Several years ago, University of Pittsburgh researchers gathered 237 adults and served them cocktails. They poured a cold, clear liquid from a Smirnoff vodka bottle into a pitcher and swirled in cranberry juice. The study participants, all moderate drinkers, were told the beverage contained alcohol, and each was given about a half hour to consume the drink. But: The researchers weren’t being totally straight up. The “vodka” was flattened tonic water. Result: All but one participant responded affirmatively when asked if they felt some degree of intoxication after finishing their nonalcoholic “cocktail.”
This is just one of thousands of studies conducted to investigate the placebo effect—a phenomenon that occurs when people experience improvements in symptoms or report other positive changes in how they feel after being given an inactive substance. Note: When negative changes occur, they are called the nocebo effect.
Bottom Line Personal spoke with internationally renowned placebo expert Luana Colloca, MD, PhD, MS, about the placebo effect and how it can be used in health care today. Her fascination with placebos began in the early days of her neuroscience education, when she was involved in an experiment involving Parkinson’s patients who had electrodes surgically implanted in their brains that allowed researchers to view their neuronal activity. These patients had been receiving injections of a dopamine-boosting drug designed to ease Parkinson’s symptoms such as rigidity. But while undergoing the surgery, they received an injection of a placebo…though they were told it was the real drug. Result: Their rigidity softened. Their brains displayed the same spike patterns associated with exposure to the actual medication. Takeaway: Patients’ reinforced expectations can be just as powerful as medication. Reinforced expectations refer to expectations associated with a prior therapeutic experience. In this case, the exposure to apomorphine prior to the injection of placebo.
Other placebo effect examples: Researchers at University of Pennsylvania found that 61% of study patients reported complete blockade of panic attacks after swallowing a sugar pill labeled “Xanax”…osteoarthritis sufferers told German researchers they experienced less knee pain after having acupuncture needles inserted in points that don’t correlate with knee pain…and patients perceived reduced cold severity and duration in a National Institutes of Health trial after they met with an empathetic doctor.
You don’t have to have a debilitating chronic condition like Parkinson’s to benefit from the placebo effect. You don’t even need to believe in the power of placebo to experience their impact. The body has its own inner pharmacy, capable of producing all manner of chemicals and compounds that mimic actual medications or substances used to manage specific symptoms. These are called endogenous compounds.
When using placebo treatments for pain, the relief reported by some individuals can be attributed to the release of…
Opioid neurotransmitters that modulate pain. Endorphins are one example of endogenous opioids. Morphine, codeine and fentanyl are synthetic opioids.
Cannabinoids—pain- and mood-improving compounds similar to those found in the Cannabis sativa plant.
How do we know these endogenous pain-relieving compounds are real and not just “in the patient’s head”? In a landmark study led by neuroscientist Jon Levine, MD, PhD, in the 1970s, patients who had just had their wisdom teeth removed were randomly assigned to receive intravenous morphine or a placebo (saline). About 40% of those in the placebo group reported significant diminishment of their pain. These people were dubbed placebo responders.
Dr. Levine and his team then surreptitiously added naloxone, a medicine that reverses and blocks opioids, to the IVs of the placebo responders. (Naloxone is an emergency drug used to rapidly reverse overdoses from opioids like heroin and fentanyl.) Adding naloxone reversed the pain-relieving placebo effects—the placebo responders’ pain levels increased almost immediately, reaching the same level of pain reported by those patients who did not initially experience relief when given a placebo. (Naloxone had no impact on placebo non-responders.)
Conclusion: Endogenous opioids largely govern placebo pain relief, indicating that patients aren’t just tricking themselves into feeling better.
While placebo effects are linked to physiological and biological changes, a patient’s beliefs and expectations help shape how he/she responds to placebos as well. Factors like the following all can make a difference, potentially activating or dampening the brain changes described above…
One familiar example of how expectations and previous experiences can influence biology: Russian physiologist Ivan Pavlov’s canine conditioning experiments. Dogs naturally salivate when they see food. By repeatedly pairing food with the sound of a bell, Pavlov eventually elicited the physiological response (salivating) from dogs solely from the tinkling of the bell, even with no food present. The expectation that food was coming was sufficient to trigger the physical response.
Modern-day example: A similar phenomenon drives the very human experience of smartphone addiction. The ping of an incoming text triggers a burst of the neurochemical dopamine, associated with pleasurable rewards. We quickly learn that looking at our phone feels good, and sooner versus later, we feel compelled to constantly check our phone with the hope of getting more dopamine hits.
This helps explain why, in a 2015 University of Pennsylvania study, chronic insomniac patients slept just as well regardless of whether they took a nightly pill containing 10 mg of zolpidem (Ambien)…or a nightly pill that they were told contained 10 mg of zolpidem but in fact only contained 5 mg.
An interesting concept gaining traction today is called open-label placebos (OLPs), in which patients receiving a placebo are specifically told, “This is a placebo.” Many researchers prefer OLPs because they eliminate ethical concerns over giving patients a placebo, which could compromise patients’ trust in their provider or possibly lead to medical harm.
In a 2018 University of Alabama at Birmingham study, open-label placebos improved cancer-related fatigue. In the study, 34 cancer survivors experiencing moderate post-treatment fatigue (four or higher on a one-to-10 scale) knowingly took pills that contained cellulose (plant fiber commonly used in foods and medications) but that had no active ingredients to relieve fatigue. After three weeks, these patients reported a 29% improvement in fatigue severity and a 39% improvement in the impact that fatigue had on their quality of life. Moreover, the benefits lasted for three weeks after they stopped taking the placebo pills. The effects were so meaningful that some study participants asked if they could receive more placebo pills. Noteworthy: It didn’t matter if the subjects believed in the placebo effect, meaning that it was the ritual of taking a pill—whether active or inert—that likely evoked the positive response.
OLPs have proven to have some degree of success for several conditions, including hot flashes, depression, migraines, chronic lower-back pain, allergies, irritable bowel syndrome and more.
The notion that we can activate our body’s innate healing properties to recover from illness or pain is exciting. The placebo response won’t heal a broken bone or cure a bacterial infection. It primarily works by improving symptoms of disease, subjective outcomes such as pain, anxiety, fatigue and the like. But besides improving quality of life, this could potentially reduce the need for costly medications, some of which have adverse or even toxic side effects.
One way to tap into the power of the placebo is to find health-care providers you trust. If you enjoy interacting with your doctor and he/she takes time with you, even better. A warm doctor-patient relationship in which you feel seen and heard can be extremely strong medicine.
In a 2015 Beth Israel Deaconess Medical Center clinical trial, acid reflux patients were randomly assigned to either a standard-length meeting (18 minutes, on average) with a doctor or an expanded meeting (42 minutes, on average). The longer meeting included the same questions as the standard one—reflux history, symptoms, prior evaluation and treatments, etc.—plus many other, more detailed ones delving into sleep, the impact of weather on the patients’ symptoms, what their reflux tasted like and more. The participants in the expanded meeting group experienced a 50% or greater improvement in symptoms over those in the shorter meetings. Best: Look for someone who is encouraging and reassuring while still being objective and realistic.
There’s also something to be said for being proactive in seeking help for what ails you. The feeling of I’m doing something can exert its own positive placebo effects. Examples: Many people who experience mood improvements when taking antidepressants do so because they expect the medication to help them. And consumers continue to purchase over-the-counter cold remedies containing phenylephrine even though the Food and Drug Administration has deemed it ineffective at relieving congestion.
You can even purchase your own placebo pills. One such product, Zeebo, has shown in randomized clinical trials to help with low back pain and COVID-related stress, anxiety and depression.
