9

Conditioning

Awakening the Body’s Inner Pharmacy

The decision to believe or not believe is not entirely in our hands. I might be happier and have better manners if I thought I were descended from the emperors of China, but no effort of will on my part can make me believe it, any more than I can will my heart to stop beating.

—Steven Weinberg, American physicist and Nobel laureate

Our Subconscious Beliefs

People who know me now think of me as a good athlete, but as I mentioned earlier, when I was in high school nobody wanted me on their team. I was clumsy and didn’t really believe I could be a winner at any sport. I remember one day when I was fifteen playing basketball on a Saturday morning at the YMCA in my hometown of Westmount in Quebec, Canada. Usually in basketball a player on one team will follow a player on the other team to try and prevent them from scoring or getting a pass. I was playing so badly that the guy on the other team, who was supposed to be following me, left me alone to do what I wanted. Instead he would cover Justin, the best player on my team, who used to pick me for his team because he was a nice guy.

So on the odd occasion when I had the ball, nobody on the opposing team would try to stop me, allowing me an open shot on the net. Despite being unmarked, I would be so nervous that I frequently missed. I don’t know why I was so clumsy and nervous, but I think it was partly because of my first gym teacher in high school.

When I started high school, I decided to try out for the basketball team. I was pretty tall, and all the cool kids played basketball. It was also a good way to avoid being bullied, as a lot of those on the basketball team bullied the kids who were not. As part of the tryout, the coach asked me to do a layup, which involves taking a couple of steps, jumping, and then hopefully scoring a basket off the backboard. I was so nervous I tried too hard and missed the net. I was not even close.

“You missed,” he said.

“Can I try again?”

“No,” he said.

“Just one more chance.”

“I can’t teach you to play ball. You’re too goofy.”

The kids waiting for their turn to try out laughed. I walked away and didn’t try out again. This experience at the hands of an authority figure helped formulate my belief that I was no good at sports.

The rowing coaches I had later on were the opposite of that basketball coach. I had three in a row—Scott Armstrong, Larry Gluckman, and Dusan Kovacevic—who really believed in me. They helped me get pretty good at rowing. After a few years of successful rowing, I went back to play basketball at the Westmount YMCA against the same guys who used to not want to pick me for the team.

I hadn’t played basketball for a long time, and these guys had been playing several days per week for years. It’s true that I was in better shape than before because of the rowing. But pulling on oars involves little hand-eye coordination and requires you to develop endurance muscles rather than the explosive muscles you need for basketball. So I should have been relatively worse. In fact, I was one of the best players on the team that day. How can we explain this? I didn’t do a randomized trial, so I can only tell you how I felt. Whereas before I was conditioned to feel overly anxious and stressed and like a loser in sports, now I approached any physical activity competition feeling confident. Scott and my other coaches had helped condition me to feel confident.

Conditioning can also have medical effects. The best evidence for this comes from trials of open-label placebos.

Open-Label Placebos

I have mentioned a few times that placebos can work even if patients know they are placebos. This seems mysterious because placebos are thought of as being powered by belief. So if we don’t believe they are (or might be) real, how could they work? We can now finally solve that mystery.

In the first of the studies that I know of open-label placebos (placebos that patients know are placebos), two Baltimore doctors by the names of Lee Park and Uno Covi gave open-label placebos to fifteen neurotic patients. They presented the placebo pills to the patients and said, “Many people with your kind of condition have been helped by what are sometimes called sugar pills and we feel that a so-called sugar pill may help you, too.” The patients took the placebos, and many of them got “quite a bit better” after having the placebo, even though they knew it was a placebo. But since these patients knew the pills were placebos, they could not expect them to work. And if they didn’t expect them to work, how did they get better?

The answer is partly that they did expect to get better for two reasons. First, the doctors gave them a positive message along with the placebo. The other reason is that the patients didn’t believe the doctors. After the placebo made them better, they thought the doctors lied and actually gave them the real drug. The Park and Covi study was small, however, and did not have a control group.

More recent, higher-quality studies confirm that open-label placebos can work. As I mentioned in Chapter 4, Ted Kaptchuk of Harvard Medical School randomized eighty patients with severe irritable bowel syndrome (IBS) to receive either no treatment or open-label sugar pill placebos. After a few weeks, Kaptchuk’s team compared their scores from the commonly used IBS Global Improvement Scale questionnaire both before and after taking the placebos with those in the no-treatment group. Those in the open-label placebo group improved by 15 percent more than those in the control group.

I did a systematic review and found five trials (260 participants) of open-label placebos. The trials investigated open-label placebo effects for irritable bowel syndrome, depression, allergic rhinitis, back pain, and attention deficit hyperactivity disorder (ADHD). The effects were positive for all the trials, and had similar effects to the open-label placebo in Kaptchuk’s trial. A problem with these studies is that it is hard to blind the patients. Patients are randomized to either an open-label placebo or no treatment, and they know which group they are in. Yet the consistency of the results in these studies suggests a real effect.

