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How can we make placebo effect work for us "on-demand"?

Image credit: https://wchh.onlinelibrary.wiley.com/doi/pdf/10.1002/psb.344; https://en.wikipedia.org/wiki/File:Cebocap.jpg#file

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Povilas S
Povilas S Dec 29, 2020
Placebo effect usually relies on someone else to deceive (or conceal some information from) the person in order to induce a positive effect on their health. But is it possible to somehow deceive yourself without being aware of it to gain benefits from that? And is deception really needed? What methods could be employed for people to self-induce it?



Placebo is a pharmacologically inert pill (containing sugar, chalk, etc.) or another fraudulent treatment method with no important (if any) physiological effect on the body which is used to elicit positive health effects through psychophysiological means. The process through which those positive changes occur is called the placebo effect. Healthcare professionals have used and continue to use placebos in their practice [1],[2]. And even though placebo effect is not easy to measure objectively and its efficiency varies greatly depending on many factors, there is no doubt that the effect itself is factual. Furthermore, it's so intertwined with the healing process and human psychology that to measure the objective effects of a particular substance or method, researchers first have to discount placebo-caused effects.

By making use of the placebo effect one could avoid or decrease (by consuming less of them) the side effects of pharmaceuticals. Placebos also don’t cost anything or cost very little compared to real medications. And for such conditions where the symptoms are subjective (e.g. pain, depression, nausea, fatigue, etc.) and active pharmaceuticals don’t treat the cause of the condition either, but only the symptoms (which would arguably be the majority of generally available medications) there’s not much difference what helps as long as it helps and the treatment which has fewer side effects would be the rational choice.

There are two main theories explaining the mechanics behind the placebo effect – expectancy theory and classical conditioning [3]. The importance of goals and motivation of the individual as contributing to this effect has also been emphasized [4]. The latter finding makes even more sense having in mind that placebo effect is especially vivid in the case of Parkinson’s disease, where the expectation of reward leads to dopamine release in the striatum which results in motor improvement [5]. For treating pain, depression, and Parkinson’s disease, placebos seem to work through the same mechanism by activating dopaminergic pathways since positive expectations are linked with dopamine release [13]. The case of Parkinson’s disease is exceptional in a way that here placebos give not only the subjectively perceived benefits (e.g. relieved pain or nausea or improved sleep quality) but the objective ones - improved motor functions. This particular disorder might serve as a link between the placebo effect and longevity research.

The usual understanding is that placebo treatment requires deception in order to work, but the effect might also occur when the person knows that he/she is receiving a placebo (this is known as open-label placebo or OLP) [6] and even be the same as in the case of deceptive placebos (DP) [7],[8]. There’s recent ongoing interest in OLP treatment and studies providing evidence for its effectiveness. The rationale (explanation of the working principles behind the placebo effect to the recipient) seems to play an important role in producing this effect during OLP treatment [8]. However, since expectations are an important part of the effect [9],[3],[10] and in the case of DP expectations are usually higher [11], it’s difficult to believe that OLPs can be as effective as DPs. Since studies proving OLP effectiveness are quite recent, more similar studies will have to be conducted for OLP effectiveness to be substantially proven. For now, they are received with a certain degree of skepticism [12]. But deceptive placebo approach (which is still the usual one) raises ethical concerns and requires a physician willing to deceive the patient. In fact, even the OLP approach might just not work on oneself, the psychological effect of someone else giving you the treatment might be a crucial part of this.



But does it have to be so? Could we come up with ways to reap the benefits of the placebo effect more quickly and directly, without involving a third party?


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Creative contributions

Making use of classical conditioning

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Povilas S
Povilas S Dec 29, 2020
Classical conditioning is one of the two main theories explaining how placebo effect works (the other being expectancy theory). And because it is based on unconscious associative learning it can be used intentionally to “deceive” yourself (or rather your body).

An active stimulus (in this particular context a biologically active drug or other active treatment) can be consumed simultaneously with a placebo (neutral stimulus) that has a distinctive feature, e.g. a particular taste, and after a certain time, the taste of the placebo pill will become associated with physiological effects that the active pill induces and your body might try to mimic them upon perceiving only a placebo. A more practical way of imagining this is a liquid in which a tasteless pharmacologically active ingredient is dissolved and then additionally a very distinctive taste is given to a liquid (e.g. bitter) and after some time of periodically consuming that drink, the active component is removed leaving just the bitter taste of otherwise inert liquid. This has been proven to work for inducing immunosuppression in mice [1],[2]. And the same process is likely to be able to activate and deactivate a wide variety of physiological functions.

