I have tried to make a coherent presentation of an argument for meaning in medicine. It should come as no surprise to know that, gently phrased,
“others disagree.” This is a highly contentious and rancorous business sometimes. In this chapter, I want to show some areas in healing which are similar to the meaning response, but can’t be explained by it. I also want to compare the meaning response with other approaches which might overlap with what I have described, and to suggest that the differences may be as much semantic as anything else. In any case, here are some limitations and challenges to the meaning response.
“Conditioning” placebo effects
Dr. Fabrizio Benedetti has done another quite remarkable experiment (Benedetti et al. 1999). It’s not easy to explain, so watch carefully. One of the dangers of narcotic painkillers is that one of their “side effects” is to de-press respiration; they reduce your ability to breathe. In this experiment, sixty people with lung cancer were having surgery to remove portions of the lung. After the surgery, they were given a narcotic (buprenorphine) through a saline drip. For three days, they would receive a fairly large dose of the narcotic in the morning, and then a much lower dose throughout the day. Dr. Benedetti measured the patient’s respiration each day just before the morning dose of narcotic, and then an hour later; he measured the volume of air (in liters) that the patient breathed in a minute. Each day, the patients breathed about 9 liters of air per minute before the in-jection and about 7.5 or 8 liters per minute an hour later. On the fourth day, patients are usually pain free and, ordinarily, don’t receive any more medication for pain. But in this case, they received one more treatment.
The patients were divided into five groups of twelve. The patients in three of the groups were told that they were going to receive one more dose of narcotic. In one of these groups, the patients were actually given a dose of placebo after being told they would get the narcotic. Their breathing was tested before the placebo, and an hour after. The amount of air that they 122
Learning, expecting, and conditioning 123 breathed dropped from 9 liters per minute to 8. The injection produced a “placebo side effect”! Two of the groups were told they would get the narcotic again, but were instead given (a small or large dose of ) naloxone, the opiate antagonist we have heard of before. In the group with the large dose, the amount of air they breathed was the same an hour after the injec-tion as it was before. The “side effect” could be blocked by naloxone (the smaller dose had a smaller effect). Hang on now, we are almost done. In the fourth group, the patients were given the same breathing test as all the others, but no placebos, no naloxone, no treatment at all. Their breathing was the same both times. The same was true with the last group which got a hidden naloxone injection; their breathing was normal both times. The day before surgery, all of the patients had been given a placebo treatment, and were told that it was the same narcotic they would get after surgery;
their breathing was checked both before and an hour after the placebo injection. The breathing was normal both times, and it did not drop.
A few more details are useful here. Although the respiratory depression here was clearly measurable, it was not so significant that the patients felt short of breath; they did not know that their breathing was depressed.
And on top of that, they didn’t generally know that these narcotics caused respiratory depression. They knew that narcotics were painkillers, but not that they were respiratory depressants.
What can we learn from this experiment? An amusing but somewhat simplistic interpretation might be that placebos can have “side effects.”30 We have already discussed the ambiguity of the notion of a drug’s “side effect”; my sense is that drugs have effects on physiology, some of them desirable, and some not desirable. What is desirable and undesirable can change with circumstance: diphenhydramine (“Benadryl”) makes you sleepy while it dries up your sinuses: if you want an antihistamine, this one makes you sleepy; if you want a sleeping tablet, this one gives you a dry mouth. In the case of opiates, it is clear that vertebrates have evolved a complex pain control mechanism involving endogenous opiates which both reduce pain and depress respiration. I don’t know why the two are linked, but they seem to be. Perhaps, in an evolutionary context, reduced respiration means that you simply can’t be as active as you might be otherwise, and rest is good for you while you are in pain. This experiment, then, indicates that the biological processes which can be triggered by meaningful experiences can be complex and robust.
But there is more to it than that. Notice that, so far as can be told from the description of the experiment, the patients didn’t know that
30Nina Etkins has written a masterful paper about “side effects” in a cross-cultural context (Etkin 1992).
124 Meaning, medicine, and the “placebo effect”
respiration decreased when they were given the drug; they didn’t expect or know that respiration would be depressed. The treatments clearly had meaning (“narcotics are powerful painkillers”), but they did not have the meaning “narcotics repress respiration,” even though that’s true. Yet the people who were given an inert medication on the final day and were told it was a painkiller had a significant drop in respiration anyway (they did not have a significant drop in pain because, by then, they were not in pain any more). This drop in respiration did not happen on the day before surgery, before the patients had “learned” it. Dr. Benedetti interprets this as evidence that we are seeing the effect of “conditioning.” What does this mean?
The best evidence of conditioning comes from studies on animals. The classic experiment involved “Pavlov’s dogs.” Dr. Pavlov was a famous Russian physiologist who, around the turn of the century, did a series of classic experiments on learning. He noticed that sometimes dogs would begin salivating even before the food was put in the bowls. So he started ringing a bell when he fed the dogs. After a while, the dogs would salivate when the bell rang. One can presume that the dogs didn’t “know” that the bell “meant” food, that is, that the reactions were not cognitive ones involving understanding or meaning.
If that’s what is happening in the case of Dr. Benedetti’s experiment, then this is not a case of the meaning response, since the patients didn’t know that one of the consequences of their treatment was respiratory repression. The patients were “conditioned” to reduce their respiration.
