This was a typical sentiment expressed by my pharmaceutical company colleagues when I asked for their opinion of the placebo effect, a phenomenon that was particularly relevant to our work given that the drugs we were developing would be tested in clinical trials.
This view was always offered amicably, but it underlined the assumption, held for decades, that the placebo effect was ‘all in the mind.’ If a patient who had been given a placebo in a drug trial got better, it was written off as part of the natural course of their illness—it would have happened anyway.
A placebo is an inactive (or dummy) treatment, in the form of a pill, injection or device, that’s administered in clinical trials to test the real drug or treatment against a control (comparison). A placebo isn’t designed to have any therapeutic effects on the patients who take it. However, in reality, it often does—and when this happens, it’s because the patients believe the placebo is the real drug or treatment: it’s their belief that does the work.
The placebo effect might appear to be an illusion, but science has shown that belief itself has real biological effects. In fact, there’s no question that belief causes chemical changes in the brain, and these changes are dependent on what a person believes.
For example, patients can believe opposite things about the same placebo and get opposite effects from it. If a patient believes that a pill (if it’s a placebo) will reduce pain, it will usually reduce pain. Yet if they had believed it would cause pain, it would have done that instead.
In the former case, the belief causes the production of the brain’s natural versions of morphine. In the US, scientists at the University of California at San Francisco showed that endogenous opioids, the brain’s own morphine, were responsible for the painkilling effects of placebos used during dental surgery.1 But crucially, the endogenous opioids are produced in response to a person’s belief or expectation that the pain will go away. If a patient believes that a pill (if it’s a placebo) will cause pain, the belief blocks these natural opioids in the brain, essentially elevating pain.2
A belief that a pill (if it’s a placebo) will help us relax will bring about a calming effect, yet if we believe it’s a stimulant, we’ll feel agitated and our heart rate and blood pressure will rise—even though, in both cases, the pill is a dummy. When a group of athletes was given substances that they believed would increase their strength and endurance, they did indeed gain strength and endurance. But the substances were placebos. Luckily, these ‘performance-enhancing placebos’ couldn’t get them banned from competition because they were, well, dummies.3
In other research, 40 patients with either asthma, emphysema or restrictive lung disease were given an inhaler containing a nebulized saline placebo but were told it contained allergens that would restrict their airways.4 Before long, 19 of the patients reacted with considerable constriction of their airways. Twelve had a full asthma attack.
When the same participants were given a different inhaler and told it would relieve their symptoms, even though it was also a saline placebo, it did relieve their symptoms.
Therefore, that one placebo inhaler either reduced or created bronchospasm in asthma sufferers, depending on what the patients believed it would do.
It’s also possible to use color as a placebo because of what it represents to us. University of Cincinnati medical professors gave a class of students pink and blue placebo pills and told them that they were stimulants and sedatives.5 It was found that the blue pills were 66 percent effective as sedatives, compared with 26 percent for the pink pills.
In other words, blue placebos were around two and a half times better than pink ones for helping people to relax. This is because for most people, blue is a calming color, and this informs some of what we believe it will do.
The way a placebo is packaged also affects its power. In a study at Keele University in the UK, 835 women were given one of four different pills for headache.6 One group received a well-known branded aspirin tablet, a second group received an aspirin tablet simply labeled “analgesic,” a third group received a placebo packaged like the name-brand aspirin, while a fourth group took a basic unbranded placebo labeled “analgesic.”
The branded aspirin worked better than the unbranded one, and, amazingly, the branded placebo worked better than the unbranded placebo—even though they were both made of sugar.
This explains why so many people swear that branded painkillers such as Nurofen or Advil work better for them than generic ibuprofen, even though they contain the same drug. There’s a significant price difference, and Nurofen has more expensive-looking packaging, so people expect more from it. Drugs are designed to carry out a biological function, but as well as the impact of a drug on the body, the mind also has an impact.
In some cases, the mind can enhance the effects of a drug—depending on what the patient believes it’s supposed to do, or on their perception of the doctor who prescribed it—and in other cases it can suppress the effects, in accordance with what they believe. We know this because some of the variation in the placebo effect simply comes down to communication between medical staff and patients.
For relatively common ailments, a doctor who shows confidence or optimism about the patient’s recovery is much more likely to see them get better than one who is unsure or pessimistic. For example, based on research showing that no firm diagnosis is made for about 40–60 percent of patients visiting general practitioners, a University of Southampton study investigated the consequences of different styles of consultation among patients in this category.
The researchers compared the outcomes of 200 patients, half of whom received a consultation conducted in a ‘positive’ manner while the other half received a consultation conducted in a ‘non-positive’ manner.7
In the ‘positive’ consultations, the patients were given a firm diagnosis and confidently told they would recover in a few days’ time. Sometimes a prescription was given, and the doctor assured the patient that it would make them better. If no prescription was given, the doctor assured the patient that none was needed.
