The Placebo Problem blog via Premier Research

For hundreds of years, the medical community has known that the mere act of receiving treatment, even if it’s just a sugar pill, can improve a patient’s symptoms. Therefore, in order to ensure that the effects of an experimental treatment are real, most randomized controlled trials (RCTs) include a placebo arm.

Placebos are most often pharmacologically inactive pills that mimic the physical characteristics of the study drug, but they can also take the form of inert medical devices, sham surgeries, and fake acupuncture. The placebo effect is broader than just patient improvement in response to this inactive treatment; it encompasses the patient’s response to the entire therapeutic context in which treatment is administered.

Details matter
There is actually not one single placebo effect, but many, all of which come together to produce symptom improvement through mind-brain responses to treatment context. Psychosocial factors such as expecting to get better, rituals of care, active engagement in treatment, and even the mere act of taking a pill can all contribute to the placebo response. Research has also shown that how the placebo is administered is just as important as what is administered. The type of placebo, the color and dosing regimen of pills, and how caring the physician acts can all influence the magnitude of the response.

Although the placebo effect was once thought to be an irrelevant and illegitimate nuisance, it is now a field of research in its own right. Multiple brain systems and neurotransmitters underlie the many components of the placebo effect, and a growing body of literature has shown that it improves health in a number of very real ways. The placebo effect doesn’t cure – it won’t shrink a tumor or heal a broken bone – but it can relieve chemotherapy-induced nausea and diminish chronic pain. It can also produce changes in physiological functions such as heart rate, blood pressure, lung function, and gastric motility, and can even lead to improved survival rates in some diseases. In general, the placebo response is most effective at relieving pain and improving depression, anxiety, and fatigue – all conditions in which symptoms are self-reported and psychological distress plays a significant role.

Placebo…uh oh
In an RCT, the true effects of the experimental treatment are those that are above and beyond the placebo response. But there is an inherent problem in this design: the bigger the placebo response, the harder it is to show that an experimental treatment is effective. Ultimately, these reduced drug-placebo differences result in a higher likelihood of a negative trial outcome despite drug effectiveness. Such late stage trial failures come at a great financial cost to pharmaceutical companies and can lead to an erroneous abandonment of viable drugs.

Indeed, a large placebo response has been the downfall of a number of major clinical trials with solid preclinical and prior clinical evidence of efficacy. In an analysis of 52 antidepressant trials that examined the relationship between placebo response magnitude and trial outcome, trials with a low placebo response fared much better than those with a high placebo response. In high placebo response trials, only 20 percent of treatment arms achieved significance, compared to 75 percent in low placebo response trials.

The magnitude of the placebo response has also been deemed the biggest contributor to trial outcome in neuropathic pain, and a high placebo response is thought to be partially to blame for the fact that more than nine out of ten late-stage trials of treatments for neuropathic and cancer pain have failed over the last decade.

Even more alarming is the fact that the placebo response is growing over time, especially in analgesic, antipsychotic, and antidepressant trials. Strangely, this increasing effect seems to be specific to the U.S., at least for trials of neuropathic pain.

In the coming weeks, we’ll be examining issues surrounding the placebo response and its rise in more detail. Our Placebo Problem series will first explore how and why the placebo effect is growing over time. We’ll then turn to the psychological and neurobiological mechanisms that are responsible for its effects. Next, we’ll look at how the placebo effect can be accurately measured in studies and the latest research on strategies to reduce it. Finally, we’ll discuss some the placebo’s opposite, the nocebo effect, where the brain’s response to treatment context negatively impacts health, as well as some ethical considerations of placebo use.


I’ll be on the lookout for updates! A fascinating study, for sure. Also, I think the way way we think is a big contributing factor. For instance, after I banged up my knee while overseas, on return, my orthopedic doc, on review of my MRI images stated, “You should be a lot farther along in your healing. This injury is not a big deal.” When I got home I thought about what he’d said and realized I was NOT wanting to go back overseas. The moment I realized I was using my injury as an excuse to avoid travel, I changed my mind. I decided if I didn’t want to go, I had to make a reasonable decision…not use my injury as an excuse. From that moment on, I gained more movement in my knee and I’m fully recovered. Our mind is VERY strong! JD

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Silicone[quote=“senior48, post:2, topic:6084”]
[/quote]I can easily understand how this can happen since we Sooo much want to be better. I know I have done a million exercises and walked over 2500 miles hoping I would improve and it hasn’t improved my balance at all.

You might like to take a look at Mike Ross, The Balance Coach…I would not have been released from PT (I’d broken my right ankle on my return trip overseas!) had I not begun his online course as my balance really improved by doing his exercises every day at home. Much less costly in the long run considering $45 each PT visit! And in a lifetime access to all of his exercise video clips…and he keeps adding more.

And there’s an exercise that a functional neurologist showed me. The amazing thing was I could literally feel my body sway into balance after a few repetitions over a couple of days. Stand in a room without a lot of visual distraction (I use my bathroom…has a counter to grab if needed). With no watch or bracelet on your wrists–hold up and out your arms; with palms raised (making a 90’ angle); focusing on your outer wrist bone, looking at your left hand, ‘write’ the letters a-k in the air; turn your head to your right hand and ‘write’ l-z in the air. The neurologist explained my brain didn’t quite know where my feet were, and doing this would help. And it marvelously did! Let me know JD

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Last year I took part in a study into the benefits of Turmeric, it was an Anti Inflammatory and Cell Damage Trial.
Some participants were given a placebo. At the end of the trial I was told Turmeric would be of no benefit to ataxia😏xB