They seem to have learned it in more or less the same way that Pavlov’s dogs learned to salivate when they heard the bell ringing.
In my view, this is a very unusual experiment. Others disagree, and say that such conditioning accounts for most, or maybe even all, of the placebo effect (Wickramasekera 1980; Ader 1997). It is clear that, in a lab-oratory, one can condition animals to do quite remarkable things. Robert Ader has done what is probably the most interesting work on this issue. He found that when rats were given a drug which suppressed their immune response along with a particular sweet flavoring, he could subsequently suppress their immune systems with the sweet flavoring alone (Ader and Cohen 1975). He has subsequently suggested that, for someone who has to take regular doses of powerful or expensive drugs, one could ran-domly replace some portion of them with inert tablets, and the same effect would be achieved as if she took all of them. But this has not been tested in people. Of course, people in such a situation would know that they were taking drugs, and would be as subject to the meaning response as anyone else, so there is no reason to believe that this would be due to conditioning. Dr. Wall (of the “gate control” theory of pain discussed
Learning, expecting, and conditioning 125 earlier) argues that there is no convincing evidence for conditioning in adult humans, and that “it may be that the passionately maintained differ-ences between cognitive and conditioned responses will collapse” (Wall 1993). I think there may be a little bit of evidence for such conditioning (Dr. Benedetti’s study with which we started this chapter) which shows that it is possible. But people come into any study or healing encounter with a lifetime of experience and knowledge of illness and healing – with a whole reservoir of meaning – which cannot easily be evaded.
Dr. Ader has written “there is, I believe, considerable heuristic value in viewing a pharmacotherapeutic regimen as a series of conditioning trials” (Ader 1997:159). Each time you take a pill, Dr. Ader might say, you would pair an unconditioned response (the effect of the drug) with the taking of the pill. In the future, simply taking the pill might evoke the effect of the drug because of conditioning.
But consider two examples. In each of two studies all the patients were diagnosed with duodenal ulcers by endoscopic analysis. Each patient took placebo tablets four times per day for four weeks, after which they were again examined with the endoscope. In each case, we might, as suggested by Dr. Ader, consider this a series of conditioning trials. In one of the studies, done in Germany, twenty-seven of thirty-four placebo-treated patients (79%) were free of ulcers after four weeks (Malchow et al. 1978), while in the other study, done in neighboring Denmark under the same circumstances, only five of thirty patients (17%) were better (Gudmand-Hoyer et al. 1977). From the point of view of conditioning, the two studies were exactly the same. But the outcome was so different that it is hard to imagine that conditioning had much to do with it. And, of course, none of these patients had taken any of the active drug to “learn” what its effects might be (as happened in Dr. Benedetti’s study). Whatever accounts for these differences, it can’t logically be what is the same in both cases.
Expectations
A number of very imaginative researchers have taken another approach to this issue and speak of placebo effects being the result of “expectancy”
or “expectation.” Irving Kirsch, the creator of “Trivaricane,” the “local anesthetic” discussed in Chapter 2, says that we can account for placebo effects, psychotherapy, hypnosis, and a number of other things, with the concept of “response expectancies.” Response expectancies are “antici-pations of one’s own automatic reactions to various situations and be-haviors.” So, if you expect that a cup of coffee will wake you up, it will, even if some sneaky researcher has secretly given you decaffeinated coffee (Kirsch and Weixel 1988).
126 Meaning, medicine, and the “placebo effect”
Robert Hahn similarly focuses on the idea of expectation in his defini-tion of “nocebos” which, he says, are “expectadefini-tions of harmful or painful events that lead to the fulfillment of those expectations” (Hahn 1995:93).
An “expectation” is another way of talking about knowledge or ex-perience. If the doctor tells you that the drug is going to cause terrible side-effects, like headaches or nausea, you are likely to “expect” them. We might, then, attribute your reaction to the medication as a consequence of expectation; or, we might attribute it to your knowledge, obtained from authoritative instruction. But there are many other circumstances where it is plausible to imagine that you know of something in some way, but have no clear sense of it as being “knowledge”; it doesn’t form any parti-cular “expectancy.” Earlier I described research showing that people who got four placebos per day healed faster than people who only got two a day. Now in the abstract, if we were to ask people “Do you expect that you will get better faster if you take four pills rather than two?” and then gave them two, they might have lower expectations than otherwise. But in the research that was actually done, there was no such prompting. It seems unlikely that, as a general rule, people have any clear expectations at all regarding the instructions “take one with each meal, and one at bedtime”
vs. “take one when you get up in the morning, and one at dinner.” But people do generally know after the age of three that four means more than two, even if they have never thought carefully (or been instructed) about the significance of this in the context of taking medication. “Knowledge”
and “meaning” seem more apt here than does “expectancy.”
Similarly, we have seen that Italian men seem to think differently about the color blue than do most other Euro-American men; it is plausible to suggest that this accounts for their unusual reaction to blue sleeping pills.
But it seems unlikely that these fans “expect” their fandom to have an effect on their sleep, any more than anyone expects Viagra to work better because it’s blue.
The only way we could elicit anything about peoples’ expectations on these matters would be to ask them directly, which could plant an expec-tation that wasn’t there before.
In any of these cases – when there are clearly created and measurable ex-pectancies and when there are not – people know things, and experience them meaningfully. They respond to what things mean (whether they
“expect” it or not).