placebo

[malernee]

[guest]

The Placebo Effect in Animals. JAVMA 215 (7): 992.
The placebo effect is recognized as a factor in the course and outcome of a variety of disease states in humans, although it is poorly understood. The most fundamental assumption is that the placebo effect involves a functional interrelationship between psychological factors and physical states of the body. Since the placebo effect seems to require recognition of the intent of the doctor's efforts, the existence of this effect in animals has been questioned based on their lack of certain cognitive capacities.

A placebo is defined as any medical intervention (including drugs, vaccinations, surgery, procedures, rituals, touch, spoken words, nutrition, or supplementation) that has a nonspecific, psychological, or psychophysiologic therapeutic effect, or that is used for a presumed specific therapeutic effect on a patient, symptom, or illness but is without specific activity for the condition being treated. Placebos were originally used in "double-blind" experimental pharmacologic trials to exclude expectations and beliefs of the patients and physicians from the evaluation of new treatments. The role of placebos has move to that of a variable to act as a control in medical research.

The three theories on placebo mechanisms receiving the most support include classical conditioning, expectancy, and endogenous opiates. In animals, a fourth theoretical mechanism involves the effect of human contact.

Conditioning: The theory that conditioning effects are the basis for placebo responses. Pavlov's dog is one example which demonstrated that repeated association of food stimulus with certain nonfood stimuli caused a type of conditioning. The animal had the same physiologic reaction to the food and nonfood stimuli. Since that time, studies show that saline injections, after repeated injections of a certain drug, can cause a conditioned stimulus. One example revealed that clinical signs of hypoglycemia (twitching, decreased activity, convulsions) were seen in rats and dogs when injected with the saline placebo, after being conditioned to daily insulin injections.

Expectancy: The cognitive model for the placebo mechanism, which assumes that the change is causally associated with the patient's specific expectation of improvement. The exact mechanism is not known, but probably involves the cognitive and emotional states of controllability, helplessness, and coping. A state of learned helplessness results when individuals do not have control over their environment, especially during times of adversity. Animal experiments using escapable and inescapable electric shock revealed that the controllability or predictability of environmental stressors is the critical factor for emotional well-being. When the individual perceives a lack of control over stressors, physiologic and pathologic changes may occur, such as suppressed natural killer cell activity, decreased tumor rejection, greater tumor size, gastric ulcers, etc. Literature investigating the expectancy model of placebo in animals was not found.

Endogenous opiates: the theory that placebo effects may be mediated by opioid neuropeptides. Endogenous opiates may play a role in the placebo response in human pain, but reports are inconsistent. Results in certain studies indicated that the narcotic antagonist naloxone diminishes or blocks placebo responses in the treatment of postoperative dental pain in humans., but other studies failed to identify that effect. Animal studies in this area are lacking and it is premature to extrapolate the results of a few human studies to animals.

Effect of human contact: animal studies documented physiologic and health effects when in contact with humans. Horse and dog heart rates decrease when petted by humans. Dogs also have changes in blood pressure, aortic blood flow, and coronary blood flow with human contact. Similar improvements in cow milk production, sow reproductive efficiency, and rat post-operative mortality rates were seen with human influence. The mechanism of this theory is unknown. Some researchers believe that this is attributable to stress reduction, but others have observed that human contact increases stress in animals, suggesting that the effects of human contact are not likely due solely to stress-mediated factors.
*****
spite of a large body of work regarding placebos and
placebo effects, it is still not generally accepted that placebo
effects, in the sense of a physiological response to an otherwise
inert stimulus that alters the course of disease, truly exist.
The concept of a placebo received its first real notoriety in
1955. Enthusiastic explorations and expositions of the placebo
effect followed for roughly the next 20 years, but by the 1970s,
little discussion about such effects was being conducted.
Placebo effects were resurrected in the 1980s and have again
found a position of prominence in the medical lexicon.

The foundation work for the current interest in placebos was
“The Powerful Placebo,” published in 1955 by Henry Beecher.
Beecher estimated that 35% of patients, in 15 trials with
different diseases, received satisfactory relief from placebo
administration alone. This figure has been widely quoted and the
paper is sill one of the most frequently cited references in
placebo literature. However, it was later shown that this
average, even if it is accurate, most likely conceals a wide
variation in placebo response among individuals ( Moerman, DE.
General medical effectiveness and human biology: Placebo effects
in the treatment of ulcer disease. Med Anthropol Quart 1983; 14:
3–16).

However, in 1997, the 1955 article was reanalyzed (Kienle,
GS, Kiene, H. The powerful placebo effect; fact or fiction. J
Clin Epidemiol 1997;50(12):1311-8). In this reanalysis,
researchers were unable to find any evidence of a placebo effect
in any of the 15 studies cited in the original paper. They did
note that there were many confounding factors that could account
for the improvement noted by the participants in the various
trials, but they concluded that there was most likely no
physiological placebo effect at all.

More recent work by Danish investigators have failed to show
that a physiological placebo effect exists. For example, a study
published in the NEJM a few years back reviewed the medical
literature from 1946 forward and found 130 studies in which a
placebo or dummy-treatment group was compared to a no-treatment
group. Of these, 114 were evaluated by means of a formal
meta-analysis (a systemized study of studies). The meta-analysis
was not able to show that placebo treatments (when compared to no
treatment at all) changed either objective symptoms of disease
(Hrobjartsson A, Gotzsche PC. Is the placebo powerless? An
analysis of clinical trials comparing placebo with no treatment.
N Engl J Med. 2001; 344(21):1594-602). Additional references:

Hrobjartsson A, Gotzsche PC.
Placebo interventions for all clinical conditions.
Cochrane Database Syst Rev. 2004;(3):CD003974.