This might be, at least to an extent, what’s happening when placebos are prescribed. If a person has ever taken, for example, sleeping pills and after some time he has insomnia again, but this time doctor prescribes him a placebo, verbal or written information about the “sleeping pills” together with the process of taking placebo pills (seeing them, tasting them, etc.) might work as a stimulus eliciting learned physiological response. When we receive any kind of treatment after some time we build a “database” of associations around different treatment methods and medical procedures, we learn or at least assume that, for example, injections work better and faster than pills and they are usually prescribed for more severe conditions, two pills will work better than one, etc. Those associations are reflected in the effectiveness of differently presented placebos . Those associations are primarily conscious, but they might work together with unconscious learning which then would activate physiological functions when receiving placebos that are presented in a certain way.

One could use simple simultaneous conditioning to test if the placebo effect might be self-induced this way without involving deception and conscious expectations and if it can then use it for their benefit. But in classical conditioning, if the neutral stimulus is presented for a longer time without active stimulus, the conditioned response becomes extinguished [3]. Therefore after some time, the placebo would have to be reinforced with active treatment again.

[1]Rosenberg, Robin; Kosslyn, Stephen (2010). Abnormal Psychology. Worth Publishers. p. 176. ISBN 978-1-4292-6356-6.

Biofeedback

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Povilas S
Povilas S Dec 31, 2020


Biofeedback is the process through which conscious control of otherwise involuntary physiological functions (such as heart rate, blood pressure, apparently involuntary muscular tensions, etc.) is achieved. This is done by first gaining awareness of them usually through technological means and then practicing to consciously alter them. Biofeedback system involves physiological sensors (such as ECG, blood pressure, skin conductivity, muscle tone sensors, brain imaging devices, etc.) and a computer with specific software to process the data and present it in real-time in a user-friendly form. A sort of video game might be designed to encourage learning to control one’s physiological processes at will, but usually, this is learned with the help of a therapist.

Physiological changes occur in response to changes in one’s thoughts, emotions, and behavior and the latter is achieved by various techniques of relaxation, visualization, mindfulness, etc. The monitoring part simply helps you observe the progress measured objectively and readjust the practice accordingly. Technology is required initially to learn this, but with practice, one can learn to induce desired physiological changes without it. Biofeedback can be used to improve health and performance or simply as a tool to enhance self-awareness.

Biofeedback is proven to be effective in treating attention deficit hyperactivity disorder (ADHD), anxiety, chronic pain, epilepsy, constipation in adults, headache in adults, hypertension, motion sickness, Raynaud's disease, temporomandibular joint dysfunction, and urinary incontinence in females and to be likely effective (not enough supportive evidence) for many other conditions [2]. Although not directly related to the placebo effect, biofeedback also makes use of similar psychophysiological mechanisms (especially behavioral conditioning) to induce desired changes in the body and in some cases might be more effective than placebo treatment .

There are biofeedback apps paired with home-use monitoring devices, like these , to practice it in a domestic setting. And though biofeedback is simple and in many cases effective technique for self-healing, it’s still little known and used in medical practice as well as by the lay population.

[1]Durand VM, Barlow D (2009). Abnormal psychology: an integrative approach. Belmont, CA: Wadsworth Cengage Learning. pp. 334. ISBN 978-0-495-09556-9.

Self-administered placebo

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Shubhankar Kulkarni
Shubhankar Kulkarni Jan 06, 2021
Self-administered placebo: I don't think this is an entirely "on-demand" placebo, biologically. But this can be done without the introduction of a third party (and, hence, whenever you want/ need) if you have the appropriate tools to measure the placebo effect.

Here is an old study that proposes a self-evaluation placebo test to measure the placebo effect of medication. The patients included in the study were not senile but were suffering from mild psychological disorders (neurosis, psychosis, personality disorder). The authors supplied the patients with questionnaires (Demographics Form, Discomfort Symptom Scale, F Scale, and Minnesota Multiphasic Personality Inventory) and a tablet (placebo medication) along with instructions for the placebo test. The instructions were to take the medication and sit in solitary in a closed room for 1 hour. Notice any changes - positive or negative and write them down. After 1 hour, the usual activities can be resumed but any changes within the first 24 hours should be recorded. After that, the questionnaires were to be filled and submitted for evaluation. Based on the reports, the participants were put on a selected therapy.

