The Placebo Effect: Beyond the Sugar Pill

The Placebo Effect: Beyond the Sugar Pill | Food & Nutrition Magazine | Volume 10, Issue 2

A growing body of research suggests placebos may aid in the treatment of certain conditions and it may have more to do with context than with pills. And while findings are compelling, it has some experts questioning the ethics of placebo treatment.

Defining Placebo and Nocebo
The term placebo in health care dates to at least the late 1700s, when British physician William Cullen used the word to describe his administration of medications at a lower dose to patients with incurable disease. Cullen claimed he did this to please and provide comfort to his patients. Although there was no cure for their disease, he knew his patients expected a treatment and offering them medication provided satisfaction. Cullen employed what is now considered an “active placebo,” when a real drug is given at a sub-therapeutic dose.

In 1811, Hooper’s Medical Dictionary defined placebo as “any medicine adapted more to please than benefit the patient.” Today, Merriam-Webster defines placebo as “a usually pharmacologically inert preparation prescribed more for the mental relief of the patient than for its actual effect on a disorder.”

While a placebo generates positive effects, a nocebo does the contrary. According to Merriam-Webster, a nocebo is “a harmless substance or treatment that when taken by or administered to a patient is associated with harmful side effects or worsening of symptoms due to negative expectations or the psychological condition of the patient.”

Beyond a Pill
Talk of placebos may conjure images of sugar pills, but research suggests a pill isn’t the only thing inducing placebo effects. The very act of visiting a health care provider may be a form of placebo. The influence of the patient-provider relationship on health outcomes is considered “placebo-rapport,” or the placebo aspect of routine care when no therapeutic intervention is given. A therapeutic ritual or treatment, such as taking a pill at the same time each day as prescribed by a doctor, is considered “placebo-treatment.”

Many studies support the potential of placebo-treatment and placebo-rapport. One example is a randomized controlled trial of people with irritable bowel syndrome who were given acupuncture with dummy needles (placebo-treatment) and spent varied lengths of time with the practitioner (placebo-rapport). The group that spent the most time with the practitioner received a 45-minute initial consultation, during which the practitioner displayed “a warm, friendly manner” and employed “active listening (such as repeating the patient’s words, asking for clarifications); empathy (such as saying ‘I can understand how difficult IBS must be for you’); 20 seconds of thoughtful silence while feeling the pulse or pondering the treatment plan; and communication of confidence and positive expectation (‘I have had much positive experience treating IBS and look forward to demonstrating that acupuncture is a valuable treatment in this trial’).” Another group received a five-minute initial consultation where interaction with the practitioner was limited, and a third group received no treatment. of confidence and positive expectation (‘I have had much positive experience treating IBS and look forward to demonstrating that acupuncture is a valuable treatment in this trial’).” Another group received a five-minute initial consultation where interaction with the practitioner was limited, and a third group received no treatment.

After six weeks, the group with the highest level of interaction with a practitioner saw significantly greater results: a higher global improvement scale, higher adequate relief of symptoms, the largest declines in symptom severity score and the greatest increase in quality of life. The group that received the five-minute consultation reported better results (with the exception of quality of life) than the group that received no treatment at all.

Not only might the length of time spent with a practitioner impact health outcomes, but some studies suggest demeanor, words and attitude of a practitioner may have influence, noting poorer outcomes or nocebo effects in people whose doctor expressed doubt in a particular treatment or who had a negative demeanor.

Placebo-rapport also may enhance the efficacy of real drugs, not only placebos. For instance, one study found that when a pain medication was administered to patients without their knowledge, it had no effect. When the medication was administered again by a clinician with the patient’s knowledge, the drug was found to be more effective than placebo.

Ethics and Deception
The deception sometimes involved in using placebos — administering fake medications or providing a fake procedure without a patient’s knowledge or consent — has some wondering how ethical placebos in practice might be.

But recent studies have shown deception may not need to be a factor. For instance, a 2016 randomized controlled study examined the impact of “open-label placebos” — knowingly taking a placebo — on lower back pain. During this study, all participants were educated on placebo effects, including how powerful placebo effects can be, the potential impact of a positive attitude on inducing placebo effects and the importance of taking the placebo pills each day. Half of the participants took placebo pills, which were in a bottle labeled “placebo pills,” and the other half continued treatment as usual without taking placebo pills.

After three weeks, the open-label placebo group saw a significant reduction in pain and disability related to pain compared to the group who did not take the placebo pills. During interviews, some participants explained they experienced increased pain on a day when they forgot to take the placebo pills and one participant even said, “it worked so well that it has to contain something.”

A 2021 systematic review identified 11 studies involving open-label placebos and found significant positive effects of open-label placebos when compared to no treatment. The conditions identified as having positive results from openlabel placebos included seasonal allergies, IBS, chronic back pain, migraine, fatigue in cancer survivors, attention deficit hyperactivity disorder, menopause hot flashes and major depressive disorder.

Placebo Conditions
Placebos target symptoms — not diseases — particularly subjective or self-perceived symptoms. For example, a placebo will not cure cancer or shrink a tumor, but it might reduce a person’s perceived pain from radiation or nausea from chemotherapy. In general, placebos are shown to be most effective for psychological conditions and there are more studies showing promise for placebos in cases such as pain management, stress-related insomnia and cancer treatment side effects.

Mechanisms of Placebo
As research continues to test the possibilities of placebos, interest on exactly how placebos work is rising. Researchers believe the answers are in the brain.

To date, research suggests placebos work by activating specific areas of the brain involving autonomic responses, or involuntary bodily functions, such as heart rate, sweating or digestion; neuroendocrine responses, or fluctuations in hormones controlled by the hypothalamus–pituitary–hormone systems; and neurotransmitters such as cannabinoids, dopamine and opioids in the brain. Awareness of the person receiving the placebo has been a key factor in studies, showing a significantly reduced response to medications and placebos when an individual is unaware of its administration.

While many specifics concerning the biological processes of the placebo effect are still uncertain, it is evident that psychological factors play a role, including the beliefs and attitude of the person taking the placebo in addition to the context in which it is given, by whom it is given and the attitudes and beliefs of the administrator.

Implications for RDNs
It may be beneficial for registered dietitian nutritionists to make note of the influence of placebo-rapport and attempt to utilize its benefits. Authors of a 2019 paper provided a framework for employing placebo-rapport, stating the phenomenon can be broken down into two key factors: the patient’s or client’s belief that a practitioner (1) “gets it” and (2) “gets me,” meaning the practitioner demonstrates knowledge and competency but also displays genuine care, empathy and engagement.

Competency is further dissected into two factors: perceived competency as it relates to the specific patient or client — showing understanding of their family history, disease and treatment — and competency in general — the practitioner’s educational background, training and ability to confidently articulate concepts. The two-factor breakdown also is true for care and empathy. One factor is patient- and client-specific — taking interest in the patient’s or client’s life outside of a health care context, listening to their stories, understanding their values, practicing active listening and using their name — and then in general, being friendly to co-workers, smiling and engaging socially.

RDNs who work with patients or clients to help manage symptoms, such as those related to IBS or cancer treatments, may particularly benefit from the concept of placebo-rapport. By emulating behaviors of practitioners in placebo effect research, such as active listening, empathy and communication of confidence — behaviors also emphasized in motivational interviewing — RDNs can serve as a positive influence for their patients and clients, which may ultimately increase the success of their nutrition therapy and health outcomes.


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Esther Ellis
Esther L Ellis, MS, RDN, LDN, is an associate editor of Food & Nutrition Magazine.