The Placebo Effect – One gadfly health researcher’s notes on a practice employed in the majority of clinical trials, plus her take on the active placebo and the nocebo – “placebo’s evil twin”

This article is reproduced with permission from June Russell’s Health Facts Website A “retired health educator, researcher, and journalist,” she says her purpose is “to educate the public about health issues and balance some of the media facts that are deceptive, inaccurate, or biased.” The views expressed here are the author’s.*

PLACEBO: In Latin, placebo means "I shall please."

A study in the Journal of Neuroscience provided direct evidence that the brain's own pain-fighting chemicals, called endorphins, play a role in the phenomenon known as the placebo effect, resulting in a reduction of pain. Dr. Jon-Kar Zubieta, Associate Professor of Psychiatry and Radiology [at the University of Michigan], says this is the first study to pinpoint specific brain chemistry for the placebo effect.(1)

Placebos are not always inert; they can have actual ingredients. When a study is reported as being "placebo controlled" (in addition to being large, randomized, and double blind) – the "gold standard" – the public is led to believe that the outcome is reliable.

Actually, some studies have excluded important variables (such as weight or diet), or have used smaller (clinically ineffective) amounts of the tested substance. When small amounts of the tested substance are used, in a dosage previously shown to be ineffective, the outcome of the study is guaranteed. For example, in the studies showing negative effects of zinc lozenges. Studies constructed in this manner skew the outcome and results, resulting in misleading conclusions. Follow-up studies that reveal the flaws or show differing results are rarely reported in the media.

In research, a placebo refers to a treatment with no known effect on the condition being studied. For a variety of reasons, ranging from narrow financial self-interest to altruistic hope of finding a cure, researchers who are not “blinded” will usually see more improvement from a drug or new therapy than there actually is. The size of the placebo effect varies from study to study and depends on the condition under investigation, but 35 percent is a frequently cited figure. What we call the placebo effect may be the natural tendency of many illnesses to get better. In drug trials, the placebo is a "dummy" pill that closely resembles the real thing. It is often made with lactose, the sugar in milk.(2)

To get permission from the Food and Drug Administration to market a new drug, its maker must show that it works better than a placebo in at least two large, controlled studies. People in the placebo group are actually getting treatment of a kind. They still have the doctors' visits with someone paying attention to their distress and trying to address it. That medical interaction, and the hope engendered by simply being in a study, may be responsible for improvement.(3)

One of the most strongly held beliefs in medicine, that dummy pills or other sham treatments greatly help many patients, has been called into question by Danish researchers who found little or no "placebo effect" in 114 studies.(4)

Researchers and other experts said that improvements might be explained by "reporting bias," where patients, thinking they are getting a powerful treatment, incorrectly judge their condition or overstate any improvement to please their doctor.

Dr. Stephen Schneider, Professor of Medicine at the University of Medicine and Dentistry of New Jersey in New Brunswick, has worked in many trials where the patients on a placebo improved. He said that simply participating in a medical study induces patients to eat better, exercise more, or otherwise pay more attention to their health. Many doctors still routinely give placebos to reassure patients who want every possible treatment – for example, antibiotics to people with colds (which cannot help), or prescribing a drug that is unlikely to work.(5)

In industry-sponsored studies of MSG, large numbers of subjects were reacting to a placebo which, by definition, should be made up of inert, non-reactive material. The placebo contained aspartame!

J.R.’s comment: Proof was found in an industry association letter in an FDA file. After objections were raised to the use of aspartame, sucrose 11 was substituted. Sucrose 11 is a substance that will also affect the findings of any study on MSG intolerance and diminish the effect of MSG. The FDA knows that sucrose and other carbohydrates diminish the effect of MSG.(6)

Vaccination is built around a "belief" system, and challenging the validity of vaccines challenges long-held foundational beliefs. However, beliefs are based on faith not facts. With only a cursory review of the literature and CDC documents, one will find the following facts:

• No vaccine has ever been proven to be completely safe. Safety studies are small and only include "healthy" children. However, after a study is completed, vaccines are given to ALL children, regardless of underlying health conditions or genetic predispositions. Our national vaccine policy does not allow for individualized options, and it has caused a myriad of health problems for many.

• Observations for side effects continue for a maximum of 14 days during a "safety" study, but complex problems involving the immune system can take weeks or even months to appear.

• A vaccine "safety" study is designed to compare a new vaccine to a "placebo," but when we examine the study more closely we discover that the "placebo" is NOT a benign, inert substance, such as saline or water. The "placebo" is another vaccine with a "known safety profile,” so if the new vaccine has the same side effects as the "placebo," the vaccine is considered to be "safe." We want to "believe" that a vaccine will protect us from infection, but several medical journal articles document that this is not necessarily so. J.R.'s note: There are seven studies listed to support this statement.