In another study, participants suffering from stress, anxiety, and symptoms of depression were given either placebo-oxytocin or placebo-serotonin drugs. The participants completed online questionnaires of measures of perceived stress (Perceived Stress Scale-10), anxiety (Cognitive Somatic Anxiety Questionnaire), and symptoms of depression (Centre for Epidemiological Studies – Depression) before and after the 3-day self-administered taken-at-home placebo medication. Both the treatments were effective in reducing the symptoms of depression but only the oxytocin group reported less stress and anxiety as compared with controls.

If we combine the two studies, a placebo can be self-administered. We need multiple treatment options to choose from to observe the placebo effect. One placebo tablet will be taken by the participant and the changes (if any) will be noted for 24 hours. The second medication can be taken after a washout period (to be identified based on the kind of disorder) and the changes will be noted in the same way using standardized questionnaires. The effect of the two (or more) medications can be compared and the one giving better results can be selected for long-term treatment. Deception, in this case, is minimum. Although the drugs are chemically the same, their packing and appearance create an illusion of it being different. Moreover, since the participant self-reports their experiences/ effects of the drug, no third party is involved. The set of tools used (the questionnaires for evaluating the well-being index) may create a sense of satisfaction of actually doing something to treat the illness. This mental satisfaction drives the placebo effect.

[1]Arthur K. Shapiro, Valerie Mike, Harvey Barten, Elaine Shapiro, Study of the placebo effect with a self-administered placebo test, Comprehensive Psychiatry, Volume 14, Issue 6, 1973, Pages 535-548, ISSN 0010-440X, https://doi.org/10.1016/0010-440X(73)90039-4. (http://www.sciencedirect.com/science/article/pii/0010440X73900394)

[2]Darragh M, Yow B, Kieser A, Booth RJ, Kydd RR, Consedine NS. A take-home placebo treatment can reduce stress, anxiety and symptoms of depression in a non-patient population. Aust N Z J Psychiatry. 2016 Sep;50(9):858-65. doi: 10.1177/0004867415621390. Epub 2015 Dec 16. PMID: 26681262.

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Povilas S
Povilas S4 months ago
As I understand the participants in both of the studies (or at least in the second one) didn't know that they are getting placebos? But what you are suggesting is that a person would know this and would choose between two apparently different types of placebos (presented in a different way, but still knowing that they are essentially the same)? And that the self-assessment of the effects of apparently different placebos would be an important part of this?
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Shubhankar Kulkarni
Shubhankar Kulkarni4 months ago
Povilas S The participants in both the studies did not know they were taking placebos. Yes, I am suggesting exactly that. The self-assessment will be an important part of this. I am thinking of updating my suggestion as I am writing this reply to you. I don't think anyone has used placebo the way I suggest. I don't know whether it will work. But here is why I think it might work -

How does placebo work? - We know something is good for us/ our body. We take it believing that it will improve our status. Just the thought that something will be beneficial causes an additional or a fast improvement, which is over and above that caused by the thing (medication, therapy) that we administer. This is when we did not know much about the placebo effect.

Now we know how placebo works. We know that placebo can be beneficial to us. Placebo is a good thing. So, instead of the medication, we may be able to use the placebo as the thing that we administer. Since we now believe that the placebo is beneficial, the placebo might in turn create a placebo effect. Does any of this make sense?

Moreover, since the person knows it is a placebo, we do not need a third party for blinding. However, I think the self-assessments are necessary for three reasons - 1. By doing the assessments, you put some work into the therapy. You invest in it. This creates an interest in your treatment, which in turn causes a placebo effect. The rewards that you expect are always proportional to your investment. As an example, here is an article that says that costly placebos work better than cheap ones (https://www.sciencedaily.com/releases/2008/03/080304173339.htm). When you pay, you invest in your treatment. This causes a greater improvement in your status. 2. You can track your improvement. You can set a goal and know when you have reached it. You can stop the treatment then. 3. You get to know more about the thing you are suffering from. You can avoid things that cause it in the future.
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Povilas S
Povilas S4 months ago
Shubhankar Kulkarni I agree with the investment part. In the first part, you seem to be talking (more or less) about open-label placebo (OLP). When the person knows that he/she is receiving a placebo and is usually explained that this should work because of the placebo effect. This approach is getting popular recently and there are more and more studies researching OLP treatment. But they are still controversial for now and more research will have to be done before they can get established as legit treatment. Some articles presented evidence that OLPs work just as well as DPs (deceptive placebos). However, this is doubtful, because the placebo effect has a lot to do with expectations and expectations are higher when you think you are receiving the real thing.