How Open-Label Placebos Work

There are two main ways that open-label placebos work. First, they are often given together with a positive suggestion. The doctor tells the patient the pill is just a placebo but adds that it “produces significant improvement for patients like you.” This suggestion creates a positive expectation, which can activate the reward mechanisms in the brain and help the body to produce its own pain-killing endorphins. But conditioning probably also plays a role in explaining how open-label placebos work. Let me say a word about conditioning.

What Do the Human Immune System and Pavlov’s Dogs Have in Common?

Russian psychologist Ivan Pavlov made conditioning theory famous in the late 1800s. Pavlov would ring a bell, then feed his dogs. After repeating the process several times, he changed his procedure. Instead of ringing then feeding, he would simply ring the bell. By that time, of course, the dogs had been conditioned to associate the sound of the bell with eating. So they would start to salivate at the mere sound of the bell, even if there was no food. Hundreds of other studies with animals, humans, and even cells have been conducted that support his conditioning theory. Conditioning is most likely the mechanism by which our prehistoric ancestors and even the very first single-celled living beings on the planet learned things.

Something many people don’t know is that the human immune system can be conditioned, too. This was first discovered in 1895 by an American researcher, John Noland MacKenzie. He had a thirty-two-year-old female patient who complained of severe asthmatic symptoms during the summer months, especially when she was near flowers. Roses seemed to cause the most severe attacks, and her symptoms included red and itchy eyes, blocked nose, sneezing, and even fever. Apart from the summer after her only child was born, she was confined to bed for most of August.

She had tried many remedies and even some “quack” cures without success. Cocaine, which at that time was widely used as medicine as well as recreationally, provided relief for about thirty minutes. Some years ago, a doctor had performed a cautery operation, which involved burning the inside of her nose with a red-hot metal rod. This was enormously painful, but seemed to work for several weeks. When she later asked MacKenzie for another cautery operation, he reminded her how painful the first one had been. She replied that the relief was well worth it.

Dr. MacKenzie did the cautery operation. Yet for some reason he didn’t believe that her fits were really caused by rose pollen. He decided to play a trick on her. He had a fake rose made and hid it behind a screen in his office. When she returned a few weeks after the operation, she reported feeling very well. She told him that earlier that day she had attempted to wear some roses, but she had suffered a reaction and so got rid of them. MacKenzie removed the slight scab from the cautery operation, which was loose in her nostril, and examined her carefully. She had no symptoms or signs of allergies: her throat and nose were completely clear.

Once he established that she had been cured, he produced the fake rose from its hiding place. When she saw it, she sneezed, scratched her nose and eyes, and spoke with a hoarse voice. She also reported having trouble breathing, and when he examined her throat he found it to be red. Her right nostril was completely blocked. He then told her that the rose was fake and she didn’t believe it until she examined the counterfeit rose herself. She saw it was a fake, but was happy to learn that the cause of her reaction was “psychological.” She came to visit him a few days later and buried her nostrils in a large, fragrant bunch of real roses without experiencing any symptoms at all. Her reaction to the fake rose was a conditioned response. Her body learned to react when she saw (what she thought was) a rose.

But how can conditioning have this effect? Allergies are autoimmune diseases, which means they are inappropriate immune-system responses. Runny noses and watering eyes are great for flushing away harmful bacteria and viruses. Inflammation, which causes the nose and throat to get congested, occurs because the immune system is dilating the vessels to let more cells that defend the body access the site of injury. But sometimes the immune system gets things wrong and unnecessarily launches our defenses against things such as pollen, despite their being harmless. Dr. MacKenzie’s patient had somehow been conditioned to launch an immune-system reaction to roses and other flowers, just as Pavlov’s dogs were conditioned to salivate upon hearing a bell. Dr. MacKenzie’s story was revolutionary, because it showed that the immune system can be conditioned.

Later animal studies replicated Dr. MacKenzie’s findings. In a 1975 rat study, American researchers Robert Ader and Nicholas Cohen divided rats into different groups. Some groups received a flavored drink containing saccharin and cyclophosphamide, a drug that suppresses the immune system. After the rats had been given this cocktail for several days, Ader and Cohen took out the cyclophosphamide and just gave the rats saccharin-laced water. They found that the saccharin water suppressed the immune system in the rats as if they had swallowed cyclophosphamide along with the saccharin water. This is because the rats’ immune systems had become conditioned to be suppressed in response to the taste of saccharin. These studies have been replicated with other animals.

