Does it work?

You’ve probably heard the term “placebo effect” before. You might also know that it has something to do with taking medication that isn’t real. While this is partly true, there is much more to know. What is it really? Why is it important to understand?

Placebo EffectA placebo is anything that seems to be a “real” medical treatment, but isn’t because it doesn’t contain any active substance meant to affect a person’s health. Most often, it’s a pill, but it could be a shot or some other type of “fake” treatment. The placebo effect is the actual psychological or physical effect a placebo treatment has on an individual. Another way of looking at it is when something fake becomes something real because of the person’s perception of it. It’s important to note that it’s not a product of the person’s imagination because it produces an actual physiologic effect. The experience changes from individual to individual, the strength varies for each disease and the response can be positive or negative. A positive outcome would be the person’s symptoms improving; whereas, a negative outcome would be the person having what appears to be side effects. It’s important to note that while placebos can affect how a person feels, numerous studies suggest that they don’t have a significant impact on a person’s underlying illnesses.

The placebo effect was first demonstrated in 1799 by British physician John Haygarth. In order to test the efficacy of the claims made by Elisha Perkins regarding his Perkins Patent Tractor in treating rheumatic patients, Dr. Haygarth used two groups of five patients. The first group received treatment using the Perkins Patent Tracker. The second group used ersatz tractors made of wood. The device made by Mr. Perkins was supposedly made of an unusual metal alloy (really made from steel or brass). The Tractors were two three-inch metal rods with pointed ends that when passed over distressed parts of the body were supposed to bring out “the noxious electrical fluid at the root of suffering.” Dr. Haygarth found that the results reported by both groups were identical. In each group, four out of five patients stated total pain relief. The results were published with no mention of a placebo response. This term wasn’t used until 1920 by T.C. Graves. Dr. Henry Beecher, a noted anesthesiologist at Harvard, became interested in the placebo effect when he was a medic in WWII and observed a decreased morphine dependency among wounded soldiers awaiting evacuation who were administered a saline solution. At a 1955 meeting of the American Medical Association, he pointed out that while colleagues might think that placebos are fake medicine, they couldn’t deny that the results were real. As a outcome of his presentation, in the last half of the 1950s, a new way to evaluate the effectiveness of medications known as the double-blind, placebo-controlled clinical trial were used. In this type of trial, neither patient nor clinician knew who was getting the active drug and who the placebo. In 1961, Walter Kennedy documented the expectations of negative or adverse effects and named it the nocebo effect (an earlier documented example had occurred in 1886, but wasn’t named). These discoveries helped us to shift our thinking from that of 17th century French philosopher, Rene Descartes, who dismissed the idea that the mind could influence the body in any way. By 1962, the Food and Drug Administration (FDA) began to require pharmaceutical companies to use the new method. Today’s standard is for any prospective new drug to outperform placebos on two independent studies in order to get approval. If both the test group and placebo group have the same reaction, the drug is deemed not to work. This is why for years the placebo effect was considered a sign of failure. However, one problem with the placebo effect is that it can be challenging to tell from the actual effects of a real drug during a study.

