New research is zeroing in on a biochemical basis for the placebo effect — possibly opening a Pandora’s box for Western medicine.
By Gary Greenberg
He knew enough about the topic that these psychologists and neuroscientists and physicians and anthropologists and philosophers had come to his city to talk about — the placebo effect, the phenomenon whereby suffering people get better from treatments that have no discernible reason to work — to call it “fake medicine,” and to add that it probably works because “people like to be cheated.”
More important, they are motivated by a conviction that the placebo is a powerful medical treatment that is ignored by doctors only at their patients’ expense.
And after a quarter-century of hard work, they have abundant evidence to prove it. Give people a sugar pill, they have shown, and those patients — especially if they have one of the chronic, stress-related conditions that register the strongest placebo effects and if the treatment is delivered by someone in whom they have confidence — will improve.
It also has, so far, resisted a full understanding, its mechanisms shrouded in mystery. Without a clear knowledge of how it works, doctors can’t know when to deploy it, or how.
In the last half of the 1950s, this calculus gave rise to a new way to evaluate drugs: the double-blind, placebo-controlled clinical trial, in which neither patient nor clinician knew who was getting the active drug and who the placebo. In 1962, when the Food and Drug Administration began to require pharmaceutical companies to prove their new drugs were effective before they came to market, they increasingly turned to the new method; today, virtually every prospective new drug has to outperform placebos on two independent studies in order to gain F.D.A. approval.
Like Franklin’s commission, the F.D.A. had determined that the only way to sort out the real from the fake in medicine was to isolate the imagination. It also echoed the royal panel by taking note of the placebo effect only long enough to dismiss it, giving it a strange dual nature: It’s included in clinical trials because it is recognized as an important part of every treatment, but it is treated as if it were not important in itself. As a result, although virtually every clinical trial is a study of the placebo effect, it remains underexplored — an outcome that reflects the fact that there is no money in sugar pills and thus no industry interest in the topic as anything other than a hurdle it needs to overcome.
In the course of conducting the study, Kaptchuk had taken DNA samples from subjects in hopes of finding some molecular pattern among the responses. This was an investigation tailor-made to Hall’s expertise, and she agreed to take it on. Of course, the genome is vast, and it was hard to know where to begin — until, she says, she and Kaptchuk attended a talk in which a colleague presented evidence that an enzyme called COMT affected people’s response to pain and painkillers. Levels of that enzyme, Hall already knew, were also correlated with Parkinson’s disease, depression and schizophrenia, and in clinical trials people with those conditions had shown a strong placebo response. When they heard that COMT was also correlated with pain response — another area with significant placebo effects — Hall recalls, “Ted and I looked at each other and were like: ‘That’s it! That’s it!’ ”
It is not possible to assay levels of COMT directly in a living brain, but there is a snippet of the genome called rs4680 that governs the production of the enzyme, and that varies from one person to another: One variant predicts low levels of COMT, while another predicts high levels. When Hall analyzed the I.B.S. patients’ DNA, she found a distinct trend. Those with the high-COMT variant had the weakest placebo responses, and those with the opposite variant had the strongest. These effects were compounded by the amount of interaction each patient got: For instance, low-COMT, high-interaction patients fared best of all, but the low-COMT subjects who were placed in the no-treatment group did worse than the other genotypes in that group. They were, in other words, more sensitive to the impact of the relationship with the healer.
full article:
What if the Placebo Effect Isn’t a Trick?
By Gary Greenberg
He knew enough about the topic that these psychologists and neuroscientists and physicians and anthropologists and philosophers had come to his city to talk about — the placebo effect, the phenomenon whereby suffering people get better from treatments that have no discernible reason to work — to call it “fake medicine,” and to add that it probably works because “people like to be cheated.”
More important, they are motivated by a conviction that the placebo is a powerful medical treatment that is ignored by doctors only at their patients’ expense.
And after a quarter-century of hard work, they have abundant evidence to prove it. Give people a sugar pill, they have shown, and those patients — especially if they have one of the chronic, stress-related conditions that register the strongest placebo effects and if the treatment is delivered by someone in whom they have confidence — will improve.
It also has, so far, resisted a full understanding, its mechanisms shrouded in mystery. Without a clear knowledge of how it works, doctors can’t know when to deploy it, or how.
In the last half of the 1950s, this calculus gave rise to a new way to evaluate drugs: the double-blind, placebo-controlled clinical trial, in which neither patient nor clinician knew who was getting the active drug and who the placebo. In 1962, when the Food and Drug Administration began to require pharmaceutical companies to prove their new drugs were effective before they came to market, they increasingly turned to the new method; today, virtually every prospective new drug has to outperform placebos on two independent studies in order to gain F.D.A. approval.
Like Franklin’s commission, the F.D.A. had determined that the only way to sort out the real from the fake in medicine was to isolate the imagination. It also echoed the royal panel by taking note of the placebo effect only long enough to dismiss it, giving it a strange dual nature: It’s included in clinical trials because it is recognized as an important part of every treatment, but it is treated as if it were not important in itself. As a result, although virtually every clinical trial is a study of the placebo effect, it remains underexplored — an outcome that reflects the fact that there is no money in sugar pills and thus no industry interest in the topic as anything other than a hurdle it needs to overcome.
In the course of conducting the study, Kaptchuk had taken DNA samples from subjects in hopes of finding some molecular pattern among the responses. This was an investigation tailor-made to Hall’s expertise, and she agreed to take it on. Of course, the genome is vast, and it was hard to know where to begin — until, she says, she and Kaptchuk attended a talk in which a colleague presented evidence that an enzyme called COMT affected people’s response to pain and painkillers. Levels of that enzyme, Hall already knew, were also correlated with Parkinson’s disease, depression and schizophrenia, and in clinical trials people with those conditions had shown a strong placebo response. When they heard that COMT was also correlated with pain response — another area with significant placebo effects — Hall recalls, “Ted and I looked at each other and were like: ‘That’s it! That’s it!’ ”
It is not possible to assay levels of COMT directly in a living brain, but there is a snippet of the genome called rs4680 that governs the production of the enzyme, and that varies from one person to another: One variant predicts low levels of COMT, while another predicts high levels. When Hall analyzed the I.B.S. patients’ DNA, she found a distinct trend. Those with the high-COMT variant had the weakest placebo responses, and those with the opposite variant had the strongest. These effects were compounded by the amount of interaction each patient got: For instance, low-COMT, high-interaction patients fared best of all, but the low-COMT subjects who were placed in the no-treatment group did worse than the other genotypes in that group. They were, in other words, more sensitive to the impact of the relationship with the healer.
full article:
What if the Placebo Effect Isn’t a Trick?