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Mind Over Matter: Placebos and Expectancies. T/F: Placebos make patients feel better; they don’t actually get better T/F: There are no negative effects of placebos T/F: Placebos can reduce asthma and make wounds heal faster

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Mind Over Matter: Placebos and Expectancies

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Mind over matter placebos and expectancies

Mind Over Matter: Placebos and Expectancies

Mind over matter placebos and expectancies

T/F: Placebos make patients feel better; they don’t actually get better

T/F: There are no negative effects of placebos

T/F: Placebos can reduce asthma and make wounds heal faster

T/F: Placebo therapy could be the end of biomedicine as we know it

T/F: Doctors can lie to patients if it is in the patient’s best interest.




  • From Latin placere - “to please” or “I will please”

  • Placebo

    • “an innocuous substance without a specific physiological effect”

      • Clearly active and not innocuous;

      • has physiological effects

    • any treatment devoid of specific actions on the patient’s symptoms or diseases that, somehow, can cause an effect upon the patient.

      • Obviously have specific actions but true that we don’t know precisely how

The placebo effect

The Placebo Effect

  • Based on expectancies

    • "anticipation of a systematic if/then relationship between events and objects." (Tolman, 1932)

  • Afflictions that have strong psychological components (pain, anxiety, and depression) tend to show high rates of placebo effects

    • ~ 65% of patients in antidepressant trials get better with drug

    • ~ 35% of patients in antidepressant trials get better with placebo

    • Many times these rates don’t differ statistically (30% rule)

  • A meta-analysis showed that antidepressants relied on the placebo effect for 75% of their effectiveness

  • The remaining 25% “real” drug effect may be a disguised placebo effect

The placebo effect cont

The Placebo Effect (cont)

  • Blocked by real drugs, e.g., opioid antagonists

  • Placebos have side effects (nocebo)

  • Placebo effects can last for a long time: over 8 weeks for panic disorder, 6 months for angina pectoris, and 2.5 years for rheumatoid arthritis.

  • Depressed patients who respond to placebos differ biochemically from those who don’t

    • Short-term depression (< 3 months) more responsive

    • Long-term depression (> 1year) not responsive

Placebo effect

Placebo Effect

  • If expectation of pain can increase pain intensity,

    • how might expectation of pain reduction influence perception?

      • Experimental results

        • 85% of Ss given placebo for relief of pain caused by Herpes (cold sores or genital sores) reported pain reduction

        • 56% of patients given sham treatment (small skin incision) for angina (heart pain) reported significant pain reduction

        • On average, 33% of Ss in placebo pain studies report pain reduction

Are many drug effects simply placebo effects

Are many drug effects simply placebo effects?

  • Placebo effects were discovered in the 1950s

    • Administering a simple sugar pill or water alleviated symptoms or even cured some diseases

  • However, it’s a minority view that it’s all placebo

  • Nonetheless, some placebo effects may be present in all drug effects

    • How do you dissociate placebo from other effects?

Nocebo i will harm walter kennedy 1961

Nocebo (“I will harm”)(Walter Kennedy, 1961)

A nocebo response occurs when a drug-trial's subject's symptoms are worsened by the administration of a placebo.

If the patient believes a substance is harmful it can cause negative effects.

The nocebo effect

The Nocebo Effect

  • Emotional state, depression, anxiety, anger, hopelessness

  • Negative health care provider

  • No love in the family

  • Cynicism, suspicion and pessimistic expectations

  • Medical students disease (hypochondriasis)

  • Cardiac neurosis is a nocebo – 75% of chest pain is due to anxiety.

Nocebo effect

Nocebo Effect

  • Approximately ¼ of patients receiving a placebo voluntarily report adverse side effects

  • When prompted, between 27% and 71% report adverse side effects

  • Usually general complaints (difficulty concentrating, nausea, fatigue)

Placebo nocebo evidence based medicine

Placebo/Nocebo Evidence Based Medicine

  • All drugs and procedures need to be tested against the placebo/nocebo effect, as high as 70% in most medications and operations.

  • Treatment benefit = therapeutic gain + natural history of illness + placebo effect-nocebo effect

Mind over matter placebos and expectancies

  • Note that if the nocebo effect is greater than the therapeutic gain and the natural history of the disease, the treatment will make the patient worse.

  • The evil eye – voodoo – witchcraft

Dealing with placebo and nocebo effects in experiments

Dealing with Placebo and Nocebo Effects in Experiments

Study Designs

(randomly assigned to experimental/placebo arms; passive vs active placebos)

  • Blinded Study- Participant doesn’t know if they are receiving treatment or placebo

  • Double-Blinded Study- Participant and Experimenter do not know if treatment or placebo is being given

  • Double-Blind, Crossover Study- Same as double-blinded, except participants get treatment and placebo in random order (controls for Ss variability)

Ethics of clinical studies

Ethics of Clinical Studies

  • Is placebo ethical?

    • Is prescribing placebos deceitful or unethical?

  • Sometimes standard therapies are found to be dangerous

Source of placebo pavlovian conditioning

Source of Placebo: Pavlovian Conditioning

Why the high responsiveness to expectation of pain relief

Why the high responsiveness to expectation of pain relief?

  • Evidence that expectation of pain relief activates mu-opioid neurotransmitter system (“endorphins”)

Red & orange indicate regions of heightened mu-opioid activity when P reports positive effect of placebo

Zubieta et al - Placebo Effects Mediated by Endogenous Opioid Activity on µ-Opioid Receptors (2005)

Other factors involved in the placebo effect cont

Other factors involved in the placebo effect (cont)

  • Natural disease progression may be cyclical

    • gets worse then gets better

  • Enrolling in a clinical trial or seeing a doctor gives some individuals a greater sense of control over the illness

  • Feelings of concern and caring from nurses, doctors, and researchers

    • A healing environment

  • Difficult to measure some illnesses/diseases

    • Scales for measuring pain/anxiety/depression are not clear cut and tend to be somewhat labile

  • Poor patient selection (no test for susceptibility to placebo)

Cognitive explanations schemata

Cognitive Explanations: Schemata

  • Organized representations of conceptually-related information that guide processing of new information

    • Facilitate memory and comprehension

    • Influence the speed of information processing and problem solving

    • Gather information into meaningful and more easily retrieved units

    • Enable the individual to fill in missing information

    • Provide greater confidence in prediction and decision making.

Creating expectations alcohol

Creating Expectations: Alcohol

  • Identified in various age, drinker groups

  • Alcohol schemas in pre-schoolers

  • Related to drinking levels

  • Predicts future drinking levels

  • Change in parallel with drinking levels

  • Experimentally manipulable with corresponding effects on drinking

  • Consistent with behavior after drinking

  • Some relationship with family history

  • Change with age before drinking

Development of alcohol expectancies

Development of Alcohol Expectancies

Alcohol expectancies cont

Alcohol Expectancies (cont)

  • With age and drinking, alcohol

    expectancies have more to do

    with arousal/sedation than whether alcohol is good or bad

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