Placebo

Question 1

Placebo-definition

Answer 1

“a substance or procedure… that is
objectively without specific activity for
the condition being treated”.

Question 2

Placebo examples

Answer 2

• pharmacological (dummy medication)
• procedure including sham surgery
• psychological (conversation/homeopathy)

Question 3

Placebo effect (definition)

Answer 3

Any improvement in a symptom or physiological condition of a subject after placebo treatment

Question 4

Placebo response (definition)

Answer 4

Neurobiological and psychophysiological response of an individual to an inert substance

Question 5

Placebo effect in active treatments

Answer 5

Placebo response can modulate effectiveness of active treatments (active–i.e. non-dummy medicines can work better if you believe they will)

Question 6

Nocebo effect (definition)

Answer 6

The harmful, unpleasant, or undesirable reactions (or responses) manifested as a result of administering a placebo, due to the subject’s pessimistic belief and expectation that the drug would produce harmful,
injurious, unpleasant, or undesirable consequences.

Question 7

Nocebo (examples)

Answer 7

Includes statements such as “This medication may worsen your symptoms” or “this medication may give you a headache”

Question 8

Placebos have _____ effectiveness

Answer 8

HIGHLY variable (10-60%)

Question 9

Beecher’s The powerful placebo” (1955)

Answer 9

Book

~ 35% of people respond to placebo

Question 10

Placebo effectiveness is dependent on…

Answer 10

Placebo effect
- doctor-patient communication
- expectation
- conditioning
Things that may give false sense of getting better:
- natural history of disease (spont. getting better)
- regression to mean
- Biases and false positives
- Co-interventions and other non-specific effects

Question 11

___% of physicians would recommend
sugar pill treatment for difficult to treat
conditions such as fibromyalgia

Answer 11

25%

Question 12

Pain killing and anxiety reducing drugs that are infused secretly without an individual’s knowledge are ____ effective than when a patient knows they are receiving them

Answer 12

LESS effective; placebo effect increase efficacy of an active drug

Question 13

Patient expectations

Answer 13

Often a consequence of physician – patient relationship and trust (if u trust your physician and they say it will work –> more likely to have placebo due to positive expectation)

Question 14

Patient expectation example: marijuana sample

Answer 14

Name of marijuana strain may alter the high you get due to expectation

Question 15

Conditioning: _____ is a conditioned stimulus and _______ are conditioned responses.

Answer 15

According to classical conditioning theory
PLACEBO = conditioned stimulus
PLACEBO EFFECT = conditioned responses.

Question 16

Classical conditioning placebo example

Answer 16

1) Start with high level of nociceptive stim
2) then pair inactive cream with decreasing noicieptive stimulation
3) patient associates decreased pain w/ cream
4) inactive cream will start to have an analgesic effect
IS THIS CONDITIONING OR EXPECTANCY–debated

Question 17

Issues with conditioning theory in placebo

Answer 17

Role of conditioning has been questioned, and some describe placebo effect purely in terms of expectancy

Question 18

For FDA approval drug must be…

Answer 18

more effective than placebo

Question 19

CLinical trials with placebo should be

Answer 19

• double blind

Question 20

Double blind

Answer 20

physician doesn’t know what they are

administering, patient doesn’t know what they are receiving

Question 21

Placebo is best in

Answer 21

patient-reported outcomes (subjective health issues)

Question 22

Placebo works best in these conditions:

Answer 22

• Pain
• Depression
• Anxiety
• Drug abuse
• Gastric Ulcers
• Crohn’s Disease
Note: GI disorder effects may be related to anxiety

Question 23

Placebo in crohn’s disease

Answer 23

• Placebo can improve endoscopic assessment of disease activity in 20% of cases (placebo response)

Question 24

“Honest placebo” effect in IBS

Answer 24

Patients with IBS experienced a significant beneficial effect even though THEY KNEW THEY WERE TAKING PLACEBO
as compared to a control group who received no pills.