In the ‘non-positive’ consultations, the doctor displayed uncertainty, saying, “I cannot be certain what is the matter with you.” If the doctor offered a treatment, they would add, “I’m not sure that the treatment I’m going to give you will have an effect.” If no treatment was given, the doctor would instead add, “and therefore I will give you no treatment.”
The prescription given was 3 mg of vitamin B1, marked “thiamine hydrochloride,” a very low dose that was essentially a placebo. After two weeks, 64 percent of the patients who had received the positive consultation were better, compared with only 39 percent of the patients who had recovered after receiving a non-positive consultation.
And it didn’t matter whether they were treated or not. The difference in how many patients recovered, almost double, was down to the way the doctor communicated with the patient.
Why does belief cause these effects? Painkilling placebos work because the person expects to feel a reduction in pain. This expectation causes their brain to produce its own natural painkillers, which then reduce the pain.
Studies at the Neurodegenerative Disorders Center at the University of British Columbia have shown believing a placebo is an anti-Parkinson’s drug causes the brain to produce the neurotransmitter dopamine.8 Here, as with painkilling effects, belief mobilizes the brain’s natural resources to meet the person’s expectations. That is, a belief about what’s supposed to happen instructs the brain to produce what it needs to produce to deliver that result.
Of course, this applies only within reason. Belief that a placebo is a chemotherapy drug doesn’t make the brain produce its own chemotherapy drug, and there could never be an ethical case to experiment with this. However, some documented spontaneous remissions in patients may have occurred because belief, or faith, mobilized the immune system.
The real versus imaginary phenomenon is much more widespread than is generally understood. The brain produces stress hormones regardless of whether we’re in a stressful situation or imagining one. It’s the feelings of stress that trigger the release of stress hormones such as adrenaline and cortisol, independently of the situation itself.
For example, two friends are sitting in a car stuck in traffic. One feels stressed at the thought of being late for her appointment, while the other knows that she can’t do much about it, so she relaxes. The first woman will have elevated cortisol and adrenaline levels. The second won’t. These levels have little to do with the situation itself, and much more to do with how each individual feels about the situation.
The same kind of thing happens with kindness. Most of us assume that the opposite of stress is peace, calm or a feeling of relaxation, but these states represent the absence of stress, not its opposite. The opposite of the feeling of stress is the feeling induced by kindness.1
In research that recorded people’s daily stress score and the approximate number of kind things said or done, stress and kindness sat opposite each other: as if on a seesaw, as kindness went up, stress came down, and vice versa. This doesn’t mean that kindness causes an absence of stressful events, only that both feelings can’t coexist, and so as we increase feelings induced by kindness, these take some of the sting out of normally stressful events.
Therefore, if you want to reduce stress, try kindness.
In a study of how packaging influences a treatment’s effectiveness, 835 women were given one of four pills for a headache: an aspirin tablet from a well-known brand, an aspirin tablet simply labeled ‘analgesic,’ a placebo packaged to look like the branded aspirin, or a basic unbranded placebo labeled ‘analgesic.’ Not only did the branded aspirin outperform the unbranded one, but, amazingly, the branded placebo worked better than the unbranded placebo by an even larger margin—even though they were both made of sugar
At the Heart Center of the University of Marburg in Germany, 124 patients scheduled for coronary artery bypass graft surgery were randomly distributed into three groups: the ‘Expect’ group, where the focus was on optimizing patients’ positive expectations of life after surgery, such as engaging in activities; the ‘Support’ group, where patients received emotional support; and the ‘Standard medical care’ group, where patients received the usual treatment.9
Six months after their surgery, patients in the ‘Expect’ group had a much greater quality of life and subjective working ability than those in the other two groups. Support was helpful too, but expecting that things would go well had by far the greatest effect. When doctors give hope to patients, helping them to expect to get better, they do get better faster.
Two hundred patients were treated with either a placebo or nothing at all, but half had “positive” consultations, where the doctor was confident they would soon recover, while half were “non-positive”—the doctor expressed uncertainty in the treatment. After two weeks, 64 percent of patients in the positive group were better, compared with only 39 percent in the non-positive group.
Just as feelings of stress produce stress hormones, kindness has its own biological products. I call these kindness hormones, the main one being oxytocin. Well-known for its importance in reproduction, breastfeeding and even social bonding, oxytocin also plays many other key roles in the body.
Just as stress hormones increase blood pressure, oxytocin lowers it. Oxytocin also has antioxidant and anti-inflammatory properties, helps with digestion and wound healing, and is even involved in the construction of heart muscle and many other cell types from stem cells.
What this means is that all these functions are impacted by how kindness feels, just as many functions in the brain and body are impacted by how stress feels.
