Placebos

Key Points

  • Placebos are supposedly inert or “make-believe” treatments often used in clinical trials.
  • Rather than having no effect on health or well-being, placebos can produce measurable physiological responses.
  • No evidence yet shows any curative effect from placebos.
  • Nocebos—side effects or other effects not related to an active therapy—can also be physically observable.
  • How healthcare professionals frame expectations for therapies and treatments can greatly influence the outcomes.

Placebos have tremendous power to make us feel better—or worse. We might think that placebos—supposedly inert or “make-believe” treatments—have no real effect on our health. But that’s not what research is finding. So far, no credible evidence links a placebo treatment to cancer remission, tumor shrinkage or other curative effect on cancer. But other physiological responses can be clinically observed from placebos, including changes in heart rate and blood pressure, symptom relief and even their own unwanted side effects. These responses can take place even when patients know that the treatment they are receiving is a placebo.

Evidence shows that the expectations that healthcare professionals set with patients for treatments can greatly influence the outcomes of those treatments. By the same token, if we believe in a complementary cancer therapy that we choose to take, it may have the same active power to make us feel better. If a therapy makes us feel better, and reduces anxiety or depression, it may stimulate immune function. That may have an as-yet unreported effect on progression or regression of disease. Or, if we see an active chemotherapy or radiation therapy as a powerful force for healing, it may reduce side effects and help us tolerate treatment better.

Physiological responses can be clinically observed from placebos, including changes in heart rate and blood pressure, symptom relief and even their own unwanted side effects.

Don’t forget that part of the power of active treatments is also their placebo effect. Placebo is related to the healing use of imagery, to the healing effects of prayer, and to many other beneficial practices. Placebo, far from being just a sham treatment or a psychological “trick”, actually reflects our deep innate ability to mobilize self-healing—or, in the case of “nocebos”—to make us feel worse. So don’t dismiss or diminish the significance of placebo. They represent our innate ability to heal ourselves.

Nancy Hepp and Michael Lerner

Introduction

Placebos—substances or treatments with no known active therapeutic effect—are often used in clinical studies as the control treatment. Patients are given a pill, shot or other therapy that has no active ingredient. Patients typically do not know whether the treatment they are receiving is “active” or placebo. Placebo treatments simulate the attention from a professional, the rituals of taking a pill or using a treatment, and the expectations that patients have for benefit or harm from active treatment. Going through the motions and rituals of an active treatment but without the active ingredient allows researchers to determine the comparative effectiveness of the active ingredient or therapy. The assumption for decades has been that these placebo treatments would have no physiological effect on patients.

This assumption has come under question. While placebos are not yet known to shrink tumors or kill viruses, researchers have found that placebo treatments “can stimulate real physiological responses, from changes in heart rate and blood pressure to chemical activity in the brain, in cases involving pain, depression, anxiety, fatigue, and even some symptoms of Parkinson’s.”1

Placebo Effects

Non-cancer Conditions

Improvements with placebos have been seen with several non-cancer conditions:

  • Common cold2
  • Asthma3
  • Migraine headaches4
  • Low back pain5

Placebos and Cancer Symptoms

Placebos have been studied with common symptoms and side effects in cancer. In a study published in Nature Scientific Reports, cancer survivors who took placebo pills reported a 29 percent improvement in fatigue severity and a 39 percent improvement in the extent to which fatigue disrupts quality of life. This effect—which was clinically significant—was recorded even though patients knew the pills they were taking were placebos without any active ingredients. Patients’ perceived benefit from the pills did not depend on whether they expected the pills to have any effect or not. Moreover, some participants reported continuing benefits three weeks after they stopped taking the placebo pills.6

However, placebos show little use as a cancer treatment. As Kaptchuk and Miller state, “though placebos may provide relief, they rarely cure.” Instead, they primarily address subjective and self-appraised symptoms, including fatigue, nausea, hot flashes and pain.7

How Placebos Work: Theories

Placebos may activate and act through the same pathways that many common medications also act through.

Kaptchuk and Miller characterize placebo effects as “improvements in patients’ symptoms that are attributable to their participation in the therapeutic encounter, with its rituals, symbols, and interactions.”8 They postulate that placebo effects rely on complex neurobiologic mechanisms involving neurotransmitters (endorphins, cannabinoids and dopamine) and activation of specific, quantifiable and relevant areas of the brain (prefrontal cortex, anterior insula, rostral anterior cingulate cortex, and amygdala in placebo analgesia)—the same pathways that many common medications also act through. One study proposed “automatic neurological processes being a possible mechanism for the effects.”9 Genetics may play a role, with certain genetic signatures associated with response to placebos.

Nocebo Effects

Look Deeper: Classical Conditioning

Ivan Pavlov conducted the original experiments establishing classical conditioning as a physiological response. For several days, Pavlov rang a bell just before feeding his dog, and before long the dog began to salivate solely upon hearing the bell and before any food was presented. The dog was classically conditioned to anticipate food on hearing the bell, and its body responded.

Examples of possible classical conditioning during cancer treatment:

  • Reduced pain after taking a pill
  • Nausea upon arrival at the facility where chemotherapy is administered

While patients and clinicians may think that placebos could help patients address symptoms without the side effects of some therapies, placebos are not entirely free of side effects. Effects not related to the physiological action of treatment—called “nocebo” effects—can occur both with placebos and with active treatments. Nocebo effects are also seen if a symptom worsens instead of improves.10

Similar to placebo effects, nocebo effects are greater when patients have been told that symptoms may worsen, and greater yet when patients are classically conditioned to expect or experience pain or some other symptom (see at right). A 2014 meta-analysis of nocebo effects concluded that “the efficacy of future pain treatments may be enhanced if both positive and negative experiences with treatments are addressed in pain patients.”11 In sum, setting expectations with patients for treatments can greatly influence the outcomes of those treatments.

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