[Neuroscience] Re: The Placebo Effect on the Rat Immune Response

John H. via neur-sci%40net.bio.net (by johnh from goawayplease.com)
Mon Dec 10 02:44:13 EST 2007

"Glen M. Sizemore" <gmsizemore2 from yahoo.com> wrote in message
news:475bf7c6$0$2858$ed362ca5 from nr2.newsreader.com...
> "John H." <johnh from goawayplease.com> wrote in message
> news:13ln9jgfhk61d62 from corp.supernews.com...
>> In the space of 3 days I have read two books citing this experiment and
>> it is baffling. Please don't try and wash it away with a rationalisation
>> of the dumbass kind, it is very obvious to any honest clinician that a
>> person's attitude can have a profound effect on disease progression. Nor
>> is this spooky, the problem can be couched within a
>> neuro-endocrine-immunological axis of understanding; though I admit that
>> paradigm certainly cannot explain all that comes under the umbrella of
>> the placebo effect. So it still might be spooky ...
>> In this experiment the Bob Ader and Nick Cohen decided to see if the
>> immune system could be trained to respond to a conditioned stimulus. The
>> paired the sweet taste of saccharine wtih an anticancer drug that
>> suppresses immune immune function, cyclophosphamide. They fed the drug
>> and the saccharine to the rats over and over again. Each time the
>> immunosuppressive drug was given the immune cell count went down. Then
>> they took away the drug and just gave the saccharine alone. The immune
>> cell count fell again. Before the conditioning process the saccharine had
>> no impact on immune cell count.
>> I cannot find a way to understand this. Yes the brain and immune systems
>> do influence each other great deal but nothing in our current
>> understanding can explain this.
>> Now if the placebo effect is about suggestion then these are very clever
>> rats. You might want to look up the Norman Cousins and Henry Beecher.
>> Then you'll really get confused. (Those two instances I can offer a
>> plausible explanation but this one has me stumped.)Why the placebo effect
>> is ignored is beyond me. I suspect it simply doesn't fit into our current
>> understanding so people wash it away with some dumbass explanation. This
>> is what happened to Ader and Cohen, initially their results were treated
>> with derision. If anyone knows if someone has come up with an explanation
>> for this effect I sure would like to hear it.
> It is not clear to me what you are asking here, John. In one sense the
> answer is "it is classical conditioning." Now, if your question involves
> "the neurobiology of classical conditioning" and this effect in
> particular - good luck. As I have said many, many times here, the way
> physiology mediates behavior is largely unknown (despite the arm-breaking
> self-back-patting of neurobiologists). We cannot explain something as
> "simple" as how a rat comes to press a lever after exposure to the
> necessary contingencies.

I'm asking for an explanation of this effect because:

it has important clinical implications.
it casts an entirely new light on the placebo effect
it is a bloody 'orphan study' Glen, I hate these things that are left lying
on the shelf.

I've consistently steered away from the cognitive stuff and headed towards
neuro-immune land now only to find the cognitive stuff is encroaching on
that territory. Classical conditioning with respect to what most label as
behavior I don't have a problem with but with these sorts of impacts on
immune function there are some rather serious questions to address not only
in relation to neuroimmunomodulation but also at the clinical level.

It is well established in brain injury studies that there can be long
lasting changes in endocrine and immunological function that have little and
typically no relationship to the nature of the organic injury. There are
even studies suggesting long term ongoing immunological activation arising
from mild brain injury and subsequent ongoing neurodegeneration. Attempts to
understand this typically focus on the organic nature of the injury but in
the vast majority of cases there is no apparent relationship. Sure, one can
speculate and find evidence for agents(eg. dendritic cells, complement
expression) which sustain immunological activation but this avoids the
important question: how the hell does this get started in the first place
and why is it being sustained in a subset of patients? This is not a mere
academic quibble about CNS function and organisation Glen, it goes right to
the heart of something I have been trying to understand for a very long
time. I'm beginning to suspect that in those patients where there are
ongoing problems emerging there may well be a conditioning component. It is
no wonder that only until recently has the medical community dismissed the
charge of malingering against these patients and acknowledged that there is
some real effect going on here. The risk with being too reductive is that
you can easily fall into the error of thinking that if there is no organic
evidence for symptoms then the patient must be malingering or a

