Editing 1526: Placebo Blocker

{{comic
| number    = 1526
| date      = May 18, 2015
| title     = Placebo Blocker
| image     = placebo blocker.png
| titletext = They work even better if you take them with our experimental placebo booster, which I keep in the same bottle.
}}

==Explanation==
This comic is a joke about the difficulty of testing a drug that is supposed to block the {{w|placebo effect}}.

A placebo experiment is used for testing a drug candidate. It has two groups: one that gets a real drug candidate, and one that gets a fake. The placebo effect describes the observation that the group that gets the fake often show signs of having received a working drug - though commonly weaker than in the group that gets an effective real drug. In this comic, [[Cueball]] is trying to test a placebo blocker.
This means that the one that gets the real thing will think that they got it because they did, and the group that gets the fake will think that they got the real thing because of the placebo effect, and this makes [[Hairbun]]'s head hurt.

[[Cueball]] states to [[Hairbun]], with a citation from the real world, that his team created a Placebo Blocker, a drug designed to prevent the placebo effect. Cueball begins to design a test for this new drug. Following typical experimental design, patients would be split into two groups: a control group, and the group that receives the treatment.

Cueball knows that the treatment given to the control group is supposed to be designed so that it is not influenced by the variable trying to be isolated. As the placebo effect ''is'' the effect under investigation, a placebo can not be used as a control treatment as a comparison with a placebo blocker. Cueball tries to design around this. In his test, both groups would receive a placebo as a treatment for an unspecified condition (the ''Treatment Placebo''); in addition the test group would receive the Placebo Blocker drug, while the control group would get a placebo pill instead (the ''Placebo-Blocker Placebo''). If this works as expected, the ''Treatment Placebo'' would be blocked by the ''Placebo Blocker'' in the test group, while in the control group, the ''Placebo-Blocker Placebo'' may have a placebo effect in blocking the placebo effect of the ''Treatment Placebo'', and the difference between these effects can be measured to test the effectiveness of the ''Placebo Blocker''.

Cueball and Hairbun think about this trial until they both develop headache from frustration. Cueball then kindly offers Hairbun a sugar pill. While this might have helped cure the headache via the placebo effect had he told her it was a headache treatment, by revealing the pill as merely a sugar pill, it may reduce the effect (though it has been shown that placebos tend to work even if the subject is aware that they are placebos).

In the title text, Cueball mentions that his sugar pills against headache works even better together with the new experimental placebo ''boosters''. Incidentally, he indicates that he keeps those in the same bottle with his sugar pills. Assuming someone believes placebo ''boosters'' are in the jar this would allow them to take the sugar pills and receive a greater placebo effect, as the placebo effect is based upon faith in the treatment, regardless of whether there are placebo ''boosters'' in the jar.

It is possible but unlikely that:
* Cueball's sugar pills are, in fact, the Placebo Blockers themselves and that, seeing Hairbun has a headache, Cueball is inspired to somehow use the opportunity as an experiment to test the Blockers
* Cueball is suggesting Hairbun take a "placebo booster" which is really a "placebo blocker", thus testing the blocker he mentioned earlier in the comic.

Questionable neuroscience research is also discussed in [[1453: fMRI]].

===Placebos===
The {{w|placebo}} effect refers to the phenomenon in which patients given an inactive treatment such as a sugar pill can still show improvement relative to an untreated patient. The placebo effect is thus very important to consider when testing new drugs, since even ineffective drugs can have a positive effect on the patients due to the placebo effect. Modern drug experiments are hence conducted as {{w|Blind experiment#Double-blind trials|double-blind trials}}, where the patients are randomly given either the treatment or a placebo without either they or the administering doctors knowing who receives the new drug and who received the placebo pill. (It is important that the doctor does not know, as if they did, it may affect the way they interact with the patient.)

Generally the patients need to believe that they are receiving an active treatment, but one [http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0015591 study] showed that the effect can occur even if the patients are told that they are receiving a placebo pill. The key factor seems to be that the patients must believe that a positive effect will occur. For example, (1) patients experience a greater effect if they believe that the treatment is expensive and (2) patients who know that they have not been given an active treatment will experience the effect if they are told that placebos can have a positive effect through the power of the mind. Furthermore, the placebo can increase the effectiveness of treatments which ''seem'' larger (this is why over-the-counter pain medication is often administered as two half-doses rather than just one full dose).

Several reasons for the placebo effect have been proposed, from study artifacts - such as under-reporting of negative outcomes by patients who think they are being treated, to neurological explanations for how mental state can translate into physical outcomes.

Placebo-blockers do actually already exist. A side-effect of the opiate antagonist {{w|Naloxone}} is that it [http://healthland.time.com/2009/08/26/a-neurological-explanation-for-the-placebo-effect/ blocks the placebo effect].

It should be noted that placebo does not actually improve the objective condition, only the patient's subjective perception of it (i.e. the patients do not get better more than they randomly would, but the placebo makes them think they do).{{Actual citation needed}}

===Mechanisms of the placebo effect===
The placebo effect is one of the greatest mysteries in modern medicine. It is typically found that the placebo effect is an effective treatment in itself in addition to the effectiveness of drugs and other treatments, and it has been found to cause small improvements to cancer outcomes. In other cases such as pain relief, the placebo effect is claimed to be comparable with the effectiveness of the drug itself - but this is a misunderstanding: this is not evidence of placebo working, but of the drug <em>not working</em>.

The comic refers to the recent study by Kathryn T. Hall, Joseph Loscalzo, and Ted J. Kaptchuk. (2015) ''[https://dx.doi.org/10.1016/J.MOLMED.2015.02.009 Genetics and the placebo effect: the placebome.]'' Trends in Mol Medicine. Volume 21, Issue 5, May 2015, Pages 285–294 - however, bear in mind that one has to treat studies very carefully ''[https://sciencebasedmedicine.org/ted-kaptchuk-versus-placebo-effects-again/ Kaptchuk vs Placebo]''

It is possible to test the placebo blocker using three groups: a test group who receive a placebo and a placebo blocker, a control group who receive a placebo but no blocker, and a second control group who receive no treatment whatsoever, as a lack of treatment is the variable that an actual placebo is designed to control for. Still it might be hard to determine if the pills are having a negative effect or blocking the placebo effect, so multiple trials with multiple illnesses may have to be carried out.

==Transcript==
:[Hairbun is standing in front of Cueball who does all the talking. Below them is a footnote.]
:Cueball: Some researchers* are starting to figure out the mechanism behind the placebo effect.
:Cueball: We've used their work to create a new drug: A ''placebo effect blocker''.
:Footnote: * Hall et al, DOI: 10.1016/J.MOLMED.2015.02.009

:[Zoom in on Cueball who now holds his arms out.]
:Cueball: Now we just need to run a trial! We'll get two groups, give them both placebos, then give one the ''real'' placebo blocker, and the other a...
:Cueball: ...wait.

:[Hairbun holds her chin, while Cueball just stand there for a beat panel.]

:[Hairbun looks again at Cueball who begins to take the lid off of a medicine bottle.]
:Hairbun: ...My head hurts.
:Cueball: Mine too.
:Cueball: Here, want a sugar pill?

{{comic discussion}}
[[Category:Comics featuring Cueball]]
[[Category:Comics featuring Hairbun]]
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[[Category:Footnotes]] <!-- non-digetic -->