo, defined as a medically inert substance or technique, which is administered like a drug. The key word there is ‘inert’. The placebo effect refers to the well-documented phenomenon in which patients feel better after receiving this fake, the infamous placebo. In other words, the mere thought that a treatment has been received causes a beneficial physical response. When defined as the negative control in all these types of studies, placebos play a critical role in modern medicine.

How powerful is this mysterious oddity? It turns out that in ailments grounded in self-awareness, such as pain, the placebo effect can be tremendous. A neuroscientist in the ’80’s conducted a study in which postoperative patients received either a secret dose of morphine, or an overt dose of a substance described as a powerful painkiller (but was actually salt water). Amazingly, patients in both groups reported the same degree of pain relief. These kinds of results have been produced by too many studies to deny the phenomenon.

Many physicians who deal with the treatment of chronic pain would agree, we need more options for controlling pain. For moderate to severe pain, we obviously have a number of narcotics, but these all have side effects. Their use is limited by serious adverse health consequences such as respiratory depression, sedation and constipation. The threat of dependence and addiction is obviously a huge concern. But fewer new drugs are “coming down the pipeline” since fewer drugs are passing the stringent requirements of the Food and Drug Administration.

There is a reason for this deficiency in the field of pain medications. A summary of many studies found that, while the responses to the drugs have remained about the same, the responses to the placebo have increased over the past two decades. Consequently, placebo’s effects on pain are now so large that pharmaceutical companies have an increasingly hard time proving drug efficacy. What studies have revealed is not that drugs are getting worse, but the placebo response is growing stronger over time. Strangely, this appears to be occurring only in the US. Additionally, placebos seem to be growing stronger not only in pain medicine, but also in the field of antidepressants and anti-psychotic studies.

How does this placebo effect occur? Most people expect the prescribed pill to have a therapeutic benefit. This expectation activates reward pathways in the brain, which, in turn, stimulate the release of substances called endorphins, which are chemically similar to opiates like morphine. It would be appropriate to call it the body’s own internal morphine-dispensing system. In response to positive expectations of treatment, your brain becomes flooded with its own supply of natural painkillers. When it comes to the topic of pain control, distinguishing between placebo and drug effects can be tricky since both activate the same mechanisms. This means that strong placebo responses could mask drug effects in painkiller trials.

Why might the placebo effect be growing stronger? One hypothesis is that the increasingly showy setting of clinical trials, along with the direct-to-consumer advertising by pharmaceutical companies, may raise patients’ expectations of drug efficacy. The strength of the placebo effect is altered by everything from the drug ads we see to our interactions with health care providers to the length of a clinical trial.

Placebos are a real and identifiable paradox, found somewhere at the interface of biology and psychology. Scientists believe it is a loose family of different terms and processes, grouped together under the heading of the placebo effect. Certainly, one component is the fact that, in the natural course of an illness, symptoms will often get better on their own. Also well recognized is people pay closer attention to signs that they are getting better, whilst tending to ignore signs they’re getting worse.

The placebo response is at least partially a learned behavior via cause and effect. This pharmacological conditioning only works if the drug is acting on a process that the brain can do naturally. Pain relief can be a conditioned response because there are endogenous pain-relieving mechanisms in the body. Painkillers activate the opioid system in the brain. Taking a pill you think is a painkiller can activate that system, to some degree.

When we take an active drug, we often feel better. That’s a memory we revisit and recreate when on placebo. We get cues about how we should respond to pain — and medicine — from our environment. In one particular study, post-op patients administered pain-relieving medication by a hidden robotic pain pump will need twice the amount of drug to get the same relief as when injected by a nurse they can see and hear. A person’s awareness they are being given something supposed to relieve pain appears to impact their perception of its effect.

Even stranger, fake surgeries are an even stronger placebo than pills. These are procedures where doctors make an incision but don’t actually do anything. A review of placebo surgeries found the fake surgery led to improvement 75 percent of the time. Surgeries intended to relieve pain produced results no different than outcomes for real surgeries for pain.

Placebos are effective for such things as pain, nausea, asthma, and phobias, with more inconsistent results for outcomes like smoking, dementia, obesity, hypertension, insomnia, and anxiety. Placebo can only help symptoms that can be modulated by the mind. Such factors as warmth, empathy, duration of interaction, and the communication of positive expectation would appear to significantly affect clinical outcomes of placebos. Yet, clearly, something physical, some biological change is taking place. Brain-imaging studies have confirmed that placebos cause measurable changes in neurobiological signaling pathways.

The new science of the placebo phenomenon is bringing greater understanding to why alternative treatments such as acupuncture and reiki help some people. We are now beginning to uncover the underlying neural mechanisms that create the placebo response, with research on-going. With this new-found knowledge, we are presented with a unique opportunity to harness the power of the mind in controlling pain. Potentially, this may allow us to someday prescribe smaller doses of pain medications to help address the opioid crisis that is ravaging America. We cannot afford to ignore a method as powerful as the placebo effect. Now we need only learn how to harness this natural and holistic treatment method.

Editor’s note: Dr. Conway McLean is a physician practicing foot and ankle medicine in the Upper Peninsula, with a move of his Marquette office to the downtown area. McLean has lectured internationally on wound care and surgery, being double board certified in surgery, and also in wound care. He has a sub-specialty in foot-ankle orthotics. Dr. McLean welcomes questions or comments atdrcmclean@outlook.com.