Most prior work in this area of research has charted the course of stress through the brain and body. We’re only now beginning to examine the side-effects of positive feelings, and they’re plentiful. Psychologically, positive feelings increase happiness, build resilience and protect against depression. They impact brain function and even cause neurological changes if they’re experienced over a period of time; they also reduce inflammation and even help us live longer.
Just as your brain doesn’t distinguish between a real stressful event and an imagined one, it’s the same with kindness. Your brain will produce kindness hormones when you’re being kind, witnessing an act of kindness, imagining one or even recalling one. In each case, you feel how kindness feels, and your feelings trigger the physiological effects as a consequence. Thinking of things that annoy us fuels feelings of stress, and subsequently the physiology of stress. Thinking kind things about people, which generates kind feelings, can be a simple way to reduce stress.
An exciting line of research into harnessing the placebo effect is placebo-controlled dose reduction (PCDR), where scientists give a drug for a few days and then, without the patients’ knowledge, swap it for a placebo. The more times the patients receive the drug, the more strongly they associate their relief of symptoms with receiving the drug, and so the stronger the effect of the placebo when the swap is made. In this way, the drug’s dosage can be reduced and eventually replaced by a placebo.
Professor Fabrizio Benedetti of the University of Turin Medical School in Italy powerfully demonstrated this effect with a study involving Parkinson’s disease patients.10
The patients were split into several groups. All but one group received a full dose of the anti-Parkinson’s drug apomorphine on day 1 of the study, and Benedetti measured their clinical response as a reduction in tremors and muscle stiffness as well as in the degree of activation of individual neurons in the brain region known to be affected by the condition. He gave the other group a placebo injection (saline) instead, and there was no clinical effect whatsoever.
Over the next few days, Benedetti swapped the drug for the placebo. One group who got the drug on day 1 received the placebo on day 2. Another group received the drug for two days, and it was swapped for the placebo on the third day. Yet another group received the drug for three days before it was swapped for the placebo on day 4.
Each time a patient received a dose of apomorphine, they had the experience of “when I receive this injection, my tremors reduce, and my muscle stiffness lessens,” and each day, the effect of the placebo became stronger.
On day 5, Benedetti did the drug-placebo swap for the final group, who had received apomorphine on the previous four days and built up the most experience with the drug. Amazingly, the strength of the saline placebo matched that of the drug, reducing tremors and muscle stiffness and activating neurons to the same degree.
Benedetti reported, “It should be noted that placebo administration following four apomorphine preconditioning trials induced clinical responses that were as large as those to apomorphine.”
These results weren’t just ‘all in the mind’ because there were measurable changes in the brain in the region that’s usually deficient in dopamine in Parkinson’s patients.
The same kind of effect has also been demonstrated with the immune system, where a phased swapping of an immunosuppressant drug (cyclosporin A) for a placebo suppressed the immune system.11 PCDR works because expectation and belief cause physical changes in biochemistry.
The aim of this line of research on the immune system is to help patients receiving organ transplants and those with autoimmune conditions such as multiple sclerosis (MS), rheumatoid arthritis and lupus. Ultimately, if PCDR could be applied to a larger range of medical conditions, it could result in a huge cost savings, allowing funds to be funneled into other areas of healthcare.
PCDR may also reduce the side-effects of medication. In one PCDR study, children with ADHD who had 50 percent of their drug dose swapped with placebo experienced fewer stimulant-related side-effects.12
In a pioneering study on the power of visualization, one group of volunteers was asked to play a sequence of five notes on a piano every day for five days, while a separate group did the same thing for the same amount of time, only without a piano. Instead, they closed their eyes and imagined they were playing the five notes in this sequence. All the participants had a brain scan every day, and at the end of the five days, the brain region that corresponded to the muscles of the fingers had changed substantially in both groups. In fact, the brains of the people who had practiced on a real piano were indistinguishable from those who had simply imagined playing the notes
To a large extent, the brain doesn’t distinguish real from imaginary, and this underpins some aspects of the placebo effect. When you imagine that something is happening, it really is happening as far as your brain is concerned, and it releases the chemical substances necessary to confirm that what you’re imagining is indeed real.
One of my favorite scientific studies is affectionately known as the piano study.13 In 1995, Alvaro Pascual-Leone, a professor of neurology at Harvard Medical School, asked a group of volunteers to play a sequence of five notes on a piano every day for five days. Each session involved playing notes for two hours, one note with each finger of the hand, moving up and down a scale of five notes.
While the volunteers did this, a separate group did the same thing, only without a piano. They closed their eyes and imagined that they were playing the five notes in this way. This is called kinesthetic imagery, and it’s where we recreate movement by vividly imagining how it feels to move.
