“Suggestible You” is the title of a book by Erik Vance. The subtitle is “The Curious Science of Your Brain’s Ability to Deceive, Transform, and Heal. This post is about the placebo response and related phenomena. This is the sixth post on this book.
This post is on nocebos. Remember that placebo is Latin for “I shall please.” Nocebo means “I shall harm.” So nocebos can be thought of as negative placebos.
In 1886 a physician named John Mackenzie was treating a woman with a serious case of hay fever and asthma. For a variety of reasons, he was not convinced that the patient’s condition was fully authentic. For her next visit he place a rose in his office. As soon as she sat it she had powerful allergic reaction that brought on an asthma attack. The flower was artificial and served as the nocebo.
Cholecystokinin (CCK) is a key messenger in activating intestinal functions, including digestion and the release of gastric acid and bile. It also plays a role in making you feel full after a good meal. But if you inject CCK into someone, it causes anxiety and nausea and can induce panic attacks. It also seems to increase pain by lessening the impact of internal opioids. Fabrizio Benedetti set up an experiment with patients recovering from minor surgery in which he gave them a drug and told them it would make their pain worse when it was actually just saline. The patients did report more pain with the saltwater injection. Then Benedetti blocked their brains’ CCK release with another drug. Now the patients felt better when the CCK was blocked. Vance wrote,”What opioids are for placebos is what CCK is for nocebos; a mechanism giving expectation power in the body. And whereas blocking opioids killed the placebo response and made patients feel worse, blocking CCK actually supercharged pain relief by allow the brain’s internal pharmacy to run wild.”
Nocebo effects are much easier to create than placebo effects. Negative expectations can be stronger than positive expectations. Vance note that nocebos and placebos in the brain take two different routes. They look similar, go to similar places, share some of the same highways, but still are totally different routes, and nocebos take all the best shortcuts. This does make sense, as the aversion to pain is fundamental not just to being human, but also to being alive. Colloca notes that although the nocebo affects the same reward/expectation regions in the brain, it also includes one more that placebos do not: fear. The hippocampus plays a key role in the storage of memories and it also plays a key role in fear conditioning anxiety. Brain imaging indicates that while the hippocampus is mostly absent from placebo effects, it lights up during the experience of nocebos.
Fear is at the heart of nocebos, and fear is a powerful emotion. Fear headlines in the news elicit much stronger responses that do pleasant ones. In 2014, even before anyone had died of Ebola in the United States, 25% of Americans were worried they or their families could contract it. Thousands of people visited doctors claiming they had signs of the virus, and 650 of those people had symptoms serious enough for their cases to be passed on to federal officials. As it turned out, only four people in the United States had the disease: a visitor who got it in Liberia, two nurses who had treated him, and a doctor who had been working in an Ebola.
So we need to be careful to not let our fears get out of hand. And let us hope that doctors make more use of nocebos in treating pain.