What it definitely suggests is that the idea of classical conditioning is
not confined to what is typically regarded as 'behavior'. Radical
behaviorists may not be surprised by the idea that immunological function
constitutes 'behavior' but if you attend an immunology conference and start
talking about the classical conditioning of immunological processes they are
likely to throw you out of the nearest exit.

The Placebo Effect

It is typically ignored these days, often intellectually discarded as the
control group phenomenon and of no real import. Eg. A study two years ago on
Zoloft for children found that the placebo rate was 30%(placebo tends to
kick around this level) and the Zoloft response was 45%. This, they so
mightily claimed, was clear proof of the efficacy of Zoloft for childhood
depression. If that is true surely one could just as powerfully, if not more
powerfully, argue that the placebo effect is a better treatment for
depression? Moreover the placebo group did not have all those side effects,
which undoubtedly gave the patient group a very real sense they were taking
an active substance; thus the patient response may well have had a placebo
effect above 30%.

Any clinician will tell you that a patient's attitude towards the condition
can have a profound influence on the course of their illness. Last time I
went to get my eyes examined by the experts I asked the optician, 'in your
experience does peoples' emotional state impact on their vision?' Her
positive response was immediate, affirmative, and almost visceral. I only
asked her this because a few weeks beforehand I read an ophthalmologist who
stated that in his clinical experience serious eye conditions were often
preceded by emotional turmoil. Yet you won't find a great deal of research
these days examining the placebo response and this in spite of the fact that
as the placebo response is often around 30% then it constitutes a
therapeutic intervention worthy of serious consideration. Just recently a
study claimed that maintaining a "macho attitude" helped ward off PTSD. Damn
right, this 'let's talk about it' bullshit can often make things worse,
research has also backed that up and for many people 'toughing it out' is
just plain common sense. Yet the philosophy of modern medicine is almost
exactly the opposite and it certainly fails in encouraging people to take
charge of their health. For example, my friends and their daughter, the 3
clinicians seen have basically said: nothing to be done, pathology will take
its course. Tough shit. Fortunately I've found a clinician who is prepared
to at least try something. Great for me by the way, I can now leave all that

How often is the placebo effect now taken as a serious therapeutic measure?
Up until World War 2 or thereabouts doctors were not that adverse to
invoking the placebo response. Certainly a fair proportion of the placebo
effect is  naturally getting better but that is far from the whole story. If
there were more studies on the impact of classical conditioning on health in
general and its relationship to the placebo effect then we might be opening
whole new treatment regimes for patients. At present though it seems that
because the placebo and simple conditioning effects tend to suggest dualism
everyone runs away from studying the same. I find it ironic that
behaviorists, so insistent as they are on matters of evidence and
epistemology, are effectively playing with fire because their ideas about
behavior cannot be reduced to molecules hence are suggestive of spookiness.
It sounds so erudite and scientific to talk about molecules and receptors
but much of this is whistling in the dark. Eg. the ligand receptor complex,
lock and key metaphor. Give me a break, as a friend of mine quipped: if you
keep throwing a key at a door in the hope it will hit the lock at the right
angle you're more likely to wear out the door than open the lock.

Fine for you Glen, coals to Newcastle, but all this throws light on why so 
many people have turned towards alternative medicine. Sure, I know there are 
big problem there but it has one huge thing its favour: the patient is given 
considerable responsibility to take charge of their health, the patient is 
not given some deterministic response. Eg. The cancer will kill you in x 
months. There was a study done years ago which found that patients were 
better at predicting their time of death than doctors. Go figure, seen it 
happen to people, they give up, they die. As I used to say to people: when 
you stop fighting you're already dead. Perhaps until now I never realised 
just how true that is.

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