Posts Tagged ‘Irritable bowel syndrome’

Suggestible You 5

March 21, 2017

“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.


Another Discovery by Benjamin Franklin

August 18, 2013

In 1784 Benjamin Franklin along with chemist Antoine-Laurent Lavoisier simulated one of Franz Mesmer‘s sessions.1 People suffering from ailments ranging from asthma to epilepsy were asked to “hug” trees they were told were specially magnetized to “cure” them. As expected, the people swooned and shook. Then the patients were told that the trees were never magnetized. But something had induced the reactions to the trees. That unknown something was later termed the placebo effect.

In 1968 the Food and Drug Administration started using placebo treatments into their golden randomized clinical trials (RCTs), to insure that it was the drug working and not just a belief that it was the drug working. So the effect was large enough that the Food and Drug Administration believed that the placebo effect, if not accounted for, could result in incorrect interpretations of the results from clinical trials.

A key factor in finding placebo effects regards the dependent measures used to assess the effects. Placebo effects were not likely to be found in such medical measures as blood pressure. However, if the measures used reflected how patients reported they felt, then placebos were quite evident. This was especially true in conditions such as pain and nausea. Before one concludes that these measures are subjective and, hence, unimportant, one should be reminded that it is the patients’ own feelings of pain and discomfort that are the most relevant factors. The Harvard psychologist Irving Kirsch found in a meta-analysis of six of the most commonly prescribed antidepressants found that 82 percent of the improvement in mood could be duplicated by giving patients a placebo pill instead of an antidepressant. In another study Kirsch and his colleagues found that the only people in whom antidepressants worked significantly better than placebo pills were patients with the most severe cases. He concluded that unless the patient is extremely depressed, an antidepressant should not be prescribed.

Placebos also work in non-psychiatric conditions, asthma being but one example. In one study, volunteers with asthma were divided into four groups. One group was given an asthma inhaler with a drug, another group was given an inhaler with a saline placebo, a sham acupuncture placebo, or nothing. How much air the volunteers could inhale and exhale before and after each treatment. Was measured. The respiratory scores of those treated with the drug rose by 20%, whereas those in the other three groups got a 7% bump. But when the volunteers were asked to rate their respiratory discomfort on a scale of 0 to10, everyone except those who received no treatment reported a 50% improvement!

The placebo effect places the physician in an ethical dilemma. If she treats the patient with a placebo, he is likely to feel better, but she must lie to the patient. However, if she does not use a placebo, possible unnecessary suffering will not be relieved.

Sometimes the placebo procedures can be employed without deception. In a study by Kirsch, Kaptchuk and their colleagues, 40 patients with irritable bowel syndrome (IBS) pills that they described truthfully as placebo pills made of an inert substance such as sugar, that had been shown in previous clinical studies to produce significant improvements in IBS symptoms thought mind-body self-healing processes. After forty days of twice daily placebos, patients reported feeling better overall along with fewer severe symptoms that 40 patients who received no treatment.

Another way to avoid deception is to enhance the doctor-patient relationship. In a different study of patients with IBS, patients were assigned to either placebo acupuncture or a waiting list. The placebo group was further divided into acupuncture with no conversation, and acupuncture with heavy doses of attention, empathy, and interaction with the practitioner. The practitioner listened to each patient’s problem, repeated the words of the patient, expressed confidence, touched the patient, and lapsed into 20 seconds of thoughtful silence. 28% of the people on the waiting list reported that their bowel symptoms had improved, 44% of the acupuncture placebo reported improvement, and 62% of those in the placebo with the enhanced doctor-patient relationship report improvement.

It should be noted that the placebo effect has a negative counterpart, the nocebo effect, Enter “nocebo” into the search box of the healthymemory blog, to find the relevant posts.

1The facts in this blog post can be found in an article, When Pretending is the Remedy, in Scientific American Mind, March/April 2013 by Trisha Gura.

© Douglas Griffith and, 2013. Unauthorized use and/or duplication of this material without express and written permission from this blog’s author and/or owner is strictly prohibited. Excerpts and links may be used, provided that full and clear credit is given to Douglas Griffith and with appropriate and specific direction to the original content.