Hrobjartsson A, Gotzsche PC.
Is the placebo powerless? Update of a systematic review with 52
new randomized trials comparing placebo with no treatment.
J Intern Med. 2004; 256(2):91-100.
*****
Some research does suggest that expectations of success affect
treatment outcomes. That is certainly not to be confused with
informed consent.

>[Additional thought: I am wary of the alties who say to me,
"Well, even if it just the placebo effect, we still have helped
the person.

Otherwise stated, this argument for use of the therapies
might be rendered as:

Premise 1: Therapies that may not have direct physiological
effects (that is, that don’t “work”) may still produce a placebo
effect in a patient.

(Unstated) premise 2: A placebo effect is better than no
real or perceived improvement in a patient's condition.

Conclusion: Therapies that may produce placebos are worthy
of consideration OR (alternative conclusion) therapies that may
produce placebos are valuable.

The problem with the argument, as stated above, is that the
premises on which it is based may be false, if for no other
reason that there may be negative effects from prescribing
placebos (nocebos), and their occurrence cannot be predicted.

> For all the complaints (some justified) in Altmedland about how
paternalistic "allopaths" are, I find the preceding argument
against true informed consent to be quite paternalistic
and infantilizing.

Right, and, in fact, it's altmedland that's paternalistic,
and demonstrably so. For example, paternalism was dominant in
the historical practice of traditional Chinese medicine (e.g.,
Dai Q. Informed consent in China: status quo and its future. Med
Law Int. 2003; 6(1):53-71).



Proper assessment during clinical trials or treatment is important in order to distinguish the placebo effect from other causes of disease resolution, such as natural resolution, specific effects of treatment, and regression to the mean (statistical concept). A better understanding of the placebo effect would help explain treatment failures (through negative placebo effects) and would provide suggestions to minimize these types of adverse effects.
1) List the four theories of the placebo mechanism noted in this article.
2) Pavlov's dog experiments fall into which theory?
3) Which theory is the cognitive model and what is its fundamental assumption?
4) T or F The improved well-being and physiologic state of animals is due to a reduction in stress.
1) Conditioning, expectancy, endogenous opiates, effect of human contact
2) Conditioning
3) Expectancy; assumes that the change is causally associated with the patient's specific expectation of improvement.
4) F The results of may studies indicate that human contact increases stress in animals; therefore, the effects of human contact

[guest]

The Placebo "Effect" is a Delusional Response

A placebo (pluh·SEE·boh, noun) is a substance or treatment with no medicinal qualities that is presented to the patient as real medicine. This deception often causes the patient to think their condition has improved. The subjectively perceived improvement in a patient's condition, that arises only from the patient's belief that a treatment will cause such improvement, is called the placebo effect.

The opposite is a nocebo (noh·SEE·boh, noun), a nonmedicinal substance that causes perceptions of harmful effects, simply because the person taking the substance expects those effects. In this case a patient may relate that they have symptoms of known (by the patient) side effects, even though they have received nothing that can have any such effects.

A patient cannot experience a true placebo effect, if they do not know that they are receiving anything that should have any effect.

A placebo response is a reaction to an effective deception. It occurs when a patient uses a worthless and inactive substance that has been misrepresented to be a worthwhile and effective substance.

If a patient knows that they are receiving a placebo (if they really understand what that is....), then their response will be a tainted, and not a true, placebo response.

A perfect experiment should, when possible, include a placebo controlled arm, but should not include any information that would give any clue to the patient that they might receive a placebo. For legal and ethical reasons, researchers have to compromise on this point, and use informed consent forms.

In fact, since a substance or method used as a "placebo", can - by definition - has no physiologic "effect" - but must be neutral - it is actually often misleading to use the word "effect". It would often be preferable to write placebo "response" instead. We thus indicate that a patient has been truly deceived, and has reacted to that deception. Their response is actually delusional.

[malernee]

There have been two quantitative studies (in Italy and Canada) in the last
few years that have showed on the neuron level (as well as dopamine
production) that indeed there is a physiologic "effect" from placebos. The
following link is the most recent which was originally published in Nature
Neuroscience. There are links on the page to the British Columbia study
"Placebo produces surprise biological effects" originally published in
Science, (vol 293, p 1164) and "Brain scans reveal placebo effect in
depressed patients", originally published in the American Journal of
Psychiatry. (vol 159, p 122).

http://www.newscientist.com/article.ns?id=dn4996

While the first two studies are not addressing the issue of pain and focus
entirely on Parkinsons, there is clearly more going on than delusion where
the placebo response is involved. Whether it is conditioning from repeated
treatment of a drug or expectation of a drug's effect is not known. But it
clearly shows up in the brain chemistry by the firing of neurons and the
release of dopamine.

[guest]

Ideally a placebo substance should have no physiologic effects, in and of itself, but the *response to the belief* (a thought process) that the substance can effect real change in a disease process can indeed cause measurable chemical changes.

So can other thought processes, without any placebo substance being used at all. Embarrassment is probably one of the best known examples. Just a thought can start a chain reaction, including changes in skin color and heart rate.

What scientists are looking for when they use placebo substances in an experiment, are for physiologic changes that can't be explained by thought processes alone. They want to know what the new medicine actually does above and beyond any reaction that simple belief can effect, since belief alone can rarely effect enough change to cure most serious diseases. Of course even a false hope can be comforting and cause relaxation and reduce stress, which can temporarily help a heart patient. Scientists are looking for ways of producing changes above and beyond those produced by false hope, which is all that many forms of so-called "alternative" medicine usually offer.