The study of the placebo effect remains underexplored and didn’t really surface as a respectable focus of study until 2004. Recently, experts have concluded that reacting to a placebo is not proof that a certain treatment doesn’t work, but rather that another, non-pharmacological mechanism is present. The reasons though aren’t fully understood. Since there are variation in response, there’s likely more than one mechanism at work. Researchers know that placebos work on symptoms regulated by the brain via a complex neurobiological reaction, including everything from increases in feel-good neurotransmitters to greater activity in certain brain regions linked to moods, emotional reactions and self-awareness. So, they may make you feel better, but they won’t cure you. It’s essential to note that participants in placebo groups can have changes in heart rate, blood pressure, anxiety levels, pain perception, fatigue and even brain activity. This shows that the brain plays a role in a person’s health and well-being. One of the most common theories as to why the placebo effect occurs is due to a person’s expectations. For instance, if someone expects a pill to do something, then it’s possible that their body’s own chemistry can cause effects similar to what a medication might have caused. Experts say there is a correlation between how strongly a person expects to have results and whether or not they happen. If positive, these expectations may cause a drop in stress hormones. On the other hand, if the person doesn’t expect the drug to work or expects to have side effects, they might have negative outcomes. In addition, there seems to be a profound effect as the result of the interaction between a patient and healthcare provider. This interaction can impact on how the body perceives symptoms because you feel you are getting attention and care. Under this theory, the placebo effect is a biological response to this act of caring. A prescribing doctor’s enthusiasm for a treatment can impact how a patient responds. People are used to taking medication and feeling better, so the simple act of taking a drug can elicit a positive response. The experience of going to the doctor, receiving care and being provided a treatment help to evoke a healing response that operates independently of a treatment’s specifics. This ritual triggers specific neurobiological pathways that modulate bodily sensations, symptoms and emotions. According to research, the more complex, ritualistic, invasive and credible the treatment appears to the patient, the more powerful the placebo effect usually is. An alternative explanation that is being studied is the release of endorphins that the placebo effect precipitates. Chemically, endorphins have a structure similar to morphine and other opiates, which means they act as the brain’s natural painkillers. Studies have shown that strong placebo responses are linked to increases in dopamine and opioid receptor activity, which are involved in reward and motivation pathways in the brain. Sometimes, researchers pair a placebo with an actual treatment until it causes the desired effect. This is known as conditioning. Another account for the placebo effect is the evolution of a human brain’s ability to moderate healing. Over thousands of years, the human body has developed helpful physiological responses to pathogens. Although conditioning and expectation are separate mechanisms, they’re likely related. A new area of study is psychoneuroimmunology, which looks at the direct effect of brain activity on the immune system. For a long time, it’s been known that a positive outlook can help stave off illness. How this occurs isn’t understood since the pathways by which the brain impacts the immune system are complex. Scientists are looking at how genes may influence people’s response to the placebo effect because it seems some people are genetically predisposed to have a better response. One study found that people with a gene variant that codes for higher levels of the brain chemical dopamine are more likely to have experience the placebo effect than those with the low-levels. Individuals with this gene also tend to have higher levels of pain perception and reward-seeking.

Researchers state that there are many factors that impact the strengthen of a person’s placebo effect. They’ve found some of things that influence the response are the nature of the illness, how strongly the patient believes the treatment will work, the type of response the patient expects to see and the type of positive messages a doctor conveys about the treatment’s effectiveness. The type of placebo plays a role too with injections causing a stronger placebo effect than a tablet. In addition, they discovered that two tablets work better than one, large tablets work better than smaller and capsules provide a stronger response than tablets. Even the color of the pills can make a difference. Pills that are red, yellow and orange are associated with a stimulant effect; whereas, blue and green are related to a tranquilizing effect. In placebo trials, blue pills have been shown to be more effective than white pills at producing a reaction. It’s not just injections and pills that can have an impression, fake procedures, such as “sham” acupuncture (uses retractable needles that don’t pierce the skin), are shown to work just as well as an actual procedure. Another aspect that effects the level of response is culture.

