“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 book is about the placebo response and related phenomena. This is the third post on this book.
Irving Kirsch took up psychology out of a philosophical curiosity about the brain. He mentored Ted Kaptchuk, a researcher who earned a Chinese doctorate in Eastern medicine and was an expert in acupuncture and other alternative therapies. These two set up a lab at Harvard and for a long time their names have been synonymous with placebo research. Kaptchuk’s work spans many complicated aspects of placebo research—genetic, biochemical—but Vance’s favorite study is a relatively simple one. He handed patients pills and told them it was a placebo. He explained that placebos had been shown to be very effective agains all manner of conditions, and so forth. When these patients took the pill, it still worked. Not as well as a secret placebo—but it worked, even though the people taking it knew it wasn’t real.
Tor Wager conducted research using functional magnetic resonance imaging f(MRI). fMRI measures blood flow in the brain. This blood flow is used to infer brain activity. It is captured in voxels. A single voxel has about 63,000 neurons in it (and four times as much connective). Nevertheless, fMRI has been invaluable in gaining insights regarding the brain. Wager used fMRI to capture the placebo effect in action. The first experiment used electric shock. The research participants saw either a red or a blue spiral on a screen warning them hey would get either a strong or a mild shock, which would hit between 3 and 12 seconds later to keep them off guard (and build expectation). Wager looked two skin creams explaining that a one was designed to reduce the pain and the other was a placebo. Actually both skin creams were placebos, but the research participants said they felt less pain with the “active” cream.
The second experiment used a hot metal pad that seared the skin for 20 seconds. This time the screen just read, “Get Ready,” and then the pad heated up. As in the first experiment, the research participants received placebo and “pain killing” creams, both of which were actually placebos. Wager surreptitiously lowered the temperature of the heat pad on the fake “active” cream, fooling the research participants into thinking that the cream was reducing the level of pain they felt. Then, in the last phase (as Collca had with Vance’s shocks), he kept the temperature high. Researchers carefully recorded how much pain the subjects reported feeling, and Wager also had their fMRI brain scans. What the research participants reported about their pain tracked perfectly with the activation of several parts of the brain associated with pain, such as the anterior cingulate cortex (which plays a role in emotions, reward systems, and empathy), the thalamus (which handles sensory perception and alertness), and the insula (which is related to consciousness and perception). Those reporting less pain from the placebo effect showed less activity in the key pain-related brain regions. And those who felt less of the placebo effect showed more activity. So these research participants were not imaging less pain; they were feeling it.
More importantly, Wager observed the route that the placebo response takes from anticipation to the release of drugs inside the brain. Pain signals normally begin in the more primitive base of the brain (relaying information from wherever in the body the pain starts) and radiate outwards. What Ager observed was backward, with the pain signals starting in the prefrontal cortex—the most advanced logic part of the brain with executive functions—and working back to the more primitive regions. Vance noted that this seemed to suggest a sort of collision of information: half originating in the body as pain, and half originating in the advanced part of the brain as expectation. Whatever comes out of that collision is what we feel.
The following summary comes directly from Vance’s book,”Pain, like any sensation, starts in the body, goes up the spine, and then travels to the deeper brain structures that distribute that information to places like the prefrontal cortex, where we can contemplate it. Placebos, on the other hand, seem to start in the prefrontal cortex (just behind the right temple) and go backward. They work their way to parts of the brain that handle opioids and release chemicals that dull the pain. That also seem to tamp down activity in the parts of the brain that recognize pain in the first place. And you feel better. All in a fraction of a second.”
How powerful these placebo effects are varies. In some people they barely register. However, in others the opioid dumps can be so powerful that people become physically addicted to their own internal opioids, similar, in theory, to how people become addicted to laudanum. One theory even suggests that chronic pain might be the result of a brain addicted to its inner pharmacy, in essence, looking for a fix.
More than opioids are involved. Over the past few decades, other brain chemical have been shown to trigger the placebo effect. Our inner pharmacy also stocks endocannabinoids—the same chemicals found in marijuana that play an important role in pain suppression—and serotonin, which is important intestinal movements and is the primary neurotransmitter involved in feelings of happiness and well-being.