‘The outer conditions of a person’s life will
always be found to reflect their inner beliefs.’
JAMES ALLEN
Imagine if scientists discovered a new drug that could improve the symptoms of (and in some cases, heal) the majority of known medical conditions – just one pill! It would make headline news all around the world and become the greatest-selling drug of all time. Yet such a thing already exists. Let me introduce you to the placebo!
A placebo is a dummy drug – a sugar pill – that’s made to look just like a real drug. It’s used in medical trials so that the drug can be tested against a control. Being a control, it’s not supposed to do anything – but it does, and it’s because patients believe it’s a real drug. It’s their belief that’s doing the work!
The placebo effect has evolved from being thought
of as a nuisance in clinical pharmacological
research to a biological phenomenon worthy of
scientific investigation in its own right.
These are the words of Fabrizio Benedetti, a neuroscience professor at Italy’s University of Turin School of Medicine who is a world authority on the placebo effect and is reported to have the most advanced placebo study lab in the world.
Since the advent of brain-imaging technology, there’s been a surge of interest in the placebo effect. Research now shows that for some conditions that have been well studied, like pain and Parkinson’s disease, for example, when a person believes that they’re taking a drug, but it’s really a placebo, their brain lights up as if they really were taking the drug and produces what it needs to produce to give them what they expect to happen.
In other words, if they expect a relief of pain, their brain produces its own painkillers; or if they expect to move better, as in the case of Parkinson’s patients, their brain produces dopamine.
The symptoms of Parkinson’s disease arise from an impaired production of dopamine in part of the brain, which affects movement. Research has now shown that Parkinson’s patients given a placebo but told that it’s an anti-Parkinson’s drug are able to move better. Brain scans show brain activation in the area that controls movement, and dopamine is actually produced in the region normally deficient. The improved movement is not just a ‘psychological’ thing. It’s a physical release of dopamine in the brain.
The production of chemicals in the brain when a person takes a placebo was first shown in 1978, when scientists at the University of California at San Francisco showed that placebo analgesia (when a person gets pain relief from a placebo) occurs because the brain produces its own natural analgesics (painkillers). It was found that these were opiates, like morphine, but they were the body’s own natural versions of morphine, which are referred to as endogenous opiates. More modern research is beginning to show that the same kind of thing happens when placebos are given for many other conditions – the brain produces a natural ‘drug’ that delivers what the person expects to happen.
There are thousands of natural substances in the brain and body. In the words of Dawson Church, author of The Genie in Your Genes,
Each of us holds the keys to a pharmacy containing
a dazzling array of healing compounds: our own
brain… Our brains are themselves generating drugs
similar to those that the doctor is prescribing for us.
In a 2005 scientific paper published in the Journal of Neuroscience, Fabrizio Benedetti wrote that ‘… placebo effects seen with different treatments are more likely to track closely with the active treatment to which they are experimentally paired’.
In other words, if a person is given a drug to treat a condition and then it’s secretly swapped for a placebo, the chemicals produced are believed to be natural versions of the drug that was originally used. If it’s a painkilling drug, the brain produces natural painkillers. If it’s an anti-Parkinson’s drug, the brain produces natural anti-Parkinson’s drugs: that is, dopamine.
Similarly, studies on depression suggest that the brain produces natural antidepressants. For instance, brain scans have now shown that taking a placebo in place of the antidepressant fluoxetine (Prozac) affects most of the same brain areas as the actual drug.
This is mind over matter at the molecular level. No longer can the placebo effect be dismissed as a figment of people’s imagination – just ‘all in the mind.’ As a former scientist in the pharmaceutical industry, I know that this is how it was generally referred to: ‘It’s all in the mind,’ or ‘It’s just psychosomatic,’ were common phrases I heard. Now we know that what’s going on in the mind actually alters our biochemistry.
When you believe something, chemicals are often produced in your brain that give you what you believe should happen.
The placebo effect is often quoted at 35 per cent, and we think this means that it works 35 per cent of the time. But this is a very broad generalization. It actually varies tremendously depending upon the illness, the nature of the medical trial, the language used by the person prescribing or dispensing the medicine, how a clinician dresses, their age, whether they have grey hair or wear glasses, and even the personality of the doctors giving the medicine – and of course the desire of the patient to get better and how much they believe that they will get better.
The placebo effect can vary from as low as 10 per cent to as high as 100 per cent in some cases. The higher figures indicate that the capacity to affect our own healing is much greater than we’d ordinarily think. In some placebo studies, that ability has been tapped into more than it has in others.