Research has shown that the human immune system can be conditioned, too. In 2002, Dr. Marion Goebel and his colleagues in Germany gave a group of thirty-four healthy male volunteers capsules containing cyclosporin A every twelve hours for three days. Cyclosporin A is a drug used to suppress the immune systems of patients given an organ transplant. When someone gets an organ from a donor, the body thinks it is a foreign invader and instructs the immune system to attack the donor organ. So doctors give drugs to the person who is receiving the organ in order to suppress their immune system until the body realizes the new organ is okay and is good for them.

Goebel mixed cyclosporin A into a cocktail containing strawberry-and-lavender-flavored milk. They deliberately chose a weird drink their participants would not have encountered before. The idea was to teach the men’s bodies to connect the strange flavor with immune suppression. In the second phase of the trial, the men continued taking their unusual drink, but this time it contained no cyclosporin A. Throughout the study, Dr. Goebel’s team measured levels of immune system cells like interleukin-2 and white blood cells. They found the participants’ immune systems continued to be suppressed even once the cyclosporin A had been removed from their flavored milk.

A few years later, Luana Colloca in Italy showed that sensations of pain can also be conditioned. The forty-six healthy volunteers in her study got either one conditioning session or four of them. The sessions involved a flashing green light followed by a mild, nonpainful electric shock to the ankle; a flashing yellow light with a lightly painful shock; or a flashing red light and a painful shock. After the participants had been conditioned to associate the different colors with no pain, mild pain, or greater pain, Colloca switched things around. Participants received mild shocks following flashing lights of all three colors. But that is not what the patients felt. After a red light flashed, they felt a painful shock. This is because they had been conditioned to associate a red light with a painful shock and a green light with a mild shock.

These conditioning studies show how open-label placebos probably work. When you go to see your doctor, the receptionist asks you to wait for them. Your doctor studied hard for years to become someone important enough that it is worth your while waiting until they are free to see you. When you make it into your doctor’s office, it is very clean and sometimes full of impressive-looking medical instruments. Your doctor may even wear a white coat and probably a stethoscope. You are given a pill or an injection, and you get better.

Whenever you went to the doctor, you repeated the same procedure. Sometimes the treatment makes you better, and sometimes you would have got better on your own. That doesn’t matter. What matters is that you learn to associate a visit to a doctor with getting better, much like Pavlov’s dogs learned to salivate when they heard the bell they had been taught to associate with food. After a few successful doctor visits, the mere act of visiting the doctor can induce relaxation, boost the immune system, and help you recover even without a pill. When I first learned about conditioning, I didn’t understand the difference between conditioning and expectancy, and many people I tell about it now ask me to explain the difference.

Much Ado About Nothing Important

Academics get paid to make big deals out of simple things. Dozens of articles are published every year on the complexities of the difference between expectancy (Chapter 8) and conditioning. In fact, the difference is pretty simple. Both involve anticipating that something good will happen.

Expectancy occurs when someone consciously expects a positive reward, as when a trusted doctor says you are taking a powerful medicine that will make you feel much better very soon. This can help you get better, because expecting something good activates parts of your brain that induce your body to create its own drugs, such as dopamine.

Conditioning, on the other hand, is when you subconsciously expect a positive reward. After visiting the doctor many times and getting better, your body might become conditioned to expect a positive reward and react accordingly even before the doctor has a chance to say or do anything. Depending on what the placebo is, your individual characteristics, and what you are suffering from, either expectancy or conditioning could be more important. More often than not, both come into play.

Takeaway: Reward and Recondition Yourself

My experience at the hands of a high school basketball coach, which I described at the beginning of this chapter, and Luana Colloca’s flashing-red-light study above show that we can be conditioned to have both positive and negative reactions. Since conditioning is a subconscious process, it can be very difficult to influence. Subconscious thoughts are usually hidden from us, and hidden things are hard to identify, let alone change. People like self-help guru Anthony Robbins say we can change our subconscious patterns very quickly, and sometimes they are right. More often than not, it takes patience and persistence for new positive thoughts to trickle down into our core so that they become part of our subconscious. The following exercise is one I have used and found helpful.

Give yourself positive rewards for your achievements. Whenever you do something good, give yourself a reward. It is best to do it immediately so that you teach your brain the connection. Here is a list of some of the rewards I give myself.

Achievement Reward
Major

Publishing major academic article

Weekend getaway

Complete five chapters of book

Medium

Submit paper

Massage

Publish blog or newsletter

Reach additional 1,000 social media followers

Small

Complete draft of paper or chapter

Long gym session

When doing this exercise for yourself, it is important not to choose things that you have no control over. There is no point in planning to give yourself a reward if the sun comes out, because you have no control over the weather. Also, while it is great to dream big (even dream very big), it is also important to break your dream down into realistic steps. If your goal is to win a 100-meter Olympic gold medal and you are not a runner, give yourself smaller rewards for benchmarks along the way. For example, give yourself a reward for joining a running club and training with them regularly for three weeks.