Question 25

In Gastric and duodenal ulcers placebo was ____ (more/less) effective than H2 blocker (cimetidine) confirmed with ____

Answer 25

Placebo was less effective, but comparable

Healing of ulcer was confirmed with endoscopy = physiological mechanism for placebo

Question 26

WEAKest palcebo effect in conditions where outcomes are _____. Examples:

Answer 26

Objective
infections, blood poisioning
neurological disorders (ex. epilepsy)

Question 27

Pitfalls in placebo clinical trials

Answer 27

• Natural history of disease
• Regression to mean
• biases and false positives
• effect of co-interventions and non-specific effects

Question 28

Natural history of disease

Answer 28

a pitfall in clinical trials

Spont remission can lead to false-positive placebo effects

Question 29

Regression to mean

Answer 29

Meta-analysis shows little placebo effect= but looked at objective AND subjective diseases
But subpopulations can show great benefits

Question 30

Biases and false positives

Answer 30

ex. physicians report better effects in depressed patients than the depressed patients report themselves

Question 31

Non specific effects

Answer 31

-patient charcteristics–placebos may work better in some cultures (germans vs Brazilians) ; alterations in life circumstance can alter depressive scores etc. (bereavement, financials)

Question 32

Co-interventions

Answer 32

Patients may self medicate or change lifestyle–influences disease state

Question 33

How to prevent pitfalls in placebo trials

Answer 33

Add a 3rd arm to the study

• drug, placebo AND no treatment
• “no treatment” group will allow for any changes in life circumstance, disease course, biases, co-interventions, etc.

Question 34

Animal model of placebo: set up

Answer 34

Used an “operant model” where animals would be subjected to mild thermal facial pain when they went for a reward (sugar
water)

Question 35

Process: animal placebo

Answer 35

1) Rats learn that putting their head through the “thermode” at 37oC (non noxious) = reward (sugar water)
2) “Thermode” @ 48oC, (noxious) get baseline score of how often rats go for reward
3) Morphine + handling = analgesia therefore rats learning SubQ injection + handling = analgesia; Morphine treated rats will seek sugar more often
4) Inject saline + handle rats –> go for sugar more frequently.
BUT Effect blocked by naloxone (therefore must have physiological basis in endogenous opioids)

Question 36

Animal model of placebo: short version

Answer 36

COndition rats to associate morphine (analgesia) with handling
WHen given subQ injection and handling –> analgesia
Analgesia is measured by how much the animal goes for the reward in the noxious hot
effect blocked by naloxone (b/c of physiological placebo response)

Question 37

Why does naloxone block animal model of placebo

Answer 37

In this case release of endogenous opioids seems to be involved in the placebo effect
–> naloxone will prevent binding and therefore effect of these endogenous opioids –> prevent analgesia

Question 38

if the substance is viewed as helpful it can ___; if it is viewed as harmful, it can cause ______ aka _____

Answer 38

HEAL; negative effects; nocebo

placebo effect is related to the perceptions and expectations of
the patient

Question 39

Pain matrix structures

Answer 39

• Anterior cingulate and prefrontal,
cortices
• Nucleus accumbens
• Amygdala
• Brainstem periaqueductal gray matter
• Spinal cord.

Question 40

What is the pain matrix

Answer 40

a group of structures that are activated during pain

Question 41

Pain matrix and placebo

Answer 41

Activity of all components of the “pain
matrix” is altered during placebo
analgesia–> decrease activation with placebo analgesia

Question 42

Pain matrix: PFC role

Answer 42

related to recalling the placebo and maintaining its cognitive presence

Question 43

Pain matrix: cingulate cortex role

Answer 43

could be related to the expectation of potential pain stimuli

Question 44

NAc and placebo

Answer 44

High placebo responses link with enhanced dopamine and mu-opioid activity in the circuitry for reward responses and
motivated behavior of the nucleus accumbens

Question 45

Analgesic placebos activate _____ through the ______ activation of ____________

Answer 45

descending inhibition ; PAG; spinal nociceptive reflexes

Question 46

Activation of ____ explains the naloxone sensitivity of placebo

Answer 46

descending inhibition through the PAG activation of spinal nociceptive reflexes

Question 47

How a neutral stimulus saccharin can cause immunosuppression in animals

Answer 47

1) learn taste of saccharin
2) Saccharin is paired in a drink with cyclophosphamide that causes immunosuppression
3) saccharin alone causes hypothalamic activation –> CRH release onto ant pit –> ACTH release onto adrenal cortex –> corticosteroids cause immunosuppression

Question 48

Placebos in pain

Answer 48

• Can also sometimes see respiratory depression (further support for endogenous opioid involvement)
• Placebo analgesia more effective the more severe the pain
• placebo saline was said to be a powerful pain killer and had same effects as morphine

Question 49

Placebo in Depression

Answer 49

• tests for new ADs are benchmarked against placebo

- some ADs like prozac had to run 5 trials before they beat placebo –what is the physiological mechansim

Question 50

Placebo effect involves…

Answer 50

• Clinician – Patient Relationship
• Expectancy and conditioning
• Effects in the brain
• Brain-body interactions

Question 51

Example of active drugs with a placebo component

Answer 51

ADs