Certain illnesses are more strongly influence by placebos. The most common are those that rely on the self-reporting of symptoms, such as depression, anxiety, sleep disorders, coughs, irritable bowel syndrome (IBS), menopause, erectile dysfunction, side effects of cancer treatment, Parkinson’s disease and chronic pain. In an effort to reduce pain, placebos are believed to work in one of two ways. They initiate the release of natural painkillers, endorphins, or they alter the individual’s perception of the pain. The effect of antidepressants is largely believed to be reliant on the placebo effect. This is also true for individuals with anxiety disorders. When it comes to coughs, one review of medication trials found that around 85% in the reduction of a cough is related to the process of taking medicine, not the active ingredients. For men with erectile dysfunction, they often respond well to placebo treatments. When it comes to Parkinson’s disease, a review of 11 clinical trials found that 16% of participants in the placebo groups showed significant improvements. In some cases, these changes lasted for 6 months. One study that involved patients with asthma found that people using a placebo inhaler didn’t do any better on breathing tests than someone who did nothing, but when asked for their perception of how they felt, the group that used the placebo inhaler reported having relief at the same level as a group that used an inhaler with actual medicine. Due to the positive outcomes, many doctors around the world use placebos to treat illnesses. In a 2008 Danish study, they found that 48% of doctors had prescribed placebos at least 10 times in the past year. Most of these instances were antibiotics for viral illnesses and vitamins for fatigue. This has led to some critics of the practice questioning the ethics of this because they feel that the doctor is misleading the patient. However, supporters feel that if the placebo has the intended effect, it should be considered an effective treatment. Another concern is that when prescribing a placebo, it could delay the correct diagnosis of a serious ailment, which could potentially open doctors and pharmacists to fraud charges. There is no question that placebos work because people don’t know they’re getting one, but there are some conditions in which a placebo can still induce results even when people know they are taking one. This would mean that patients wouldn’t be deceived. A study published in Science Translational Medicine in 2014 looked at this exact concept. The researchers tested how people reacted to migraine pain medication. The study group was divided into three sub-groups. One group took a medication labeled with the drug’s name, another took a placebo that was labeled “placebo” and the third group took nothing. The results showed that the placebo was 50% as effective as the real drug to reduce pain after a migraine attack. The researchers surmised that the reason behind this reaction was the simple act of taking a pill.

This means that treating yourself with your mind should be possible. The idea isn’t new, it has been around for millennia. It’s just that science is now exploring what elements are needed to produce the response. One of the key ingredients is engaging in healthy living by eating right, exercising, having quality social time and meditating. These activities are positive interventions in their own right, but the level of attention you give them can enhance their benefits, which goes a long way when it comes to healing. As a result of numerous studies, we’ve come to understand that our thoughts and feelings can powerfully influence our experiences with pain and other illnesses in ways that drugs can’t.

It seems that the placebo effect is becoming stronger at least in some areas. A study published in the journal Pain in 2015 analyzed 84 clinical trials of pain medication conducted between 1990 and 2013. It was found that the efficacy of placebos had risen sharply, narrowing the gap between them and drugs’ effect on average from 27% to 9%. However, the only studies in which this increase was detected were done in the United States. This has led some researchers to feel that patients in the US are conditioned to expect greater benefit from drugs because of the fact that medications are allowed to be marketed directly to consumers. We’re one of only two countries that allow this. Another possible reason was that the larger and longer-duration trials are more common in America, which have led to them being done at organizations whose nurses’ only job is to conduct drug trials. This could create a more placebo-triggering therapeutic interaction. Regardless of the reason, it’s causing a problem when trying to develop new medications. Most new drugs are able to pass the first couple of stages of the FDA approval process, but now are frequently failing in the larger late-stage trials. According to the study, over 90% of pain medications now fail at this stage. As a result of this, many industry experts are hoping to find a way to identify placebo responders and exclude them from clinical trials. One option they’re looking at is the person’s genome, or as some scientists refer to it as placebome. This is thought to be the chemical pathway along which healing signals travel throughout your mind and body. It is thought that along this pathway is where the brain translates the act of caring into physical healing, which turns on the biological processes that relieve pain, reduce inflammation and promote health. This concept has led some to speculate that some treatments fail to work not because the drug and the individual are biochemically incompatible, but as a result of the drug interfering with some individuals’ placebo response. When thinking about it this way, the placebo effect is no long just some constant to be taken from the drug effect but an integral part of a complex interaction among genes, drugs and mind. If this is true, the placebo-controlled clinical trial, one of the cornerstones of modern medicine, is deeply flawed.

One thing is for sure, in order to use the beneficial powers of the placebo effect, we need to better understand it. If they can be used alongside pharmaceutical interventions, it can improve medical treatments. The good news is they have no serious side-effects and can’t be overdosed on, which means they could be an adaptable, effective, safe and cheap way to improve the quality of life of many people!