Why We Respond to Placebos: Psychological Mechanisms of the Placebo Effect Prof. Irving Kirsch University of Hull

Hypotheses Global mechanisms –Anxiety reduction –Faith and hope –Positive emotion –Therapeutic relationship Local mechanisms –Classical conditioning –Response expectancy

Origins of the Global Hypothesis Stress Health Depression Anxiety Inferences to Positive Emotions

Correlates of Positive Emotions Longevity –Healthy Adults –AIDS patients Immune function –Risk of cold –NK cell cytotoxicity

Inducing Positive Emotions Satisfaction with psychotherapy –Compassionate touch (Alagna et al., 1979) Recovery from surgery –A Room with a View (Ulrich, 1984) Cardiovascular recovery from stressor –Emotional content of film (Fredrickson & Levenson, 1998)

Augmenting the Placebo Effect (Kaptchuk et al., 2008) Irritable Bowel Syndrome Wait list Placebo –10 minute neutral 1 st session Augmented Placebo –45 minute 1 st session –Warmth and Empathy –Positive expectation

Symptom Severity

Quality of Life

Local Mechanisms Simultaneous vs. Sequential Administration Montgomery & Kirsch (1996)

Effect blocked by naloxone (Benedetti et al., 1999)

Global mechanisms –Anxiety reduction –Faith and hope –Positive emotion –Therapeutic relationship –Endorphin release Local mechanisms –Classical conditioning –Response expectancy

Local Mechanisms: Expectancy Conditioning vs. and

Conditioning Model of Placebo Effects Active Treatment (US) Improvement (UR) (CR) Vehicle (pill, capsule, etc.) (CS)

Conditioned Enhancement of Placebo Analgesia (Voudouris et al., 1985; 1989; 1990) Placebo cream Less Pain stimulus Pain Before conditioning

Conditioning Trials (Voudouris et al., 1985; 1989; 1990) Placebo cream Even less pain Surreptitiously lowered stimulus intensity

Old Classical Conditioning Theory (The Stimulus Substitution Model) Conditioning trials Conditioned response Rescorla, R. A. (1988). Pavlovian conditioning: It's not what you think it is. American Psychologist

Contemporary Conditioning Theory (Rescora, 1988) Conditioning trials Representation of US (Expectancy) Response Other sources of information

Blocking the Conditioned Augmentation Effect (Montgomery & Kirsch, 1997; also see Watson et al., 2007)

Conditioned enhancement of the placebo effect (Montgomery & Kirsch, 1997)

Correlation between Expectancy and Pain: r =.70

Pain Reduction with Expectancy Controlled (Montgomery & Kirsch, 1997)

Why Placebo Analgesia Cannot be an Automatic Conditioning Effect Humans –Placebo effects mimic drug effects Placebo morphine lowers pain Laboratory animals –Morphine CR: increased pain –Chlorpromazine CR: increased activity Conditioned compensatory responses (Siegel, 1983; Siegel et al., 2000)

A Two-Factor Theory of Placebo Effects Therapeutic Relationship Other Contextual Factors Conditioning Other information sources Positive Emotion Response Expectancy Placebo Effect

A Two-Factor Theory of Placebo Effects Therapeutic Relationship Other Contextual Factors Conditioning Other information sources Positive Emotion - depression - anxiety Response Expectancy Other Placebo Effects - pain alertness

Antidepressants as Active Placebos

Individual Differences The Search for the Placebo Responder

Ibuprofen and Trivaricaine

The pain stimulus

Session1 Second trial First trial IbuprofenNone Trivaricaine

Session 2 (exactly the same) Second trial First trial IbuprofenNone Trivaricaine

Consistency of the Placebo Effect

Personality Correlates Experimental settings –Dispositional pessimism predicts the nocebo effect (Geers et al., 2004) Clinical settings –Responding to “enhanced” placebo associated with extraversion low neuroticism openness to experience (Kelley et al., under review)

A Two-Factor Theory of Placebo Effects Therapeutic relationship Other Contextual Factors Conditioning Other information sources Positive Emotion Response expectancy Placebo Effect Personality?