Researching vaccinations and the vaccine industry will seriously change your "beliefs" in vaccines.(7)

"Real" acupuncture no better than placebo for migraines? A new study of more than 300 patients, published in the Journal of the American Medical Association, reported that both "real" and "sham" acupuncture reduced migraine pain, compared with no treatment at all. The problem is, there's no such thing as "sham" acupuncture – acupuncture anywhere in the body has the ability to affect the nervous system and lead to the reduction in pain. So the first problem with the study was that the placebo wasn't really a placebo. Second, the treatment was the same for each patient – in reality, acupuncturists develop individualized treatment plans based on a person's unique symptoms.

J.R.'s note: Also, researcher Dr. Dedra Buchwald noted that acupuncturists generally customize treatments for each patient and often combine acupuncture with other forms of treatment, something that cannot be done in a clinical trial. Acupuncture certainly works in acute pain control and in some conditions of chronic pain.(9)

An article in The Wall Street Journal (June 18, 2004) reported that "Drug makers seek to bar 'placebo responders' from trials." In other words, spot the troublemakers, keep them out of the trials, and the outcome will be much more in line with desired results. Accurate results are secondary to desired results when an FDA approval of a cash cow pharmaceutical is in the balance. This would corrupt the basic design of clinical studies.(10)

By subtracting the placebo response from the drug response, it then is expected to determine the “real” effects of the drug itself. This is an illusion. The placebo response may actually determine the drug response. When given by a non-caring physician, both drugs and placebos are less effective, and the distinction in response between the "active" drug and placebo can be wiped out (Lancet, 1994). Physicians tend to be as confused as researchers about the nature of placebo. The effectiveness of a medical treatment is not a fixed property of the treatment itself; it is a highly variable quantity that may be more strongly influenced by the relationship between the doctor and patient than by any other factor.(11)

A different research group found that some simple dietary changes may help protect the heart of people over age 60. Heart rate variability is an important marker of cardiac health. Taking 2 g of fish oil a day increased the positive index more than the placebo, which was soy oil.(12)

Greek researchers found that dark chocolate makes blood vessels less thick and more flexible. This study was in the American Journal of Hypertension (2005), a peer-reviewed journal – reputable research. Terri Graedon reported that the poor people on placebo didn't get anything. They didn't get a low flavonoids chocolate. They just had to pretend they were eating chocolate.(13) J.R.'s comment: The placebo was "nothing?" Time and again we see that studies, even studies that are published in a peer-reviewed journal, don't guarantee accuracy.

“Active” Placebos

More recently, drug companies have begun to produce "active placebos." These pills, unlike the sugar or starch pills of old, contain ingredients that mimic the common side effects of the drug under study. An active placebo might, for example, cause dry mouth if the drug to be tested was Elavil™, but it probably wouldn’t cause drowsiness because Elavil™ is used to treat sleep disorders. It would be important to know whether people slept better with a placebo that wouldn’t have that effect.

Sometimes a prescription medication is used as an active placebo. In a study published in the New England Journal of Medicine (March 2005), the combination of morphine and gabapentin for relief of neuropathic pain was compared to each drug alone and to an active placebo. The placebo used was lorazepam, a benzodiazepine medication with [anti]anxiety and sedative properties, with a common effect of dizziness. Two of the most common side effects of both morphine and gabapentin are dizziness and sleepiness. Approximately one-third of the patients, reported Medscape, guessed that they were receiving an active drug while they were receiving the lorazepam placebo, which could have decreased the difference between treatment with gabapentin or placebo. However, even so, the trial results showed significantly better results for the combination of gabapentin and morphine than either drug alone, and the poorest results from the lorazepam placebo.(14)

It seems that pharmaceutical companies routinely make their own placebo pills for each trial and even formulate them to mimic expected drug reactions. This tends to destroy any pretense of "scientific drug testing." Could that be the reason for some of those hundreds of thousands of deaths reportedly caused by pharmaceutical drugs every year and why the medical system has become a leading cause of death in the western world?15

There is really no such thing as an inert substance. Placebo pills are still called sugar pills. Is sugar inert? If you take a sugar pill, your body will have a reaction, especially if you have an insulin disorder. If you are given that pill as a part of a drug research trial, your reaction becomes a factor in the research. The drug companies choose the ingredients and they make their own placebo pills for research purposes. Sometimes they purposely put ingredients in the placebos that match those in the drug, thereby affecting results of the trial. They are not required to disclose the ingredients they use. Does that sound "inert" or "inactive" to you? Suddenly the idea of a "sugar pill" doesn't seem so innocent anymore.

Before conducting human trials for drugs, pharmaceutical companies often are fully aware of the many side effects of the products they're testing. So, for instance, if a drug is known to cause dizziness and hypertension, the drug company running the test wants the placebo to have the same side effects. They have an explanation for this. They say the placebo should mimic the drug being tested so that the control group of the experiment will have side effects similar to the placebo group. Without that, they claim, the results of a blind study would be compromised.

