Is Your Pain Medication Effective or Was It Placebo Effect?

By Dr. Lynn Webster, PNN Columnist

Most of us have been prescribed a medicine at some time in our lives. And if we got better, we probably assumed it was because the medication was effective.

However, this may not have been completely true. A positive result following the use of a medication may have little to do with the drug.

If you're a M*A*S*H fan, you may have seen an episode called "Major Topper." In that show, Colonel Potter suggests they treat people in pain with a placebo because there is a morphine shortage — and it works. Did that mean their pain wasn’t real?

Placebos Work So Well They Can Fool Researchers

One of the greatest challenges in evaluating the efficacy of medical treatments is to minimize what is known as the placebo effect. The benefit provided by a treatment during clinical trials may appear to be significant. However, the treatment may fail to be approved by the FDA if the benefits for patients who receive a placebo are too similar to those who receive active treatment.

Drug approval requires that active treatment results are meaningful and differ statistically from placebo results, even though both may provide similar outcomes when compared to a baseline. 

I study drugs for their potential to be abused— what the FDA calls a Human Abuse Potential (HAP) study. People who participate in HAP studies must admit they recreationally use the class of drug which is undergoing evaluation, and must report a strong preference for the drug when compared to a placebo.


Most people would be surprised to learn that as many as 50% of the test subjects who commonly use a drug recreationally cannot adequately differentiate between the active drug and the placebo. Even more surprising is that one in five subjects report a much greater preference or “getting high" experience with the placebo than with the active drug.

There are several reasons for this. It could be that they don’t realize researchers know which drug they received and in what order. They are simply hoping to guess correctly because they want to participate in the study. Or the subjects may be anticipating an effect that they want (to get high) and that anticipation creates the effect in the reward center of their brain without even using an active drug.

This effect is not limited to drugs. As a principal investigator in a study, I surgically implanted wires at the base of the occiput (the skull) to stimulate occipital nerves in an attempt to prevent or treat migraine headaches. Although all subjects underwent the operation and were implanted with the wires, only half received active stimulation. The other half were programmed with a sham pattern of stimulation.

When the study was unblinded, we discovered that almost everyone in both groups (active and placebo) derived remarkable, but similar, relief from the therapy.

We concluded it was their expectation that an invasive procedure would be therapeutic that provided the positive outcome. Unfortunately, the positive results of both treatment and placebo meant the new procedure could not be approved on the basis of our testing.

Placebos Work Even When People Know About Them

Ted Kaptchuk, a Harvard Medical School professor of medicine, is the director of the Program in Placebo Studies at the Beth Israel Deaconess Medical Center. In a recent episode of NPR's "Hidden Brain" podcast, Kaptchuk recounts similar results when testing the placebo effect.

However, his research added a new twist. Kaptchuk wanted to see what would happen if he used "radical honesty" to determine the potential of the placebo effect. Instead of tricking patients into believing they may receive an actual treatment instead of a placebo, Kaptchuk told his subjects they would receive a placebo. In other words, no actual drug would be administered to subjects and they were all aware of that.

Surprisingly, he found that a placebo could still work. "Hidden Brain" host Shankar Vedantam also talked to Linda Bonanno, who participated in Kaptchuk's study. Bonanno explained that Kaptchuk gave her a placebo to treat her irritable bowel syndrome and it eased the agonizing pain she had been living with for years.

The pain did not return until Kaptchuk stopped "prescribing" the placebo. For Bonanno, what seemed to help the most was the trusting relationship she had with Kaptchuk. The warmth and caring of her health care provider may have been enough to mitigate her pain.

As we know, pain isn't just a physical experience. It is a complex emotional experience that has psychological, social and spiritual elements. If a doctor's empathy, warmth, listening and caring can ease a patient's pain, that shouldn’t call into question whether the patient's pain was real. It simply makes the case that a trusting relationship with a healthcare provider is as important for successful treatment as the medication or procedure itself.  


