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

Glen M. Sizemore via neur-sci%40net.bio.net (by gmsizemore2 from yahoo.com)
Mon Dec 10 17:00:50 EST 2007

"John H." <johnh from goawayplease.com> wrote in message 
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> "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.

But there is no explanation - not at the physiological level. At the 
behavioral level, it is explained by the contingent relationship between the 
saccharin (CS) and the cancer drug (US).
> 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.

But, nonetheless, we can predict some things about what would happen under 
certain circumstances, and we can accurately predict by recognizing the 
phenomenon as classical conditioning. If the predictions are borne out, we 
become more certain that we have appropriately named the phenomenon. Oh, 
BTW, I see nothing "cognitive." Indeed, I find the term "cognitive" to be 

> 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
> hypochondriac.

I agree that conditioning probably plays a bigger role in some things than 
we have realized. It is now widely speculated that, for example, many 
overdoses occur because a person shoots up in unfamilair sorroundings. They 
shoot the same dose, but the normal environment in which they shoot up 
function as CSs that elicit compensatory responses.

> 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.

Maybe. But that says something about them and not the cogency of the notion 
that we are talking about classical conditioning. There is no question that 
when talk turns to behavior, the bullshit starts flying. There is nothing 
new here - mainstream psychology (i.., cognitive "science") is largely 
bullshit, but they have corrupted many.

> 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
> behind.
> 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.

GS: Needless to say, I am in agreement. This and related issues.

>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.

GS: Hmmm. Well behaviorists are somewhat unlikely to be called "dualists," 
but I can certainly resonate with your point. If you stick at the behavioral 
level, you are going to be regarded as not really a scientist. Of course I 
find this silly and offensive, but all you can do is keep pushing your view. 
As I said here before, there is a little wind of change blowing. I have 
mentioned O'Regan and Noe, as well as Bennett and Hacker. Unfortunately 
these guys don't see how much they are supporting the behaviorist position, 
Bennett and Hacker attacking a straw man version of it.

> 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.

Needless to say I agree. There is no question that neurobiology is a real 
science, but cognitive "science," which has great impact on much of 
neurobiology is a complete and utter conceptual disaster. The brain mediates 
conditioning phenomena, and conditioning phenomena account for much 

> 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.

Yeah, there's something there and it is behavioral (not cognitive, whatever 
that is).


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