“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 fifth post on this book.
Vance describes the story of a man diagnosed ten years ago being severely debilitated in late stage Parkinson. He volunteered for an experiment in which the medication was directly injected into a critical part of the brain. To control for the placebo effect, these experiments require sham surgery that copies everything about the surgery except for the critical drug injected into the brain. The study involved 51 participants. Twenty-four people got the real surgery and 27 got the sham surgery. The drug proved to be a failure. However, the participant of interest did show a remarkable recovery. However, he was one of those who had received sham surgery.
This dramatic example makes the point that there are large individual differences in the response to placebos. Kathryn Hall of Harvard University was interested in studying possible genetic bases for this enhanced responsively. She discovered the COMT gene. The COMT genes codes for an enzyme in the brain, also called COMT, or catechol-O-methyltransferase. Vance writes that this is one of the best-studied brain pathways in the world, and may be the most fascinating link he has discovered as a science writer.
Here’s how it works. Dopamine has enormous power and is important for body movement and good moods. However, it is possible to have too much of a good thing. A mechanism is need to sweep up the bits we don’t need—the extra dopamine molecules floating around our skull that aren’t doing anything useful. COMT gets rid of the excess dopamine molecules. COMT is an extremely long and complicated enzyyme. Fortunately, it is one within its machinery that defines how well it works. Depending upon an individual’s genetics there are two types of this crucial portion of the enzyme: valine (val) or methionine (met). If one’s brain has val in that one spot, the enzyme performs its job of removing excess dopamine. However, if the enzyme has met in that one spot, it is much less effective. The brain is left with lots of excessive dopamine.
Remember that each trait in the body is a combination from each of the parents. COMT works in a similar manner. So we have val/met, but also val/vals and met/mets. So 25% of the population are val/vals,and 25% are met/mets, 50% of the population are val/mets.
Hall conducted an experiment pairing COMT genes with placebos. She enrolled 262 patients with irritable bowel syndrome (IBS) into an experimental treatment involving acupuncture. She selected patients with either moderate or severe cases of IBS and then divided them into three groups. One group, the true control group, was put on a waiting list and given nothing. The other two groups were told that they would get acupuncture, but they were unknowingly given fake acupuncture. Half of the participants got treatment from a comforting, caring acupuncturist while the others got treatment from a cold, uncaring acupuncturist.
Here are the results. People on the waiting list stayed the same regardless of their genes.
Met/mets with the uncaring acupuncturist did better than the val/vals, but just barely.
Val/vals with the caring acupuncturist did about as well as the val/vals with the uncaring acupuncturist and all the people on the waiting list. In short, no placebo effect.
The val/mets who got the caring acupuncturist did about five times better.
The results of the met/mets who got the caring doctor went through the roof.
Clearly the kind words meant something totally different to one genotype than it did with the others. Hall had divided the placebo responders into measurable groups.Met/mets—those people who were born with lazy enzymes and a little too much dopamine in their responses were more prone to placebo responses.
Although the COMT gene plays a large role in the creation of the COMT enzyme, it’s not the only gene that does so. Other genes help build the enzyme that can boost or cripple its performance, as well as all the other genes in you body that affect dopamine. COMT also goes after epinephrine and norepinephrine, neurotransmitters that are key to regulating adrenaline, cardiac, function, and our response to stress.
So, in summary, the interactions are complex. But different factors that contribute to the immune response are being identified. Genes, the administrator of the placebo, and our fellow human beings are factors.