Lynn R. Webster, MD, is a vice president of scientific affairs for PRA Health Sciences and consults with the pharmaceutical industry. He is author of the award-winning book, The Painful Truth” and co-producer of the documentary,It Hurts Until You Die.” You can find him on Twitter: @LynnRWebsterMD.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Can Sugar Pills Relieve Chronic Pain?

By Pat Anson, PNN Editor

“Sugar pills relieve pain for chronic pain patients”

That is the actual headline in a news release issued this week by the Feinberg School of Medicine at Northwestern University. If you’re a pain sufferer and that doesn’t make you laugh or get your blood boiling – then the rest of this article probably will.

So be forewarned.

In an age when many chronic pain patients are being urged to try yoga, meditation, acupuncture and plain old aspirin, Northwestern researchers have concluded that many could find pain relief in a sugar pill.

That conclusion is based on a lengthy but small study of 63 patients with chronic back pain.  Twenty patients were given no treatment, while the rest were given a placebo – a sugar pill that they were told was pain medication. No one was given an actual painkiller.

Over the course of 8 weeks, participants tracked their pain on a smartphone app, MRI brain images were taken, and psychological profiles of each patient were made.


The study, published in the journal Nature Communications, found that about half the patients who took the placebo had a 30 percent reduction in pain, a level considered just as effective as a real painkiller.

Researchers said patients who responded to the sugar pills had a similar brain anatomy and psychological traits. The right side of their emotional brain was larger than the left, and they had a larger sensory area than people who did not respond to the placebo. The placebo responders also were more emotionally self-aware, sensitive to painful situations and mindful of their environment.

“This is the first brain imaging RCT (randomized controlled trial) specifically designed to study chronic pain patients receiving placebo pills compared to a no treatment arm,” said senior study author A. Vania Apkarian, PhD, a professor of physiology at Northwestern University Feinberg School of Medicine.  

“Daily pain ratings from a smart phone revealed that patients receiving placebo pills showed stronger pain reduction and a higher response rate compared to patients in the no treatment arm, indicating that placebo pills successfully induced analgesia that could not be explained by the natural history of the patient or the mere exposure to the study.”

Doctors ‘Should Seriously Consider’ Placebos

Although his study is small and needs to be replicated, Apkarian thinks doctors should put his findings to work.

"Clinicians who are treating chronic pain patients should seriously consider that some will get as good a response to a sugar pill as any other drug," he said. "They should use it and see the outcome. This opens up a whole new field."

Giving pain patients sugar pills would not only save healthcare costs, Apkarian says they would eliminate the risk of addiction and other side-effects from pharmaceutical drugs.

"It's much better to give someone a non-active drug rather than an active drug and get the same result," Apkarian said. "Most pharmacological treatments have long-term adverse effects or addictive properties. Placebo becomes as good an option for treatment as any drug we have on the market."

The medical community has long known about the potency of the placebo effect and put it to use. Doctors as far back as the late 18th century used placebo treatments “more to please than benefit the patient.”

Today, the gold standard of clinical trials is a “placebo-controlled study” in which some participants are given sugar pills and sham treatments. The medication or therapy being studied has to be found more effective than the placebo for the study to be considered a success.

Time magazine recently published a cover story on placebos, sharing the stories of real patients who find relief in placebo pills even though they know they’re fake.

You don’t need to enroll in a clinical study to take placebos. You can buy a bottle of Zeebo’s “honest placebo pills” for $14.95 on Amazon. Some of the reviews for Zeebo are hilarious.

“I have not bought this product, but just reading about it brightened my day. And the comfort of knowing that if I ever needed a good placebo, its right here available with free shipping and two day delivery. I feel better already!” said one reviewer.

“The pills do every thing promised, which is nothing,” wrote another reviewer. “I purchased them in the forlorn hope that they would fool my demented wife that they helped to relieve her chronic pain. I didn't expect much going in and I wasn't disappointed.”

Ibuprofen No Better Than Placebo for Back Pain

By Pat Anson, Editor

When it comes to treating back pain, anti-inflammatory drugs such as ibuprofen work no better than a placebo, according to new Australian study.

