Topic :

Analgesic effect of placebo in clinical trials

PRESENTED BY : PRIYANKA DEY
BWU/BPH/18/013

Guided by :Ms. Somasri Shannigrahi (ASSISTANT PROFESSOR)

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 Placebo
• A placebo is a medical treatment or procedure designed to deceive the participant of a clinical
experiment.

• It does not contain any active ingredients but often still produces a physical effect on the individual.[1]

• The placebo effect is a real neurobiological phenomenon and that the brain's 'inner pharmacy' is a critical
determinant for the occurrence of psychobiological and behavioural changes relevant to healing
processes and well-being.[2]

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 HOW DOES THE PLACEBO EFFECT WORKS ?

• A placebo treatment can have a positive therapeutic effect in a patient, even though the pill or
treatment is not active. This is known as the “placebo effect” or “placebo response”.

• The placebo effect depends upon the relationship between one’s mind and body .Its all about what
a person expectation from the drug .

• The effect of the drug is directly proportional to the thought of one person for that taken medicine.

• Conscious anticipation and unconscious conditioning represent two of the major mechanism
through which the patient may produce a therapeutic effect .

• Expectancy seems to be an important psychological mediator of placebo effect, it is likely to be

operated alone . [3]
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 Placebo analgesia
• The placebo for analgesia is related to patients perception or direct experience of a treatment i.e
what the patient is seeing , hearing any verbal information about the treatment actively this
sensory information with the memories of previous experiences and current experiences.

• In fact the verbal suggestion along with the treatment may enhance the effect of placebo and
decrease the effect of pain medicine to an extent where there is no longer any important
difference between the effect of two treatment .Also emotional factors such as satisfied with the
treatment , reduced level of anxiety and stress act as an additive factor for the placebo
treatment , but fear may block these effect .[4]

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 Morphine injection Placebo injection Placebo and naloxone injection

Placebo uptake Placebo uptake

Reward pathway is Reward pathway is

Morphine
activated activated
Naloxone

Endorphin
released

Opoid receptor

Pain persists
Termination of pain Termination of pain

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 The placebo effect and the brain
• Brain imaging studies have stated that the expectation of placebo analgesia is associated with
increase activity in the left anterior cingulate , right precentral and lateral prefrontal cortex and
the left periaqueductal grey matter.

• Pain relief after placebo administration is associated with decrease in activity at the pain
processing region , including the medial thalamus , primary , secondary somatosensory cortex ,
the dorsal posterior insula , the mid insula , the anterior insula and the dorsal cingulate cortex.[5]

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 Hormone response
• Neurotransmitter study have shown that placebo analgesia effect may be mediated by the release of
endogenous opioid .Placebo effect that are non–Opoid mediated can be blocked by cannabinoid receptor
antagonist.

• The hormones such as oxytocin and vasopressin which are involved in social behaviour have been show to
increase the placebo effect in some population .

• Positron emission study (PET) studies supported the assumption that reward and release of dopamine may
be central to placebo effect .But dopamine antagonist haloperidol doesn’t seem to block the Placebo
effect .Genetic information suggests that the enzymes like catechol-O-methyltransferase(COMT) are involved
in the metabolism of dopamine to be a genetic locus of the placebo response , although more investigation
are necessary.[6]

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 Clinical trial of placebo
• A placebo is used in clinical trials to test the effectiveness of treatments and is most often used in drug
studies.

• For instance, people in one group get the tested drug, while the others receive a fake drug, or placebo, that
they think is the real thing.

• This way, the researchers can measure if the drug works by comparing how both groups react.

• Recent research demonstrates that placebo effects are genuine psychobiological phenomenon attributable
to the overall therapeutic context, and that placebo effects can be robust in both laboratory and clinical
settings.

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 Is the ‘placebo effect’ just a myth?
• In an opinion article, Australian researchers argue that the 'placebo effect' - the idea that we can
start to recover from illness after being given a sugar pill, simply because our brains and bodies
believe we've really been treated - isn't a real thing.

• They reviewed the evidence used to support the ideas behind the placebo effect, and say it is all
flawed and that placebos only ever have a very small effect on patients. The scientists say they
are concerned about the use of placebos in clinical practice, so decided to see if the placebo
effect was a myth that needed to be debunked, and their work suggests it may be.[7]

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 Nocebo

A nocebo effect is said to occur when negative expectations of the patient regarding a treatment cause the
treatment to have a more negative effect than it otherwise would have.For example, when a patient
anticipates a side effect of a medication, they can suffer that effect even if the "medication" is actually an
inert substance.[8]

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 Conclusion
Placebo can be true or a myth but more studies are required to clarify. But placebo has the ability to
show postive effects and may clinically show improvement .

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References
[1]-Hostiuc S, Rentea I, Drima E, Negoi I. Placebo in Surgical Research: A Case-Based Ethical Analysis and Practical
Consequences. Biomed Res Int. 2016;2016:2627181. doi: 10.1155/2016/2627181. Epub 2016 Aug 10. PMID: 27595098;
PMCID: PMC4995345. Sorin Hostiuc, Irina Rentea,Eduard Drima and Ionut Negoi
[2]- Požgain I, Požgain Z, Degmečić D. Placebo and nocebo effect: a mini-review. Psychiatr Danub. 2014 Jun;26(2):100-7.
PMID: 24909245.
[3].[7]-Abhishek A, Doherty M. Mechanisms of the placebo response in pain in osteoarthritis. Osteoarthritis Cartilage. 2013
Sep;21(9):1229-35. doi: 10.1016/j.joca.2013.04.018. PMID: 23973135.
[4]-Colloca L. Placebo effects in pain. Int Rev Neurobiol. 2020;153:167-185. doi: 10.1016/bs.irn.2020.04.001. Epub 2020 Jun 9.
PMID: 32563287.
[5]-Benedetti F, Mayberg HS, Wager TD, Stohler CS, Zubieta JK. Neurobiological mechanisms of the placebo effect. J Neurosci.
2005 Nov 9;25(45):10390-402. doi: 10.1523/JNEUROSCI.3458-05.2005. PMID: 16280578; PMCID: PMC6725834.
[6]-Manchikanti L, Giordano J, Fellows B, Hirsch JA. Placebo and nocebo in interventional pain management: a friend or a
foe--or simply foes? Pain Physician. 2011 Mar-Apr;14(2):E157-75. PMID: 21412379.
[7]-Jonas WB. The Myth of the Placebo Response. Front Psychiatry. 2019 Aug 16;10:577. doi: 10.3389/fpsyt.2019.00577.
PMID: 31474888; PMCID: PMC6707261.
[8]-Rossettini G, Camerone EM, Carlino E, Benedetti F, Testa M. Context matters: the psychoneurobiological determinants of
placebo, nocebo and context-related effects in physiotherapy. Arch Physiother. 2020 Jun 11;10:11. doi: 10.1186/s40945-020-
00082-y. PMID: 32537245; PMCID: PMC7288522.

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Thank you

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