In the TV ads for the allergy medication Claritin™, the voice-over says “The most common side effects with Claritin™, including headache, drowsiness, fatigue and dry mouth, occurred about as often as they did with a sugar pill.” Just what kind of "sugar pill" were they using that caused headache, drowsiness, fatigue, and dry mouth? Sounds to me like a sugar pill with a little something added. They want us to believe that their powerful medication will produce side effects no more serious than what you'd get with a little dab of sugar.

Dr. Beatrice Golomb, MD, PhD, Assistant Professor of Medicine at the University of California, San Diego, has been actively fighting the research establishments that claim that placebos are inactive substances. Dr. Golomb wants scientists to provide a list of placebo ingredients so trial results can be properly evaluated. To level the playing field, Dr. Golomb suggests that drug companies start divulging all placebo ingredients. She also recommends that a standardized set of placebos be developed that would have known and predictable side effects. This would go a long way toward eliminating the pharmaceutical industry's cynical manipulation of test data. Do the physicians and researchers who work independently from the pharmaceutical giants know the truth about the placebos?(16)

The Nocebo Effect: Placebo’s Evil Twin

While the placebo effect refers to health benefits produced by a treatment that should have no effect, patients experiencing the nocebo effect experience the opposite: Nocebo is Latin for "I will harm." They presume the worst, health-wise, and that's just what they get. "Nocebos often cause a physical effect, but it's not a physically produced effect," said Irving Kirsch, a psychologist at the University of Connecticut in Storrs who studies the ways that expectations influence what people experience. "What's the cause? In many cases it's an unanswered question."

The flood of brain chemicals, it appears, has everything to do with what the mind expects. One of the most important things about a pill is its color. A Dutch study found that most people considered red and orange pills to be stimulating, with blue and green-colored pills more likely to have a depressant effect.(17)


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Footnotes: [Note: readers who have questions about any of these footnotes should direct them to June Russell at]

1. "Placebo effect not purely psychological," Health Tips,, September 2005 [reporting on "Placebo Effects Mediated by Endogenous Opioid Activity on u-Opiod Receptors," Journal of Neuroscience, by Jon-Kar Zubieta, et al., August 24, 2005].

2. "Study casts doubt on the placebo effect," Harvard Health Letter, August 2001.

3. "Drug makers seek to bar 'placebo responders' From Trials,” by Leila Abboud, staff reporter for The Wall Street Journal, June 18, 2004.

4. New England Journal of Medicine, May 24, 2001.

5. "Danish researchers take aim at 'placebo effect' – Scientists find dummy pill to be of little or no value," Associated Press, printed in The Daily Progress newspaper, Charlottesville, VA, May 24, 2001.

6. "Placebo problems: MSG dangers and deceptions,", October 6, 2003.

7. "The belief in vaccines," by Dr. Sherri Tenpenny (nationally renowned and respected vaccine expert), New Awareness Seminars, as cited in, August 2004.

8. "About alternative med," Cathy Wong, ND,, May 2005.

9. "Acupuncture not effective for Fibromyalgia: Study," HealthScout, July 2005.

10. "Guarded Response," Health Sciences Institute e-Alert, July 22, 2004.

11. The Four Pillars of Healing, book by Leo Galland, MD, 1997.

12. “People's Pharmacy,” National Public Radio health show, April 16, 2005.

13. “People's Pharmacy,” National Public Radio, July 2, 2005, show #548.

14. "What is a placebo?", November 2005.

15. "Prescribing a placebo," Health Supreme news blog, by Sepp Hasslberger,, November 2003.

16. Health Sciences Institute e-Alert, July 25, 2002.

17. "The nocebo effect: Placebo's evil twin," Washington Post Health, April 30, 2002.

* The disclaimer at is as follows: “Information on June Russell's Health Facts site is collected and condensed from various print and electronic sources. Though I make every effort to provide the correct information, I do not guarantee accuracy. I am not liable for errors, omissions, or use or misuse of information, services, or products mentioned on this site. I make no medical claims for the authenticity or efficacy of the information presented within this site or links to other sites. If you have, or suspect you have, an illness or medical condition, see your physician, naturopath, or other qualified health professional for diagnosis, guidance and supervision prior to self-treatment. By visiting or viewing this site you make a contractual agreement to all terms and conditions of this disclaimer.”


Note: The information provided here is not intended to diagnose, treat, cure, mitigate, or prevent any disease. If you have a health condition, see your physician for diagnosis and treatment advice. Never make any changes in your nutritional and other health support plans without your physician’s explicit review and consent. It is essential for you and your healthcare providers to work as a mutually-informed team.

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