A lot of placebo research has focused on pain, partly because it’s easy to study in that we don’t have to wait until someone is in pain to study it, but can induce it experimentally. In one Canadian study that induced heat pain in volunteers, more than 70 per cent of them had relief from their pain after they took a placebo. And MRI brain scans showed a reduction in activity in regions of the brain that are pain-responsive.
Placebo effects are common and sometimes high with some heart drugs. Many scientists believe that this is due to the strong brain–heart link. In 2007 a drug company reported results of a trial for a new drug for congestive heart failure. Tests showed that the drug improved the condition of 66 per cent of patients, which is very good. But the placebo improved 51 per cent of patients.
In a trial of the cholesterol-lowering drug clofibrate, which was used extensively in the 1980s and 90s, the five-year survival rate for patients on the drug was 80 per cent. The placebo was 79.1 per cent.
In a 1997 study of drugs used to treat benign enlargement of the prostate gland, more than half of the men on the study had a significant reduction of their symptoms after receiving placebos.
Placebo effects are also known in the treatment of chronic fatigue. In a 1988 trial of the drug acyclovir as a possible treatment for chronic fatigue syndrome (CFS), conducted by scientists at the National Institute of Allergy and Infectious Diseases in the USA, 46 per cent of people improved on the drug and 42 per cent on the placebo.
In a 1996 study that trialled the steroid hydrocortisone as a possible treatment, 50 per cent of people improved on the placebo. One woman in her thirties with severe CFS who was ‘very significantly impaired’, had ‘no energy, couldn’t work and spent most of her time at home’ showed a remarkable recovery after receiving placebos.
Results like these don’t mean that the disease isn’t real, as some people believe in the case of CFS, which is also known as myalgic encephalomyelitis (ME). Similarly, sometimes we assume that a drug doesn’t work if it’s little better than a placebo. But this isn’t always entirely correct. Sometimes, a person’s belief or expectation of recovery can do such a good job that it can mask the effect of a drug.
Research has even shown that the same substance can act as both a placebo and a nocebo (the nocebo effect is the opposite of the placebo effect, where a patient develops negative symptoms). In a 1969 paper published in Psychosomatic Medicine, 40 asthmatics were given an inhaler containing a placebo (water vapour) but were told that it contained allergens that would cause bronchoconstriction (constriction of the airways).
Nineteen of them (48 per cent) then suffered considerable constriction of their airways, with 12 of the group experiencing a full asthma attack. But when they were then given another inhaler and told that it would relieve their symptoms, it did, even though it also contained water vapour.
One person in the study was told that the inhaler contained pollen. She then swiftly developed hay fever as well as airway constriction. In a second experiment she was told that the inhaler just contained allergens but no pollen. This time she only developed asthma symptoms. In a third experiment she was again told the inhaler contained pollen and once again she developed hay fever as well as asthma.
These kinds of observations teach us something very important about the mind’s ability to impact the body. A thought or belief isn’t just ‘all in the mind’. The mind is more than something we use to interpret the world. A thought or belief isn’t something nebulous that kind of floats off into the ether. Mind and emotions impact the physical state of the body. They can even enhance performance.
A 2007 placebo study described an experiment that simulated an athletics competition involving non-professional athletes who had regularly been given morphine in training (for the study). On the day of the competition, however, the morphine was secretly swapped for a placebo.
Yet when they competed, the athletes’ performance was at the same level as it would have been if they’d actually taken morphine. The body naturally produces its own drugs, although they aren’t drugs in the anabolic steroids sense but natural substances that, in this case, might help us to perform at high levels.
A 2007 study conducted at Harvard University even found that people who get the same level of exercise receive different benefits from it depending on whether they believe it’s good exercise or not.
The study involved 84 hotel-room maids whose job actually provided enough exercise to exceed the US Surgeon General’s recommendation for daily exercise. However, the women didn’t know this and most didn’t see themselves as physically active at all. In fact, when the scientists surveyed them, they learned that 56 of the women didn’t believe that they got any exercise at all. So, they split the women into two groups.
With one group, the scientists went through with the women all of the activities that they did during the day, from lugging heavy equipment around, vacuuming and changing bedsheets to general cleaning, and pointed out that they were getting a lot of exercise, sharing with them how many calories each activity burned. They told the women that their daily activities actually exceeded the Surgeon General’s recommendations. They didn’t tell the other group anything.
