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 may be present.

How placebos work is still not quite understood, but it involves a complex neurobiological reaction that includes everything from increases in feel-good neurotransmitters, like endorphins and dopamine, to greater activity in certain brain regions linked to moods, emotional reactions, and self-awareness. All of it can have therapeutic benefit. The placebo effect is a way for your brain to tell the body what it needs to feel better.

But placebos are not all about releasing brainpower. You also need the ritual of treatment. When you look at these studies that compare drugs with placebos, there is the entire environmental and ritual factor at work. You have to go to a clinic at certain times and be examined by medical professionals in white coats. You receive all kinds of exotic pills and undergo strange procedures. All this can have a profound impact on how the body perceives symptoms because you feel you are getting attention and care(2).

High-quality research shows arthroscopy to treat osteoarthritis, wear and tear of the meniscus in the knee, and to remove inflamed and thickened bone and tissue in the shoulder is no better than 'placebo surgery' (4).

But in studies testing surgical procedures, getting a placebo can mean going under the knife. So-called sham surgeries are a kind of extreme placebo, where patients undergo all the rituals and scars of a surgical procedure except for the part meant to help (5). These patients benefit surprisingly often: In about three-quarters of sham-controlled studies, there’s some improvement, according to a 2014 review. And they actually benefited just as much as those who got the actual intervention a whopping half the time. And therein lies perhaps the greatest contribution of sham surgeries: helping shine light on popular surgical interventions that might be shams themselves.

Placebo-controlled surgical trials are feasible and provide high-quality data on efficacy of surgical treatments. The surgical placebo entails a considerable risk for study participants. Consequently, a placebo should be used only if justified by the clinical question and by methodological necessity (6).

Placebos often work because people don't know they are getting one. But what happens if you know you are getting a placebo?

A study  by researchers and published in Science Translational Medicine explored this by testing how people reacted to migraine pain medication. One group took a migraine drug labeled with the drug's name, another took a placebo labeled "placebo," and a third group took nothing. The researchers discovered that the placebo was 50% as effective as the real drug to make you feel a reduced pain after a migraine attack.

The researchers think that a driving force beyond this reaction was the simple act of taking a pill. People associate the ritual of taking medicine as a positive healing effect . Even if they know it's not medicine, the action itself can stimulate the brain into thinking the body is being healed.

But the reality is there is no actual healing!

A study published online by PLOS Biology may have identified what goes on in the brain during a placebo effect (3). Researchers used functional magnetic resonance imaging to scan the brains of people with chronic pain from knee osteoarthritis. Then everyone was given a placebo and had another brain scan. The researchers noticed that those who felt pain relief had greater activity in the middle frontal gyrus brain region, which makes up about one-third of the frontal lobe.

Scientists have come to recognize that there is not one response to a placebo but many. They refer to the sum total of patients’ responses to the administration of the placebo as the placebo response. This includes some proportion of the response that likely would have occurred in the absence of any treatment such as the natural history of a disease, regression to the mean, and response bias. Natural history denotes the change, up and down, of the symptoms over time. Regression to the mean refers to a statistical principle that if a variable is extreme on its first measurement, it will tend to be closer to the average on its second measurement, and vice versa. Response bias is the tendency for study participants to provide answers they believe investigators want to hear. The placebo effect is the proportion of improvement or worsening that remains after controlling for all the other incidental effects (7).

So it is all in the brain. It plays tricks with you! And makes you act like a fool!

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