In a recent HealthGuidance.org article (What Is the Placebo Effect and Why Is it Getting Stronger?) we examined the placebo effect, and the growing havoc it is wreaking in drug studies. For reasons that no one seems to understand, the placebo effect seems to be growing stronger, so much so that many drug trials are failing, because the placebos (inert sugar pills) given to the control group in the studies seem to "work" just as well as the actual drugs being tested. Many drugs that had shown much greater effectiveness than placebos in the past now can no longer do so, with the result that fewer and fewer drug studies can be replicated.
Now there is evidence that your ability to benefit from a placebo may depend on your genes. In the study, reported last month in the journal PLoS One, researchers analyzed DNA from 104 subjects suffering from irritable bowel syndrome, looking in particular at the catechol-O-methyltransferase (COMT) gene, which has been shown to regulate dopamine levels in the brain. Some COMT genes generate higher levels of dopamine than others, and people with these high-dopamine COMT genes have been found in past studies to react to pain more acutely and to seek rewards – both physical and psychological – more strongly than people with the low-dopamine COMT genes. The researchers suspected this might be a factor in whether people respond to placebos or not.
The subjects in the study were divided into three groups. One group was told that they were on the waiting list for treatment of their irritable bowel syndrome, and thus received no treatment, acting as the control group. A second group received what appeared to be acupuncture, but from curt, brusque, uncaring practitioners with no "bedside manner." The third group also received what appeared to be acupuncture, but from a warm, friendly, outgoing and caring practitioner. In reality all of the "acupuncture" was fake, using needles that retracted rather than pierce the skin, so all patients in both the second and third groups were essentially receiving a placebo.
What the researchers found was that patients who carried the high-dopamine version of the COMT gene were more likely to report that their symptoms improved than patients with the low-dopamine COMT gene. Furthermore, the patients with the high-dopamine version of the COMT gene were more than six times more likely say that the fake acupuncture "worked" for them when it was given by the caring practitioner.
What does this tell us?
Well, first it tells scientists that there is at least one explanation for why some people are more likely to respond to placebos than others, and that explanation may be genetic. Second, and possibly more important when it comes to designing protocols for future drug trials, these findings may provide researchers with a future mechanism for improving the quality and validity of those drug studies. If the scientists conducting them have a way of determining which subjects are more likely to respond to placebos, as a result of carrying the high-dopamine version of the COMT gene, they may be better able to accomplish the real goal of the drug trials – which is to distinguish the effects created by the real drug from the effects created by the placebo response.
As study author Kathryn Hall, a researcher at Beth Israel Deaconess Medical Center in Massachusetts says, "This is a possible way to discern who is going to be a placebo responder or non-responder in a clinical trial." Being able to know this in advance by testing subjects for the presence of the high-dopamine version of the COMT gene may provide the key to being able to make drug trials work again.