After a month, the scientists took physical measurements of the women. The group who now knew that they were getting good exercise had lost weight and there was a decrease in their waist-to-hip ratio, body mass index and body fat percentage, and a 10 per cent reduction in their blood pressure. It’s a powerful thing, the mind!
The things that you believe can even affect your academic performance. A 2006 study published in the journal Science examined the mathematics scores of 220 female students who had read one of two different fake research reports. Half read a fictitious report claiming that scientists had discovered genes on the Y chromosome (which only men have) that gave men a 5 per cent advantage over females in mathematics. The other fake paper claimed that men had a 5 per cent advantage only because of the way teachers stereotyped girls and boys at an early age.
When the students were tested, the group who believed that the difference was just stereotyping did much better than those who thought that they had a genetic disadvantage.
The placebo effect is often seen as a nuisance in medical trials. Therefore, some companies try to remove it in an attempt to get a more accurate picture of how well the drug works. But things don’t always go to plan.
In a typical trial, patients are given either a drug or a placebo. The ones who improve on placebo are called ‘placebo responders’ and are then removed from the trial. A new trial then begins that doesn’t have any known placebo responders. But some studies have shown that if, say, 35 per cent of people improve on placebo in the first trial, then in the second one, even though the placebo responders have been removed, a new 35 per cent of patients still respond to the placebo.
This is a total enigma for many companies who set up the trials. But the reason for this result in these trials lies in the only factor that hasn’t changed between the two studies – the doctors! They still say the same things and communicate with the same enthusiasm from one study to the next. What they say, how they say it, their enthusiasm for the treatment and how they relate to the people receiving it matters a lot.
For example, in a 1954 study, patients with bleeding ulcers were given water injections but told either that the injections would cure them or that they were being given experimental injections of undetermined effectiveness. Of the patients who were told that the injections would cure them, 70 per cent showed excellent improvement. But of the group who were told that it was an experimental injection, only 25 per cent improved.
In another study, Fabrizio Benedetti tested the effects of a hidden placebo on arm pain. When a placebo was secretly given through a saline drip, the pain level didn’t change. But when a placebo injection (of saline) was given in full view of the patients and they were told, ‘I’m going to give you a painkiller. Your pain will subside after some minutes. Be calm and comfortable and report your pain sensation during the next minutes,’ the pain diminished.
In a 1978 study involving dental injections, patients were given either an ‘oversell’ message about a placebo tablet they received before an injection in the mouth, where the dentists made the drug sound really great, or an ‘undersell’ message where the dentists made out that the drug might or might not work. The patients who had the oversell message had much less pain when they had their injection, as well as less anxiety and fear, than the patients who were given the undersell message.
And in a 1987 British Medical Journal paper titled ‘General practice consultations: is there any point in being positive?’ 200 patients were given either a positive consultation or a negative one (for minor ailments). For the positive consultations, the patients were told what was wrong and that they would be better in a few days. For the negative consultations, the doctors told them that they weren’t certain what was wrong.
Two weeks later, 64 per cent of those who had a positive consultation reported that they were better, but only 39 per cent of the negative consultation patients reported being better. The ‘power of positive consultation’ was almost twice as good as the power of a negative one.
Knowing how enthusiastic to be in conveying a message can be a challenge for today’s doctors. On the one hand, they know that what they say counts, but on the other hand they have to be responsible in conveying the truth about what the drugs have been proven to do, including their limits. But what they say clearly matters, as does how they say it. Current research shows that language, mannerisms, empathy, warmth and authority, as well as enthusiasm and confidence, have a considerable effect.
More research is needed to permit the doctors more freedom in what they can and can’t say, as well as in what’s the most effective way to say something. But it’s up to you what you believe. A lot of power lies within you. And by this I mean that you have the ability to think, feel and believe, and your thinking, feeling and what you believe can affect your biochemistry.
Although some of these results point to the power of a doctor’s personality, the personality of the patient also affects how they receive the message and therefore how well the placebo works for them.
Between 2005 and 2007, scientists at the University of Toledo in Ohio, USA, compared the responses of optimists and pessimists to placebos. Over a series of experiments, they gave the optimists and pessimists a tablet (placebo) and told them that it would make them feel unwell. The pessimists responded more and felt more unwell than the optimists. Then the scientists gave the optimists and pessimists placebo sleep treatment and told them it would make them sleep better. This time, the optimists responded more and slept better than the pessimists.
Optimists are more likely to benefit from something that’s going to make them better, while pessimists are more likely to respond to something that’s supposed to make them worse.