Each volunteer had a daily brain scan, and at the end of the five days, those who had played the notes on the piano had considerable changes in the brain region connected to their finger muscles; however, the same was true of the volunteers who had imagined playing the notes. In fact, on comparing the scans, it wasn’t possible to tell whether a scan came from a person who had played the notes with their fingers or with their mind.
It was already known at the time of the piano study that athletes could enhance their performance by practicing visualization, but this was the first brain-imaging confirmation of what’s actually happening when a person visualizes something. The prevailing belief among sports coaches was that visualization worked by enhancing an athlete’s focus and their motivation to train and practice. Any notion that the brain was actually changing was dismissed as pseudoscience.
Following copious amounts of research, it’s now well understood that the optimum way to enhance performance in any sport or movement is to combine physical practice with visualization. Studies show that physical practice plus visualization is more effective than physical practice alone, which is better than visualization alone.
The key to making visualization work is repetition, which has been shown to impact brain networks, shaping them toward producing what it is we’re imagining. My first experience of this kind of repetition was positive affirmations, which do something similar. The Psychology Dictionary defines an affirmation as “a brief phrase which is spoken again and again in an effort to plant seeds of happy and positive notions, conceptions and attitudes into
one’s psyche.”1
In the late nineteenth century, the French psychologist Emile Coue noted that his patients often recovered faster if he helped them to expect to get better. So he developed what he called autosuggestions, the best known of which is “Every day, in every way, I’m getting better and better.”
Nowadays we refer to autosuggestions as positive affirmations, or as positive self-affirmations when they affirm our core values. They help us to think and feel more positively and, as a consequence, take positive affirmative action.
Serious research into affirmations began in the 1980s, when the American social psychologist Claude Steele published a paper on his self-affirmation theory.2 This posits that humans are fundamentally motivated to maintain a positive self-view—that is, a general perception of ourselves as good, virtuous, competent, stable, capable of free choice and having a sense of control over important outcomes in our lives. Self-affirmations, then, are statements that affirm our core values; for example, if one has a core value of kindness, the affirmation would be something like, “I am a good person.” Research has shown that when we state something that affirms our values in this way, it makes us think and feel more positive; we’re also much more likely to indulge in healthy behaviors and to take positive steps to improve our lives. This is especially the case when affirmations are repeated.
This kind of practice has also helped hundreds of people to recover faster after a stroke. In multiple studies, stroke patients received either standard physiotherapy or physiotherapy plus visualization, and those who added visualization to their physiotherapy improved to a greater degree and much faster than those who did physiotherapy alone.
For example, in a University of Cincinnati study, after each physiotherapy session, chronic stroke patients listened to a tape that guided them through visualizations of moving the hand, arm and shoulder of their impaired side.14 When tested after six weeks, the patients’ arm function was significantly better than that of patients in a control group who did relaxation after physiotherapy.
A large meta-analysis has since referred to visualization as a “viable intervention” for people recovering from a stroke.15 Further analyses suggest that in some stroke patients, visualization even helps repair some damaged brain regions. In others, the area responsible for movement switches to a new brain location that isn’t damaged, permitting neuroplasticity there and a return to more able movements.
In one study, researchers reported that the brains of stroke patients who used visualization had undergone some degree of cortical reorganization as a consequence of their mental practice.16
Research is revealing that the division between real and imaginary, as far as the brain is concerned, is becoming increasingly blurred. Following evidence that volunteers were able to raise immune system antibody levels by visualizing their increase, researchers at the United Lincolnshire Hospitals NHS Trust in the UK conducted a randomized controlled trial of women receiving treatment for breast cancer.1
All the women received their scheduled treatment (chemotherapy, surgery, radiotherapy and hormone therapy), but half also did daily visualization sessions that involved visualizing the immune system destroying cancer cells. Many imagined their immune cells as piranha fish or even as a Pac-Man character. Some visualized macrophages gobbling cancer cells.
The women in the visualization group were found to have much higher levels of key immune cells, such as natural killer cells, T cells and T helper cells, than those who didn’t visualize, even after four cycles of chemotherapy. The researchers reported that the immune system was still showing high cytotoxicity against cancer cells after the four cycles, but only in the women who were visualizing their immune cells destroying cancer cells.
Adapted from Why Woo-Woo Works: The Surprising Science Behind Meditation, Reiki, Crystals, and Other Alternative Practices, by David R. Hamilton, PhD (Hay House, 2021).
Main Article
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Healing with kindness
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References |
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1 |
David R. Hamilton, The Five Side Effects of Kindness (Hay House UK, 2018) and The Little Book of Kindness (Gaia, 2019) |
Positive affirmations
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psychologydictionary.org/affirmation/ |
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Adv Exp Soc Psychol, 1988; 21: 261–302 |
Visualization against cancer
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References |
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1 |
Breast, 2009; 18: 17–25 |
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