Blind chance

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Povilas S
Povilas S Dec 31, 2020
Probably the simplest way to make your expectations work for your benefit or at least to test how much placebo effect can influence you is to sort of mimic a placebo-controlled clinical trial on yourself. In double-blind placebo-controlled studies neither those who are receiving test treatment (usually some kind of pharmaceutical) nor those who are giving the treatment know which subjects are receiving the real thing and which the placebo. This way even those who are giving the treatment can’t influence the results by giving conscious or subconscious clues to the recipients. Of course, the expectations are lower when you know there’s a ½ chance you will not receive an active substance, but they are still present.

This can be imitated in a domestic setting and only takes two people. This would be a sort of game, but it might reveal interesting results. The person who will test the substance prepares the set of containers. An equal number of them should be filled with an active substance and the same number with a placebo substance that has identical or as alike as possible qualities – color, smell, taste, etc. The second person is out of sight at this stage to not know which containers contain what. Then the first person leaves the room and the second person mixes the set prepared by the first person and invites the first person to do the test. The first person then randomly chooses a container (this could be done blindfolded) and consumes the substance. All the containers should also be marked by the first person to finally know which ones were filled with placebos, but this should be done in a way that the second person wouldn’t see that when mixing (for example with down-facing labels on the bottom of each container). After sufficient time would pass, e.g. a purported duration of the effects of an active substance, the first person would evaluate the experience and guess whether he/she took a placebo or not and then would be allowed to see the label. Ideally, this should be repeated many times (on different days, for example) for the person to get a chance to experience both cases (ideally an equal number of times) and compare them. This way one can test not only to what extent a placebo can affect you but also to what extent the effect of an active substance is a placebo effect.

One good substance for this kind of test I can think of is coffee. Good quality decaf coffee tastes almost exactly the same as normal one. But taste is not necessarily an obstacle, in the case of medications gel capsules might be used to avoid tasting both substances. This kind of blind testing could probably be done alone, but then one needs to come up with a way how to mix the containers without having the slightest clue which one is which. Some centrifuge-like device is an option.
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Manel Lladó Santaeularia
Manel Lladó Santaeularia3 months ago
Okay, the method is interesting, but I wonder what is the purpose of that apart from researching the placebo effect? I mean, if a person has a disease and needs a treatment, it would not be ethical to give them a placebo when you can give them the proper treatment, especially if you don't know yet whether they have the same effect. It would not make sense in a practical setting and would not be about "making the placebo effect work for us", unless I am missing something.

The only case where I can see this as useful are situations like chronic pain where, you have a person who needs chronic medication (which will have its negative side effects). In that case, having a similar effect from placebo, you could avoid those effects.
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Povilas S
Povilas S3 months ago
Manel Lladó Santaeularia If you are talking about this particular contribution, I was directing it more towards a personal use in a home-like setting. In fact generally, when starting this session I more had that kind of use in mind - how can people like you and me make use of it by "tricking themselves"?

Good novel ideas can of course contribute to better placebo use in clinical settings also. But the session is not about how can we make placebo effect work for us, because it's already been used in clinical settings for a long time and it is proved to work. It's more about how can we make it work "on-demand", it's about the deception vs knowing aspect. Placebos mostly work because of the deception element. Can we somehow bypass this and simplify the process?

Now about usefulness/ethics. Placebos generally don't treat the disease itself, they mostly affect subjectively perceived symptoms like pain, sleep quality, nausea, etc. One exception to this, that I know of, is Parkinson's disease, where placebos improve patient's motor functions also (an objective benefit), there might be more such cases that are not yet discovered.

But let's face it - arguably the majority of commonly used medications, don't treat the cause of the disease either, they alleviate the symptoms, that's it. So in those cases, there's not much difference what to use, as long as it helps and placebos have the benefit of not causing harmful side effects.

So if a person is taking sleeping pills or painkillers at home, it would be helpful if they could get the same effect by using something pharmacologically inert. Or at least they could lower the consumption of pharmacologically active drugs this way, if not fully replace them. That's why some doctors keep prescribing placebos to their patients even though it's not very ethical.
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Manel Lladó Santaeularia
Manel Lladó Santaeularia3 months ago
Povilas S Okay, I see your point. However, most drugs work better than placebo, otherwise they wouldn't be approved for clinical use. The fact that you can se an improvement when using placebo, compared to not treating, doesn't mean placebo is as good as the treatment.

Thus the question becomes: Would you willingly take a pill that you don't know if it will do 100% effect or 15% effect? Or would you rather take the one that has 100% effect? I believe this is very disease/symptom dependent, but I don't see how you could fully replace a pharmacologically active drug in that way.

If we talk about withdrawal symptoms (class E adverse reactions) then I would definitely think that could be useful in this particular case.

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