We can boost the power of the placebo, and one way is through what’s called conditioning. In a typical conditioning experiment, scientists give a patient a real drug for a couple of days and then secretly swap it for a placebo on the following day. Of course, the patient doesn’t suspect anything, so when they receive their ‘medicine’ (placebo) they expect to get the level of relief they’ve been getting when taking the actual drug. And they do. They’ve been ‘conditioned’ to believe that each injection or tablet will work, just as Pavlov’s dogs were conditioned to salivate when they heard a bell ring.
Studies suggest that the longer conditioning is carried out, the more powerful the effect; the deeper into the body’s systems the mind can penetrate, the more powerful the placebo becomes. In some conditioning experiments the placebo effect has been boosted to 100 per cent – that is, everyone is affected.
In one experiment, scientists gave volunteers a flavoured drink containing a chemical called ‘cyclosporin A’ that suppressed the immune system. Each time the volunteers took the drink, their immune systems weakened. After several days the scientists swapped the drink for one that didn’t contain any ‘cyclosporin A’, but the volunteers still developed weakened immune systems. If, on the first day, the scientists had given the patients a drink and told them it would weaken their immune system, it wouldn’t have had as much of an effect. The placebo effect would have been less.
Similarly, in an experiment conducted by Fabrizio Benedetti where volunteers were given a placebo and were told it was a drug that would reduce pain, it reduced pain levels. But when the scientists told the volunteers that the drug would increase growth hormone levels, it had no effect. To alter growth hormone levels, the scientists needed to boost the power of the placebo.
They conditioned subjects with a substance called sumatriptan, which is known to boost growth hormone levels. After a few days of taking sumatriptan, which resulted in increased growth hormone levels, the patients secretly received a placebo instead. Yet their growth hormone levels still increased. On the first day the placebo had no effect, but, through conditioning, the mind had associated taking sumatriptan with changed hormone levels, even though the subjects weren’t consciously aware of the changes.
In 2016, Fabrizio Benedetti of the University of Turin School of Medicine in Italy showed that Parkinson’s disease patients could be given placebos instead of full doses of the medicine apomorphine.
If a patient was given a placebo right away, without any previous experience of apomorphine, it didn’t produce any clinical result. But if a person had received one or more prior doses of apomorphine, the placebo worked. And it worked in proportion to the number of prior doses the person had received.
In other words, it seemed that their brains learned. For example, if the person had received two prior doses of apomorphine, the placebo worked better than if they’d received just one dose. But if they’d received three or four prior doses, then the placebo was even stronger. The strength of the placebo increased according to the number of prior doses of apomorphine a patient received.
Clinical improvements were measured as changes in muscle rigidity at the wrist and also in the activity of single neurons in the brain. When patients received placebos, muscle rigidity reduced and individual neurons in the brain increased in activity. Amazingly, if patients had been given four prior injections of apomorphine before their placebo, the clinical and neuronal improvements were as good from a placebo as they were from apomorphine itself.
In another study, patients were given morphine for three days and it was secretly swapped for a placebo on the fourth day. The patients received the same level of pain reduction as they did when they were given morphine.
The implications of this are many, but they include the fact that for some conditions, a person could be weaned from a drug and have it replaced by a placebo. The placebo might not replace the drug entirely, but it might reduce how much of the drug the person needs to take. In so doing, it could save health services around the world huge amounts of money, which could be put to good use in improving patient care in other areas.
At the time of writing this chapter, as well as for Parkinson’s disease and pain, Placebo Controlled Dose Reduction (PCDR), as it’s known, has been shown to work in small trials for ADHD, psoriasis, some allergies, and conditions that require a suppression of the immune system, including lupus and multiple sclerosis. It’s even being considered for use in avoiding transplant rejection.
The brain contains trillions of neural circuits that are linked to every part of the body. We condition our neural circuits to fire over and over again, so when we take a pill or have an injection, even though it’s a placebo, the same circuits fire as when we took the drug. This is because our unconscious awareness associates the pill or injection with immune or hormonal changes, as the two studies described above show.
If we tried to consciously affect our growth hormone levels, dopamine levels or immune systems we might not have much success (although you’ll learn how to impact the immune system later in the book). Conditioning boosts the power of placebos or the power of the mind; it allows us to change systems in the body that we wouldn’t ordinarily be able to. It really shows that we have considerable power to affect ourselves using our mind. We just need to tap into that power.
Later in the book we’ll learn that we can alter the body’s systems another way and thus boost the power of the mind through visualization.