Researchers at the University of Sydney conducted a meta-analysis (a study of studies) of 35 clinical trials involving over 6,000 people with back pain, and found that non-steroidal anti-inflammatory drugs (NSAIDs) provide little benefit. The study was published in the Annals of the Rheumatic Diseases.

NSAIDs are effective for spinal pain, but the magnitude of the difference in outcomes between the intervention and placebo groups is not clinically important. At present, there are no simple analgesics that provide clinically important effects for spinal pain over placebo,” wrote lead author Gustavo Machado, PhD, of The George Institute for Global Health. “There is an urgent need to develop new drug therapies for this condition.”

Back pain is the world’s leading cause of disability, with about 80 percent of adults experiencing back pain at some point in their lives.

Opioids are usually not prescribed for simple back pain, leaving patients little alternative but over-the-counter pain relievers such as NSAIDs, a class of drugs that includes both aspirin and ibuprofen. NSAIDs are known to raise the risk of gastrointestinal and cardiovascular problems.

The Australian study found that NSAIDs reduced pain and disability somewhat better than a placebo or dummy medication, but the results were not statistically important.

"NSAIDs do not provide a clinically important effect on spinal pain, and six patients must be treated with NSAIDs for one patient to achieve a clinically important benefit in the short-term," wrote Machado. “When this result is taken together with those from recent reviews on paracetamol (acetaminophen) and opioids, it is now clear that the three most widely used, and guideline-recommended medicines for spinal pain do not provide clinically important effects over placebo.”

The study did not evaluate non-pharmacological treatments for back pain, such as exercise, physical therapy or chiropractic care.

NSAIDs are widely used to treat everything from fever and headache to low back pain and arthritis. They are found in so many different products -- such as ibuprofen, Advil and Motrin -- that many consumers may not be aware how often they use NSAIDs. 

Placebo Effect is All in Our Heads

By Pat Anson, Editor

A new study has given researchers a better understanding why some people given a simple sugar pill will say it significantly reduces their pain.

It’s all in their heads.

Using functional magnetic resonance brain imaging (fMRI), scientists at the Northwestern Medicine and the Rehabilitation Institute of Chicago (RIC) have identified for the first time the region of the brain that's responsible for the "placebo effect" in pain relief. It’s an area in the front part of the brain -- called the mid frontal gyrus -- that also plays a key role in our emotions and decision making.

In two clinical trials involving 95 patients with chronic pain from osteoarthritis, researchers found that about half of the participants had mid frontal gyrus that had more connectivity with other parts of the brain and were more likely to respond to the placebo effect.

The use of fMRI images to identify these “placebo responders” and eliminate them from clinical trials could make future research far more reliable. It could also lead to more targeted pain therapy based on a patient’s brain images, instead of a trial-and-error approach that exposes patients to ineffective and sometimes dangerous medications.

"Given the enormous societal toll of chronic pain, being able to predict placebo responders in a chronic pain population could both help the design of personalized medicine and enhance the success of clinical trials," said Marwan Baliki, PhD,  a research scientist at RIC and an assistant professor of physical medicine and rehabilitation at Northwestern University Feinberg School of Medicine.

“This can help us better conduct clinical studies by screening out patients that respond to placebo and we can just include patients that do not respond. And we can measure the efficacy of a certain drug in a much more effective manner.”

Baliki told Pain News Network that differences in the brain could explain why some prescription drugs – such as Lyrica (pregabalin) – are effective in giving pain relief to some patients, but not for others.

“If we do the same with Lyrica, maybe we can find another area of the brain that can predict the response to that drug,” he said.

The study findings are being published in PLOS Biology.

"The new technology will allow physicians to see what part of the brain is activated during an individual's pain and choose the specific drug to target this spot," said Vania Apkarian, a professor of physiology at Feinberg and study co-author. "It also will provide more evidence-based measurements. Physicians will be able to measure how the patient's pain region is affected by the drug."

Currently, most clinical studies involving pain are conducted on healthy subjects in controlled experimental settings. Those experiments usually induce acute pain through immersion in cold water, pressure or some other type of applied pain. Baliki says there are significant differences between acute and chronic pain, and the experiments often translate poorly in clinical settings where pain is usually chronic.