Lecture 6- Placebos Flashcards
Placebo
- control treatment with similar appearance, but without its specific activity
Two arm trial
- placebo group (placebo effect) + treatment group (specific effect)
Three-arm trial
placebo group (placebo effect) + treatment group (specific effect) + untreated group (natural history)
The placebo paradox
placebo in RCTs
- nuisance factor
- noise in system
- obsures “real” treatment effects
- non-specific
placebo in clinical practice
- useful therapeutic tool
- good clinical practice involves factors other than specific treatments
contribution of placebo in clinical trials
- 8 different conditions, placebo has dramatic effect
- ex: phobias: placebo> active
- acute pain —> placebo doesn’t do much
- chronic pain —> placebo has more of an effect
pain is multidimensional
- emotion and cognition can have a +/- effect on pain
Influence of doctor-patient relationship on placebo
- group not informed before surgery
- 2nd group informed of pain expectations, positive
- acute phase: control group reported a much higher level of pain than the informed special care group
Contextual factors influencing placebo (hidden/open manner)
- different analgesics given to patients
- drugs given in a hidden manner (computer delivery pump given to patient at unknown times) or open (via nurse)
- if there was a nurse present —> reported much less pain than if they were completely unaware
Pharmacological conditioning of placebo
- morphine to chronic pain patient —> analgesia
- sugar pill —> no response
- during study, was the acquisition phase: patient given sugar pill + morphine = to induce unconditioned response
- evocation: just give sugar pill, patients reported feeling analgesia
- can pharmacologically condition patients into thinking they are getting a pain-relieving drug
Opioid conditioning and expectation placebo involves _____
Opioid conditioning and expectation placebo involves endogenous opioids
- subjects underwent ischemic pain
- condition people with morphine on day 2, 3
- 4th day: tell them you are giving them morphine, but actually saline —-> still get pain response
- day 4: giving naloxone (opioid antagonist)—> no placebo reported by patient
- if you do this conditioning and give expectations, there is endogenous opioids triggered in the body that help with analgesia
Non-opioid conditioning and expectation ____
Non-opioid conditioning and expectation DOES NOT involve endogenous opioids
- condition individual with something thats not an opioid —> placebo effect involves the endogenous
How is non-opioid conditioning placebo mediated?
- by CB1 cannabinoid receptors
- placebo involves the endocannabinoid ss
conditioning with opioid –> placebo effect involves
endogenous opioids
conditioning with non-opioid, placebo effect involves
- placebo effect involves endocannabinoids
Effect of branding on headache pain reporting
Placebo affecting neurochemistry
- Placebo activates endogenous opioid system
- looked at regions of brain involved in pain transmission
- gave them mu opioid receptor tracer
- induced pain
- gave placebo
- found that even though the patient was taking placebo, endogenous opioids were being released in areas associated with pain
- also asked subjects “how much pain are you feeling”
- reported pain correlated with the mu opioids being released in the brain
Placebo activates ___ circuits
Placebo activates dopaminergic circuits
- also involved in placebo
- activated in subjects who received placebo
- amount of pain reported correlates with amount of dopamine released in the brain of these individuals
Does placebo occur in animals?
- measure the time it takes for animal to withdraw its paw
- group 4: pharmacologically conditioned with morphine in first few days, later given saline
- group 5: given naloxone on final day
- group 6: conditioned with non-opioid (ASA)
- placebo effect occurring in group 4
- endogenous opioid system occurring in animals as well
- naloxone + non opioid —> no placebo effect
Morphine-induced placebo effect
Aspirin-induced placebo effect
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Nocebo effect
- expectations or information stating that procedure will be more painful leads to increased pain response
- fear
- nervousness
- negative emotions
- involves cholecystokinin release
- proglumide = CCK antagonist
hidden situation: P administered —> doesn’t do anything (doesn’t cause pain)
open situation: syringe full of saline “this is gonna hurt” —> reported pain (nocebo)
given increasing doses of CCK antagonist —> able to block nocebo
CCK involved in expectation/ nocebo effect
psychological induction of pain
- normal subjects
- placed electrodes on head
- old electrical current was going to be passed through their heads (no current was actuallygiven)
- patients describe headache
- focusing on pain can itself cause pain
what can block the nocebo response
- proglumide
- proglumide = CCK antagonist
Summary
- placebo has an influence on how physicians should treat patients
- can have positive effects
- complement treatment strategies
- placebo contributes to clinical trial outcomes
- placebo/nocebo has cle