Self Hypnotism

October 30, 2011

It has been said that all hypnotism is actually self hypnotism. The New Scientist published an interesting article1 on hypnotism. It describe the treatment program that Peter Whorwell has developed for irritable bowel syndrome (IBS). IBS is a serious disorder that results in some sufferers contemplating suicide. Whorwell presents a tutorial to his patients on how the gut functions. Then he has his patients effectively hypnotize themselves to use visual and tactile sensations of warmth and to imagine the bowel working normally. The United Kingdom’s National Institute for Health and Clinical Excellence has recommended hypnosis as an effective treatment for IBS. Whorwell has shown that under hypnosis some IBS patients can reduce the contractions of their bowel, something that can not normally be done under conscious control2. Their bowel linings become less sensitive to pain.

The question is why this works. Irving Kirsch of the University of Kull thinks that hypnosis taps into physiological pathways that are similar to those involved in the placebo effect (See the Healthymemory Blog Post, “Placebo and Nocebo Effects”). The medical conditions that benefit from the placebo effect and hypnotism are similar. They both involve suggestion and expectation. The disappointing part is that there are individual differences in how well people respond to hypnosis.

For those who do respond well to hypnosis, the effects can be quite impressive. A common test used in studies of pain perception is called the cold presser test. The research participant is asked to keep her hand in ice water for as long as she can stand it. This does become quite painful. The research participant gives ratings of the pain as it increases as the time in the ice water increases. Eventually, the pain becomes unbearable and the participant removes the hand. People who are effectively hypnotized can keep their hand in the bucket for a long period of time. They are told when to remove their hand to prevent organic damage. They also give accurate ratings of the pain, so although they remain aware of the painful stimulus, the pain remains bearable.

1Marchant, J. (2011). Hypnotise Yourself. New Scientist, 27 August, 35.

2Journal of Psychosomatic Research, 64, p. 621.

© Douglas Griffith and, 2011. Unauthorized use and/or duplication of this material without express and written permission from this blog’s author and/or owner is strictly prohibited. Excerpts and links may be used, provided that full and clear credit is given to Douglas Griffith and with appropriate and specific direction to the original content.

Placebo and Nocebo Effects

October 16, 2011

Although you’ve probably heard of placebo effects, it is less likely that you have heard of nocebo effects. The placebo effect occurs when an inert substance, say a sugar pill or a saline injection, has curative or beneficial effects. The nocebo effect is the opposite; merely believing that a drug has harmful effects can make you suffer them. The nocebo effect can even kill.1

The expression, “It’s only a placebo effect” has almost become a cliché. But the placebo effect is one of the most amazing effects in medicine. It underscores the role that the psychology of the mind plays in healing. No respectable research in medicine can be done without a placebo control. Otherwise the effect of whatever is being tested could be attributed to a placebo effect. Placebo effects are the rule, rather than the exception, and they can be substantial.

What is more remarkable is that placebos work even when the people receiving them know that they are placebos. In one study2 the experimental group was given placebo pills with the open label placebo pills presented as “placebo pills made of an inert substance, like sugar pills, that have been shown in clinical studies to produce significant improvement in irritable bowel syndrome (IBS) through mind-body self healing processes.” The no treatment control group had the same quality of interaction with the providers, but they were not given the placebo.

The placebo group showed significantly higher scores than the control group on the IBS Global Improvement Scale, the IBS Symptom Severity Scale, and the IBS Adequate Relief Scale.

So the placebo effect cannot be simply the result of deception. Somehow, belief, a psychological variable, affects the body.

1Marchant, J. (2011). Fool Yourself. New Scientist, 27 August, 33.

2Kaptchuk, T.J., Friedlander, E., Kelley, J.M., Sanchez, M.N., Kokkotou, E., Singer, J.P., Kowalczykowski, M., Miller, F.G., Kirsch, I., Lembo, A.J. (2010). Placebos without Deception: A Randomized Controlled Trial in Irritable Bowel Syndrome. Http://